Precision and surface quality of pure titanium (Ti) castings for dental and biomedical uses are limited because of the high melting temperature and the violent reactivity of Ti with mold materials during casting procedures. This feasibility study evaluates an experimental low-melting Ti-Co alloy in term of its microstructure and physical and mechanical properties. Tensile samples of Ti-12 wt % Co alloy were cast under a protective argon atmosphere. The melting range of the cast samplers was determined. Cast samples were annealed at 1010°C for various time intervals in order to homogenize microstructures. Microstructures were examined by optical and scanning electron microscopy. Tensile strength and microhardness tests were performed and correlated with microstructures resulting from annealing processes. Ti₂Co intermetallic compound coexisted with Ti-Co solid solution in all samples. The melting range of the alloy was 1062–1088°C, which is 568°C lower than that of Ti. The thickness of the surface oxide scale on cast samples was dramatically reduced to 1–3 μm because of the low-melting nature of the alloy. Solution treatment at 1010°C for 100 h yields the highest tensile strength. Ultimate tensile strength is measured from 852 to 1240 MPa which is stronger than currently used dental alloys. Microhardness values were ranged from 341 to 488 KHN and elongation was from 1.2 to 1.8%. Both microhardness and percentage elongation are similar to those of dental Co-Cr alloys. One hundred hours of annealing dissolved dendritic boundaries and transformed the alloy to a more microductitle matrix, however, the intermetallic compound of Ti₂Co remained. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

This study investigated the effect of shape, size, and surface modification of hydroxyapatite (HAP) fillers on the degree of conversion (DC) and mechanical properties of a model BisGMA/TEGDMA composite initially and after 4 weeks of storage. Ten percent of conventional glass fillers were replaced by HAP spheres (Sph), silicon-doped spheres (Sph_Si), whiskers (Wh), silicon-doped whiskers (Wh_Si), and nanosized HAP particles (Nano). Spheres were specifically structured agglomerates consisting of a central void and radially orientated primary particles, whereas whiskers were compact monocrystals. DC, Vickers hardness (HV), flexural strength (Fs), flexural modulus (Ef), compressive strength (Cs), and compressive modulus (Ec) were tested. There were no significant differences in the DC between all tested groups. HV decreased by 5.4–17% with the addition of HAP, while Fs increased by 13.9–29% except in Nano group (decrease by 13%). After storage, Sph and Sph_Si groups showed similar HV, Ef, Cs and Ec and higher Fs than the control. The fracture mode of HAP spheres was through the central void whereas whiskers showed longitudinal delamination, transverse, and mixed fractures. HAP spheres with or without silicon- doping have a potential to be part of the filler content of dental composites. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

A large number of resorbable bone graft substitutes are being marketed as porous, but the total porosity being referred does not take into account many of the biologically important physical aspects of porosity. Therefore, to allow the direct comparison of different commercial products, there is a need to adopt guidelines for a standardized characterization. The aim of the study was to assess a microcomputed tomography-based method for the characterization of porous biomaterials to allow head-to-head comparison of these materials. The study included two commercial biomaterials (Actifuse^® and ChronOs^®) and three experimental biomaterials (sintered bioactive glass microspheres, porous alginate (Alg), and porous Alg/hydroxyapatite composite). In addition to porosity and pore size distributions, the interconnectivity of the pores was assessed by an iterative blocking of interconnections. The biomaterials were characterized in their original morphologies (granules or cones). Differences between the materials were demonstrated. Actifuse^® had the broadest distributions of pores and interconnections. ChronOs^® had a substantial fraction of closed pores (10%). Other materials had closed porosity below 1%. Due to the thinner walls of the lattice, the Alg-based materials had high total porosity (>80%). Discrepancies were found between the porosity values reported by the manufacturers and the values obtained in this study. The proposed method is plausible for the systematic characterization of porous biomaterials. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The surfaces of three chitosan samples, differing only in their degrees of deacetylation and of carboxyethyl chitosan were chemically characterized by X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectroscopy, X-ray diffraction, and Fourier transform infrared, both before and after sterilization with ethylene oxide. Unexpected elemental ratios suggest that surface chemical modification occurred during the processing of the original chitin, with further surface modification on subsequent sterilization, despite previous reports to the contrary. Cell viability was evaluated by direct contact methyl thiazole tetrazolium and lactate dehydrogenase assays between the chitosan particles and A549 human epithelial cells, which demonstrated that the modifications incurred on sterilization are reflected in biocompatibility changes. All the samples were found to be biocompatible and nontoxic before sterilization and remained so subsequently. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Further development of ceramic materials for total hip replacement aim to increase fracture toughness and further reduce the incidence of bearing fracture. Edge loading due to translational mal positioning (microseparation) has replicated stripe wear, wear rates, and bimodal wear debris observed on retrievals. This method has replicated the fracture of early zirconia ceramic-on-ceramic bearings. This has shown the necessity of introducing microseparation conditions to the gait cycle when assessing the tribological performance of new hip replacement bearings. Two novel ceramic matrix composite materials, zirconia-toughened alumina (ZTA) and alumina-toughened zirconia (ATZ), were developed by Mathys Orthopädie GmbH. In this study, ATZ-on-ATZ and ZTA-on-ZTA bearing combinations were tested and compared with alumina-on-alumina (Al₂O₃-on-Al₂O₃) bearings under adverse microseparation and edge loading conditions using the Leeds II physiological anatomical hip joint simulator. The wear rate (±95% confidence limit) of ZTA-on-ZTA was 0.14 ± 0.10 mm³/million cycles and that of ATZ-on-ATZ was 0.06 ± 0.004 mm³/million cycles compared with a wear rate of 0.74 ± 1.73 mm³/million cycles for Al₂O₃-on-Al₂O₃ bearings. Stripe wear was evident on all bearing combinations; however, the stripe formed on the ATZ and ZTA femoral heads was thinner and shallower that that formed on the Al₂O₃ heads. Posttest phase composition measurements for both ATZ and ZTA materials showed no significant change in the monoclinic zirconia content. ATZ-on-ATZ and ZTA-on-ZTA showed superior wear resistance properties when compared with Al₂O₃-on-Al₂O₃ under adverse edge loading conditions. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

In this study, we explore the selective culturing of human mesenchymal stem cells (hMSCs) on Si-based diffractive platforms. We demonstrate a single-step and flexible method for producing platforms on nanostructured porous silicon (nanoPS) based on the use of single pulses of an excimer laser to expose phase masks. The resulting patterns are typically 1D patterns formed by fringes or 2D patterns formed by circles. They are formed by alternate regions of almost unmodified nanoPS and regions where the nanoPS surface has melted and transformed into Si nanoparticles. The patterns are produced in relatively large areas (a few square millimeters) and can have a wide range of periodicities and aspect ratios. Direct binding, that is, with no previous functionalization of the pattern, alignment, and active polarization of hMSCs are explored. The results show the preferential direct binding of the hMSCs along the transformed regions whenever their width compares with the dimensions of the cells and they escape from patterns for smaller widths suggesting that the selectivity can be tailored through the pattern period. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

A Plasma electrolytic oxidation (PEO) process was used to produce bioactive coatings on Ti. PEO coatings with Ca/P atomic ratio of 1.7 and 4.0 were fabricated and characterized with respect to their morphology, composition, and microstructure. AC and DC electrochemical tests were used to evaluate the effect of (i) organic additives (amino acids, proteins, vitamins, and antibiotics) in alpha-minimum essential medium (α-MEM) on electrochemical stability of noncoated and PEO-coated Ti and (ii) coating composition, microstructure, and corrosion behavior on the cell response in α-MEM. PEO-coated Ti showed higher corrosion resistance than the noncoated Ti in MEM with and without organic additives by an order of magnitude. The corrosion resistance in α-MEM decreased with time for nonmodified Ti and increased for PEO-coated Ti; the latter was because of the adsorption of the proteins in the coating pores which increased the diffusion resistance. The presence of Ca and P in titanium oxide coating at the Ca/P ratio exceeding that of any stoichiometric Ca–P–O and Ca–P–O–H compounds facilitates faster osteoblast cell adhesion. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

A liquid-to-solid gelling polymer system, such as the poly(ethylene glycol) diacrylate-pentaerythritol tetrakis (3-mercaptopropionate) (PEGDA-QT) system, can fill cerebral aneurysms more completely than current embolization materials, reducing the likelihood of aneurysm recurrence. PEGDA-QT gels were formulated using PEGDA of different molecular weights (PEGDA₅₇₅ and PEGDA₇₀₀), and their characteristics were examined in vitro. Experiments examined gel time, mass change, crosslink integrity, cytotoxicity, and protein release capabilities. In general, PEGDA₅₇₅-QT gels were more hydrophobic, requiring an initiating solution with a higher pH (pH 9.5) to achieve a gel time comparable to PEGDA₇₀₀-QT gels, which used an initiating solution at pH 9.19. The mass change and crosslink integrity of gels were analyzed over time after gels were submerged in 150 mM phosphate buffered saline. After 380 days, PEGDA₅₇₅-QT gels achieved a maximum mass increase of 72% due to water uptake, while PEGDA₇₀₀-QT gels doubled their initial mass (100% increase) by 165 days. Compression tests showed that PEGDA₇₀₀-QT gels hydrolyzed more quickly than PEGDA₅₇₅-QT gels. Cytotoxicity assays showed that in general, PEGDA₅₇₅-QT negatively affected cell growth, while PEGDA₇₀₀-QT gels promoted cell viability. Sustained, controlled release of lysozyme, a 14.3 kDa protein, was achieved over an 8-week period when loaded into PEGDA₇₀₀-QT gels, but PEGDA₅₇₅-QT gels did not show sustained release. These studies show that although they are similar in composition, these PEGDA-QT gel formulations behave considerably differently. Although PEGDA₇₀₀-QT gels swell more and degrade faster than PEGDA₅₇₅-QT gels, their cytocompatibility and protein release characteristics may prove to be more beneficial for in vivo aneurysm treatment. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Visual impairment affects over 285 million people worldwide and has a major impact on an individual's quality of life. Tissue engineering has the potential to increase the quality of life for many of these patients by preventing vision loss or restoring vision using cell-based therapies. However, these strategies will require an understanding of the microenvironmental factors that influence cell behavior. The eye is a well-organized organ whose structural complexity is essential for proper function. Interactions between ocular cells and their highly ordered extracellular matrix are necessary for maintaining key tissue properties including corneal transparency and retinal lamination. Therefore, it is not surprising that culturing these cells in vitro on traditional flat substrates result in irregular morphology. Instead, topographically patterned biomaterials better mimic native extracellular matrix and have been shown to elicit in vivo-like morphology and gene expression which is essential for tissue engineering. Herein we review multiple methods for producing well-controlled topography and discuss optimal biomaterial scaffold design for cells of the cornea, retina, and lens. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

This study evaluated the cytotoxicity of experimental adhesive systems (EASs) on odontoblast-like cells. Paper discs (n = 132) were impregnated with 10 µL of each EAS—R1, R2, R3, R4, and R5 (in an ascending order of hydrophilicity), followed by photoactivation. R1 and R2 are nonsolvated hydrophobic blends, R3 represents a simplified etch-and-rinse adhesive system, and R4 and R5 represent simplified self-etch adhesive systems. Discs were immersed in Dulbecco's modified Eagle's medium for 24 h to obtain eluates applied on MDPC-23 cell cultures. No material was applied on discs used as control (R0). Cell viability [3-(4,5-dimethythiazol-2-yl)−2,5-diphenyl tetrazolium bromide assay], total protein (TP) production, alkaline phosphatase (ALP) activity, type of cell death, and degree of monomer conversion Fourier transform infrared (%DC-FTIR) were evaluated. Data were analyzed by Kruskal–Wallis and Mann–Whitney tests (α = 0.05). Considering R0 (control) as having 100% of cell viability, R1, R2, R3, R4, and R5 reduced the metabolic activity of cells by 36.4, 3.1, 0.2, 21.5, and 65.7%, respectively, but only R1 and R5 differed from R0. Comparing with R0, lower TP production was observed for R1, R4, and R5, while ALP activity decreased for R1 and R5. Necrotic cell death was predominant for all EASs, but only R1, R4, and R5 differed from R0. Only R5 presented a different apoptotic cell death ratio from R0. R1 presented the lowest %DC (ca. 37%), whereas R4 and R5 presented the highest (ca. 56%). In conclusion, R2 and R3 were not toxic to the MDPC-23 cells, suggesting that the degree of hydrophilicity or %DC of the EASs alone were not responsible for their cytopathic effects. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The introduction of silicone hydrogel (SiHy) contact lenses to the consumer marketplace necessitates study of the susceptibility of these lenses to spontaneous deposition by hydrophobic lipid components of ocular tears. The use of radioisotopes to measure lipid sorption on SiHy contact lenses gives precise and accurate results but requires institutional infrastructure and compels efficient lipid removal from the lens. This study compares three methods of quantitating phospholipid and cholesterol sorption on SiHy lenses using radiolabeled cholesterol and phosphatidylcholine that were sorbed on lenses from an artificial tear fluid. A triple extraction technique using n-propanol gives the most reliable results. Comparison of sorption on SiHy lenses shows that balafilcon A and senofilcon A lenses sorb similar amounts, while lotrafilcon B lenses sorb comparatively less. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Electrospinning is one of the most simple and effective methods to prepare polymer fibers with the diameters ranging from nanometer to several micrometers. Poly(L-lactide)-co-poly (ɛ-caprolactone) (P(LLA-CL)) fibers and P(LLA-CL)/heparin coaxial composite fibers herein were successfully prepared by single electrospinning and coaxial electrospinning, respectively. The prepared endothelialized P(LLA-CL) and P(LLA-CL)/heparin vascular grafts were used in the Beagle dogs experiment to evaluate the feasibility of thus made different scaffolds for substitution of dog femoral artery in early period, medium term, and long term, meanwhile the pure P(LLA-CL) vascular graft was used as the control group during all the experiments. The animal model was established by using the graft materials to anastomose both femoral arteries of dogs. The vascular grafts patency rates (i.e., the unobstructed capacity of blood vessel) were detected by color Doppler flow imaging technology and digital subtraction angiography. To observe the histological morphology at different periods, the vascular grafts were removed after 7, 14, and 30 days, and the corresponding histological changes were evaluated by hematoxylin and eosin staining. The experimental results show that in the early period, the patency rates of pure P(LLA-CL) graft, endothelial P(LLA-CL) graft, and P(LLA-CL)/heparin graft were 75%, 75%, and 100%, respectively; in the medium term, the patency rates of pure P(LLA-CL) graft and endothelial P(LLA-CL) graft were 25%, whereas that of P(LLA-CL)/heparin graft was 50%; the patency rates of pure P(LLA-CL) graft and endothelial P(LLA-CL) graft were down to 0%, whereas the patency rate of P(LLA-CL)/heparin graft was 25% in the long term. This preliminary study has demonstrated that P(LLA-CL)/heparin coaxial composite fiber maybe a reliable artificial graft for the replacement of femoral artery. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The aim of this study is to investigate the mechanical behavior of model methacrylate-based dentin adhesives under conditions that simulate the wet oral environment. A series of monotonic and creep experiments were performed on rectangular beam samples of dentin adhesive in three-point bending configuration under different moisture conditions. The monotonic test results show a significant effect of loading rate on the failure strength and the linear limit (yield point) of the stress-strain response. In addition, these tests show that the failure strength is low, and the failure occurs at a smaller deformation when the test is performed under continuously changing moisture conditions. The creep test results show that under constant moisture conditions, the model dentin adhesives can have a viscoelastic response under certain low loading levels. However, when the moisture conditions vary under the same low loading levels, the dentin adhesives have an anomalous creep response accompanied by large secondary creep and high strain accumulation. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Interventional oncology procedures such as thermal ablation are becoming routine for many cancers. Hydrodissection—separating tissues with fluids—protects tissues near the treatment zone to improve ablation's safety and facilitate more aggressive treatments. However, currently used fluids such as normal saline and 5% dextrose in water (D5W) migrate in the peritoneum, reducing their protective efficacy. As a hydrodissection alternative, we investigated a thermoreversible poloxamer 407 (P407) solution. Such a material can be injected as a liquid which then forms a semi-solid gel at body temperature without syneresis. The desired gelation temperature of 32°C was achieved with 15.4 wt/wt % P407. Viscosity analysis revealed the lowest viscosity and ideal injection point was at 14°C. Solution viscosity increased during gelation, to a peak of 65 kPa*s at 40°C. The electrical impedance of P407 was significantly greater than isotonic saline, but lower than D5W, indicating its potential for electrical protection. The P407 gel was similar to other hydrodissection fluids at ultrasound and CT imaging. Ex vivo liver ablations showed that P407 protects neighboring tissues, but may require a thicker barrier for comparable protection to D5W. Overall, we found that the P407 solution is a feasible alternative to traditional hydrodissection fluids and warrants additional study. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Calcium phosphate cements (CPCs) are established in surgery as temporary bone replacement materials. The most common and important class of CPC, transformed into nanocrystalline hydroxyapatite after setting, is characterized by good biocompatibility and osteoconductivity. However, acceleration of remodelling is in the focus of ongoing research. In the present study, the bone healing efficacy of Biocement D (BioD) modified with mineralized collagen alone (BioD/coll) or in combination with osteocalcin (BioD/coll/OC), O-phospho-L-serine (BioD/coll/PS), sodium citrate (BioD/coll/cit), and polylactide (BioD/coll/PL), respectively, was evaluated in a large animal model. Resorption of the bone substitutes and new bone formation were studied in cyst-like jaw defects of minipigs after filling with the unmodified BioD and the modified BioD variants, respectively. Histomorphometric analysis revealed small differences between the different cement types with respect to resorption. However, new bone formation was improved in case of defects repaired with BioD/coll/OC and BioD/coll/PS and slightly improved in case of BioD/coll and BioD/coll/PL. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

In this study, the coagulation-induced resistance to flow in small-diameter nonpermeable Tygon tubes and permeable expanded polytetrafluoroethylene (ePTFE) vascular grafts was characterized by measuring the upstream pressure needed to purge the coagulum from the tube lumen. This purging pressure was monitored using a closed system that compressed the contents of the tubes at a constant rate. The pressure system was validated using a glycerin series with well-defined viscosities and precisely controlled reductions in cross-sectional area available for flow. This system was then used to systematically probe the upstream pressure buildup as fibrin glue, platelet-rich plasma (PRP) or whole blood coagulated in small-diameter Tygon tubing and or ePTFE grafts. The maximum purging pressures rose with increased clot maturity for fibrin glue, PRP, and whole blood in both Tygon and ePTFE tubes. Although the rapidly coagulating fibrin glue in nonpermeable Tygon tubing yielded highly consistent purging curves, the significantly longer and more variable clotting times of PRP and whole blood, and the porosity of ePTFE grafts, significantly diminished the consistency of the purging curves. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Textile meshes frequently are implanted in the abdominal wall to reinforce a hernia repair. However, revisions for mesh associated complications confirm that these devices are not completely free of risk. Explanted devices offer an opportunity to define the impact of mesh structure on tissue response. This retrieval study analyses the tissue reaction to 623 polypropylene mesh samples (170 class 1 with large pores, and 453 class 2 with small pores) explanted for pain, infection, or recurrence. Histopathological assessment included morphometry of inflammatory infiltrate (IF) and connective tissue (CT), and of collagen 1/3 ratio. Half of the meshes were removed after more than 23 month. Despite large inter-individual differences removal for infection showed more IF than for pain or recurrence with significant correlation of IF with CT. Class 1 meshes with large pores showed less IF, CT, fistula formation, calcification, and bridging than class 2 meshes with small pores. Meshes removed for recurrence showed a lowered collagen 1/3 ratio in 70%. Large pore class 1 meshes showed an improved tissue response and may be considered as favorable to prevent inflammatory side effects. The presence of lowered collagen 1/3 ratio in most of the samples with recurrences stresses the relevance of an intact healing process. Late manifestation of complications demands long-lasting follow-up. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Poly(lactide-co-glycolide) (PLGA) and elastin-like polypeptide (ELP) have been widely used as a biodegradable scaffold and thermoresponsive matrix, respectively. However, little attention has focused on the combinatorial use of these biomaterials for tissue engineering applications. An ELP matrix TGPG[VGRGD(VGVPG)₆]₂₀WPC (referred to as REP) contains multiple Arg-Gly-Asp motifs. This study fabricated porous PLGA scaffolds coated with various concentration of matrix via thermally induced phase transition to improve adhesion-mediated proliferation and differentiation of neural progenitor cells. Matrix-coated scaffolds were characterized by FTIR, SEM, and hematoxylin and eosin staining with respect to coating efficiency, porosity, and pore size and shape. On the matrix-coated scaffolds, cells grew as a single cell or associated each other to form a multicellular layer or cluster. In biological evaluations, cell adhesion and proliferation were significantly promoted in a matrix concentration-dependent manner. More importantly, in combination with retinoic acid, the differentiation of progenitor cells into neuronal and astroglial lineages was highly stimulated in the cells cultured on matrix-coated scaffolds than on untreated controls. Taken together, our results indicated that the REP matrix-functionalized PLGA scaffolds are suitable for improving neuronal cell functions, and thus applicable for neural tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Postoperative adhesion often causes serious adverse effects such as bowl obstruction, chronic abdominal pain, pelvic pain, and infertility. We previously reported that a poly-L-lactic acid (PLLA) nanosheet can efficiently seal a surgical incision without scarring. In this report, we examined whether the PLLA nanosheet can form an effective anti-adhesion barrier in partial hepatectomy accompanied by severe hemorrhaging in rats. To evaluate the anti-adhesive property of the nanosheet, the liver wound surface was covered with TachoComb^®, a well-known hemostat material used in clinical procedures, and then with the PLLA nanosheet. Dressing the wound surface with TachoComb^® alone caused severe adhesion with omentum and/or residual parts of the liver. By contrast, combinational usage of TachoComb^® and the PLLA nanosheet significantly reduced such adhesion, presumably by inhibiting the permeation of oozing blood cells and the infiltration of fibroblastic cells. Moreover, the nanosheet displayed low permeability against serum proteins as well as cells in vitro, supporting the notion that the PLLA nanosheet has anti-adhesive properties in vivo. These results strongly suggested that the PLLA nanosheet is a promising material for reducing unwanted postoperative adhesion. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Dural closure after the neurosurgery can prevent postoperative complications. Although many types of dural substitute have been developed, most of them lack functional and structural characteristics compared with the natural dura mater. In this study, we used electrospinning method to fabricate a multilayer scaffold to promote dural repair. The inner layer of the scaffold that faces the brain tissue is composed of poly-lactic acid (PLA) to reduce tissue adhesion. The middle layer of the scaffold is composed of poly-ɛ-caprolactone and PLA, which provides a watertight seal. The outer layer of the scaffold contains a large amount of collagen to promote cell attachment and proliferation. The results from in vitro study and an animal model have shown that this multilayer fibrous scaffold has sufficient mechanic strength and biochemical properties to enhance dural repair. Therefore, fabrication of scaffold with multiple functional and structural layers may provide a novel approach for tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Intracoronary stents have markedly improved the outcomes of catheter-based coronary interventions. Intracoronary stent implantation rates of over 90% during coronary angioplasty are common. Stent implantations are associated with a small but statistically significant number of adverse outcomes including restenosis, thrombosis, strut malapposition, incomplete strut endothelialization, and various types of stenting failure. Better matching of biomechanical properties of stents and lesions could further improve the clinical outcome of intracoronary stenting. Thus, in this article, we assess the need for advanced intracoronary stent–lesion matching. We reviewed the data on biomechanics of coronary stents and lesions to develop knowledge-based rationale for optimum intracoronary stent selection. The available technical information on marketed intracoronary stents and the current understanding of the biomechanical properties of coronary lesions at rest and under stress are limited, preventing the development of knowledge-based rationale for optimum intracoronary stent selection at present. Development of knowledge-based selection of intracoronary stents requires standardization of mechanical stent testing, communication of the nonproprietary technical data on stents by the industry and dedicated research into procedural stent–lesion interactions. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

An electrospun fiber mat using a new composite consisting of siloxane-containing vaterite (SiV) and poly(lactic-co-glycolic acid) (PLGA) (denoted by SiP_LGVH) was prepared with the aim of applying it as a membrane for use in a guided bone regeneration (GBR) system. Another electrospun fiber mat using a previously described composite consisting of SiV and poly(L-lactic acid) (denoted by SiPVH) was also prepared as a comparative sample. SiP_LGVH fiber mats showed superior results in terms of mechanical tensile properties and cellular behavior. Their elongation before failure was about eight times higher than that of SiPVH. The numbers of osteoblast-like cells that proliferated on the SiP_LGVH fiber mats, regardless of the hydroxyapatite coating, were comparable to that of SiPVH. The cells spread more, two dimensionally, on the SiP_LGVH fiber mats, since the pores between fibers were narrowed down because of swelling of the PLGA matrix during cell culture. This two-dimensional cellular proliferation quality on the SiP_LGVH fiber mats is expected to be suitable for materials used in GBR, leading to control of infiltration of the soft tissue and great tissue integration with the surrounding tissue. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

This works reports the development and preliminary assessment of a new bioreactor for culturing large-sized three-dimensional constructs in bone tissue engineering. The bidirectional continuous perfusion bioreactor (BCPB) promotes mechanical stimulation of cells through the creation of shear forces induced by flow perfusion. The main innovation consists in the possibility of culturing scaffolds of large dimensions that can be suitable for the regeneration of critical sized defects. The functionality of BCPB was preliminarily evaluated by culturing starch–polycaprolactone scaffolds/goat bone marrow stromal cells for 14 and 21 days. Cylindrical blocks were stacked (42 mm thick). Static culture was used as controls. The samples were collected for DNA, alkaline phosphatase (ALP), scanning electron microscopy (SEM), and histological analysis. The results showed higher ALP levels in the bioreactor cultures than those obtained under static conditions. The number of cells in constructs cultured in the bioreactor showed lower values compared to static cultures, suggesting that static conditions tend to privilege the metabolic path way for cellular proliferation while dynamic conditions tend to privilege the metabolic path for osteogenic differentiation. SEM observations show that, the migration and cell distribution was observed in the bioreactor. These results demonstrate the feasibility and the benefit of culturing constructs in BCPB. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Bone tissue engineering is a new approach for the repair of orbital defects. The aim of the present study was to evaluate prefabricated beta-tricalcium phosphate (β-TCP) combined with autologous bone marrow stromal cells (BMSCs) to repair orbital wall defect in canine models. Defects measuring 10 mm in diameter were created in the orbital medial walls of 12 dogs. The orbits were randomly divided into five groups: group 1, repaired with osteogenesis-induced BMSCs/TCP constructs; group 2, repaired with noninduced BMSCs/TCP constructs; group 3, repaired with β-TCP scaffolds only; group 4, normal group; group 5, negative control (bone defect without treatment). Computed tomography (CT) scanning, gross observation, bone density measurements, micro–CT, and histological observations were performed. In group 1, new bone was observed with only a small amount of residual material, and bony union was achieved 3 months after surgery. In contrast, the constructs showed slow degradation with minimal bone formation in groups 2 and 3. Furthermore, the appearance and bone density of the constructs in group 1 were similar to that of normal bone: the constructs were covered with complete mucosa, and new alveolate plate grew into the ethmoidal sinuses. A large bone defect remained in group 5. This study demonstrated that biologic scaffolds composed of β-TCP and osteogenesis-induced BMSCs have been successfully used to restore bone functionality in animal models, which may provide a potential clinical approach for orbital wall repair and bone regeneration in humans. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Neural interfaces have traditionally been fabricated on rigid and planar substrates, including silicon and engineering thermoplastics. However, the neural tissue with which these devices interact is both 3D and highly compliant. The mechanical mismatch at the biotic–abiotic interface is expected to contribute to the tissue response that limits chronic signal recording and stimulation. In this work, novel ternary thiol-ene/acrylate polymer networks are used to create softening substrates for neural recording electrodes. Thermomechanical properties of the substrates are studied through differential scanning calorimetry and dynamic mechanical analysis both before and after exposure physiological conditions. This substrate system softens from more than 1 GPa to 18 MPa on exposure to physiological conditions: reaching body temperature and taking up less than 3% fluid. The impedance of 177 µm² gold electrodes electroplated with platinum black fabricated on these substrates is measured to be 206 kΩ at 1 kHz. Specifically, intracortical electrodes are fabricated, implanted, and used to record driven neural activity. This work describes the first substrate system that can use the full capabilities of photolithography, respond to physiological conditions by softening markedly after insertion, and record driven neural activity for 4 weeks. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Astrocytes support structure of central nervous system (CNS) and provide nutrients to neurons. When CNS is injured, astrocytes are activated and produce glia scar. There are debates if the reactive astrocytes give beneficial or harmful effects on neuronal regeneration. In vitro tissue culture systems successfully have been used to investigate how the astrocytes activity is regulated in response to environmental conditions. Physicochemical characteristics of supporting materials for tissue culture are one of the most important environmental conditions. Electrospun nanofiber has physical uniqueness such as high surface area to volume ratio and high porosity, which is favorable to tissue culture. However, cellular activities can also be regulated in response to surface chemistry, which can be modified easily and diversely. Poly(ε-caprolactone) (PCL) is widely used for a scaffold for tissue culture. In this research, oxygen plasma-treated PCL nanofiber was assessed to ascertain whether it can have such potentials to regulate astrocytes activity. As a result, oxygen plasma treatment increased the hydrophilicity of the PCL nanofiber which made adhesion and viability of astrocytes enhanced without cytotoxicity Activation of astrocytes in the plasma treated scaffolds was confirmed by the fact of upregulation of glial fibrillary acidic protein. Above all, oxygenated nanofiber provides an initial culture environment which makes astrocytes activated. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

A new type of polypropylene (PP) hernia mesh, modified with poly(l-lactic acid) (PLLA), was developed and used to repair rat abdominal wall defect. The PP mesh was first treated with oxygen plasma and then grafted with PLLA in phosphorus pentachloride (PCl₅) solution in dichloride methane. The water contact angle changed during the procedure, and the coverage percentage of PLLA on the PP was about 80%. ATR-FTIR spectroscopy measurements showed the existence of carbonyl group absorption peak (1756.9 cm⁻¹), and atomic force microscope and scanning electron microscope morphological observation indicated that the surface of the PP mesh was covered with PLLA graft. X-ray photoelectron spectroscopy spectra was used to probe chemical group changes and confirmed that the PLLA was grafted onto the PP. A total of 36 Sprague–Dawley rats were randomly divided into six groups, and they received either modified meshes (experimental groups) or PP meshes (control groups) to repair abdominal wall defects. All animals survived until the end of the experiment. Rats in each group were dissected after the operation (after 1 week, 2 weeks, and 1 month, respectively), and the adhesion effects were evaluated. Sections of the mesh parietal peritoneum overlap were examined histologically and graded for inflammation reaction. Compared with the control groups, the experimental groups showed a better ability to resist peritoneal cavity adhesions (P < 0.05), and there was no increase in inflammation formation (P > 0.05). This new type of PLLA-modified PP mesh displayed an additional property of antiadhesion in animal abdominal wall defect repair. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Industrial manufacturing of prosthesis components could take significant advantage by the introduction of new, cost-effective manufacturing technologies with near net-shape capabilities, which have been developed during the last years to fulfill the needs of different technological sectors. Among them, metal injection molding (MIM) appears particularly promising for the production of orthopedic arthroplasty components with significant cost saving. These new manufacturing technologies, which have been developed, however, strongly affect the chemicophysical structure of processed materials and their resulting properties. In order to investigate this relationship, here we evaluated the effects on electrochemical properties, ion release, and in vitro response of medical grade CoCrMo alloy processed via MIM compared to conventional processes. MIM of the CoCrMo alloy resulted in coarser polygonal grains, with largely varying sizes; however, these microstructural differences between MIM and forged/cast CoCrMo alloys showed a negligible effect on electrochemical properties. Passive current densities values observed were 0.49 µA cm⁻² for MIM specimens and 0.51 µA cm⁻² for forged CoCrMo specimens, with slightly lower transpassive potential in the MIM case; open circuit potential and R_p stationary values showed no significant differences. Moreover, in vitro biocompatibility tests resulted in cell viability levels not significantly different for MIM and conventionally processed alloys. Although preliminary, these results support the potential of MIM technology for the production of CoCrMo components of implantable devices. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The effects of carbamide peroxide, hydrogen peroxide and cola soft drink on the topographic modifications of commercially-pure titanium (CP-Ti) and Ti-6Al-4V were investigated. Ti discs were divided into 18 groups (n = 4) based on the solution treatment and Ti type. Specimens were immersed in 3 mL of each solution for 4 h per day (for the remaining 20 h, discs were left dry or immersed in artificial saliva) for 15 days. For control, specimens were immersed in only artificial saliva. Ti surfaces were examined using scanning electron (SEM) and atomic force (AFM) microscopes and their surface roughness (in µm) and surface chemical modifications were investigated. Data were analyzed by ANOVA and Tukey's test (α = 0.05). Groups immersed in 35% hydrogen peroxide showed the highest roughness (Ra) (171.65 ± 4.04 for CP-Ti and 145.91 ± 14.71 for Ti-6Al-4V) (p < 0.05), followed by groups treated with carbamide peroxide 16% (110.91 ± 0.8 for CP-Ti and 49.28 ± 0.36 for Ti-6Al-4V) and 35% (65.67 ± 1.6 for CP-Ti and 53.87 ± 1.98 for Ti-6Al-4V); treatment with artificial saliva did not affect the results. These values were statistically superior to those observed prior to the treatment and to those of the control group (31.0 ± 0.99 for CP-Ti and 29.95 ± 0.58 for Ti-6Al-4V). Cola soft drink did not alter the surface roughness of either Ti type (p > 0.05). SEM and AFM revealed dramatic changes in the specimens surfaces immersed in the 35% hydrogen peroxide, mainly for CP-Ti. No detectable chemical modifications on the Ti surface were observed. Bleaching agents promoted significant changes in Ti topography, which could affect the longevity of implants treatments. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

In cartilage repair, scaffold-assisted one-step approaches are used to improve the microfracture (Mfx) technique. Since the number of progenitors in Mfx is low and may further decrease with age, aim of our study was to analyze the chondrogenic potential of freeze-dried polyglycolic acid-hyaluronan (PGA-HA) implants preloaded with mesenchymal stem cells (MSCs) in vitro and in a rabbit articular cartilage defect model. Human bone marrow-derived MSC from iliac crest were cultured in freeze-dried PGA-HA implants for chondrogenic differentiation. In a pilot study, implants were loaded with autologous rabbit MSC and used to cover 5 mm × 6 mm full-thickness femoral articular cartilage defects (n = 4). Untreated defects (n = 3) served as controls. Gene expression analysis and histology showed induction of typical chondrogenic marker genes like type II collagen and formation of hyaline-like cartilaginous tissue in MSC-laden PGA-HA implants. Histological evaluation of rabbit repair tissue formation after 30 and 45 days showed formation of repair tissue, rich in chondrocytic cells and of a hyaline-like appearance. Controls showed no articular resurfacing, tissue repair in the subchondral zone and fibrin formation. These results suggest that MSC-laden PGA-HA scaffolds have chondrogenic potential and are a promising option for stem cell-mediated cartilage regeneration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Cuttlefish bones (CBs) have emerged as attractive biomaterials because of their porous structure and components that can be converted into hydroxyapatite (HAp) via a hydrothermal reaction. However, their brittleness and low strength restrict their application in bone tissue engineering. Therefore, to improve the compressive strength of the scaffold following hydrothermal conversion to a HAp form of CB (CB-HAp), the scaffold was coated using a polycaprolactone (PCL) polymer at various concentrations. In this study, raw CB was successfully converted into HAp via a hydrothermal reaction. We then evaluated their surface properties and composition by scanning electron microscopy and X-ray diffraction analysis. The CB-HAp coated with PCL showed improved compressive performance and retained a microporous structure. The compressive strength was significantly increased upon coating with 5 and 10% PCL, by 2.09- and 3.30-fold, respectively, as compared with uncoated CB-HAp. However, coating with 10% PCL resulted in a reduction in porosity. Furthermore, an in vitro biological evaluation demonstrated that MG-63 cells adhered well, proliferated and were able to be differentiated on the PCL-coated CB-HAp scaffold, which was noncytotoxic. These results suggest that a simple coating method is useful to improve the compressive strength of CB-HAp for bone tissue engineering applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Stoichiometric strontium-incorporated hydroxyapatite (Sr-HA) with different Sr concentrations [Sr/(Sr+Ca)] were synthesized using a wet chemical approach and characterized by X-ray diffraction, Fourier-transformed infrared absorption, X-ray photoelectron spectroscopy, and Rietveld Structure Refinement. The crystal lattice parameter, Sr distribution, chemical state of Sr, and also the relationships between their variations and the Sr concentrations have been intensively studied. The results show that both the crystal lattice parameters and crystal plane space of Sr-HA remarkably increase with the Sr concentration increasing. Whether Sr preferably occupies the Ca(I) site or Ca(II) site after incorporated into apatite lattice depends on the Sr number incorporated into apatite. All the Sr ions completely occupy the Ca(II) sites when the Sr concentration is below 5%. With the exception of partial Sr ions occupying the Ca(II) sites, the other Sr ions start to occupy the Ca(I) sites when the Sr concentration doped in HA is beyond 10%. The ratio of Sr ions occupying the Ca(I) sites increases with the further raising Sr concentration up to 20%. The Sr ions inherit the chemical state and environment of the original Ca(I) or Ca(II) site after incorporated into apatite. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Microorganisms from the oral cavity may settle at the implant–abutment interface (IAI). As a result, tissue inflammation could occur around these structures. The databases MEDLINE/PubMed and PubMed Central were used to identify articles published from 1981 through 2012 related to the microbial colonization in the implant–abutment gap and its consequence in terms of crest bone loss and osseointegration. The following considerations could be put forward, with respect to the clinical importance of IAI: (a) the space present at the IAI seems to allow bacterial leakage to occur, in spite of the size of this space; (b) bacterial leakage seems to occur at the IAI, irrespective of the type of connection. More studies are necessary to clarify the relationship between leakage at IAI and abutment connection designs; (c) losses at the peri-implant bone crests cannot be related to the IAI size, since few studies have shown no relationship. Also, the microbial leakage at the IAI cannot be related to the bone crest loss, since there are no articles reporting this relationship; remains controversial the influence of the IAI position on the bone crest losses. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Cytotoxicity and subcutaneous tissue reaction of innovative blends composed by polyvinylidene fluoride and polyvinylidene fluoride-trifluoroethylene associated with natural polymers (natural rubber and native starch) forming membranes were evaluated, aiming its applications associated with bone regeneration. Cytotoxicity was evaluated in mouse fibroblasts culture cells (NIH3T3) using trypan blue staining. Tissue response was in vivo evaluated by subcutaneous implantation of materials in rats, taking into account the presence of necrosis and connective tissue capsule around implanted materials after 7, 14, 21, 28, 35, 60, and 100 days of surgery. The pattern of inflammation was evaluated by histomorphometry of the inflammatory cells. Chemical and morphological changes of implanted materials after 60 and 100 days were evaluated by Fourier transform infrared (FTIR) absorption spectroscopy and scanning electron microscopy (SEM) images. Cytotoxicity tests indicated a good tolerance of the cells to the biomaterial. The in vivo tissue response of all studied materials showed normal inflammatory pattern, characterized by a reduction of polymorphonuclear leukocytes and an increase in mononuclear leukocytes over the time (p < 0.05 Kruskal–Wallis). On day 60, microscopic analysis showed regression of the chronic inflammatory process around all materials. FTIR showed no changes in chemical composition of materials due to implantation, whereas SEM demonstrated the delivery of starch in the medium. Therefore, the results of the tests performed in vitro and in vivo show that the innovative blends can further be used as biomaterials. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Although histology has proven to be a reliable method to evaluate the ossoeintegration of a dental implant, it is costly, time consuming, destructive, and limited to one or few sections. Microcomputed tomography (µCT) is fast and delivers three-dimensional information, but this technique has not been widely used and validated for histomorphometric parameters yet. This study compared µCT and histomorphometry by means of evaluating their accuracy in determining the bone response to two different implant materials. In total, 32 titanium (Ti) and 16 hydroxyapatite (HA) implants were installed in 16 lop-eared rabbits. After 2 and 4 weeks, the animals were scarified, and the samples retrieved. After embedding, the samples were scanned with µCT and analyzed three-dimensionally for bone area (BA) and bone-implant contact (BIC). Thereafter, all samples were sectioned and stained for histomorphometry. For the Ti implants, the mean BIC was 25.25 and 28.86% after 2 and 4 weeks, respectively, when measured by histomorphometry, while it was 24.11 and 24.53% when measured with µCT. BA was 35.4 and 31.97% after 2 and 4 weeks for histomorphometry and 29.06 and 27.65% for µCT. For the HA implants, the mean BIC was 28.49 and 42.51% after 2 and 4 weeks, respectively, when measured by histomorphometry, while it was 33.74 and 42.19% when measured with µCT. BA was 30.59 and 47.17% after 2 and 4 weeks for histomorphometry and 37.16 and 44.95% for µCT. Direct comparison showed that only the 2 weeks BA for the titanium implants was significantly different between µCT and histology (p = 0.008). Although the technique has its limitations, µCT corresponded well with histomorphometry and should be considered as a tool to evaluate bone structure around implants. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The incomplete endothelialization of especially small-caliber vascular prostheses after implantation in patients is a major disadvantage in cardiovascular interventions. The lack of an endothelium leads to the occurrence of thrombosis at the luminal surface of artificial vascular prostheses. Thus, the development of new graft materials and coatings for induction of complete endothelialization on the implant surfaces is a promising approach to improve hemocompatibility and maintain long-term graft patency. In this study, we designed a rotation model to evaluate the early endothelial cell (EC) seeding efficiency of different small-caliber vascular devices, such as stents and vascular grafts. The suitability of the designed rotation model for endothelialization studies was investigated by seeding and cultivation of prostheses with ECs followed by scanning electron microscopy. Furthermore, the viability of attached ECs was determined by calcein acetoxymethyl ester (AM) staining. The rotation model consisting of low-cost medical disposables enabled sterile incubation and cultivation of ECs with vascular devices. Simultaneously, the rotation of the bioreactor ensured a uniform distribution and adhesion of cells to the devices. Calcein AM staining of adherent cells on prostheses revealed excellent cell viability. Moreover, using the designed rotation model, an influence of different coatings and materials on the adhesion and spreading of ECs was demonstrated. The rotating bioreactor described and used in this study not only saves time and money but is also eminently useful for the accelerated preclinical evaluation of the endothelialization efficiency of different materials and surface coatings of small-caliber vascular devices. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) composite scaffolds have shown great potential for bone-tissue engineering applications. In this work, ceramic scaffold with different HA/β-TCP compositions (pure HA, 60HA/40β-TCP, and 20HA/80β-TCP) were fabricated by a robotic-assisted deposition (robocasting) technique using water-based hydrogel inks. A systematic study was conducted to investigate the porosity, mechanical property, and degradation of the scaffolds. Our results indicate that, at a similar volume porosity, the mechanical strength of the sintered scaffolds increased with the decreasing rod diameter. The compressive strength of the fabricated scaffolds (porosity ≈ 25–80 vol %) varied between ∼3 and ∼50 MPa, a value equal or higher than that of human cancellous bone (2–12 MPa). Although there was a slight increase of Ca and P ions in water after 5 month, no noticeable degradation of the scaffolds in SBF or water was observed. Our findings from this work indicate that composite calcium phosphate scaffolds with customer-designed chemistry and architecture may be fabricated by a robotic-assisted deposition method. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

For successful peripheral nerve regeneration, a complex interplay of growth factors, topographical guidance structure by cells and extracellular matrix proteins, are needed. Aligned fibrous biomaterials with a wide variety in fiber diameter have been used successfully to support neuronal guidance. To better understand the importance of size of the topographical features, we investigated the directionality of neuronal migration of sensory ND7/23 cells on aligned electrospun poly(lactic-glycolic acid) PLGA fibers in the range of micrometer and submicrometer diameters by time-lapse microscopy. Cell trajectories of single ND7/23 cells were found to significantly follow topographies of PLGA fibers with micrometer dimensions in contrast to PLGA fibers within the submicrometer range, where cell body movement was observed to be independent of fibrous structures. Moreover, neurite alignment of ND7/23 cells on various topographies was assessed. PLGA fibers with micrometer dimensions significantly aligned 83.3% of all neurites after 1 day of differentiation compared to similar submicrometer structures, which orientated 25.8% of all neurites. Interestingly, after 7 days of differentiation ND7/23 cells on submicrometer PLGA fibers increased their alignment of neurites to 52.5%. Together, aligned PLGA fibers with micrometer dimensions showed a superior influence on directionality of neuronal migration and neurite outgrowth of sensory ND7/23 cells, indicating that electrospun micro-PLGA fibers might represent a potential material to induce directionality of neuronal growth in engineering applications for sensory nerve regeneration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The ethyl-4-dimethylaminobenzoate (EDAB) is widely used as a coinitiator of the camphorquinone (CQ), but in acidic circumstances it might present some instability, reducing the polymerization efficiency of the material. Considering this, new coinitiators are being evaluated. Hence, this study evaluated the kinetic of polymerization (KP), the degree of conversion (DC), and the rate of polymerization (R_P) of experimental resin adhesives containing 1,3-diethyl-2-thiobarbituric acid (TBA) as a coinitiator of the CQ. The experimental monomeric blend was prepared with bisphenol A glycidyl dimethacrylate, 2-hydroxyethyl methacrylate, and acidic monomers. CQ was added at 1 mol % as photoinitiator. Six groups were formulated: four containing concentrations of 0.1, 0.5, 1, and 2 mol % of TBA, one without coinitiator, and the last one containing 1 mol % of EDAB (control group). The KP and the R_P were performed using real-time Fourier Transform infrared spectroscopy. The group without coinitiator has not formed a polymer, whereas the addition of TBA resulted in the conversion of monomers in polymer. The DC of the adhesives was as higher as the increase in the TBA content. The group with 2 mol % of TBA presented improved DC and reactivity (R_P) than the other groups and the control one. Hence, the TBA has performed as a coinitiator of the CQ for the radical polymerization of methacrylate resin adhesives and it has improved the DC and the reactivity of the materials. Thus, it is a potential coinitiator for the photopolymerization of dental materials. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater , 2013.

Drug-polymer composite coatings, composed of styrene–isobutylene–styrene (SIBS) tri-block copolymers, are frequently used in controlled drug release biomedical device applications. In this work, we used atomic force microscopy to characterize the effects of different drug loadings and polymer chemistries (i.e., block copolymer ratio) on the variation of surface structures and compositions of SIBS-tetracycline (SIBS-TC) cast composites including tetracycline (TC) drug amount, drug phase size distribution, and drug and polymer phase morphologies. We tested the structural variations by fabricating and characterizing two types of composite specimens, that is, SIBS15 and SIBS30, composed of 15 and 30 Wt % of polystyrene (PS), respectively. The differences in the distribution of TC drug, PS, and polyisobutylene (PIB) polymer phase structures observed in SIBS15 and SIBS30 resulted in more drug at the surface of SIBS30 compared to SIBS15. To support the experimental findings, we have determined the Hildebrand solubility parameter of TC using molecular dynamics (MD) computation and compared it to the polymer components, PS and PIB. The MD results show that the solubility parameter of TC is much closer to that of PS than PIB, which demonstrates a higher thermodynamic stability of TC–PS mixtures. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

In this study, the in vivo wear of highly cross-linked polyethylene (CLPE) cups against alumina ceramic femoral heads was evaluated by radiographic and retrieval analysis. The radiographic wear of six ethylene oxide gas-sterilized (i.e., non-cross-linked) conventional polyethylene (PE) cups with the mean follow-up of 20.9 years and 60 CLPE cups with the mean follow-up of 7.4 years was measured. The retrieved 16 PE cups with clinical use for mean 21.5 years and 10 CLPE cups with clinical use for mean 2.9 years was evaluated as a retrieval analysis. In the radiographic analysis, the linear wear of CLPE cups was significantly lower (99% reduction) compared to conventional polyethylene cups. The results of retrieval analyses for both cups were similar to those of radiographic analyses. Even when third-body wear occurred during clinical use, no surface damage was observed on the surface of ceramic femoral heads. The surface is not sensitive to third-body wear, and hence, the ceramic femoral head has a great advantage in terms of the wear of CLPE under third-body wear conditions. In conclusion, CLPE cups used with alumina ceramic femoral heads in total hip arthroplasty should have favorable wear resistance in several in vivo situations. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The lung has a huge inner alveolar surface composed of epithelial cell layers. The knowledge about mechanical properties of lung epithelia is helpful to understand the complex lung mechanics and biomechanical interactions. Methods have been developed to determine mechanical indices (e.g., tissue elasticity) which are both very complex and in need of costly equipment. Therefore, in this study, a mechanostimulator is presented to dynamically stimulate lung epithelial cell monolayers in order to determine their mechanical properties based on a simple mathematical model. First, the method was evaluated by comparison to classical tensile testing using silicone membranes as substitute for biological tissue. Second, human pulmonary epithelial cells (A549 cell line) were grown on flexible silicone membranes and stretched at a defined magnitude. Equal secant moduli were determined in the mechanostimulator and in a conventional tension testing machine (0.49 ± 0.05 MPa and 0.51 ± 0.03 MPa, respectively). The elasticity of the cell monolayer could be calculated by the volume–pressure relationship resulting from inflation of the membrane-cell construct. The secant modulus of the A549 cell layer was calculated as 0.04 ± 0.008 MPa. These findings suggest that the mechanostimulator may represent an adequate device to determine mechanical properties of cell layers. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Objectives: It was the aim of this study to analyze osseointegrative properties of porous additive manufactured titanium implants made by direct metal laser sintering in a sheep model after an implantation period of 2 and 8 weeks.

Material and Methods: Three different types of implants were placed in the pelvis of six sheep. In each sheep were placed three standard machined (M), three sandblasted and etched (SE), and three porous additive manufactured (AM) implants. Of these three implants (one per type) were examined histologically and six implants were tested biomechanically. Additionally a semiquantitative histomorphometrical and qualitative fluorescent microscopic analysis were performed.

Results: After 2 and 8 weeks bone-to-implant-contact (BIC) values of the AM surface (2w: 20.49% ± 5.18%; 8w: 43.91% ± 9.69%) revealed no statistical significant differences in comparison to the M (2w: 20.33% ± 11.50%; 8w: 25.33% ± 4.61%) and SE (2w: 43.67 ± 12.22%; 8w: 53.33 ± 8.96%) surfaces. AM surface showed the highest increase of the BIC between the two observation time points. Considering the same implantation period histomorphometry and fluorescent labelling disclosed no significant differences in the bone surrounding the three implants groups. In contrast Removal-torque-test showed a significant improve in fixation strength (P ≤ 0.001) for the AM (1891.82 ± 308, 44 Nmm) surface after eight weeks in comparison to the M (198.93±88,04 Nmm) and SE (730.08 ± 151,89 Nmm) surfaces.

Conclusion: All three surfaces (M, SE, and AM) showed sound osseointegration. AM implants may offer a possible treatment option in clinics for patients with compromised bone situations. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Antibiotic resistant bacterial infections are a growing problem in patient care. These infections are difficult to treat and severely affect the patient's quality of life. The goal of this translational experiment was to investigate the antimicrobial potential of cationic steroidal antimicrobial-13 (CSA-13) for the prevention of perioperative device-related infections in vivo. It was hypothesized that when incorporated into a polymeric device coating, the release of CSA-13 could prevent perioperative device-related infection without inhibiting skeletal attachment. To test this hypothesis, 12 skeletally mature sheep received a porous coated titanium implant in the right femoral condyle. Group 1 received the titanium implant and an inoculum of 5 × 10⁸ CFU of methicillin-resistant Staphylococcus aureus (MRSA). Group 2 received a CSA-13 coated implant and the MRSA inoculum. Group 3 received only the CSA-13 coated implant and Group 4 received only the implant—without the CSA-13 coating or MRSA inoculum. In conclusion, the CSA-13 combination coating demonstrated bactericidal potential without adversely affecting skeletal attachment. The CSA-13 containing groups exhibited no evidence of bacterial infection at the conclusion of the 12 week study and established skeletal attachment consistent with Group 4. In contrast, all of the Group 1 animals became infected and required euthanasia within 6–10 days. The significance of this finding is that this combination coating could be applied to implanted devices to prevent perioperative device-related infections. This method may facilitate significantly reduced incidences of device-related infections as well as a new method to treat and prevent resistant strain bacterial infections. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

A biodegradable fibrous tube was fabricated by electrospinning method using a combination of Poly(lactic-co-glycolic acid) (PLGA) and gelatin dissolved in trifluoroethanol (TFE). Different ratios of the two polymers (PLGA/Gelatin: 1/9, 3/7, 5/5) were used for electrospinning to determine the optimum condition appropriate for intestinal stent application. Fiber morphology was visualized and analyzed using a scanning electron microscope (SEM). Characterizations of physical properties were done according to its tensile strength, surface hydrophilicity, swelling ability, and biodegradability. Biocompatibility of the scaffolds was investigated in vitro using IEC-18 (Rat intestinal epithelial cell). Cell proliferation was quantified using MTT assay and cell adhesion behavior was visualized by SEM and confocal laser scanning microscope. PLGA/Gelatin (5/5) was determined to have adequate material properties and sufficient in vitro biocompatibility. This was then implanted in a male Sprague-Dawley rat for 14 days to determine in vivo behavior of the sample. Histological examination on the intestinal tissue surrounding the graft showed normal morphology comparable to non-implanted intestine. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Meniscal tears in the avascular zone have a poor self-healing potential, however partial meniscectomy predisposes the knee for early osteoarthritis. Tissue engineering with mesenchymal stem cells and a hyaluronan collagen based scaffold is a promising approach to repair meniscal tears in the avascular zone. 4 mm longitudinal meniscal tears in the avascular zone of lateral menisci of New Zealand White Rabbits were performed. The defect was left empty, sutured with a 5–0 suture or filled with a hyaluronan/collagen composite matrix without cells, with platelet rich plasma or with autologous mesenchymal stem cells. Matrices with stem cells were in part precultured in chondrogenic medium for 14 days prior to the implantation. Menisci were harvested at 6 and 12 weeks. The developed repair tissue was analyzed macroscopically, histologically and biomechanically. Untreated defects, defects treated with suture alone, with cell-free or with platelet rich plasma seeded implants showed a muted fibrous healing response. The implantation of stem cell-matrix constructs initiated fibrocartilage-like repair tissue, with better integration and biomechanical properties in the precultured stem cell-matrix group. A hyaluronan-collagen based composite scaffold seeded with mesenchymal stem cells is more effective in the repair avascular meniscal tear with stable meniscus-like tissue and to restore the native meniscus. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Functionally gradient bio-coating material was built by laser deposition. Co-Cr-Mo material was deposited on a Ti-6Al-4V substrate transitioning from 0% to 100%. Control over the cooling rate is shown to be a key to reduce the effects of thermal expansion differences of the materials. The microstructures and composition of the functionally gradient material (FGM) were characterized using an optical microscope, SEM, EDS, and XRD. EDS results showed a gradual transition to 50% Co-Cr-Mo and ∼100% Co-Cr-Mo on the top layer. XRD analysis showed the absence of a brittle intermetallic phase that forms between Titanium and Cobalt. As the amount of Co-Cr-Mo increased, the microhardness of the FGM samples significantly increased. A comparison was made between Co-Cr-Mo deposited on SS316L substrates as well as Ti-6Al-4V. The bonding strength of the coatings on both substrates was tested and found to meet the ASTM standard requirement. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

In vitro expansion of transplantable hematopoietic stem cells (HSCs) is a very promising approach for different clinical applications. We have recently developed a new culture system that facilitates in vitro expansion of transplantable cord blood HSCs. In our study, we constructed a recombinant adenovirus Ad-GFP/human leukemia inhibitory factor (hLIF) expressing hLIF. The hLIF gene was delivered into human embryo lung fibroblast cell line WI-38 via infection with Ad-GFP/hLIF. Then, the transgenic cells were cultured on regenerated silk fibroin (SF) films as feeder layer cells for expansion of cord blood CD34⁺ cells. Our results showed that the hLIF transgenic WI-38 cells cultured on SF could express hematopoiesis-related cytokines at higher levels compared with control groups. The hLIF-expressing feeder layer cells cultured on SF in combination with cytokines more efficiently expanded CD34⁺ cells and CD34⁺CD38⁻ cells. The percentages of adhesion molecules on the expanded CD34⁺ cells in transgenic feeder layer cells cultured on SF were higher than those of control groups. Interestingly, the migration rate assessed by transwell assay was also significantly higher than those of control groups, which suggests that transgenic feeder layer cells cultured on SF has powerful ability to maintain the homing capacity of expanded CD34⁺ cells. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The low surface roughness of disposable contact lenses made of a new siloxane-hydrogel loaded with hyaluronic acid is reported, as studied by atomic force microscopy (AFM). Before the wear, the surface is characterized by out-of-plane and sharp structures, with maximum height of about 10 nm. After a wear of 8 h, evidence of two typical morphologies is provided and discussed. One morphology (sharp type) has a similar aspect as the unworn lenses with a slight increase in both the height and the number of the sharp peaks. The other morphology (smooth type) is characterized by troughs and bumpy structures. Wettability and clinical performances are also discussed, the latter deduced by the ocular-surface-disease index (OSDI). The main finding arising from this work is the indication of correlation between the change of the OSDI before and after wear and the lens surface characteristics obtained by AFM. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The Intergel® ferric crosslinked hyaluronate (FeHA) adhesion prevention solution (APS) (FDA) is associated with serious post-operative complications (Henley, http://www.lawyersandsettlements.com/features/gynecare-intergel/intergel-timeline.html, 2007; FDA, 2003; Roman et al., Fertil Steril 2005, 83 Suppl 1:1113–1118; Tang et al., Ann Surg 2006;243(4):449–455; Wiseman, Fertil Steril 2006;86(3):771; Wiseman, Fertil Steril 2006;85(4):e7). This prompted us to examine the in situ stability of crosslinked HA materials to hyaluronidase lyase degradation. Variables such as ferric ionic crosslink density, HA concentration, gel geometry, and molecular weight (MW) of HA polymer were studied. Various formulations of the crosslinked “in house” [Isayeva et al., J Biomed Mater Res: Part B – Appl Biomater 2010, 95B (1):9–18] FeHA (0.5%, w/v; 30, 50, 90% crosslinked), the Intergel® FeHA (0.5%, w/v; 90%), and the non-crosslinked HA (0.05–0.5%, w/v) were degraded at a fixed activity of hyaluronidase lyase from Streptomyces hyalurolyticus (Hyase) at 37°C over time according to the method [Payan et al., J Chrom B: Biomed Sci Appl 1991;566(1):9–18]. Under our conditions, the data show that the crosslink density affects degradation the most, followed by HA concentration and then gel geometry. We found that MW has no effect. Our results are one possible explanation of the observations that the Intergel® FeHA APS (0.5%, w/v; 90%) material persisted an order of magnitude longer than expected [t_1/2 = 500 hrs vs. t_1/2 = 50 hrs (FDA; Johns et al., Fertil Steril 1997;68(1):37–42)]. These data also demonstrate the sensitivity of the in vitro hyaluronidase assay to predict the in situ stability of crosslinked HA medical products as previously reported [Sall et al., Polym Degrad Stabil 2007;92(5):915–919]. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

An in vitro method was developed for estimating in vivo degradation time of sutures made from synthetic bioresorbable polyesters. Model compounds and a number of commercially available bioresorbable suture products were used to establish the applicability of this hydrolysis profile methodology. Hydrolysis profiles on tested bioresorbable sutures were determined as a function of size and chemical composition. This method of accelerated absorption testing may shorten product development time and reduce the need for animal testing. In addition, the methodologies presented have the potential to provide insight into the loss of mechanical properties with time. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Gadolinium nanoparticle-catalyzed single-walled carbon nanotubes (Gd-SWCNTs) have recently shown potential in vitro as high-performance T₁ magnetic resonance imaging (MRI) contrast agents (CAs). Their preclinical safety assessment at nontoxic dosages is essential for MRI applications. Herein, the in vivo (in rats) pharmacodynamics of Gd-SWCNTs (water solubilized with the amphiphilic polymer PEG-DSPE) at the organ, tissue, molecular, and genetic level is reported. Gd-SWCNT, commercially available iron catalyzed SWCNTs (Fe-SWCNTs, control 1) and PEG-DSPE (control 2) solutions were intravenously injected at a potential nontoxic therapeutic dose (0.5 mg/kg body weight, single bolus). Postinjection, bright-field optical microscopy showed their macroscale distribution in lung, liver, kidney, brain, and spleen up to 5 days. Raman and transmission electron microscopy (TEM) showed their presence at the nanoscale within hepatocytes. Their effects on the host organ tissue, molecular, and genetic level were analyzed after 1, 5, 10, 20, and 30 days by histology, biomolecular [lipid peroxidation, plasma tumor necrosis factor TNF-α assay, microarrays] assays. The results indicate that Gd-SWCNTs neither cause any inflammation, nor damage to the above organs, nor any significant change in the lipid peroxidation or plasma proinflammatory cytokine (TNF-α) levels for all the groups at all time points. Global gene expression profile of liver (main organ for the metabolism) after day 1 treatment with Gd-SWCNTs shows that the gene regulation is directed toward maintaining normal homeostasis. The results taken together indicate that PEG-DSPE water-solubilized Gd-SWCNTs at potentially nontoxic dosages have pharmacodynamics similar to other commercially available Fe-SWCNTs and are suitable for future preclinical development as in vivo MRI CAs. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Three-dimensional interconnected porous poly(ε-caprolactone) scaffolds have been prepared by a novel solventless scaffold fabrication approach combining cryomilling and compression molding/porogen leaching techniques. This study investigated the effects of processing parameters on scaffold morphology and properties for tissue regeneration. Specifically, the effects of molding temperature, cryomilling time, and porogen mix were examined. Fifty percentage of porous scaffolds were fabricated with a range of properties: mean pore size from ∼40 to 125 μm, water uptake from ∼50 to 86%, compressive modulus from ∼45 to 84 MPa, and compressive strength at 10% strain from ∼3 to 4 MPa. Addition of 60 wt % NaCl salt resulted in a ∼50% increase in porosity in multimodal pore-size structures that depended on the method of NaCl addition. Water uptake ranged from ∼61 to 197%, compressive modulus from ∼4 to 8.6 MPa, and compressive strength at 10% strain from ∼0.36 to 0.40 MPa. Results suggest that this approach provides a controllable strategy for the design and fabrication of 3D interconnected porous biodegradable scaffolds for load-bearing tissue regeneration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The biocompatibility and bioactivity of biomaterials used for hard tissue repair are closely related to their adsorption capacities for bone-related proteins. In the present study, three types of calcium phosphate (CaP) ceramic particles with different phase composition or microstructure were fabricated, and their protein adsorption abilities were investigated by a self-made device under the simulated dynamic physiological circumstance. The results of X-ray diffraction, field emission scanning electron microscopy, mercury penetration test, and nitrogen sorption test showed that the irregular hydroxyapatite (HA) ceramic particles obtained by conventional drying and sintering (named as HA-C) had fewer micropores and lower specific surface area (SSA) than did the spherical HA or biphasic calcium phosphate (BCP) ceramic particles made by spray drying and sintering (named as HA-S and BCP-S, respectively). The dynamic protein adsorption study proved that both the phase composition and microstructure of CaP ceramic particles affected their adsorption capacities for those bone-related proteins. The spherical HA-S and BCP-S particles with abundant micropores and high SSA showed higher adsorption of serum proteins, including fibronectin and vitronectin, than the irregular HA-C did. On the other hand, in spite of the relatively high concentration of bovine serum albumin (BSA) in the binary bone morphogenetic protein 2 (BMP-2)/BSA solution, BMP-2 adsorption on the three CaP ceramic particles increased with the increase in its initial concentration. Similarly, HA-S and BCP-S particles had a larger amount of the adsorbed BMP-2 per gram solid than HA-C did. Therefore, it could be believed that the difference of various CaP ceramics in the phase composition and microporous structure would affect their binding capacity for those bone-related proteins and thus lead to their difference in osteoinduction. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Biofilm implant-related infections cost the US healthcare system billions of dollars each year. For several decades, device coatings have been developed that actively release antimicrobial compounds in an attempt to prevent these infections from developing. To date, few coatings have been put into clinical use. These have shown limited to no efficacy in clinical trials. Recent data have shown the in vitro and in vivo efficacy of a novel active release coating that may address the limitations of coatings that are used clinically. In this study, the novel active release coating was characterized to gain an understanding of the effects of combining an antimicrobial additive, cationic steroid antimicrobial-13 (CSA-13), to a medical grade polydimethylsiloxane (PDMS) material. Results indicated that the addition of CSA-13 did influence the physical properties of the PDMS, but not with adverse effects to the desired material properties. Furthermore, there was no indication of chemical reactivity. It was shown that CSA-13 was uniformly dispersed as small particles throughout the PDMS matrix. These particles were able to dissolve and elute out of the PDMS within a 30-day period. The results of this work suggested that the PDMS with CSA-13 was thermally, chemically and physically stable when used as a device coating to treat local infection and/or prevent biofilm implant-related infections from developing. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Tailor-made porous titanium implants show great promise in both orthopedic and dental applications. However, traditional powder metallurgical processes require a high-cost mold, making them economically unviable for producing unique devices. In this study, a mixture of titanium powder and an inlay wax binder was developed for moldless forming and sintering. The formability of the mixture, the dimensional changes after sintering, and the physical and mechanical properties of the sintered porous titanium were evaluated. A 90:10 wt % mixture of Ti powder and wax binder was created manually at 70°C. After debindering, the specimen was sintered in Ar at 1100°C without any mold for 1, 5, and 10 h. The shrinkage, porosity, absorption ratio, bending and compressive strength, and elastic modulus were measured. The bending strength (135–356 MPa), compression strength (178–1226 MPa), and elastic modulus (24–54 GPa) increased with sintering time; the shrinkage also increased, whereas the porosity (from 37.1 to 29.7%) and absorption ratio decreased. The high formability of the binder/metal powder mixture presents a clear advantage for fabricating tailor-made bone and hard tissue substitution units. Moreover, the sintered compacts showed high strength and an elastic modulus comparable to that of cortical bone. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Commercial root end filling materials, namely two zinc oxide eugenol-based cements [intermediate restorative material (IRM), Superseal], a glass ionomer cement (Vitrebond) and three calcium-silicate mineral trioxide aggregate (MTA)-based cements (ProRoot MTA, MTA Angelus, and Tech Biosealer root end), were examined for their ability to: (a) release calcium (Ca²⁺) and hydroxyl (OH⁻) ions (biointeractivity) and (b) form apatite (Ap) and/or calcium phosphate (CaP) precursors. Materials were immersed in Hank's balanced salt solution (HBSS) for 1–28 days. Ca²⁺ and OH⁻ release were measured by ion selective probes, surface analysis was performed by environmental scanning electron microscopy/energy dispersive X-ray analysis, micro-Raman, and Fourier transform infrared spectroscopy. IRM and Superseal released small quantities of Ca²⁺ and no OH⁻ ions. Uneven sparse nonapatitic Ca-poor amorphous CaP (ACP) deposits were observed after 24 h soaking. Vitrebond did not release either Ca²⁺ or OH⁻ ions, but uneven nonapatitic Ca-poor CaP deposits were detected after 7 days soaking. ProRoot MTA, MTA Angelus, and Tech Biosealer root end released significant amounts of Ca²⁺ and OH⁻ ions throughout the experiment. After 1 day soaking, nanospherulites of CaP deposits formed by amorphous calcium/magnesium phosphate (ACP) Ap precursors were detected. A more mature ACP phase was present on ProRoot MTA and on Tech Biosealer root end at all times. In conclusion, zinc oxide and glass ionomer cements had little or no ability to release mineralizing ions: they simply act as substrates for the possible chemical bonding/adsorption of environmental ions and precipitation of nonapatitic Ca-poor ACP deposits. On the contrary, calcium-silicate cements showed a high calcium release and basifying effect and generally a pronounced formation of more mature ACP apatitic precursors correlated with their higher ion-releasing ability. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

This article proposes less-invasive subperiosteal bone-bonding devices capable of realizing rapid osseointegration and the acquisition of fundamental knowledge required for their development. Three candidates were prepared: titanium rod specimens with a machined surface (Bare), hydroxyapatite (HAp) coating, and hydroxyapatite/collagen (HAp/Col) nanocomposite coating. To investigate bone formation around these rods, each specimen was placed under the periosteum of a male Sprague-Dawley rat calvarium. Four weeks after surgery, the samples were evaluated via histomorphometrical analyses and bonding strength tests. All the Bare specimens and more than half of the HAp specimens were encapsulated with fibrous tissue, whereas all the HAp/Col specimens were almost completely surrounded by new bone tissue without encapsulation. Histomorphometrical analyses showed that the HAp/Col group had the greatest bone contact ratio among all candidates (p < 0.05). Further, a bonding strength test indicated that the HAp/Col group exhibited the greatest bonding strength to bone (p < 0.05). Thus, HAp/Col-coated rods are considered as the best candidate materials for achieving rapid osseointegration onto a bone surface. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

This study investigates the feasibility of using an adipose-derived mesenchymal stem cell (ASC)-seeded acellular dermal matrix (ADM) along with low-level laser therapy (LLLT) to repair bone defect in athymic nude mice. Critical-sized calvarial defects were treated either with ADM, ADM/LLLT, ADM/ASCs, or ADM/ASCs/LLLT. In micro-computed tomography scans, the ADM/ASCs and the ADM/ASCs/LLLT groups showed remarkable bone formation after 14 days. Additionally, bone regeneration in the ADM/ASCs/LLLT group was obvious at 28 days, but in the ADM/ASCs group at 56 days. Bone mineral density and bone tissue volume in the ADM/ASCs/LLLT group significantly increased after 7 days, but in the ADM/ASCs group after 14 days. Histological analysis revealed that the defects were repaired in the ADM/ASCs and the ADM/ASCs/LLLT group, while the defects in the ADM and the ADM/LLLT groups exhibited few bone islands at 28 and 56 days. The successful seeding of ASCs onto ADM was confirmed, and LLLT enhanced the proliferation and the survival of ASCs at 14 days. Our results indicate that ASC-seeded grafts promote bone regeneration, and the application of LLLT on ASC-seeded ADM results in rapid bone formation. The implantation of an ASC-seeded ADM combined with LLLT may be used effectively for bone regeneration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Dental resins containing 12-methacryloyloxydodecylpyridinium bromide (MDPB) showed potent antibacterial functions. Recent studies developed antibacterial resins containing nanoparticles of silver (NAg). The objectives of this study were to develop an adhesive containing dual agents of MDPB and NAg for the first time and to investigate the combined effects of antibacterial adhesive and primer on biofilm viability, metabolic activity, lactic acid, dentin bond strength, and fibroblast cytotoxicity. MDPB and NAg were incorporated into Scotchbond Multi-Purpose (SBMP) adhesive “A” and primer “P”. Five systems were tested: SBMP adhesive A; A + MDPB; A+NAg; A + MDPB + NAg; P + MDPB + NAg together with A + MDPB + NAg. Dental plaque microcosm biofilms were cultured using mixed saliva from 10 donors. Metabolic activity, colony-forming units, and lactic acid production of biofilms were investigated. Human fibroblast cytotoxicity of bonding agents was determined. MDPB + NAg in adhesive/primer did not compromise dentin bond strength (p > 0.1). MDPB or NAg alone in adhesive substantially reduced the biofilm activities. Dual agents MDPB + NAg in adhesive significantly reduced the biofilm viability compared with each agent alone (p < 0.05). The greatest inhibition of biofilms was achieved when both adhesive and primer contained MDPB + NAg. Fibroblast viability of groups with dual antibacterial agents was similar to control using culture medium without resin eluents (p > 0.1). In conclusion, this study showed for the first time that the antibacterial potency of MDPB adhesive could be substantially enhanced via NAg. Adding MDPB + NAg into both primer and adhesive achieved the strongest antibiofilm efficacy. The dual agent (MDPB + NAg) method could have wide applicability to other adhesives, sealants, cements, and composites to inhibit biofilms and caries. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Plasma electrolytic oxidation (PEO) is a relatively new surface modification process that may be used as an alternative to plasma spraying methods to confer bioactivity to Ti alloy implants. The aim of this study was to compare physical, chemical and biological surface characteristics of two coatings applied by PEO processes, containing different calcium phosphate (CaP) and titanium dioxide phases, with a plasma-sprayed hydroxyapatite (HA) coating. Coating characteristics were examined by X-ray diffraction, energy dispersive X-ray spectroscopy, scanning electron microscopy, surface profilometry, and wettability tests. The biological properties were determined using the human osteoblastic cell line MG-63 to assess cell viability, calcium and collagen synthesis. The tests showed that PEO coatings are significantly more hydrophilic (6%) and have 78% lower surface roughness (Ra) than the plasma-sprayed coatings. Cell behavior was demonstrated to be strongly dependent on the phase composition and surface distribution of elements in the PEO coating. MG-63 viability for the TiO₂-based PEO coating containing amorphous CaPs was significantly lower than that for the PEO coating containing crystalline HA and the plasma-sprayed coating. However, collagen synthesis on both the CaP and the TiO₂ PEO coatings was significantly higher (92% and 71%, respectively) than on the plasma-sprayed coating after 14 days. PEO has been demonstrated to be a promising method for coating of orthopedic implant surfaces. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Local administration of drugs can enhance regeneration, prevent infection, or treat postsurgical pain. If used in conjunction with implants, coating strategies should allow the choice of a drug or combination of drugs, their doses, localization, and release due to intraoperative considerations. Current coating technologies lack the ability for personalized medicine strategies. Here, we describe a new intraoperative strategy for drug delivery that allows a personalized approach as local drug delivery by implant coating. A polyvinylalcohol (PVA) patch provides rapid attachment to implant surfaces by cyanoacrylate (CA) adhesives. The CA polymerization was initiated by water uptake of the patch due to exposure to a humid environment. The coating strength depended on the type of the CA, the time of external pressing load and humidification, the properties of the patch and the implant surface. The CA adhesive penetrated and polymerized within the patch without impeding the bioactivity of the embedded molecules or strongly altering the protein release pattern after attachment to the implant surface. The use of CA in combination with the PVA patch proved to be noncytotoxic in vitro. This technology platform opens the possibility for personalized medicine to locally administer drugs due to intraoperative requirements. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Porous calcium polyphosphate (CPP) structures with 30 volume percent porosity and made by solid freeform fabrication (SFF) were implanted in rabbit femoral condyle sites for 6-wk periods. Two forms of SFF implants with different stacked layer orientation were made in view of prior studies reporting on anisotropic/orthotropic mechanical properties of structures so formed. In addition, porous CPP implants of equal volume percent porosity made by conventional sintering and machining methods were prepared. Bone ingrowth and in vivo degradation of the three different implant types were compared using back-scattered scanning electron microscopy (BS-SEM) of implant samples and quantitative analysis of the images. The results indicated bone ingrowth with all samples resulting in 30–40% fill of available porosity by bone within the 6-wk period. In the 6-wk in vivo period, approximately 7–9% loss of CPP by degradation had occurred. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Hydrogels formed from self-assembling synthetic oligopeptides have been studied for almost 2 decades for use in tissue engineering and drug delivery. Although a great deal has been learned about the microstructure of these materials, there remain questions about how peptide filaments are ordered to form a gel. These unanswered questions leave a disconnect between our understanding of the observed nanoscale mechanical properties of peptide filaments and the macroscale properties of the gels they constitute. This study helps to bridge this gap by examining the role of filament length and interfilament crosslinks in determining bulk mechanical properties. Microindentation was used for mechanical characterization, and microstructure was observed using thin-section transmission electron microscopy images of gels embedded in resin. Results suggest a gel structure in which filaments are not densely bundled as previously suggested and confirm that crosslinking can be an effective strategy to increase the stiffness of self-assembling oligopeptide gels. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The aim of this paper is to quantify the adhered fibronectin (FN; by adsorption and/or grafting) and the exposure of its cell adhesive motifs (RGD and FNIII7-10) on poly(ethyl acrylate) (PEA) copolymers whose chemical composition has been designed to increase wettability and to introduce acid functional groups. FN was adsorbed to PEA, poly(ethyl acrylate-co-hydroxyethyl acrylate), poly(ethyl acrylate-co-acrylic acid), and poly(ethyl acrylate-co-methacrylic acid) copolymers, and covalently cross-linked to poly(ethyl acrylate-co-acrylic acid) and poly(ethyl acrylate-co-methacrylic acid) copolymers. Amount of adhered FN and exhibition of RGD and FNIII_7–10 fragments involved in cell adhesion were quantified with enzyme-linked immunosorbent assay tests. Even copolymers with a lower content of the hydrophilic component showed a decrease in water contact angle. In addition, FN was successfully fixed on all surfaces, especially on the hydrophobic surfaces. However, it was demonstrated that exposure of its cell adhesion sequences, which is the key factor in cell adhesion and proliferation, was higher for hydrophilic surfaces. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

To improve the treatment of helminthiasis, filariasis, and colorectal cancer, albendazole-associated chitosan nanoparticles (ABZ-CS-NPs) were prepared using the emulsion crosslinking volatile technique with contained sodium tripolyphosphate as the crosslinking agent and Poloxamer 188 as the auxiliary solvent. The structural characteristics of the NPs were determined using X-ray diffraction to analyze the interaction between CS and the drug. The NPs were then evaluated in terms of their physicochemical characteristics, drug release behavior, in vivo pharmacokinetic parameters, and biodistribution in animal studies. ABZ-loaded NPs with a uniformly spherical particle sizes (157.8 ± 2.82 nm) showed efficient drug loading, encapsulated efficiency, and high physical stability. The drug release from ABZ-CS-NPs was extended over several periods. Kinetic models were then fitted to determine the release mechanisms. ABZ and its metabolite albendazole sulfoxide (ABZSX) were analyzed in rats with mebendazole as the internal standard using reversed-phase high-performance liquid chromatography. Compared with the ABZ suspension groups, the relative bioavailability values of ABZ and ABZSX were 146.05 and 222.15%, respectively. In addition, the plasma concentration versus time curve is consistent with that of the two compartment models in the plasma concentration versus time curve. The results indicate that the ABZ-loaded NPs are promising novel ABZ candidates for passive diffusion in the treatment of hydatid cysts in the liver via oral administration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.

Reducing the osseointegration time for biomedical titanium implants in surgical patients is an important goal. However, a huge controversy exists over the effectiveness of osseointegration of the surface layer by plasma electrolytic oxidation (PEO), which is a widely favored surface modification for titanium-based implants. In this study, various surface coatings, including anatase-TiO₂ (A-TiO₂), rutile-TiO₂ (R-TiO₂), hydroxyapatite (HAp), strontium-containing hydroxyapatite (Sr-HAp), and dual-phase HAp-TiO₂ were synthesized on titanium implants by PEO. A comparative study of osseointegration performance (both in vitro and in vivo) and bone/implant adhesion strength conducted using push-out thrust tests were demonstrated. The in vitro experimental test results agree strongly with the in vivo test results: the dual-phase HAp-TiO₂ coating exhibits the superior cell adhesion and differentiation condition among all of the coatings in the in vitro tests and therefore has the highest push-out bonding strength of 5.37 MPa after 12 wk of implantation in the in vivo test. The HAp-containing coatings benefit from its bioactivity and therefore perform the others in terms of long-term osteocyte growth (from the in vitro results) and the extent of osseointegration (from the in vivo results). The dual-phase HAp-TiO₂ coating provides the advantages of both the bioactive HAp and structural enhancement by the TiO₂, effectively promoting osseointegration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

In this research, we studied improvement of mechanical properties of dimethacrylate-silica based dental composites by addition of Fuller's Earth (FE) clay. Three composites were made as base compounds consisting of 68, 58, and 48 wt % resin and 31, 41, and 51 wt % silica, respectively. Afterward, the composites were modified by adding FE. Mechanical properties including flexural strength, flexural modulus, work-of-fracture, fracture toughness, and microhardness were measured. Clay particles and fracture surface of composites consisting of 51 wt % silica (with and without FE) were examined by SEM. Measured results showed that flexural strength, work-of-fracture, flexural modulus, and microhardness of all composites increased by including FE nanofibers. Fracture toughness except for composite including 51 wt % silica had similar variations. It seems that locating FE nanofibers in weak resin region among silica particles leads to strengthening mechanisms, such as bridging and crack deflection, which cause improvement in mechanical properties. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Calcium phosphate (CaP) particles as a carrier in an injectable bone filler allows less invasive treatment of bony defects. The effect of changing granule size within a poloxamer filler on the osteointegration of silicate-substituted calcium phosphate (SiCaP) bone substitute materials was investigated in an ovine critical-sized femoral condyle defect model. Treatment group (TG) 1 consisted of SiCaP granules sized 1000–2000 μm in diameter (100 vol %). TG2 investigated a granule size of 250–500 μm (75 vol %), TG3 a granule size of 90–125 μm (75 vol %) and TG4 a granule size of 90–125 μm (50 vol %). Following a 4 and 8 week in vivo period, bone area, bone-implant contact, and remaining implant area were quantified within each defect. At 4 weeks, significantly increased bone formation was measured in TG2 (13.32% ± 1.38%) when compared with all other groups (p = 0.021 in all cases). Bone in contact with the bone substitute surface was also significantly higher in TG2. At 8 weeks most new bone was associated within defects containing the smallest granule size investigated (at the lower volume) (TG4) (42.78 ± 3.36%) however this group was also associated with higher amounts of fragmented SiCaP. These smaller particles were phagocytosed by macrophages and did not appear to have a negative influence on healing. In conclusion, SiCaP granules of 250–500 μm in size may be a more suitable scaffold when used as an injectable bone filler and may be a convenient method for treating bony defects. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The aim of the study was to investigate the biocompatibility and osteogenic effectiveness of the porous nanohydroxyapatite/polyamide 66 (n-HA/PA66) scaffold material that was cultured with the rat bone marrow mesenchymal stem cells (rBMSCs), under the static culture condition and the dynamic perfusion culture condition in vitro, and to investigate whether the 3D perfusion culture condition was better in provoking proliferation of rBMSCs than the 3D static culture condition. The Methyl thiazolyl tetrazolium (MTT) assay, alkaline phosphatase (ALP) activity assay, Osteocalcin (OCN) assay and scanning electron microscope (SEM) were used to observe the proliferation and differentiation of rBMSCs. The samples were respectively harvested at 1st, 3rd, 7th, 14th, and 21st days and effect comparisons were made between the two of the culture conditions. The results showed that values of MTT, ALP, and OCN were increased continuously and revealed a significant difference between the two culture conditions (p < 0.05). On the 14th day, SEM revealed calcified nodules 2–8 μm in diameter in the lamellar structure. Under the static culture condition, the pores were covered with the cells looking like a piece of blanket, but under the perfusion culture condition the cells were observed to have a 3D lamellar structure. In conclusion, the porous n-HA/PA66 scaffold material can be used as a good candidate material for the bone scaffold construction in the tissue engineering because of its excellent 3D structure, which can greatly improve the proliferation and differentiation of rBMSCs and make them proliferate and osteogenesis even better under the perfusion culture condition. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

A soft tissue defect is often an unavoidable consequence of various surgical procedures or a result of trauma. Recently, intraoperative use of xenograft as a patch to the soft tissue defect has become popular with various products available in the market. In this study, mechanical properties of the OrthADAPT™ Bioimplants (Pegasus Biologics, Irvine, CA), new xenograft products composed of collagen from equine pericardium, were evaluated individually and against an existing bioimplant product. The OrthADAPT™ Bioimplants have three subtypes which differ in the degree of crosslinking of collagen strands. The three products are named as FX, PX, and MX in the order of the degree of collagen crosslinking and likely durability in vivo, with FX most dense in crosslinking and hence most durable. The three subtypes underwent three destructive mechanical tests: tensile strength, suture pull-out strength, and burst strength test. In tensile strength and suture pull-out strength tests, the three products were compared with CuffPatch™, a similar collagen-based xenograft product from a competing manufacturer. In the burst strength test, the three products were compared with untreated equine pericardium tissue. In tensile strength and suture pull-out strength tests, the products FX and MX were shown to have mechanical properties that were comparable with CuffPatch, while the mechanical strength of PX was significantly inferior to FX and CuffPatch in tensile strength test. In burst strength test, there were no differences in mechanical properties among the three OrthADAPT Bioimplants. This study demonstrates the biomechanical equivalence of OrthADAPT with CuffPatch. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2007

Infection of titanium (Ti)-based orthopedic implants is a growing problem due to the ability of bacteria to develop a resistance to today's antibiotics. As an attempt to develop a new strategy to combat bacteria functions, Ti was anodized in the present study to possess different diameters of nanotubes. It is reported here for the first time that Ti anodized to possess 20 nm tubes then followed by heat treatment to remove fluorine deposited from the HF anodization electrolyte solution significantly reduced both S. aureus and S. epidermidis growth compared to unanodized Ti controls. It was further found that the sterilization method used for both anodized nanotubular Ti and conventional Ti played an important role in the degree of bacteria growth on these substrates. Overall, UV light and ethanol sterilized samples decreased bacteria growth, while autoclaving resulted in the highest amount of bacteria growth. In summary, this study indicated that through a simple and inexpensive process, Ti can be anodized to possess 20 nm tubes that no matter how sterilized (UV light, ethanol soaking, or autoclaving) reduces bacteria growth and, thus, shows great promise as an antibacterial implant material. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part 2013.

Pluronic micelles were prepared for ophthalmic delivery by incorporation of ethyl acetate as a dispersion agent and their surfaces were modified by chitosan to improve their bioavailability. The micelles disperse well in the solution and have a core-shell like structure with a particle size ranging from 93 to 181 nm for drug unloaded, 123–232 nm for drug-loaded, and a zeta potential between 6.1 and 9.2 mV, indicating very suitable use as ophthalmic carrier. The in vitro serum stability tests indicate the particle size of the micelles was very stable during the serum absorption. The turbidity test reveals that the prepared micelles were very stable under phosphate buffered saline environment, which can prevent the blurred vision. The loading efficiency of metipranolol in micelles can be as high as 83%. Finally, the in vitro and in vivo studies indicate the pluronic micelles modified by chitosan have sustained release behavior and good pharmacological response. As the results, the pluroic-chitosan micelles system provides a potential opportunity in decreasing frequency of administration and improving patient compliance for ocular drug delivery. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

In this study, a porous oxide layer was formed on the surface of nickel-titanium alloy (NiTi) by plasma electrolytic oxidation (PEO) with the aim to produce a polymer-free drug carrier for drug eluting stent (DES) applications. The oxidation was performed galvanostatically in concentrated phosphoric acid electrolyte at low temperature. It was found that the response of NiTi substrate during the PEO process was different from that of bulk Ti, since the presence of large amount of Ni delayed the initial formation of a compact oxide layer that is essential for the PEO to take place. Under optimized PEO conditions, the resultant surface showed porosity, pore density and oxide layer thickness of 14.11%, 2.40 × 10⁵ pores/mm² and 0.8 μm, respectively. It was additionally noted that surface roughness after PEO did not significantly increase as compared with that of original NiTi substrate and the EDS analyses revealed a decrease in Ni/Ti ratio on the surface after PEO. The cross-section morphology showed no discontinuity between the PEO layer and the NiTi substrate. Furthermore, wettability and surface free energy of the NiTi substrate increased significantly after PEO treatment. The PEO process could be successfully translated to NiTi stent configuration proving for the first time its feasibility for such a medical device and offering potential for development of alternative, polymer-free drug carriers for NiTi DES. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Ni-free Ti alloys are a potential strategy to overcome the risk of Ni-adverse reactions and rigidity mismatch for implant materials. Here, we report the biological behavior induced for two promising candidate alloys—Ti19.1Nb8.8Zr (M_S temperature of 46°C and elastic modulus of 74 GPa) and Ti41.2Nb6.1Zr (elastic modulus of 67 GPa)—on cultured MG63 cells, as well as their physical and chemical properties. Contact angle results revealed the hydrophobic character of the former alloy (59.02° ± 2.35°) attributed to the presence of the martensitic phase, while the latter one presented a hydrophilic response (67.77° ± 2.78°). Results showed also that the cell adhesion response (after 4 and 8 h of incubation) in both substrates was not statistically different to that obtained in the cp Ti as control material. These surfaces induced well spread cell morphology with cytoplasmic extension like filopodia of up to 100 μm even at short culture times and presented an uninterrupted proliferation after longer incubation times (9 days). A decrement in the proliferation rate was appreciated from the Ti19.1Nb8.8Zr surface at that time, which was attributed to an earlier activation of the cell differentiation stage, as confirmed by the twofold increment of alkaline phosphatase activity. The results also evidenced that the presence of a 2 nm thick layer of amorphous Nb₂O₅, which was detected on both alloys, has a significant effect on cell behavior favoring the cell adhesion and morphology response of the new alloys studied. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

A new strategy to improve silicon-based endodontic treatment tightness by dentine hydrophobization is presented in this work: root dentine was silanized to obtain a hydrophobic dentine-sealer interface that limits fluid penetration. This strategy was based on the grafting of aliphatic carbon chains on the dentine through a silanization with the silane end groups [octadecyltrichlorosilane (OTS) and octadecyltriethoxysilane]. Dentine surface was previously pretreated, applying ethylenediaminetetraacetic acid and sodium hypochlorite, to expose hydroxyl groups of collagen for the silane grafting. Collagen fibers exposure after pretreatment was visible with scanning electron microscopy, and Fourier transform infrared (FTIR) spectroscopy showed their correct exposition for the silanization (amide I and II, with 1630, 1580, and 1538 cm^-1 peaks corresponding to the vibration of CO and CN bonds). The grafting of aliphatic carbon chains was confirmed by FTIR (peaks at 2952 and 2923 cm^-1 corresponding to the stretching of CH bonds) and by the increasing of the water contact angle. The most efficient hydrophobization was obtained with OTS in ethyl acetate, with a water contact angle turning from 51° to 109°. Gas and liquid permeability tests showed an increased seal tightness after silanization: the mean gas and water flows dropped from 2.02 × 10^-8 to 1.62 × 10⁻⁸ mol s^-1 and from 10.8 × 10⁻³ to 5.4 × 10⁻³ µL min⁻¹, respectively. These results show clear evidences to turn hydrophilic dentine surface into a hydrophobic surface that may improve endodontic sealing. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Functional graded materials provided us one new concept for artificial articular cartilage design with graded component and graded structure. In this article, a novel functional material design was proposed by functionalizing hydroxyapatite (HA) particles in poly(vinyl alcohol) (PVA) hydrogel. The goal of the present study was to fabricate a multilayer gradient HA/PVA gel biocomposites through layer-by-layer casting method combining with freeze/thaw cycle technology and establish a mechanical model to predict the compressive mechanical properties of multilayer gradient gel biocomposites. The results showed that the compressive strength of the multilayer gradient gel biocomposites increased with the rise of HA content, but it presented decreasing trend with the rise of interlayer gradient concentration of HA particles. Furthermore, the compressive strength of multilayer gradient biocomposites would be approximately predicted by the established mechanical model. The maximum error between theoretical compressive strength predicted by the model and the experimental strength is less than 7%. On the other hand, the compressive mechanical properties of multilayer gradient composites could be designed and controlled by the mechanical model as established in this study. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The present study evaluated the use of this self-activated shape memory alloy (SMA) device, with a focus on its effects in the region under the periosteum. Twelve Japanese white rabbits were used in this study. The device was inserted under the periosteum at the forehead. In the experimental group, the device was pushed, bent, and attached to the bone surface and fixed with a titanium screw. In control group, the device was only inserted under the periosteum. After 14 days, the screw was removed and the mesh was activated in the experimental group. Rabbits were sacrificed 5 and 8 weeks after the operation and newly formed bone was histologically and radiographically evaluated. The quantitative data by the area and the occupation of newly formed bone indicated that the experimental group had a higher volume of new bone than the control group at each consolidation period. Histologically, some newly formed bone was observed and most of the subperiosteal space underneath the device was filled with fibrous tissue, and a thin layer of immature bone was observed in the control group. In the experimental group, multiple dome-shaped bones, outlined by thin and scattered trabeculae, were clearly observed under the SMA mesh device. The use of self-activated devices for the periosteal expansion technique may make it possible to avoid donor site morbidity, trans-skin activation rods, any bone-cutting procedure, and the following intermittent activation procedure. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Two types of DNA/protamine complexes were prepared from protamine sulfate and 7000 base pair (bp) DNA or original DNA to investigate the effect of the molecular weight of DNA on zeta potential, cell viability, flowability, soft tissue response, and biodegradation rate. The 7000 bp DNA/protamine complex had a negative charge while the original DNA/protamine complex had a positive charge. The cell viabilities (90.4–106.8%) of these complexes were close to each other. The 7000 bp DNA/protamine complex became a softer dough than that of the original DNA/complex when both were kneaded with water. In vivo, the original DNA/protamine complex showed a milder tissue response. The original DNA/protamine complex almost disappeared 30 days after implantation. The 7000 bp DNA/complex disappeared approximately 2 weeks after implantation and areas where samples were implanted became empty. Thereafter, the empty space was gradually replaced by new soft tissues. The original DNA/protamine complex showed low intercalation and groove binding ratios of daunorubicin hydrochloride. Results indicate that high DNA condensation by cationic protamine protected the penetration of degradation enzymes into these complexes. It was found that a high molecular weight of DNA reduced the biodegradation rate and flowability. This study suggests that DNA/protamine complexes could be candidates for biomaterials that control biodegradation rates and flowability. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) is a biocompatible and bioresorbable copolymer that has generated research interest as a bone scaffold material. However, its brittleness and degradation characteristics can be improved upon. We hypothesized that blending with medical-grade polycaprolactone (PCL) can improve degradation and mechanical characteristics. Here, we report the development of solvent-blended PHBHHx/PCL for application as a potential biomaterial for tissue engineering. Enhanced yield strength, yield strain and Young's modulus occurred at 30/70 blend when compared with PHBHHx and PCL. Polarized light microscopy demonstrated PHBHHx and PCL to exist as morphologically and optically distinct phases and, together with thermal analyses, revealed immiscibility. Hydrophilicity improved with the addition of PCL. Accelerated hydrolytic studies suggested predictable behavior of PHBHHx/PCL. Notably, 30/70 blend exhibited similar degradation behavior to PCL in terms of changes in crystallinity, molecular weight, morphology, and mass loss. Finally, human fetal mesenchymal stem cells (hfMSCs) were evaluated on PHBHHx/PCL using live/dead assay and results suggested encouraging hfMSC adhesion and proliferative capacity, with near-confluence occurring in PHBHHx and 30/70 blend after 5 days. Taken together, these are encouraging results for the further development of PHBHHx/PCL as a potential biomaterial for tissue engineering. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The growing demand for better implant aesthetics has led to increased research on the development of all-ceramic dental implants. The use of microtextured coatings with enhanced properties has been presented as a viable way to improve tissue integrability of all-ceramic implants. The aim of this study was to evaluate the effects of different densities of anisotropic microtextured silica thin films, which served as a model coating, on the behavior of human osteoblast-like cells. The differential responses of human osteoblast-like cells to anisotropic silica microtextures with varying densities, produced via a combination of sol–gel and soft lithography processing, were evaluated in terms of alignment, elongation (using fluorescence microscopy), overall cellular activity, and the expression/activity levels of alkaline phosphatase (ALP). Statistical analysis was conducted using one-way ANOVA/Tukey HSD post hoc test. The thin films were thoroughly characterized via scanning electron microscopy/energy dispersive spectroscopy, Fourier transform infrared, and contact angle measurements. Thin film characterization revealed increased nanoscale roughness and reduced wettability on the micropatterned surfaces. Cell culture experiments indicated that the microtextures induced cell alignment, elongation, and guided colonization on the surface. Cells cultured on denser micropatterns exhibited increased metabolic activity (t = 14–21 days). The early expression/activity levels of ALP released into the medium were found to be significantly higher only on the least dense micropattern. These results suggest the possibility that microstructured silica thin films could be used to guide and enhance peri-implant cell/tissue responses, potentially improving tissue integration for metallic and all-ceramic dental implants. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Ceramic-on-metal (COM) hip replacements, where the head is BIOLOX® Delta ceramic and the liner is CoCrMo alloy, have demonstrated reduced wear under standard simulator conditions compared to metal-on-metal (MOM) bearings. COM hips are now being used clinically around the world. MOM hip resurfacings have raised concerns regarding poor clinical performance and increased in vivo wear was associated with steeply inclined acetabular components and translationally malpositioned components. The aim of this study was to compare the wear rates of MOM and COM total hip prostheses under adverse edge-loading conditions in a hip simulator test. COM and MOM 36 mm hip prostheses were tested in a hip simulator, with liners mounted to provide a clinical inclination angle of 55°. A simplified gait cycle and microseparation conditions were applied for two million cycles in 25% new born calf serum. The overall mean volumetric wear rate of COM bearings under adverse conditions was 0.36 ± 0.55 mm³/million cycles; this was significantly less than MOM wear (1.32 ± 0.91 mm³/million cycles). Under these adverse conditions; the contact zone on the head intersects the rim of the cup causing substantially elevated contact stresses, disrupting the protective boundary and mixed lubrication regime causing changes in types and severity of wear mechanisms. In COM bearings, the harder head does not become damaged when there is lubricant starvation and wear does not accelerate. In conclusion, COM bearings showed reduced wear compared to MOM bearings under standard and adverse clinically relevant simulator conditions and COM bearings may provide an advantage over MOM bearings under edge-loading conditions clinically. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The number of hydroxyl groups on a Ti–29Nb–13Ta–4.6Zr (TNTZ) alloy surface was controlled through H₂O₂ treatment for further improvement of the adhesive strength and durability against water of TNTZ/silane layers (SILs)/segmented polyurethane (SPU) composites. The effect of the terminal functional groups on the adhesive strength of SPU on TNTZ, and the adhesiveness of SPU on TNTZ against water was investigated. Three types of silane-coupling agents were used to bind TNTZ and SPU: methacryloxypropyltrimethoxysilane (γ-MPTS), aminopropyltriethoxysilane (APS), and mercaptopropyltrimethoxysilane (γ-MPS). The adhesive strength of each composite was evaluated by shear bonding tests. The number of hydroxyl groups increases with an increase in treatment time at a H₂O₂ concentration of 5% (v/v). On the other hand, an increase from 5% (v/v) to 30% (v/v) in H₂O₂ concentration leads to a decrease in the number of hydroxyl groups on the TNTZ surface because at higher H₂O₂ concentrations, the reaction that consumes the hydroxyl groups is dominant. The shear bonding strength is doubled compared with the untreated TNTZ/SIL/SPU interface. Although the shear bonding strength decreases after immersion in water for 30 days when APS and γ-MPS are used, TNTZ/γ-MPTS/SPU composites exhibit good durability to water and maintain an equivalent shear bonding strength before immersion in water. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Fragmin/protamine microparticles (F/P MPs) have been used as a cell carrier for adipose-derived stromal cells (IR-ASCs) in inbred male Fisher 344 rats, and for preservation and controlled-release of fibroblast growth factor (FGF)-2 and various cytokines in inbred rat plasma (IRP)-DMEM (Dulbecco's modified Eagle's medium) gel. In this study, we investigated the capability of an IRP-DMEM gel containing F/P MPs and/or FGF-2, as a three-dimensional (3D)-culture, to expand IR-ASCs. We found that IR-ASCs grow faster under 3D-culture conditions in low IRP (3%)-DMEM gel containing F/P MPs and FGF-2 without any animal serum than those under 2D-culture in low inbred rat serum (3%)-DMEM with F/P MPs and FGF-2. About 0.3 mL of IR-ASCs (about 4,000,000 cells mL⁻¹) grown in IRP (6%)-DMEM gel containing F/P MPs and FGF-2 disappeared 8 days after subcutaneous injection in rats, suggesting that they are rapidly biodegradable. The number of large (diameter ≥200 μm or containing ≥100 erythrocytes), medium (diameter = 20–200 μm or containing 10–100 erythrocytes) and small (diameter ≤20 μm or containing 1–10 erythrocytes) capillaries after injection with IR-ASCs in an IRP-DMEM gel containing both F/P MPs and FGF-2, as well as the thickness of tissue granulation per microphotograph at the injected site, was significantly higher than those after injection with IR-ASCs in an IRP-DMEM gel containing either FGF-2 or F/P MPs. Thus, IRP-DMEM gel containing F/P MPs and FGF-2 are useful and safe IR-ASC carriers that facilitate cell proliferation, vascularization, and tissue granulation locally at injection sites. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

In this study, five commercially available poly(methyl methacrylate) PMMA bone cements were tested to investigate the effects of antibiotics on the severity of crevice corrosion. Bone cements with varying chemistry were also tested. A test method was developed in part reference to ASTM F746-04. Cylindrical specimens were fitted with a bone cement tapered collar, creating consistent crevice conditions. Crevice corrosion was then studied using potentiodynamic polarization techniques in 0.9% NaCl solution (pH7.4) at 37°C. Surface analyses using a light microscope and scanning electron microscopy were also conducted to investigate the surface morphology after accelerated electrochemical testing. Initial testing of commercially available bone cements indicated that different PMMA bone cements can affect the initiation and propagation mechanism of crevice corrosion. Further studies, utilising electrochemical and mass spectroscopy techniques, have identified that the addition of radiopaque agent and antibiotics affect the initiation mechanisms of 316L stainless steel, whilst significantly increasing the extent of propagation in CoCrMo alloys. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Caveolin is an essential and signature protein of caveolae. Caveolin-1 participates in signal transduction processes by acting as a scaffolding protein that concentrates, organizes and functional regulates signalling molecules within caveolar membranes. Beta-tricalcium phosphate (β-TCP) has been widely used for scaffold in tissue engineering due to its high biodegradability, osteoconductivity, easy manipulation, and lack of histotoxicity. To better understand the role of caveolin-1 in bone homeostasis and response to β-TCP scaffold, β-TCP was implanted into the dog mandible defects in beagle dogs, and gene expression profiles were examined focused on the molecular components involved in caveolin-1 regulation. Here we showed the quantitative imageology analysis characterized using in vivo micro-computed tomography (CT) images at 4 and 7 days after β-TCP implanted in dog mandibles. The bone reformation by using the β-TCP scaffolds began within 4 days of surgery, and was healing well at 7 days after surgery. Higher mRNA level of caveolin-1 was observed in β-TCP-implanted Beagle dog mandibles compared with controls at day 4 and day 7 post-surgery. The enhancement of caveolin-1 by β-TCP was further confirmed by immunohistochemistry and immunofluorescence analysis. We further revealed increased Smad7 and Phospho Stat3 expression in β-TCP-implanted specimens. Taken together, these results suggest that the enhancement of caveolin-1 play an important role in accelerating bone formation by β-TCP. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Porous polymethylmethacrylate (PMMA) has been used as an alloplastic bone substitute in the craniofacial complex, showing integration with the surrounding soft and hard tissue. This study investigated the physicochemical properties of curing and cured mixtures of a PMMA-based bone cement and a carboxymethylcellulose (CMC) gel porogen. Four formulations yielding porous PMMA of varied porosity were examined; specifically, two groups containing 30% (w/w) CMC gel in the mixture using a 7% (w/v) or 9% (w/v) stock CMC gel (30-7 and 30-9, respectively) and two groups containing 40% (w/w) CMC gel (40-7 and 40-9). An additional group comprising solid PMMA without CMC was investigated. The incorporation of the CMC gel into the PMMA bone cement during polymerization decreased the setting time from 608 ± 12 s for the solid PMMA to 427 ± 10 s for the 40-9 group, and decreased the maximum temperature from 81 ± 4°C for the solid PMMA to 38 ± 2°C for the 40-9 group. The porous PMMA groups exhibited reduced compressive strength and bending modulus and strength relative to the solid PMMA. All the porous PMMA formulations released more unconverted methylmethacrylate (MMA) monomer and N,N-dimethyl-p-toluidine (DMT) from cured specimens and less MMA and DMT from curing specimens than the solid PMMA. The data suggest that the physicochemical properties of the porous PMMA formulations are appropriate for their application in craniofacial space maintenance. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Abdominal adhesions are one of the major problems associated with abdominal surgeries or abdominal trauma. There are many different therapeutic options to prevent these adhesions, for example, the application of barrier films made of biodegradable polymers like alginate. For many application relevant parameters (mechanical stability, elasticity, erosion, and mucoadhesivity of the films), the extent of cross-linking with divalent cations, such as calcium, is essential to obtain alginate films with clinically ideal properties. All these properties can eventually be strongly influenced by the composition of the films. For this reason, the manufacture of thin films (≈20 µm) was improved to accurately control the calcium content and distribution as well as the time and process of cross-linking. The aim of this work was to find the best suited method to evenly distribute the calcium ions in the alginate films and to obtain films with controlled erosion times as well as sufficient flexibility and stability. Furthermore, the influence of plasticizers on the mechanical stability and elasticity was tested to find the amount and type of plasticizers that have to be added to produce the best suited films. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Parkinson's is a major neurodegenerative disorder that occurs due to loss of dopaminergic neurons in basal ganglia. Conventional therapy includes surgery that involves lot of risk and administration of levodopa which is accompanied by poor bioavailability, short half-life, and side effects. In the present study, poly(butylene succinate) (PBSu) microspheres-based drug delivery system to improve the bioavailability of the drug levodopa was evaluated for the first time. Biodegradable porous and smooth PBSu microspheres were prepared by double emulsion solvent evaporation technique (W/O/W) and the effect of solvent and surfactant was studied. The maximum encapsulation efficiency achieved was 53.93% and 62.28% for porous and smooth microspheres, respectively. In vitro drug release was studied in phosphate buffered saline and simulated CSF buffer of pH 7.4. Initially a burst effect followed by sustained release of drug was obtained for about 32 h and 159 h for porous and smooth microspheres, respectively. The release rate was higher in simulated CSF when compared with PBS, due to higher concentration of sodium ions and cations in simulated CSF. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Polycaprolactone-tricalcium phosphate (PCL-TCP), a new composite scaffold, has been shown to facilitate early revascularization and speed up bone regeneration process. The objective of this study was to evaluate the effect of PCL-TCP seeded with mesenchymal stem cells (MSCs) on healing of the vertical bone critical sized defect in dog's mandible. Bone marrow aspirate from dog humerous was cultured and the stemness of the cells was examined by differentiation staining methods and flow cytometric analysis. Third passage subculture cells (5 × 10⁵ cells) were loaded on 20 × 10 × 10 mm³ and incubated for 48 h. The presence of MSCs in the pores was evaluated by scanning electron microscope. Bilateral mandibular premolar teeth were extracted in four dogs and the buccal and lingual bone plates were reduced to make a vertical defect. Cell-loaded scaffolds were fixed in right side and left side received pure PCL-TCP scaffolds as a control side defects. Histomorphometric analysis after 8 weeks of the scaffold implantation showed higher amount of lamellar bone in the test side (48.63%) than control side (17.27%) (p < 0.05).The results suggest that PCL-TCP may be an appropriate scaffold for loading MSCs in bone regeneration. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

A novel anorganic bovine bone xenograft with enhanced bioactivity and osteoconductivity was prepared by an ion substitution method using sodium hypochlorite. Bovine bone granules were defatted, washed, and then soaked in sodium hypochlorite solution at room temperature. Subsequently, the granules were dried and then heat-treated at 1000°C with sodium hypochlorite. As a control, bovine bone granules were prepared with the same conditions but without sodium hypochlorite treatment. Phase, functional group, and elemental analyses by XRD, FTIR, and EPMA showed that the granules heat-treated without and with sodium hypochlorite were pure hydroxyapatite and sodium-chlorine-bearing hydroxyapatite, respectively. After soaking in simulated body fluid (SBF) for 1 week, low crystalline hydroxyl carbonate apatite fully covered the surface of sodium-chlorine-bearing hydroxyapatite, whereas it formed little on the hydroxyapatite surface. After soaking in SBF and deionized water, ICP-AES and IC analyses showed that the dissolutions of calcium, sodium, chlorine, and hydroxyl ions from sodium-chlorine-bearing hydroxyapatite notably increased compared with those from hydroxyapatite. This resultantly increased the ionic activity product of apatite in SBF and induced new formation of low crystalline hydroxyl carbonate apatite. The cytotoxicity test by BCA assay showed that there were no statistically significant differences between hydroxyapatite and sodium-chlorine-bearing hydroxyapatite. In addition, sodium-chlorine-bearing hydroxyapatite showed better osteoconductivity in the calvarial defects of New Zealand white rabbits within 4 weeks compared with that of hydroxyapatite. The results suggest that this novel anorganic bovine bone xenograft possesses encouraging potential for use as a bone grafting material due to better bioactivity and osteoconductivity than hydroxyapatite. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Magnesium and its alloys have gained significant attention recently as potential alternatives for biodegradable materials due to their unique biodegradability, biocompatibility, and mechanical properties. However, magnesium alloys tend to have high corrosion rates in biological liquids, thus presenting a potential problem if a magnesium implant/device needs to maintain mechanical integrity for a sufficient period under practical physiological conditions. In this study, hydroxyapatite nanoparticles were used to form magnesium based metal matrix nanocomposites (MMNC) through two processes: friction stir processing (FSP) and a two-state nanoprocessing (TSnP) combining liquid state ultrasonic processing and solid state FSP. In addition, laser surface melting (LSM) was carried out for further surface treatment. In vitro immersion tests indicated that the corrosion rate of MMNC decreased by 52% compared with pure Mg through FSP. Potentiodynamic polarization tests showed that the corrosion current of MMNC decreased by 71% and 30%, respectively, by TSnP and LSM when compared with pure Mg or untreated counterparts. This study suggests that fabrication of MMNC and further processing through FSP and LSM can robustly enhance the corrosion resistance of magnesium, which will boost its potential for biological applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

The aim of this study was to evaluate of flexural strength of some adhesive resin cements. Three dual-cure composite resin cements (Nexus 3; Variolink II, Panavia F) were prepared. The manufacturer's mixing directions for the cements were followed. Adhesive resin cement was mixed, placed in the rectangular portion of the mold. Fifteen specimens were prepared for each cements. The cements were light-activated with light lamp for 40 s on both and top and bottom surfaces. The each cement specimens were divided into three groups according to time of storage and stored in distilled water for 24 h, 15, and 30 days. Total 45 specimens were stored at 37°C (98.6 0F) in distilled water for 24 h, 15, and 30 days prior to tests. The flexural strength was tested wıth a universal testing machine at a crosshead speed of 0.5 mm/min (0.02 in.) The maximum load was recorded as MPa. The results were analyzed by Analysis of Variance and Duncan test. The Panavia F resin cements content Bisphenol A was showed the highest flexural strength (80.80 MPa) (11.71 ksi) for 24 h. The lowest flexural strength was observed in Nexus 3 (51.00 MPa) (7.39 ksi). It was found significant interaction of material and time (p < 0.05). The types of cement and time of storage was statistically significant on the flexural strengths (p < 0.001). © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.

Novel multifunctional bioresponsive gelatin and alginate based hydrogels with in-built antioxidant regenerating system and antimicrobial properties were successfully synthesized. These hydrogels are based on the versatile reactions catalyzed by cellobiose dehydrogenase (CDH). CDH uses cellobiose and cello-oligosacharides as electron donors to reduce oxidized phenolic antioxidants, quinones, or molecular oxygen to H₂O₂ (a well-known antimicrobial agent). The antioxidant regenerating system consisting of CDH and cellobiose increased the ability of catechol to quench nitric oxide (NO), superoxide (O₂⁻) and hydroxyl radicals (OH^•) in solution and when incorporated into hydrogels. The CDH loaded into the hydrogels free of oxidized phenolic antioxidants and quinones reduced molecular to H₂O₂ resulting in the complete inhibition of the growth of Stapylococcus aeureus, Bacillus subtilis, Pseudomonas putida, Escherichia coli and Cellulomonasmicrobium cellulans. This study therefore presents a new concept for synthesizing multifunctional bioresponsive chronic wound dressing polymers with in-built continuous antioxidant system able to continuously quench [reactive oxygen species (ROS) and reactive nitrogen species (RNOS)], and antimicrobial properties able to prevent microbial colonization of wound. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013.