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Regenerative Medicine (regenerative + medicine)
Terms modified by Regenerative Medicine Selected AbstractsTissue Engineering: Stem Cell Aligned Growth Induced by CeO2 Nanoparticles in PLGA Scaffolds with Improved Bioactivity for Regenerative Medicine (Adv. Funct.ADVANCED FUNCTIONAL MATERIALS, Issue 10 2010Mater. [source] Stem Cell Aligned Growth Induced by CeO2 Nanoparticles in PLGA Scaffolds with Improved Bioactivity for Regenerative MedicineADVANCED FUNCTIONAL MATERIALS, Issue 10 2010Corrado Mandoli Abstract Hybrid 2D polymeric,ceramic biosupports are fabricated by mixing a nanostructured CeO2 powder with 85:15 poly(D,L -lactic- co -glycolic acid) (PLGA)/dichloromethane solutions at specific concentrations, followed by solvent casting onto pre-patterned molds. The mold patterning allows the orientation of ceramic nanoparticles into parallel lines within the composite scaffold. The ability of the produced films to host and address cell growth is evaluated after 1, 3, and 6 days of culturing with murine derived cardiac and mesenchymal stem cells (CSCs and MSCs), and compared with PLGA films without ceramics and loaded with nanostructured TiO2. Aligned cell growth is observed only for scaffolds that incorporate oriented ceramic nanoparticles, attributed to the nanoceramic ability to modulate the roughness pitch, thus improving cell sensitivity towards the host surface features. Better CSC and MSC proliferative activity is observed for CeO2 composites with respect to either TiO2 -added or unfilled PLGA films. This evidence may be related to the nanostructured CeO2 antioxidative properties. [source] Advances and Applications of Biodegradable Elastomers in Regenerative MedicineADVANCED FUNCTIONAL MATERIALS, Issue 2 2010Maria Concepcion Serrano Abstract When elastomers were first proposed as useful materials for regenerative medicine a few decades ago, their high versatility and suitability for a diverse and wide range of in vivo applications could not have been predicted. Due to their ability to recover after deformation, these materials were first introduced in tissue engineering in an attempt to mimic the mechanical properties of the extracellular matrix. Furthermore, elastomeric characteristics have been described as important criteria for cell interaction by modulating cellular behavior. From soft to hard tissues, elastomers have demonstrated degradation, mechanical, and biocompatibility requirements in accordance with the target tissue. In this feature article, biodegradable synthetic polyester elastomers that have been reported in the literature are discussed, with special focus on those that show promise for in vivo tissue replacement. Their satisfactory performance in vivo shows the promise of elastomers for use in regenerative medicine. However, further investigation is required to demonstrate the prospect of elastomer-based therapies in clinical trials. [source] The Implications of Polymer Selection in Regenerative Medicine: A Comparison of Amorphous and Semi-Crystalline Polymer for Tissue RegenerationADVANCED FUNCTIONAL MATERIALS, Issue 9 2009Michelle D. Kofron Abstract Biodegradable polymeric scaffolds are being investigated as scaffolding materials for use in regenerative medicine. While the in vivo evaluation of various three-dimensional (3D), porous, biodegradable polymeric scaffolds has been reported, most studies are ,3 months in duration, which is typically prior to bulk polymer degradation, a critical event that may initiate an inflammatory response and inhibit tissue formation. Here, a 6,month in vitro degradation and corresponding in vivo studies that characterized scaffold changes during complete degradation of an amorphous, 3D poly(lactide- co -glycolide)(3D-PLAGA) scaffold and near-complete degradation of a semi-crystalline3D-PLAGA scaffold are reported. Using sintered microsphere matrix technology, constructs were fabricated in a tubular shape, with the longitudinal axis void and a median pore size that mimicked the architecture of native bone. Long-term quantitative measurements of molecular weight, mechanical properties, and porosity provided a basis for theorization of the scaffold degradation process. Following implantation in a critical size ulnar defect model, histological analysis and quantitative microCT indicated early solubilization of the semi-crystalline polymer created an acidic microenvironment that inhibited mineralized tissue formation. Thus, the use of amorphous over semi-crystalline PLAGA materials is advocated for applications in regenerative medicine. [source] Regenerative Medicine: (Adv. Mater.ADVANCED MATERIALS, Issue 32-33 200932-33/2009) Biomaterials are essential "elements" in Regenerative Medicine strategies. The role of such smart polymer systems (center left) is to support or control the endogenous regeneration for a specific duration and therefore are designed to degrade (upper left), to control cell function (lower right), substitute the extracellular matrix (background), or to control the sustained release of bioactive molecules (upper right). Images in the front cover courtesy of Andreas Lendlein, Dieter Hofmann, Anna Marie Lipski, Michael Schossig, Jay C. Sy, and V. Prasad Shastri. [source] Materials in Regenerative MedicineADVANCED MATERIALS, Issue 32-33 2009V. Prasad Shastri First page of article [source] Perspectives and Challenges in Tissue Engineering and Regenerative MedicineADVANCED MATERIALS, Issue 32-33 2009Robert Langer This Essay provides a concise overview on the achievements and future challenges in regenerative medicine and tissue engineering. [source] Hydrogels in Regenerative Medicine,ADVANCED MATERIALS, Issue 32-33 2009Brandon V. Slaughter Abstract Hydrogels, due to their unique biocompatibility, flexible methods of synthesis, range of constituents, and desirable physical characteristics, have been the material of choice for many applications in regenerative medicine. They can serve as scaffolds that provide structural integrity to tissue constructs, control drug and protein delivery to tissues and cultures, and serve as adhesives or barriers between tissue and material surfaces. In this work, the properties of hydrogels that are important for tissue engineering applications and the inherent material design constraints and challenges are discussed. Recent research involving several different hydrogels polymerized from a variety of synthetic and natural monomers using typical and novel synthetic methods are highlighted. Finally, special attention is given to the microfabrication techniques that are currently resulting in important advances in the field. [source] Multipotent adult progenitor cell transplantation increases vascularity and improves left ventricular function after myocardial infarction Beatriz Pelacho, Yasuhiro Nakamura, Jianyi Zhang, Jeff Ross, Yves Heremans, Molly Nelson-Holte, Brad Lemke, Julianna Hagenbrock, Yuehua Jiang, Felipe Prosper, Aernout Luttun and Catherine M. Verfaillie.JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 4 20072007; 1: 5, Journal of Tissue Engineering, Regenerative Medicine The original article to which this Erratum refers was published in Journal of Tissue Engineering and Regenerative Medicine 1; 2007, 51,59. [source] Welcome to the Journal of Tissue Engineering and Regenerative MedicineJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 1 2007Rui L. Reis Editor-in-Chief [source] Recent Progress in Artificial Organs and Regenerative Medicine in JapanARTIFICIAL ORGANS, Issue 5 2010Yoshinori Mitamura First page of article [source] Visions for Regenerative Medicine: Interface Between Scientific Fact and Science FictionARTIFICIAL ORGANS, Issue 10 2006C. James Kirkpatrick Abstract:, This article gives a brief overview of the authors' views on the future development of tissue engineering with respect to the challenges both to the materials and life sciences. Emphasis will be placed on the advantages of three-dimensional bioresorbable polymers in combination with relevant molecular cues and the application of autologous stem or progenitor cells. There is a requirement for much more diversity in the synthesis of so-called "intelligent" materials, which respond to external stimuli, as well as the development of novel drug and gene delivery systems. In addition, much more basic research is necessary in developmental biology and the application of modern cell and molecular biology to biomaterial questions. [source] Regenerative Medicine for Cardiovascular Disorders-New Milestones: Adult Stem CellsARTIFICIAL ORGANS, Issue 4 2006A. Ruchan Akar Abstract:, Cardiovascular disorders are the leading causes of mortality and morbidity in the developed world. Cell-based modalities have received considerable scientific attention over the last decade for their potential use in this clinical arena. This review was intended as a brief overview on the subject of therapeutic potential of adult stem cells in cardiovascular medicine with basic science findings and the current status of clinical applications. The historical perspective and basic concepts are reviewed and a description of current applications and potential adverse effects in cardiovascular medicine is given. Future improvements on cell-based therapies will likely provide remarkable improvement in survival and quality of life for millions of patients with cardiovascular disorders. [source] Is It True that Artificial Organ Technologies Will Be Replaced by Regenerative Medicine in the 21st Century?ARTIFICIAL ORGANS, Issue 7 2003Yukihiko Nosé M.D. Ph.D. No abstract is available for this article. [source] Regenerative medicine in dermatology: biomaterials, tissue engineering, stem cells, gene transfer and beyondEXPERIMENTAL DERMATOLOGY, Issue 8 2010Christina Dieckmann Please cite this paper as: Regenerative medicine in dermatology: biomaterials, tissue engineering, stem cells, gene transfer and beyond. Experimental Dermatology 2010; 19: 697,706. Abstract:, The term ,regenerative medicine' refers to a new and expanding field in biomedical research that focuses on the development of innovative therapies allowing the body to replace, restore and regenerate damaged or diseased cells, tissues and organs. It combines several technological approaches including the use of soluble molecules, biomaterials, tissue engineering, gene therapy, stem cell transplantation and the reprogramming of cell and tissue types. Because of its easy accessibility, skin is becoming an attractive model organ for regenerative medicine. Here, we review recent developments in regenerative medicine and their potential relevance for dermatology with a particular emphasis on biomaterials, tissue engineering, skin substitutes and stem cell-based therapies for skin reconstitution in patients suffering from chronic wounds and extensive burns. [source] Regenerative medicine in the treatment of peripheral arterial diseaseJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2009Erica B. Sneider Abstract The last decade has witnessed a dramatic increase in the mechanistic understanding of angiogenesis and arteriogenesis, the two processes by which the body responds to obstruction of large conduit arteries. This knowledge has been translated into novel therapeutic approaches to the treatment of peripheral arterial disease, a condition characterized by progressive narrowing of lower extremity arteries and heretofore solely amenable to surgical revascularization. Clinical trials of molecular, genetic, and cell-based treatments for peripheral artery obstruction have generally provided encouraging results. J. Cell. Biochem. 108: 753,761, 2009. © 2009 Wiley-Liss, Inc. [source] Thoracoscopic cell sheet transplantation with a novel deviceJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 4 2009Masanori Maeda Abstract Regenerative medicine with transplantable cell sheets fabricated on temperature-responsive culture surfaces has been successfully achieved in clinical applications, including skin and cornea treatment. Previously, we reported that transplantation of fibroblast cell sheets to wounded lung had big advantages for sealing intraoperative air leaks compared with conventional materials. Here, we report a novel device for minimally invasive transplantation of cell sheets in endoscopic surgery, such as video-assisted thoracoscopic surgery (VATS). The novel device was designed with a computer-aided design (CAD) system, and the three-dimensional (3D) data were transferred to a 3D printer. With this rapid prototyping system, the cell sheet transplantation device was fabricated using a commercially available photopolymer approved for clinical use. Square cell sheets (24 × 24 mm) were successfully transplanted onto wound sites of porcine lung placed in a human body model, with the device inserted through a 12 mm port. Such a device would enable less invasive transplantation of cell sheets onto a wide variety of internal organs. Copyright © 2009 John Wiley & Sons, Ltd. [source] Bone Marrow-Derived Cells Implanted into Freeze-Injured Urinary Bladders Reconstruct Functional Smooth Muscle LayersLUTS, Issue 1 2010Tetsuya IMAMURA Regenerative medicine offers great hope for lower urinary tract dysfunctions due to irreversibly damaged urinary bladders and urethras. Our aim is the utilization of bone marrow-derived cells to reconstruct smooth muscle layers for the treatments of irreversibly damaged lower urinary tracts. In our mouse model system for urinary bladder regeneration, the majority of smooth muscle layers in about one-third of the bladder are destroyed by brief freezing. Three days after wounding, we implant cultured cells derived from bone marrow. The implanted bone marrow-derived cells survive and differentiate into layered smooth muscle structures that remediate urinary dysfunction. However, bone marrow-derived cells implanted into the intact normal urinary bladders do not exhibit these behaviors. The presence of large pores in the walls of the freeze-injured urinary bladders is likely to be helpful for a high rate of survival of the implanted cells. The pores could also serve as scaffolding for the reconstruction of tissue structures. The surviving host cells upregulate several growth factor mRNAs that, if translated, can promote differentiation of smooth muscle and other cell types. We conclude that the multipotency of the bone marrow-derived cells and the provision of scaffolding and suitable growth factors by the microenvironment enable successful tissue engineering in our model system for urinary bladder regeneration. In this review, we suggest that the development of regenerative medicine needs not only a greater understanding of the requirements for undifferentiated cell proliferation and targeted differentiation, but also further knowledge of each unique microenvironment within recipient tissues. [source] Biotech news from industryBIOTECHNOLOGY JOURNAL, Issue 1 2009Article first published online: 20 JAN 200 Three-year $28M drug discovery collaboration: Evotec-Novartis Regenerative medicine: Sigma-Aldrich/D-Finitive Cell Technologies Industrial prizes [source] Application for regenerative medicine of epithelial cell culture-vistas of cultured epitheliumCONGENITAL ANOMALIES, Issue 3 2006Hajime Inoue ABSTRACT This review describes culture techniques for the epithelial system as well as trends in the clinical application of cultured keratinocytes in our department and the possibility of applying the techniques to other organs. Cultured epithelium and cultured dermis in particular have considerably preceded regeneration of other organs in the field of regenerative medicine. Since 1988 we have grafted cultured keratinocytes by the Rheinwald-Green modified method in at least 500 patients with large skin defects. As a result of the establishment of a culture technique for individual patients, it is now possible to prepare enough regenerated epithelium to cover the body surface area of as many as 10 adult patients in approximately three weeks after collecting 1 cm2 of skin, and then remaining cultured keratinocytes can be cryo-preserved for two-stage dermatoplasty at another site. This procedure makes it possible to avoid frequent skin collection from the same patient and thereby improves patients' quality of life and activities of daily living. On the other hand, to solve the problem of regenerated epithelium shrinking and problems with graft efficiency on dermis defect lesion, we have developed a proteinase-resistant regenerated dermis by mixing a certain protein with a fibrin scaffold. Recently we also took the initiative in grafting hybrid-type regenerated trachea in an animal experiment by using the epithelial and dermal cell culture technique, and some results of the graft were obtained. [source] Anterior,posterior patterning of neural differentiated embryonic stem cells by canonical Wnts, Fgfs, Bmp4 and their respective antagonistsDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 8 2009Marijke Hendrickx Embryonic stem (ES) cells are pluripotent and can differentiate into every cell type of the body. Next to their potential in regenerative medicine, they are excellent tools to study embryonic development. In this work the processes of neural induction and neural patterning along the antero-posterior (A/P) body axis are studied and evidence suggests a two step mechanism for these events. First, neural induction occurs by default in the primitive ectoderm, forming anterior neural tissue and thereafter, a series of factors can posteriorize this anterior neurectoderm. In a gain-of-function/loss-of-function approach using mouse ES cells, we show that Fgf2 has the strongest caudalizing potential of all Fgfs tested. Furthermore, Bmp4 and Wnt3a, but not Wnt1, can caudalize the neurectodermal cells. The effect of the antagonists of these factors was also examined and though Dkk1 and Noggin clearly have an effect that opposes that of Wnt3a and Bmp4 respectively, they fail to anteriorize the neurectoderm. The patterning effect of SU5402, an Fgf receptor inhibitor, was rather limited. These data confirm that in the mouse, two steps are involved in neural patterning and we show that while Fgf4, Fgf8 and Wnt1 have no strong patterning effect, Fgf2, Wnt3a and Bmp4 are strong posteriorizing factors. [source] Establishment of a chick embryo model for analyzing liver development and a search for candidate genesDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 6 2005Yuji Yokouchi The liver plays a crucial role in metabolism. There is considerable interest in how the liver develops, as such knowledge could prove of importance in regenerative medicine. However, our understanding of liver development remains somewhat limited. We have developed a model system using the chick embryo that is cost effective and is easy to manipulate experimentally. We performed four fundamental studies: (i) construction of an atlas of the developing chick liver; (ii) identification of differentiation marker genes in the developing chick embryo; (iii) development of germ-layer specific electroporation; and (iv) establishment of organ culture from the developing chick liver. Using this system, we have been able to demonstrate the functions of candidate genes within a shorter period and in a more cost-effective manner. In parallel with the establishment of this system, we examined the expression patterns of genes known to be required for organ development in the developing chick embryo in order to identify genes also involved in liver development. To date, we have found sixteen genes that are expressed in the developing chick liver (GELD, genes expressed in liver development). This knowledge will be fundamental to the establishment of the basic technology for engineering liver tissue in the future. [source] gfap and nestin reporter lines reveal characteristics of neural progenitors in the adult zebrafish brainDEVELOPMENTAL DYNAMICS, Issue 2 2009Chen Sok Lam Abstract Adult neurogenesis arises from niches that harbor neural stem cells (NSC). Although holding great promise for regenerative medicine, the identity of NSC remains elusive. In mammals, a key attribute of NSC is the expression of the filamentous proteins glial fibrillary acidic protein (GFAP) and NESTIN. To assess whether these two markers are relevant in the fish model, two transgenic zebrafish lines for gfap and nestin were generated. Analysis of adult brains showed that the fusion GFAP,green fluorescent protein closely mimics endogenous GFAP, while the nestin transgene recapitulates nestin at the ventricular zones. Cells expressing the two reporters display radial glial morphology, colocalize with the NSC marker Sox2, undergo proliferation, and are capable of self-renewal within the matrix of distinct thickness in the telencephalon. Together, these two transgenic lines reveal a conserved feature of putative NSC in the adult zebrafish brain and provide a means for the identification and manipulation of these cells in vivo. Developmental Dynamics 238:475,486, 2009. © 2009 Wiley-Liss, Inc. [source] Stretching the limits: Stem cells in regeneration scienceDEVELOPMENTAL DYNAMICS, Issue 12 2008David L. Stocum Abstract The focus of regenerative medicine is rebuilding damaged tissues by cell transplantation or implantation of bioartificial tissues. In either case, therapies focus on adult stem cells (ASCs) and embryonic stem cells (ESCs) as cell sources. Here we review four topics based on these two cell sources. The first compares the current performance of ASCs and ESCs as cell transplant therapies and the drawbacks of each. The second explores somatic cell nuclear transfer (SCNT) as a method to derive ESCs that will not be immunorejected. The third topic explores how SCNT and ESC research has led to the ability to derive pluripotent ESCs by the dedifferentiation of adult somatic cells. Lastly, we discuss how research on activation of intrinsic adult stem cells and on somatic cell dedifferentiation can evolve regenerative medicine from a platform consisting of cell transplantation to one that includes the chemical induction of regeneration from the body's own cells at the site of injury. Developmental Dynamics 237:3648,3671, 2008. © 2008 Wiley-Liss, Inc. [source] A challenge for regenerative medicine: Proper genetic programming, not cellular mimicryDEVELOPMENTAL DYNAMICS, Issue 12 2007Angie Rizzino Abstract Recent progress in stem cell biology and the reprogramming of somatic cells to a pluripotent phenotype has generated a new wave of excitement in regenerative medicine. Nonetheless, efforts aimed at understanding transdifferentiation, dedifferentiation, and the plasticity of cells, as well as the ability of somatic cells to be reprogrammed, has raised as many questions as those that have been answered. This review proffers the argument that many reports of transdifferentiation, dedifferentiation, and unexpected stem cell plasticity may be due to aberrant processes that lead to cellular look-alikes (cellular mimicry). In most cases, cellular look-alikes can now be identified readily by monitoring gene expression profiles, as well as epigenetic modifications of DNA and histone proteins of the cells involved. This review further argues that progress in regenerative medicine will be significantly hampered by failing to address the issue of cellular look-alikes. Developmental Dynamics 236:3199,3207, 2007. © 2007 Wiley-Liss, Inc. [source] Adult bone marrow,derived stem cells for organ regeneration and repairDEVELOPMENTAL DYNAMICS, Issue 12 2007Florian Tögel Abstract Stem cells have been recognized as a potential tool for the development of innovative therapeutic strategies. There are in general two types of stem cells, embryonic and adult stem cells. While embryonic stem cell therapy has been riddled with problems of allogeneic rejection and ethical concerns, adult stem cells have long been used in the treatment of hematological malignancies. With the recognition of additional, potentially therapeutic characteristics, bone marrow,derived stem cells have become a tool in regenerative medicine. The bone marrow is an ideal source of stem cells because it is easily accessible and harbors two types of stem cells. Hematopoietic stem cells give rise to all blood cell types and have been shown to exhibit plasticity, while multipotent marrow stromal cells are the source of osteocytes, chondrocytes, and fat cells and have been shown to support and generate a large number of different cell types. This review describes the general characteristics of these stem cell populations and their current and potential future applications in regenerative medicine. Developmental Dynamics 236:3321,3331, 2007. © 2007 Wiley-Liss, Inc. [source] ,-cell development: the role of intercellular signalsDIABETES OBESITY & METABOLISM, Issue 2008R. Scharfmann Understanding in detail how pancreatic endocrine cells develop is important for many reasons. From a scientific point of view, elucidation of such a complex process is a major challenge. From a more applied point of view, this may help us to better understand and treat specific forms of diabetes. Although a variety of therapeutic approaches are well validated, no cure for diabetes is available. Many arguments indicate that the development of new strategies to cure diabetic patients will require precise understanding of the way ,-cells form during development. This is obvious for a future cell therapy using ,-cells produced from embryonic stem cells. This also holds true for therapeutic approaches based on regenerative medicine. In this review, we summarize our current knowledge concerning pancreatic development and focus on the role of extracellular signals implicated in ,-cell development from pancreatic progenitors. [source] Regenerative medicine in dermatology: biomaterials, tissue engineering, stem cells, gene transfer and beyondEXPERIMENTAL DERMATOLOGY, Issue 8 2010Christina Dieckmann Please cite this paper as: Regenerative medicine in dermatology: biomaterials, tissue engineering, stem cells, gene transfer and beyond. Experimental Dermatology 2010; 19: 697,706. Abstract:, The term ,regenerative medicine' refers to a new and expanding field in biomedical research that focuses on the development of innovative therapies allowing the body to replace, restore and regenerate damaged or diseased cells, tissues and organs. It combines several technological approaches including the use of soluble molecules, biomaterials, tissue engineering, gene therapy, stem cell transplantation and the reprogramming of cell and tissue types. Because of its easy accessibility, skin is becoming an attractive model organ for regenerative medicine. Here, we review recent developments in regenerative medicine and their potential relevance for dermatology with a particular emphasis on biomaterials, tissue engineering, skin substitutes and stem cell-based therapies for skin reconstitution in patients suffering from chronic wounds and extensive burns. [source] Therapeutic angiogenesis and vasculogenesis for tissue regenerationEXPERIMENTAL PHYSIOLOGY, Issue 3 2005Paolo Madeddu Therapeutic angiogenesis/vasculogenesis holds promise for the cure of ischaemic disease. The approach postulates the manipulation of spontaneous healing response by supplementation of growth factors or transplantation of vascular progenitor cells. These supplements are intended to foster the formation of arterial collaterals and promote the regeneration of damaged tissues. Angiogenic factors are generally delivered in the form of recombinant proteins or by gene transfer using viral vectors. In addition, new non-viral methods are gaining importance for their safer profile. The association of growth factors with different biological activity might offer distinct advantages in terms of efficacy, yet combined approaches require further optimization. Alternatively, substances with pleiotropic activity might be considered, by virtue of their ability to target multiple mechanisms. For instance, some angiogenic factors not only stimulate the growth of arterioles and capillaries, but also inhibit vascular destabilization triggered by metabolic and oxidative stress. Transplantation of endothelial progenitor cells was recently proposed for the treatment of peripheral and myocardial ischaemia. Progenitor cells can be transplanted either without any preliminary conditioning or after ex vivo genetic manipulation. Delivery of genetically modified progenitor cells eliminates the drawback of immune response against viral vectors and makes feasible repeating the therapeutic procedure in case of injury recurrence. It is envisioned that these new approaches of regenerative medicine will open unprecedented opportunities for the care of life-threatening diseases. [source] Porous Structures: In situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide-Based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering (Adv. Funct.ADVANCED FUNCTIONAL MATERIALS, Issue 17 2010Mater. Abstract Synthetic biodegradable polymers serve as temporary substrates that accommodate cell infiltration and tissue in-growth in regenerative medicine. To allow tissue in-growth and nutrient transport, traditional three-dimensional (3D) scaffolds must be prefabricated with an interconnected porous structure. Here we demonstrated for the first time a unique polymer erosion process through which polymer matrices evolve from a solid coherent film to an assemblage of microspheres with an interconnected 3D porous structure. This polymer system was developed on the highly versatile platform of polyphosphazene-polyester blends. Co-substituting a polyphosphazene backbone with both hydrophilic glycylglycine dipeptide and hydrophobic 4-phenylphenoxy group generated a polymer with strong hydrogen bonding capacity. Rapid hydrolysis of the polyester component permitted the formation of 3D void space filled with self-assembled polyphosphazene spheres. Characterization of such self-assembled porous structures revealed macropores (10,100 ,m) between spheres as well as micro- and nanopores on the sphere surface. A similar degradation pattern was confirmed in vivo using a rat subcutaneous implantation model. 12 weeks of implantation resulted in an interconnected porous structure with 82,87% porosity. Cell infiltration and collagen tissue in-growth between microspheres observed by histology confirmed the formation of an in situ 3D interconnected porous structure. It was determined that the in situ porous structure resulted from unique hydrogen bonding in the blend promoting a three-stage degradation mechanism. The robust tissue in-growth of this dynamic pore forming scaffold attests to the utility of this system as a new strategy in regenerative medicine for developing solid matrices that balance degradation with tissue formation. [source] |