Macromolecular Bioscience

Cover image for Vol. 17 Issue 2

Editor-in-Chief: Kirsten Severing, Editor: Anne Pfisterer

Online ISSN: 1616-5195

Associated Title(s): Advanced Healthcare Materials, Macromolecular Chemistry and Physics, Macromolecular Materials and Engineering, Macromolecular Rapid Communications

Special Series: Stem Cells

Under the guest-editorship of Suwan N. Jayasinghe this series publishes in an on-going fashion invited articles by leading researchers working on advanced polymers for stem cell research.


Advanced Polymers for Stem Cell Research - From Laboratory to Clinic

stemcells_13_7_1_Editorial.jpgSuwan N. Jayasinghe

Guest-editor Suwan N. Jayasinghe introduces the third and last part of the series: Advanced Polymers for Stem Cell Biology and Medicine. In this final part it is further demonstrated how the exploration of biopolymers can lead to a wide range of applications from stem cell culturing to their exploration as vehicles for cells and/or genes. Again, this series demonstrates how progress in this highly interesting field can only be reached by the bridging of several disciplines of research and development.

Macromol. Biosci., DOI: 10.1002/mabi.201300064


In Vitro Neo-Cartilage Formation


Sumrita Bhat, Lars Lidgren and Ashok Kumar*

Limited blood supply and the avascular nature of articular cartilage restrict its self-repair capacity, frequently leading to osteoarthritis. Researchers from India and Sweden focus on scaffolds for tissue repair from natural polymers, for example gelatin, chitosan, and agarose in the form of composites. A novel way of fabrication, known as cryogelation, is presented, in which matrices are synthesized at sub-zero temperature. Cell seeded scaffolds incubated under appropriate conditions result in the accumulation of matrix components on the surface of the gel in the form of neo-cartilage. Neo-cartilage exhibits similarity to native cartilage with respect to its physical, mechanical and biochemical properties. Based on these similarities it can provide a new approach for the treatment of localized joint injuries.

Macromol. Biosci., DOI: 10.1002/mabi.201200484


The Fate of Tissue Development

stemcells_13_7_3_Kumar.jpgAnuj Tripathi, Tanushree Vishnoi, Deepti Singh, and Ashok Kumar*

Cell to matrix interactions affect in vitro cell adherence and proliferation and further decide the fate of tissue development for biomedical applications. This study demonstrates the role of crosslinking in altering the surface properties of 3D porous cryogel matrices. Glutaraldehyde and 1-ethyl-3(3-dimethylaminopropyl)-carbodiimide crosslinkers are used separately for the crosslinking of alginate and gelatin, respectively. The difference in crosslinking affects the physiochemical properties of these matrices leading to variable cell behavior as demonstrated using four different cell types. The present study demonstrates the successful use of controlled crosslinking in directing the cell growth for tissue engineering.

Macromol. Biosci., DOI: 10.1002/mabi.201200398


Phenotype-Independent Effects of Retroviral Transduction in Human Dental Pulp Stem Cells

stemcells_13_7_4_Egbuniwe.jpgObi Egbuniwe,* Andrew D. Grant, Tara Renton, and Lucy Di Silvio*

There has been considerable progress in the development of biopolymers that could impact directly on in vivo stem cell fate. Present-day biopolymers are being designed to mirror the well-described relationship existing between stem cells and the extracellular matrix. Researchers from London highlight the importance of the maintenance of cell viability and the development of human tissue-sourced stem cell lines. A better understanding of in vitro responses of these specialized cells to changes in their tightly regulated microenvironments will allow the utilization of their full therapeutic potential in biomimetic constructs

Macromol. Biosci., DOI: 10.1002/mabi.201300020


Artificial Organs

stemcells_12_8_1_seifalian.jpgAchala de Mel, Alexander M. Seifalian,* Martin A. Birchall

This review by Alexander M. Seifalian (University College London) gives a deep and comprehensive understanding of the design, methods, and complexity of materials used to mimic and replace organs. Reconstruction and replacement of organs with tissue engineered materials is becoming reality as first-in-man experiences have been successful. One of the challenges in this field is to integrate cells into predesigned 3D materials. Greater integration of cells with biomaterial scaffolds requires biochemical modifications and topographical changes, which could create an artificial niche for cells to reside within the 3D scaffolds. Therefore, precise knowledge of cell/material interactions is indispensable. The review covers several aspects of tissue engineering like complexity of tissue-engineered implants, scaffold design for structural support, cell/material interactions and live monitoring of cell/material interactions.

Macromol. Biosci., DOI: 10.1002/mabi.201200039


Hydrogel/Mineral Composites for Bone Tissue Repair


Ameya Phadke, Yu-Ru V. Shih, Shyni Varghese*

Bone consists of an inorganic apatite-like mineral phase as well as an organic protein phase composed primarily of type-I collagen, proteoglycans, and noncollagenous proteins. To mimic this structure, researchers in the USA and Taiwan have synthesized a hydrogel/mineral composite through templated mineralization of polyanionic hydrogels. These materials were found to promote osteogenic differentiation of human mesenchymal stem cells even in the absence of osteogenesis-inducing medium supplements. The potential of these materials to provide an instructive environment for osteogenic differentiation of stem cells is shown here. This study thus demonstrates the development of an osteoinductive synthetic material containing bone-like calcium phosphate mineral as a promising candidate for bone tissue repair.

Macromol. Biosci., DOI: 10.1002/mabi.201100289


Maintaining Stem Cells with Hydrogels

stemcells_12_8_3_Kuhn.jpgYongxing Liu, Lyndon F. Charles, Thomas I. Zarembinski, Kalle I. Johnson, Sarah K. Atzet, Robin L. Wesselschmidt, Mark E. Wight, Liisa T. Kuhn*

Traditionally the maintenance and the propagation of stem cells require feeder cells like mitotically inactivated mouse embryonic fibroblasts or human fibroblasts. The use of these cells comes with some drawbacks like problems in large-scale culture, limited genetic manipulations of the human pluripotent stem cells, and xeno-contamination, particularly when mouse feeder cells are used. Widely used feeder-free systems like MatrigelTM are problematic as they might still carry xenogeneic pathogens and vary from lot to lot. Liisa Kuhn (University of Connecticut Health Center) and coworkers now showed that a fully defined gelatin-modified hyaluronan hydrogel (HyStem-CTM) is able to maintain mouse embryonic stem cells and human induced pluripotent stem cells (hiPSCs) in culture while retaining their growth and pluripotent characteristics. Modified HA hydrogels like the one shown here provide a safer direction towards completely animal-free conditions for clinical application, handling, and understanding of hPSCs.

Macromol. Biosci., DOI: 10.1002/mabi.201200043


Hydrogels from Natural Polysaccharides as 3D Cell Delivery System

Stemcells_12_7_4_leVisage_.jpgMélanie Lavergne, Mohammed Derkaoui, Catherine Delmau, Didier Letourneur, Georges Uzan and Catherine Le Visage

Human endothelial colony-forming cells (ECFCs) are considered as promising cell therapy tools for vascular diseases. They usually suffer from a very low survival rate when directly injected into the diseased tissue. Therefore it can be advantageous to use porous scaffold biomaterials as a cell delivery system. Researchers in France have now synthesized polysaccharide-based scaffolds and successfully cultured ECFCs in these materials. It could be demonstrated that the dextran/pullulan hydrogels maintain the ECFC's vascular properties for up to 7 days in vitro and do not affect cell proliferation, viability, or motility. These results demonstrate the high potential of these materials as scaffolds for endothelial progenitor delivery for the treatment of vascular diseases.

Macromol. Biosci., DOI: 10.1002/mabi.201100431


Electrospun PLA Fibers for Controlled TCP Release

stemcells_12_7_3_Loboa__.jpgMahsa Mohiti Asli, Behnam Pourdeyhimi and Elizabeth G. Loboa*

One of the challenges in bone tissue engineering is to find a scaffold that is biocompatible, degradable, promotes the cellular interactions and possesses adequate mechanical properties. Recent studies showed that the presence of tricalcium phosphate (TCP) induces and accelerates osteogenic differentiation of human adipose-derived stem cells (hASC) and encourages rapid ossification. Researchers around Loboa (North Carolina State University) now created scaffolds that release TCP. They studied PLA based and TCP loaded, electrospun fibers with different fiber morphologies to evaluate release profiles and their effects on hASC differentiation. Single component and porous fiber scaffolds show a burst release whereas core-stealth fibers show a steady release. These findings will be of great importance for bone tissue engineering applications.

Macromol. Biosci., DOI: 10.1002/mabi.201100470


Fiber Thickness to Direct Stem Cell Differentiation

stemcells_12_7_2_Zhang.jpgAshleigh Cooper, Matthew Leung and Miqin Zhang*

The design of artificial extracellular matrix has gained great importance for regenerative medicine. Miqin Zhang (University of Washington, Seattle) and coworkers developed a fiber matrices system that is able to direct the differentiation of human embryonic stem cells in the absence of any soluble signals. The electrospun chitosan-based fibers were synthesized with diameters ranging from 0.4-1.1 μm. The researchers could show that the changes in fiber thickness are enough to induce differentiation. Thinner fibers induced cell commitment to the osteogenic and hepatic cells whereas lager fibers lead to neuronal differentiation. This system might have great potential in tissue engineering for directed cell-based therapy.

Macromol. Biosci., DOI: 10.1002/mabi.201100269


PLLA/MWCNT Composites as Conductive Biomaterials

stemcells_12_7_1_Armentano.jpgErlantz Lizundia, Jòsè Ramon Sarasua, Francesco D'Angelo, Aldo Orlacchio, Sabata Martino, Josè Maria Kenny, and Ilaria Armentano*

Structural and functional properties of biocompatible polymers can be modified by blending them with inorganic compounds. Researchers around Ilaria Armentano in Bilbao synthesized a composite material of Poly(L-lactide acid) and multiwalled carbon nanotubes (MWCNT) which changes the surface roughness as well as the thermal and electrical properties of the biomaterial. Already with a MWCNT weight fraction of 0.33% the material's conductivity increases by six orders of magnitude. The MWCNT form a three dimensional network in the polymer matrix that even at higher nanotube content is not toxic for Human mesenchymal stem cells. This novel current-conducting material might offer new strategies for the treatment of nerve and muscle tissue.

Macromol. Biosci., DOI: 10.1002/mabi.201200008


Understanding Embryo Formation

stemcells_12_5_3_Levenberg.jpgRoey Tzezana, Stanislav Reznik, Jacob Blumenthal, Eyal Zussman, and Shulamit Levenberg*

Specific processes in biology, especially the events leading to embryo formation, have always been perplexing, mainly due to our inability to replicate the process in vitro, or to form accurate models mimicking the processes which transpire in the young embryo. Development is highly influenced by morphogens and growth factors, naturally occurring substances that act as intercellular messengers and regulate cell migration, proliferation and differentiation. Levenberg and co-workers try to replicate the physicochemical microenvironment observed during the embryonic development by creating morphogenic gradients through the thickness of hydrospun scaffolds. Poly(ε-caprolactone) fibers were loaded with all-trans-retinoic acid (ATRA), and designed to release it at a predetermined rate. The presented results indicate that morphogen gradients can regulate stem cell differentiation patterns. Future interdisciplinary studies of this nature will make use of this and other tissue engineering techniques toward obtaining further insights into the intricacies of developmental biology.

Macromol. Biosci., DOI: 10.1002/mabi.201100312


Multifunctionalized Nanoparticle Systems for Treatment of Central Nervous System Diseases


Susana R. Cerqueira, Barbara L. Silva, Joaquim M. Oliveira, Joao F. Mano, Nuno Sousa, Antonio J. Salgado,* and Rui L. Reis*

Drug delivery to the central nervous system (CNS) has been a considerable challenge in biomedical research in the past decades. The unique environment and the complexity of the mechanisms involved have hindered the development of new and efficient treatment of neurological disorders such as Alzheimer's and Parkinson's diseases, multiple sclerosis etc. The efficiency of the treatment involving CNS disorders is commonly diminished by the toxicity, reduced stability, and lack of targeting of the administered neuroactive compounds. Rui Reis and co-workers now multifunctionalize carboxymethylchitosan/polyamidoamine (CMCht/PAMAM) dendrimer nanoparticles (NP) by coupling the CD11b antibody and loading an anti-inflammatory corticosteroid into the nanoparticles. The new system revealed no cytotoxicity when added to glial and microglial primary cell cultures. Furthermore, a novel NP uptake profile by astrocytes and oligodendrocytes was achieved with the new modified NPs.

Macromol. Biosci., DOI: 10.1002/mabi.201100294


Gelatin-Based Hydrogels as Potential Implantable Carriers for Stem Cells

stemcells_12_3_2_Lendlein.jpgBenjamin F. Pierce, Erik Pittermann, Nan Ma, Tim Gebauer, Axel T. Neffe, Magdalena Hoelscher, Friedrich Jung, and Andreas Lendlein*

Common polymeric bulk materials such as polystyrene, polycarbonate, and poly(propylene) have been successfully applied as substrates for mesenchymal stem cells (MSC) attachment, proliferation, and differentiation. However, these plastics are not ideal as implantable systems for applications in regenerative therapies as more specific requirements such as degradability need to be fulfilled for the next generation of biomaterials. MSC show a high viability on gelatin-based networks with tailorable properties. A. Lendlein and co-workers show that gelatin crosslinked with lysine diisocyanate ethyl ester in water yield degradable, sterilizable, and non-toxic hydrogels. Such materials are promising biomaterial candidates that merit further study as possible stem cell niches.

Macromol. Biosci., DOI: 10.1002/mabi.201100237


Polymeric Systems for Tissue Engineering and Biomedical Applications

stemcells_12_3_1_Ravichandran.jpgR. Ravichandran, S. Sundarrajan,* J. R. Venugopal, S. Mukherjee, and S. Ramakrishna*

Smart stimuli-responsive polymeric systems with smart surfaces are used for engineering a biological construct embedded with cells and biomolecules/drugs. Upon suitable stimuli such as pH in vivo, the polymer unwinds and becomes hydrophobic, thereby delivering cells and biomolecules to the target organ in the human body.
S. Ramakrishna and co-workers (National University of Singapore) highlight the exciting advancements in these polymeric systems that relate to biological and tissue engineering applications. Additionally, several aspects of technology namely scaffold fabrication methods and surface modifications to confer biological functionality to the polymers are being discussed. Their ultimate objective is to emphasize these underutilized adaptive behaviors of the polymers so that novel applications and new generations of smart polymeric materials can be realized for biomedical and tissue engineering applications.

Macromol. Biosci., DOI: 10.1002/mabi.201100325


Polymer-based Scaffold Designs For In Situ Vascular Tissue Engineering: Controlling Recruitment and Differentiation Behavior of Endothelial Colony Forming Cells

stemcells_13_2_1_Fioretta.jpgEmanuela S. Fioretta,* Joost O. Fledderus, Ewelina A. Burakowska-Meise, Frank P. T. Baaijens, Marianne C. Verhaar, Carlijn V. C. Bouten

In situ vascular tissue engineering aims to provide off-the-shelf cell-free vascular substitutes that accommodate in vivo cell recruitment, differentiation, and tissue formation at the site of implantation. Smart scaffold designs are required to guide and control this process, e.g., by recruiting and differentiating circulating cells into the different lineages that constitute the vessel wall.

Macromol. Biosci., DOI: 10.1002/mabi.201100315


Mechanical Properties and Topographical Features in Concert - Influence on Cell Migration

stemcells_12_1_1_Reinhart-King.jpgJonathan M. Charest, Joseph P. Califano, Shawn P. Carey, and Cynthia A. Reinhart-King*

Both substrate topography and mechanical properties can influence cell behavior. While multiple groups have investigated the effect of topographically patterned substrates, most studies have used materials with a Young’s modulus E that is significantly above physiological ranges. On the other hand, many groups have studied the effect of substrate stiffness on cell behavior. Little is known about the interplay of these two parameters. Reinhart-King and co-workers (Cornell University, Ithaca, USA) present a method to introduce topographical features into polyacrylamide (PA) hydrogel substrates that span a wide range of physiological E values. Two common microfabrication techniques were used in the study of mechanobiology: micromolding and microcontact printing. The scientists find that cells exhibit contact guidance regardless of the stiffness of the substrate. Additionally, cells are capable of climbing tall features regardless of substrate stiffness. The procedures outlined will serve as a basis for further investigations of the integration of mechanical and topographical cues by cells.

Macromol. Biosci., DOI: 10.1002/mabi.201100264


A Dextran-Based Polymer as Cell-Detaching Substrate

stemcells_12_1_2_Gerecht.jpgGuoming Sun, Sravanti Kusuma, and Sharon Gerecht*

In order for stem cells to be translated into clinical use, they must be treated with substances that will not harm their surface proteins and be cultured on biocompatible substrates which will not pose a threat to the patient once the cells are implanted. Sharon Gerecht and co-workers synthesized a dextran-based, biodegradable, temperature-sensitive polymer - TSDAIE - and tested it as a novel, substrate for nonenzymatic cell detachment. The concentration of TSDAIE affects endothelial progenitor cell (EPC) attachment, which is thereby used to optimize the concentration of TSDAIE for coating. At the determined optimal concentration, TSDAIE is found to be compatible for use in EPC culture as revealed by cell attachment, spreading, proliferation, and phenotype. Because of its complete biodegradability, TSDAIE can be used directly in the culture of stem cells without requiring the additional step of removing nondegradable polymer. This advantage can expedite stem cell scale-up for clinical use.

Macromol. Biosci., DOI: 10.1002/mabi.201100258


Tissue-Specific Stem Cell Differentiation in an in vitro Airway Model

stemcells_11_11_2_Pryterch.jpgZoë Prytherch,* Claire Job, Hilary Marshall, Victor Oreffo, Martyn Foster, and Kelly BéruBé

The respiratory tract is the primary site of exposure to airborne compounds, with the bronchial epithelium providing one of the first lines of defense. Developing model systems that imitate normal physiology is important and relevant to today's testing of drugs and other therapies. Z. Prytherch and co-workers developed a fully differentiated in vivo like model of the human bronchial epithelium. Developmental characterization includes (i) trans-epithelial electrical resistance, (ii) morphology, and (iii) bronchial cell specific stains/markers. Characterization at all levels was essential, not only in order to fully validate the model as a viable alternative, but also, to later elucidate the mechanisms of action of the model during injury and repair, either during disease processes or following a challenge with a given xenobiotic.

Macromol. Biosci., DOI: 10.1002/mabi.201100181


Pullulan Hydrogels for Skin Regeneration

stemcells_11_11_1_Gurtner.jpgVictor W. Wong, Kristine C. Rustad, Jason P. Glotzbach, Michael Sorkin, Mohammed Inayathullah, Melanie R. Major, Michael T. Longaker, Jayakumar Rajadas, and Geoffrey C. Gurtner*

Wound healing after cutaneous injury proceeds through highly coordinated stages of repair to restore the damaged tissues. In the initial stage, reactive oxygen species (ROS) are secreted in order to kill bacteria and defend the disrupted skin barrier. However, an elevated level of ROS may lead to cell damage and an impaired response to injury. G. C. Gurtner and co-workers could now show that pullulan-based hydrogel scaffolds exhibit potent antioxidant properties that enhance the survival and engraftment of mesenchymal stem cells both in vitro and in vivo. This biomimetic hydrogel displays significant potential as a cell-scaffold construct for skin regeneration in high oxidative stress environments.

Macromol. Biosci., DOI: 10.1002/mabi.201100180


Advanced Polymers for Stem Cell Research - The Series Continues

stemcells_11_11_Editorial.jpgSuwan N. Jayasinghe

Guest-editor Suwan N. Jayasinghe introduces the second part of the series: Advanced Polymers for Stem Cell Biology and Medicine. This part is meant to further introduce advances and viewpoints in the creation and development of novel synthetic polymers and the exploration of natural polymers for their utilization in stem cell biology and medicine. The selected articles will demonstrate the applicability of biopolymers for studying basic biological processes and functions while also introducing the capacity for such advanced biomaterials for their evaluation in the clinic.

Macromol. Biosci., DOI: 10.1002/mabi.201100263


A Library of Polyureas for Ligament Tissue Engineering

stemcells_11_8_2_Cosgriff.jpgHugh Benhardt, Nick Sears, Tyler Touchet, and Elizabeth Cosgriff-Hernandez*

Biocompatible and biodegradable materials that have been investigated for ligament tissue engineering include natural polymers and synthetic materials. Recently, poly(ester urethanes) were investigated as ligament grafts due to their exceptional mechanical properties and highly tunable structure; however, these grafts are susceptible to hydrolytic degradation that occurs independent of tissue regeneration. To address this limitation, Cosgriff-Hernandez and co-workers (Texas A&M University) synthesized polyureas containing collagen-derived peptides which enable cellular release of proteases to dictate degradation rates. The addition of cell-responsive degradation to one of the most versatile classes of biomaterials makes these hybrid grafts promising candidates for tissue engineered ligament grafts.

Macromol. Biosci., DOI: 10.1002/mabi.201100063


Polymeric Scaffold for Adipose Stem Cells in Bone Tissue Engineering

stemcells_11_6_1_Smit.jpgPieter-Paul A. Vergroesen, Robert-Jan Kroeze, Marco N. Helder, and Theodoor H. Smit*

In orthopaedics, there is an unmet need for graft material to provide support, fill voids and enhance biological repair of bone defects. Using donor bone from the patient (autografts) has been the standard procedure as it is well established, safe, relatively cheap, however, it also involves an additional surgery that is associated with pain, infections, vascular injuries etc. Allografts (bone from other patients stored in a bone bank) is a reasonable alternative but has disadvantages such as non-specific inflammations and prolonged healing times. Fat-derived stem cells and synthetic polymers open new, more practicable routes for bone tissue engineering. T. H. Smit and co-workers highlight the potential of poly(L-lactide-co-caprolactone) (PLCL) to serve as a radiolucent scaffold in bone tissue engineering. An in vivo spinal fusion study in a goat model provides a preclinical proof-of-concept for a one-step surgical procedure with ASCs in bone tissue engineering.

Macromol. Biosci., DOI: 10.1002/mabi.201000433


A Tool for Studying Stem Cells during Wound-Healing Processes

stemcells_11_8_1_Grimaldi.jpgAnnalisa Grimaldi,* Serena Banfi, Jacopo Vizioli, Gianluca Tettamanti, Douglas M. Noonan, and Magda de Eguileor

Matrigel (MG), a basement membrane extract, is an injectable biopolymer that can be used for implanting cells, providing improved incorporation in host tissues. MG loaded with cytokine can be used for the recruitment in vivo of specific cell populations and as a vector for the preparation of cell cultures. A. Grimaldi and co-workers demonstrate that the injection of MG supplemented with interleukin-8 (IL-8) in the leech Hirudo medicinalis can be used to purify cell populations showing the same morpho-functional and molecular mechanisms of specific populations of vertebrate hematopoietic precursor cells involved in tissue repair. These cells spontaneously differentiated into myofibroblasts. This approach highlights how the innovative use of a cytokine-loaded biopolymer for an in vivo cell sorting method, applied to a simple invertebrate model, can be a tool for studying myofibroblast cell biology and its regulation, step by step.

Macromol. Biosci., DOI: 10.1002/mabi.201000452


ECM Functionalized Microcavities to Control Hematopoietic Stem and Progenitor Cell Fate

stemcells_11_6_3_Pompe.jpgIna Kurth, Katja Franke, Tilo Pompe,* Martin Bornhäuser, and Carsten Werner

Bone marrow (BM) constitutes a specialized microenvironment supporting hematopoietic stem and progenitor cell (HSPC) homeostasis, which is known as "stem cell niche". Even though HSPC have already been studied for more than three decades the complexity of the BM-HSPC interplay impedes the full understanding of stem cell properties and their destiny. Tile Pompe and co-workers use now polymeric microcavities functionalized with extracellular matrix (ECM) components as an experimental in vitro model to investigate principles of HSPC fate control. Using human CD133 + HSPC they could demonstrate distinct differences in HSPC cycling and differentiation dependence on the adhesion ligand specificity (i.e., heparin, collagen I) and cytokine levels. The presented microcavity platform provides a powerful in vitro approach to explore the role of exogenous cues in HSPC fate decisions and can therefore be instrumental to progress in stem cell biology and translational research toward new therapies.

Macromol. Biosci., DOI: 10.1002/mabi.201000432


Injectable Scaffold for Cardiac Tissue Engineering


Jennifer M. Singelyn and Karen L. Christman*

Injectable materials are attractive therapeutic options for cardiac repair, including treatment of the heart following a myocardial infarction (MI), because they offer the potential of minimally invasive delivery. Christman and co-workers have recently developed an injectable hydrogel that is derived from decellularized ventricular tissue. The decellularized myocardium is processed to create a liquid, injectable matrix, thus offering a cardiac specific scaffold. In this study they investigate the effects of cross-linking with glutaraldehyde on the cardiac hydrogel stiffness, degradation properties, cellular migration, and catheter injectability in vitro. While in vivo studies will be critical to validate these findings, this study demonstrates that the material properties of the myocardial matrix can be altered to meet potential tissue engineering requirements for myocardial repair following an MI, while maintaining catheter injectability.

Macromol. Biosci., DOI: 10.1002/mabi.201000423


Moving Gradient Generation to the Third Dimension

stellcells_11_4_2_Murphy.jpgEric H. Nguyen, Michael P. Schwartz, and William L. Murphy*

Soluble concentration gradients such as growth factor gradients play a critical role in controlling tissue formation during embryonic development. The critical importance of soluble signaling in biology has motivated numerous studies aimed at modeling gradient generation in vitro. Many previous studies have applied soluble signaling gradients to cells in two-dimensional (2D) culture. Techniques for the generation of these gradients within three-dimensional biomaterial scaffolds are just beginning to emerge. When applied to tissue engineering applications, biomimetic morphogen gradients may offer an unprecedented level of control over tissue development. This review presents emerging toolsets that lend themselves to the generation of these gradients.

Macromol. Biosci., DOI: 10.1002/mabi.201000448


Low Thrombogenicity Coatings for Vascular Grafts

stemcells_11_4_3_Bureau.jpgSashka Dimitrievska, Marion Maire, Gerardo A. Diaz-Quijada, Lucie Robitaille, Abdellah Ajji, L'Hocine Yahia, Maria Moreno, Yahye Merhi, and Martin N. Bureau*

Vascular polyethylene terephthalate (PET) grafts have shown good performance in large vessels (> 6mm) applications. However, in small diameter applications, high failure-rates due to thrombosis and compliance mismatch-induced myointimal hyperplasia are encountered. To address the urgent unmet need for small-diameter (2–6mm) vascular grafts, proprietary high-compliance nonwoven PET fiber structures were modified with various polyethylene glycol (PEG) concentrations using poly(vinylamine) (PVA) as a cross-linking agent. These PEG coated nonwoven PET structures have the advantages of (1) being based on a well-known and accepted polymer in the vascular prosthesis field, (2) showing artery-matching compliance, and (3) having a highly biostable and minimally thrombogenic off-the-shelf coating.

Macromol. Biosci., DOI: 10.1002/mabi.201000390


Biodegradable Elastomers for Tissue Engineering and Cell–Biomaterial Interactions


Christopher J. Bettinger*

Synthetic biomaterials serve as a cornerstone in the development of clinically focused regenerative medicine therapies. Recent improvements in biodegradable elastomeric materials utilize natural extracellular matrix proteins as inspiration to yield a new class of materials with superior degradation kinetics, desirable biocompatibility profiles, and mechanical properties that closely match those of soft tissues. This review describes several classes of synthetic biodegradable elastomers and associated fabrication techniques that are relevant to scaffold development. The application of these materials to select tissue engineering models is also discussed.

Macromol. Biosci., DOI: 10.1002/mabi.201000397


Agarose-Alginate Cryogel for Bioengineering Applications

stemcells_11_1_3_Kumar.jpgAnuj Tripathi and Ashok Kumar*

Agarose and alginate are two natural polysaccharides which are biodegradable, biocompatible, inert, and have soft tissue like mechanical properties. Therefore, they possess great potential in bioengineering applications. Here, agarose-alginate (AA) scaffolds are synthesized using the cryogelation technology in different formats like monolith, sheet, discs, and beads. In cell-material interactions, fibroblast (NIH-3T3) cells show good adherence and proliferation on these scaffolds presenting its potential application in soft tissue engineering. Further experimental results indicate that the AA cryogel might be used as a support matrix for cell immobilization and as a filter to remove heavy metals from wastewater. These cryogels do have a number of unique features that make them an important class of soft materials for developing multi-featured scaffolds as a novel carrier for bioengineering applications.

Macromol. Biosci., DOI: 10.1002/mabi.201000286


How to Sterilize PET Fibers for Vascular Grafts

stemcells_11_1_2_Bureau.jpgSashka Dimitrievska, Alain Petit, Charles J. Doillon, Laura Epure, Abdellah Ajji, L'Hocine Yahia, and Martin N. Bureau

Polyethylene terephthalate (PET) scaffold with mechanical properties similar to those of small arteries constitute an attractive candidate for regenerative medicine and tissue engineering with observed stem cell differentiation potential. One of the essential pre-conditions for further clinical application is the ability of the scaffold to withstand sterilization. Martin N. Bureau and co-workers investigate the effect of low temperature plasma (LTP) and ethylene oxide (EtO) sterilizations on PET vascular grafts in terms of chemical modifications and in vitro and in vivo biocompatibility. While their in vitro cytotoxicity shows similar fibroblastic viability, non-woven PET fibers sterilized using EtO and low LTP show different macrophage activation in both direct and indirect macrophage contact assays.

Macromol. Biosci., DOI: 10.1002/mabi.201000268


Advanced Polymers for Stem Cell Biology and Medicine

stemcells_11_1_1_Jayasinghe.jpgSuwan N. Jayasinghe

While polymers have always been central to both biology and medicine, stem cells have proven their potential in repairing or replacing tissue only within the last decade. Revolutionary advancements have only been possible through collaborations between chemists, biologists, engineers, and clinical researchers. In order to elucidate how such collaborations have brought new insight to the exploration of advanced natural and synthetic polymers in conjunction with stem cells this new special series, guest-edited by Suwan N. Jayasinghe, will publish invited contributions from eminent scientists in the field.

Macromol. Biosci., DOI: 10.1002/mabi.201000370