Advanced Healthcare Materials

Graphene quantum dots (GQDs) have decent cellular internalization capability through both energy-independent and energy-dependent pathways. The internalized GQDs shows a lower cytotoxicity than that of the micrometer-sized GO sheets.

A flexible and transparent anti-bacterial film is prepared by depositing polyterthiophene incorporating porphyrin onto the poly(ethylene terephthalate) sheet by a simple and rapid oxidation polymerization method. The film can generate singlet oxygen by FRET from polyterthiophene to porphyrin to effectively kill the adsorbed bacteria under white light.

Ultrasensitive ratiometric fluorescent pH probes based on dual dye-labeled pH-responsive diblock copolymer micellar scaffold are constructed. The pH-sensitive emitting nature of BTPE dyes and emission turn-on of CMA moieties triggered by pH-actuated micelle-to-unimer of diblock scaffold synergistically contribute to the observed ≈250-fold changes of BTPE/CMA emission intensity ratios in the whole pH range. Two-photon ratiometric fluorescent pH mapping of intracellular gradients subjected by pH-responsive micellar nanoparticles in their endocytic pathway has been thus achieved.

Vaterite (CaCO₃) is used as a phase stabilizer of amorphous celecoxib to increase the apparent aqueous solubility of the substance. The effect is attributed to the mesoporous structure of the particles that constrain the ability for the celecoxib to crystallize. The results demonstrate the feasibility of using vaterite, which is already recognized as GRAS by the FDA, as an excipient for increasing the oral bioavailability for Type II BCS drugs.

Lanthanide-doped sodium gadolinium fluoride upconverting nanoparticles are shown to efficiently decrease the relaxation time of protons in aqueous media and provide a positive contrast in MRI applications. In particular, ultrasmall nanoparticles that are less than 5 nm in diameter are shown to have the lowest relaxometric ratios reported to date and a very strong vascular enhancement for times of at least 90 min in the mouse model.

A multifunctional nanoarchitecture with ordered molecular structures is designed and constructed as a platform for multiplexed surface biofunctionalization. The nanoassembly enters cells via caveolae-dependent endocytosis and specifically targets mitochondria. Upon cytotoxic peptide modification, the nanoassembly exhibits dramatically enhanced anticancer activities.

A versatile and efficient multidomain delivery system facilitating the cell uptake of the proteins p53 and Cytochrome C is obtained by supramolecular assembly. Such nanotransporters contain a streptavidin protein core functioning as a bio-adapter, second generation polyamidoamine dendrons for cell uptake as well as a therapeutic protein as cargo. The delivery and functional activity of tumor suppressor p53 or pro-apoptotic cytochrome c are studied in detail.

A peptide-labeled paramagnetic/upconversion nanoprobe (UCNP-Gd-RGD) is designed and synthesized. It demonstrates high specificity towards U87MG cells and preferential retention in subcutaneous U87MG tumors. The tumor boundary delineation is successfully achieved through in vivo upconversion fluorescence and MRI studies. This dual-modal nanoprobe holds the potentials in preoperative MR imaging and intra-operative fluorescence-guided surgery

Herein, a nanoceria-triggered intracellular drug delivery platform using β-CD@CeO₂-capped Fc-MSN is reported. CeO₂ has different enzyme-mimetic activity at different pH conditions. It can be a capping agent and an antioxidant cell protector at physiological pH condition, while at low pH conditions, such as in lysosome, it triggers self-uncapping and has synergetic anticancer effect.

Nanomedicines are emerging as promising tools to improve health. Silk nanoparticles of defined surface charge and size can be obtained using acetone desolvation and are readily loaded with a chemotherapeutic agent and used as a nanomedicine. These silk-based nanoparticles are able to serve as a lysosomotropic delivery platform and can overcome cancer cell drug resistance.

In contrast to compounds exhibiting no (Z⁺ = N⁺) or insufficient (Z⁺ = P⁺) antibacterial effectiveness, arsonium (Z⁺ = As⁺)-containing lipophosphoramides can simultaneously inhibit bacteria while safely and efficiently delivering DNA into eukaryotic cells, thereby leading to luciferase (Luc) reporter gene expression. Such poly-functional nano-carriers may therefore be particularly suitable for gene therapy strategies under infected conditions such as within the airways of cystic fibrosis patients.

The conjugation of reverse transcriptase inhibitors to a versatile self-assembly motif affords hydrogelators that self-assemble to form supramolecular nanofibers as the matrices of hydrogel. Prostate acid phosphatase drastically enhances the elasticity of hydrogels that are biocompatible and release the inhibitors. This type of hydrogels is both anti-inflammatory and anti-HIV.

An anionic crosslinker is synthesized based on a natural polysaccharide, chondroitin sulfate (CS), by introducing methacrylate groups (CSMA). By systematic adjustment of the substitution degree of methacrylation on CS and the weight percent of CSMA and poly(2-dimethylaminoethyl methacrylate) (PDMAEMA), sol-type copolymers are obtained as a gene-delivery vector. The combination of CS and PDMAEMA not only reduces the cytotoxicity of PDMAEMA, but also facilitates better transfection efficiency than PDMAEMA because of the recognition of CS by CD44 receptors on cell surfaces.

Oil-filled lipid nanoparticles (NPs) have excellent compatibility with medium-chain ester derivatives of docetaxel (DX). The synthesized DX lipid conjugate enhances the drug loading, entrapment and retention in liquid oil-filled lipid NPs. The stable anchoring of DX lipid conjugate in the long-circulating NPs leads to significant enhancements in blood exposure and efficacy in vivo.

Magnetic spheroid manipulation can be carried out in hanging drops to generate distinctly structured heterotypic microtissues through sequential addition of cells or spheroid to homotypic spheroids. These spheroids can also be incorporated in a droplet-based assay to screen for therapeutic efficacy in prolonged studies. This simple and versatile technique can offer potential benefits in tissue engineering and drug screening applications.

Multifunctional polymersomes loaded with maghemite nanoparticles and grafted with an antibody, directed against human endothelial receptor 2, are developed as novel MRI contrast agents for bone metastasis imaging. Upon administration in mice bearing bone tumor grown from human breast cancer cells, MR images show targeting and enhanced retention of antibody-labeled polymersomes at the tumor site.

Patterning of bioactive enzymes with subcellular resolution is achieved by dispensing droplets of dextran (DEX) onto polyethylene glycol (PEG)-covered cells though a glass capillary needle connected to a pneumatic pump. This technique is applied to purify colonies of induced pluripotent stem cells (iPSCs) from mouse embryonic fibroblast (MEF) feeder cultures and inefficiently induced iPSC colonies by selectively dissociating the iPSCs with proteases.

Neural stem cells maintain their tumor tropism after internalizing gold nanorods. When exposed to a laser, the loaded cells heat up, destroying surrounding tumor cells.

Application of high-intensity focused ultrasound to drug-loaded superhydrophobic meshes affords triggered drug release by displacing an entrapped air layer. The air layer within the superhydrophobic meshes is characterized using direct visualization and B-mode imaging. Drug-loaded superhydrophobic meshes are cytotoxic in an in vitro assay after ultrasound treatment.

The combined effect of mussel-inspired polydopamine (PDA) surface functionalization and topographical cues on the behavior of skeletal myoblasts is described. On PDA-modified nanofibers, myogenic protein expression and the fusion of myoblasts are increased significantly compared with those on unmodified nanofibers. The multinucleate myotubes on the aligned nanofibers are oriented in a direction parallel to the nanofibers.

Surface functionalization of human red blood cells (hRBCs) with fluorescent and magnetic silica core-shell nanoparticles is used to design a carrier suitable for multimodal imaging with a long circulating time. The coated magnetic hRBCs show no hemolytic activity, while the advantage of the affinity of proteins for silica allows a further coating.

The evaluation of biocompatibility is an important step in the development of novel biomaterials. In the case of bone cements, such biocompatibility studies are either based on cell culture experiments or on in vivo experiments. This article presents evaluation of biocompatibility of a composite composed of bone cement and microparticulate drug delivery system in an ex vivo trabecular bone model. The presented ex vivo model is a potential alternative to animal testing with improved relevance compared to cell culture testing.

Nanoparticles target tumor cells by pH-controlled means: Nanoparticles carry three synergistic delivery functions: 1) tumor tissue targeting by the EPR effect; 2) tumor cell targeting by pHLIP-mediated membrane-localization; and 3) tumor cell uptake by adsorptive-mediated endocytosis.

Excised human skin responds to influenza virus-like particle (VLP) vaccines delivered via intradermal (ID) or coated microneedle (MN) injection. Microarray heat maps highlight changes in expression of genes responsible for key immunomodulatory processes and viral response, including cell recruitment, activation, migration and T cell interaction. Morphological changes in Langerhans cells at the site of antigen deposition permit cell migration through the skin epidermis.

Using a novel coarse-grained peptide/polymer model, large-scale molecular dynamics simulations are performed to examine spontaneous self-assembly of peptide amphiphiles resulting in the formation of nanostructures of various sizes and shapes as a function of the electrostatics and temperature. Different self-assembly mechanisms are deciphered and a phase diagram delineating regions of morphological transitions at different solvent conditions is constructed.

A bacterial cellulose (BC) nanofibrillar patch is proposed as a new wound healing platform for tympanic membrane (TM) perforation. In vitro and in vivo studies demonstrate that the BC nanofibrillar patch promotes the TM healing speed and rate as well as recover the function of TM.

Doxorubicin is used together with the modified polysaccharide as a wall material to fabricate microcapsules through electrostatic interaction and Schiff's base covalent bonding by a simple template method. Doxorubicin can be released responsively and sustainably from the capsules in the tumor microenvironment in vitro. The cell cytotoxicity experiments demonstrate that the doxorubicin-based microcapsules have high efficiency to kill cancer cells.

Novel injectable chitosan sponges based on rapid ionic crosslinking using guanosine 5′-diphosphate are introduced. The rapid gelation, high water retention, desirable physicochemical properties, soft tissue-like mechanical properties and excellent cytocompatibility make these injectable sponges promising candidates for tissue regeneration and drug delivery applications.

Design of targeted PEGylated G5 dendrimers loaded with a chemotherapeutic agent: PEG is coupled to G5 and functionalized with NAcGal sugar molecules or SP94 peptide targeting ligands. NAcGal- and SP94-functionalized PEGylated G5 particles bind to their specific receptors expressed on the surface of hepatic cancer cells triggering receptor-mediated endocytosis, followed by PEG shedding and release of the loaded chemotherapeutic agent.

A microreplication method is presented to transfer nature optimized vascular network of leaf venation into various synthetic matrixes. The biomaterial hydrogel with these microfluidic networks is proven to facilitate the growth of endothelial cells and simultaneously function as convection pathways to transport nutrients and oxygen in a pump-free bioreactor setup, which is crucial for the long-term viability of encapsulated cells.

A novel superhydrophobic biodegradable coating with micro-/nanometer rough structure, fabricated by co-electrospraying poly(L-lactide) (PLLA) and modified silica nanoparticles (MSNs), exhibits good anti-adhesion behavior towards bacteria and cells in the initial culturing phase, which makes it a promising technology for preparing medical device coatings.

Biodegradability of graphene is a crucial issue concerning the clinical translation of graphene based nano-bio systems. Our confocal Raman imaging study reveals clear evidence of macrophage mediated degradation of tissue bound graphene under in vivo conditions over a period of 90 days in mouse models. In vitro studies conducted in macrophage cell lines also supports the in vivo observations.

Europium-doped GdPO₄ hollow spheres/polymer core-shell nanoparticles were functionalized with ovalbumin (OVA) as a model antigen and an oligonucleotide (CpG) that stimulated the immune response. These functionalized core-shell nanoparticles were used as vaccines, where they enabled efficient delivery of an antigen to target sites, tracking of the vaccines using non-invasive clinical imaging technology.

A bioresorbable airway stent that would eliminate the current requirement for surgical removal after use is reported. This new stent, made of bioresorbable APS elastomer, is designed with mechanical properties comparable to current silicone stents, made of a novel bioresorbable elastomer, APS, which has a highly tunable stiffness, degradation rate, and a triggered degradation mechanism. Initial results of the fabrication, degradation properties, and mechanical properties of these prototype stents are reported.

Grafting of enantiopure chiral poly(glycerol methacrylate) onto gold effectively blocks adhesion of THP-1 cells. In contrast, broad cell spreading is observed on a bare surface, and a weak cell adhesion on a racemic self-assembled monolayer. The dissimilar cell repulsion of enantiopure and racemic coatings is due to a higher hydration of the former, an indirect result of chiral ordered conformations adopted by these enantiopure polymers.

Efficient antibacterial agents in vitro and in vivo: Lys-coated mesoporous silica nanoparticles (MSNs⊂Lys) with bacterial targetability and adhesive capabilities show five-fold enhanced antibacterial activity in vitro and over two-fold antibacterial efficacy in the intestines of mice, as compared to controls.

The synergistic effects resulting from the assembly of well-defined structures at the nano-GO surface, in addition to its morphology, surface chemistry and its intrinsic optical, mechanical and electronic properties, allow the development of new multifunctional hybrid materials with a high potential in multimodal cancer therapy. A comprehensive review of the fundamental properties of nano-GO requirements for cancer therapy and the first developments of nano-GO as a platform for this purpose is presented.

Extremely efficacious gene transfection vector: The rapid and facile modification of PEI with commercially available TMC produces an extremely efficacious gene delivery vector with minimal cytotoxicity. Functionalization of PEI is easily controlled by PEI:cyclic carbonate feed ratios and allows for the addition of functionality. Modified PEIs hold great potential as gene delivery systems due to easy synthesis, scalability, low cost, low toxicity and outstanding transfection capacity

A dual therapeutic cassette is presented composed of two distinct compartments that contain the combined nanostructures of (1) DNA and RNA as both anticancer container and target ligand and (2) gold nanocrystal as a localized heat inducer. This multimodular platform shows a powerful synergistic killing effect that results in prostate cancer regression both in vitro and in vivo.

Recombinant human albumin derived nanoparticles (ANPs) are engineered to overcome multiple barriers that challenge drug delivery and tumor chemotherapy. By integrating distinct technological features of nanoscale size variation, collagenase decoration, and modification with dual, complementary drugs (curcumin and riluzole), the ANPs can undergo enhanced intracellular uptake, penetrate deeper into solid tumor matrices, and exhibit significantly enhanced overall efficacy against melanoma in a tumor spheroid model.

A disulfide-crosslinked hydrogel made from ultrasmall peptides is introduced. Crosslinked gels are more elastic and better able to maintain shape integrity. Using facile chemistry, RGD (or other bioactive signals) can be conjugated onto the peptide fibers. Gels formed are biocompatible and support the three-dimensional distribution of cells.

This article reports the development and in vivo evaluation of liposomal lauric acids (LipoLA) as a new, effective and safe nanotherapeutic agent for the treatment of Propionibacterium acnes infection. Using a mouse ear model, topically applying LipoLA in a gel form onto the infectious site results in completely killing the bacteria without inducing acute toxicity to normal skin.

A newly developed collagen based pseudo-periosteum that simulates the motif of native perisoteum has a strong influence on spatially alignment and proliferation of stem cells. Importantly, the pseudo-periosteum-covered porous scaffold significantly promotes osteogenesis when compared with the pseudo-periosteum-free scaffold, indicating the important potential of periosteum in bone remolding and healing.

Dimers of gold nanoparticles are employed to build surface enhanced Raman scattering (SERS)-based tags. The nanoparticles are held together by a small Raman-active molecular linker and surface-functionalized with stabilizing polyethylene glycol, fluorescent dyes, and cell-specific targeting moieties. Upon incubation with cancerous cells, the tags demonstrate high sensitivity at low incubation times, high selectivity, retained activity upon endocytosis, low cytotoxicity, and more effective tumor phenotype detection compared to traditional fluorescence- based approaches.

A microHall (μHall) sensor platform is developed to detect rare pathogens in unprocessed clinical samples. The system employes an array of μHall elements to accurately enumerate individual, magnetically tagged bacteria under flow conditions. It allows direct bacterial detection in unprocessed samples, which not only improves the overall throughput but also simplifies assay procedures.

A MEMS device is designed and fabricated for programmable drug delivery. The device is demonstrated to be used for tailoring the drug dosages for disease treatment in an in vitro study on pancreatic cancer cell colonies. It provides a promising novel platform for individualized disease treatment in future medicine and automatic in vitro test in drug development industry.

A novel technique combining the precision of block copolymer templating with anodisation allows for highly defined nanopatterning of non-planar Ti surfaces. Highly ordered titania nanodots can be created, and the technique has the capability for fine tuning of topography dimensions. In vitro results show that these nanopatterns have the potential to improve osteoinduction at Ti implant surfaces.

Graphene oxide can be loaded on cotton fabrics via various ways, and such a composite shows high anti-bacterial properties with minimal skin irritation.

A small molecule, glucosamine, is used as targeting moiety for insulin-secreting beta cell separation in artificial cell mixtures and tissue samples. The specificity of glucosamine allows it to be used in cell sorting applications. In addition, a thrombin-specific cleavable peptide was used as an intermediary to release nanoparticles from cell surfaces to facilitate cell attachment and proliferation.

Lipid-based oxygen microparticles have been described as a means to administer oxygen gas intravenously as a means to reverse systemic hypoxemia. This work describes the bulk manufacture of concentrated, gas-filled microparticles using a high shear homogenizer, creating microparticles which are stable at room temperature for 100 days. These microparticles transfer oxygen to human blood within seconds of contact in vitro, without signs of hemolysis or complement activation.

Lactococcus lactis is modified to express a fibronectin fragment (FNIII_7-10) as a membrane protein. This interphase, based on a living system, can be further exploited to provide spatio-temporal factors to direct cell function at the material interface. This approach establishes a new paradigm in biomaterial surface functionalization for biomedical applications.

An effective targeted and pH-responsive drug delivery system: The unique combination of dendrimer chemistry and carbon nanotubes allows the generation of multifunctional nanodevices for high-payload encapsulation of a model anticancer drug doxorubicin with pH-responsive release behavior and targeting specificity, providing an efficient strategy for targeted cancer therapy.

Platelet-rich-plasma (PRP) shows unique antimicrobial properties both in vitro and in vivo. An implant-associated spinal infection rabbit model shows that PRP treatment leads to a significant reduction in bacterial burdens together with a significant improvement in wound healing. PRP could be an advanced healthcare material against postoperative implant-associated infections.

A dense diamond nanoneedle array is capable of rapidly and conveniently delivering fluorescent probe and drug molecules to a large number of cells. This simple approach paves the way for potential high-throughput delivery of genes, drugs, and fluorescent probes into cells without endocytosis.

Protein-based mixed micelles with variable avidities to fibrinogen at different temperature regimes are reported. Such a system has potential drug delivery applications as a blood circulating depot that will only be released in situ upon a specific trigger such as temperature (in the current design), pH or oxidative stress.

This work illustrates a strategy for the design of molecularly defined immunotherapies, using a blend of supramolecular peptide self-assembly and active site-directed protein capture.

The in vivo wound healing response to polymer scaffolds at the cell biology level remains little investigated. Here, a variety of scaffolds are applied to wounds and it was found that re-epithelialisation was perturbed and the gap junction protein Connexin 43 is deleteriously up-regulated. Through bioactivation of scaffolds using Connexin 43 antisense oligodeoxynucleotides, the biocompatibility of scaffolds for clinical use can be improved.

SS-cleavable proton-activated lipid-like material (ssPalm) functions as a key element in a lipid nanoparticle in which pDNA is encapsulated. The ssPalm contains dual sensing motifs that can respond to the intracellular environment; a proton-sponge unit (tertiary amines) that functions in response to an acidic environment (endosome/lysosome), and disulfide bonding that can be cleaved in a reducing environment (cytosol).

Free-standing, micropatterned silica nanotube membranes are in situ fabricated using a micropatterned silica-coated collagen hybrid hydrogel as template. They are substrate-free, and not only maintained their micropatterned microstructure well, but also exhibited strong cell contact guidance ability to direct cell alignment and differentiation, indicating their good potential for biomedical applications.

Hydrogel bilayers containing photoencapsulated cells self-fold into curved and micropatterned bio-origami geometries. Self-folding is driven by differential swelling of the hydrogel layers and a variety of microstructured bilayers can be photopatterned simultaneously. Bio-origami hydrogels can be used to direct the growth of cells into anatomically relevant 3D geometries for long-term cell culture studies.

New switchable hydrogels are developed. Under acidic conditions, hydrogels undergo self- cyclization and can catch and kill bacteria. Under neutral/basic conditions, hydrogels undergo ring-opening and can release killed bacterial cells and resist protein adsorption and bacterial attachment. Smart hydrogels also show a dramatically improved mechanical property which is highly desired for biomedical applications.

Current three dimensional culture models mimicking organ systems and disease concepts in vitro are reviewed. It is predicted that these models will become increasingly important for understanding pathomechanisms of disease, drug screening and testing. Advancements in combining engineered micro-environments with human cell lines that mimic retinal architecture may also allow the study of disease mechanisms such as those occurring in age-related macular degeneration, the most common cause of blindness in the Western World.

The recent development of reactive oxygen specie (ROS)-responsive materials is inspired from numerous disease states, such as cancer and inflammation, involving the overproduction of ROS. ROS-responsive materials available today employ two general mechanisms: i) solubility switch and ii) degradation upon exposure to ROS. These materials can be used for drug and cell delivery to interact with the pathophysiological states more intelligently.

Malaria parasites can move extremely fast on different substrates. Using a set of tunable substrates with changed ligand spacing and elasticity it is shown that a small chemical compound that stabilizes the actin cytoskeleton can compensate the motility defects of parasites that lack a surface protein important for substrate adhesion.

Chitosan drug loaded matrices are electrodeposited on conductive surfaces and modified by simple dip coating processes with an ionic crosslinker solution. Drug release is evaluated in different pH conditions mimicking possible changes due to local inflammation or disease. The method is intended to functionalize capsules for drug delivery into the eye.

Bacterial biofilms pose persistent and costly challenges in many healthcare contexts. A non-bactericidal approach to preventing biofilm formation in the human pathogen P. aeruginosa is reported. The approach is based on the gradual release of a potent, non-bactericidal inhibitor of biofilm growth from thin polymer coatings, and can inhibit biofilm formation on film-coated surfaces and adjacent uncoated interfaces by up to 90%. This small-molecule inhibitor is not toxic to mammalian cells at concentrations required for strong anti-biofilm activity, suggesting that this approach is suited for further investigation in biomedical contexts.

An integrated microfluidic microfiltration platform containing a unique surface micromachined poly-dimethylsiloxane (PDMS) microfiltration membrane (PMM) and microbeads conjugated with antibodies is reported for rapid, efficient and high-throughput on-chip isolation, enrichment, and stimulation of subpopulations of immune cells from blood specimens. Furthermore, the PMM-integrated microfiltration platform, coupled with a no-wash homogeneous chemiluminescence assay (“AlphaLISA”), allows rapid and sensitive on-chip immunophenotyping assays for subpopulations of immune cells isolated directly from minute quantities of blood samples.

Dendritic cells (DCs) are an important target for vaccine delivery. It is shown that antibody functionalized polymer capsules can effectively target DCs; however, the internalization is highly dependent on the specific receptor targeted. This work highlights the importance of considering factors such as how the antibody/capsule is internalized, rather than just the target specificity.

Therapeutic poly(lactic acid) (PLA) nanofibrous matrices can trigger drug release through hybrid fabrication with plant viral nanoparticles (PVNs). PVNs comprise the native virus, Red clover necrotic mosaic virus, and a cancer therapeutic, doxorubicin. PVNs reversibly open and close with the appropriate environmental stimuli; the drug releases from the virus and diffuses through the polymeric matrix.

In order to overcome the inadequacies in current oral mucosal treatment methods, a modular treatment strategy is proposed which utilize biotin-streptavidin affinity linkages for developing multilayered polymeric self-assemblies. It is hypothesized that affinity based layer-by-layers (LBL) can be self-assembled through a series of mouth rinse over the oral wound surface, which will offer a desired regenerative treatment strategy through its stable barrier effects. Hence, evaluating the barrier stability of LBLs against harsh intraoral environment is a key requirement to validate its application in oral wounds.

Exposure to carbon nanotubes induces significant changes in cellular biomechanics. Using nanoindentation, it is observed that the exposed cells have significantly higher stiffness when compared to controls, especially at the nuclear region, and significant increases in surface area.

Reducing ferromagnetic particle size is an important strategy to improve their positive effect on image through the suppression of their negative effect, demonstrated by ultrasmall manganese ferrite nanoparticles prepared from an environmentally-friendly aqueous route. These ultrasmall particles exhibit pronounced paramagnetic characteristics and nontoxicity, making them efficient T₁-positive contrast agent and manganese contrast agents for manganese enhanced MRI.

An optical nanosphere sensor is developed for the removal of toxic metals from drinking water and blood. The sensor design creates highly accessible, flexible, and fine-tuned surfaces, which make unique sensing/removal systems that are inexpensive, simple, and highly sensitive to multiple metal ions. The design exhibits potential counteractions and inhibitions toward toxic effects associated with elevated blood lead levels.

The excellent cytocompatibility of single-layer CVD graphene is demonstrated by showing that primary adult retinal ganglion cells can directly survive on its surface without any supporting glial layer or protein coating. These results confirm the great potential of graphene as a biocompatible material for interfacing neurons, opening a new route for the development of a novel generation of flexible and high-sensitive neural prostheses.

A two-component hydrogel based on a Dock-and-Lock self-assembling mechanism is engineered with photo-triggerable secondary crosslinks. Physical Dock-and-Lock hydrogels are based on specific molecular interactions between polypeptide components and are injectable and rapidly self-healing. Secondary crosslinked physical- chemical hydrogels have increased mechanical properties, slower erosion, and remain self-adhesive.

Silver-containing PHBHV-g-PMAA microfibrous scaffolds with antibacterial activity are successfully engineered according to a sustainable “green chemistry” approach. It relies on a two-step procedure: UV photografting of poly(methacrylic acid) (PMAA) in aqueous media from the surface of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBHV) fibers via a “grafting from” method, followed by the complexation of the in situ photogenerated silver nanoparticles immobilized by carboxyl groups from tethered PMAA chains.

The promise of a new nanomaterial, Cu_2–xSe nanocrystals, as a contrast agent for photoacoustic imaging is demonstrated. The Cu_2–xSe nanocrystals exhibit strong optical absorption at near infrared wavelengths that can efficiently penetrate tissue. In vivo photoacoustic tomography using this nanomaterial as the contrast agent provides clear three-dimensional resolution of a sentinel lymph node in a rat model.

Mesoporous silica/calcium phosphate composite loaded with immunopotentiator tuberculin purified protein derivative (PPD-MS/CaP) as an effective adjuvant for cancer immunotherapy is synthesized. The adjuvant induces an enhanced activation of antigen-presenting cells, such as GM-CSF secretion by differentiated THP-1 cells. The adjuvant mixed with liquid-N₂-treated tumor tissue effectively triggers anti-tumor immune response and greatly inhibits in vivo tumor growth.

Natural protein based nano-/microparticles are manufactured and functionalized by BMP-2. The functionalized particles can associate with mesenchymal stem cells actively, boost differentiation, alleviate cytotoxicity and perform controlled release.

Gadolinium and europium ions are incorporated into a mesoporous silicate framework; a potential theranostic platform to achieve bimodal medical imaging capability. These nanomaterials outperform the commercially available T₁ MRI contrast agent, Omniscan with the added benefit of exhibiting photoluminescence properties.

Upon controlled UV illumination, disulfide bonds in bovine α-lactalbumin (BLA) are selectively broken, leading to self-assembly of the BLA and doxorubicin (DOX) molecules into nanoparticles via hydrophobic interactions and intermolecular disulfide bonds. Such protein–drug nanoparticles have synergistic anticancer activity in vitro and tumor-homing specificity in vivo, which are of great potential for systemic drug delivery in cancer therapy.

A novel strategy for combination chemotherapy (platinum and demethylcantharidin) via a polymer–(tandem drugs) conjugate for enhanced cancer treatment is demonstrated. Cisplatin can be released inside cell by reduction to attack DNA, while DMC will be hydrolyzed subsequently to block DNA-damage-induced defense mechanisms by serine/threonine phosphatase PP2A inhibition. Synergistic effect of the polymer–(tandem drugs) conjugate causes complete suppression of H22 liver tumor xenografts without recurrence.

Functionalization of kappa carrageenan by introducing photocrosslinkable moieties enables the formation of dual crosslinked hydrogels. The modification results in formation of highly porous hydrogel networks with tunable mechanical properties that can bear repetitive loading cycles without deformation. By micromolding approaches, fabrication of spatially controlled geometries renders the development of cell-patterned platforms for different biomedical and biotechnological applications.

A novel method for fabricating both multilayer stacked 2D and 3D tubular constructs composed of sheets of aligned collagen fibers is described. These structures are created by decellularizing native tendon and sectioning the material into thin sheets using a cryo-microtome. This fabrication method preserves the collagens natural strength as well as the fiber structure which would aid in directing aligned cell growth.

A human serum albumin derived core-shell DOX delivery system is prepared based on an innovative protein denaturing-backfolding strategy. This system possesses a considerable DOX loading capacity, a two-step controlled drug release mechanism, attractive biocompatibility and narrow size distribution inherited from the monodisperse albumin backbone, as well as fast cellular uptake and masking of HSA epitopes due to cationization and pegylation.

A degradable integrated bi-layered scaffold for osteochondral tissue engineering is fabricated. The ability of the scaffold to support in vitro simultaneous matrix deposition, adequate cell growth and cell differentiation of two distinct cell lineages, human mesenchymal stem cells and chondrocytes, in designated bone and cartilage layers of the scaffold, is demonstrated.

Playing a central role in the development of gram-negative sepsis, endotoxins are attractive therapeutic targets. However, their direct removal from protein-rich fluids remains challenging. We present a magnetic separation-based approach using polymyxin B-functionalized metal nanomagnets to eliminate endotoxin from human blood in vitro. Functional assays show an attenuated inflammatory response from human endothelial cells and less chemotactic activity in purified samples.

A novel method utilizing nanofabrication techniques is used to create surfaces with enhanced endothelial adhesion and retention under flow. The system utilizes nanotexture, charge, and ligands all combined together, uniquely assembled on the substrata surface, to create ensemble nanotextured surfaces. This system may be of particular utility for enhancing flow-resistant endothelialization of cardiovascular devices.

The “tower microneedle” (TM) via reverse drawing lithography for intravitreal injection by fabricating a long hollow microneedle on the blunt hypodermic needle: The hollow hole between the microneedle and hypodermic needle is aligned concentrically, and fifteen degree bevel angle is introduced to TM by laser cutting to achieve intravitreal injection with minimal damage to eye tissue.

A stem cell-encapsulated hydrogel laden microfluidic device with the function of gradient generation that can steer distinct specialized differentiation of stem cells on the hydrogel slab was developed in this study. This microfluidic model can be used to construct the interfacial tissues such as articular cartilage and relevant osteointegration of the cartilage graft.

Drug release triggered by an external non-invasive stimulus is of great interest for the development of new drug delivery systems. The preparation of an electroresponsive multiwalled carbon nanotube/poly(methylacrylic acid) (MWNT/PMAA)-based hybrid material is reported. The hydrogel hybrids achieve a controlled drug release upon the ON/OFF application of an electric field, giving rise to in vitro and in vivo pulsatile release profiles.

Plasticity and reciprocity of breast cancer cells to various extracellular matrice (ECMs) are three-dimensionally analyzed in quantitative way in a novel and powerful microfluidic in vitro platform. This successfully demonstrates the metastatic potential of cancer cells and their effective strategies of ECM proteolytic remodeling and morphological change, while interacting with other cells and invading into heterogeneous ECMs.

A successful combination of anti-biofouling and ion-interaction for endotoxin (ET) selective removal from protein solutions is realized via the immobilization of two ordinary polymers, PEG and PLL, which have protein resistance and endotoxin adsorption properties, respectively, together onto azide-functional polystyrene (PS-N₃) microspheres (MSs) using a surface click reaction. Toxic copper ions residu is successfully minimized by the addition of 2,2′-bipyridine (BiPy).

Porous scaffolds for tissue engineering applications consisting of hollow alginate fibers are presented. They are prepared using self-made shell/core nozzles and a 3D plotting device. Such materials open up the possibility to generate biodegradable tissue constructs with a preformed vascular system or can act as matrices for engineering of complex organs or 3D tissue models.

A multicomponent magneto-dendritic nanosystem (MDNS) was designed for rapid tumor cell targeting, isolation, and high-resolution imaging by a facile bioconjugation approach. The highly efficient and rapid-acting MDNS provides a convenient platform for simultaneous isolation and high-resolution imaging of tumor cells, potentially leading towards an early diagnosis of cancer.