|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | | Nanoscale surfacing for regenerative medicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 Sep;2(5):478-95 Authors: Yang Y, Leong KW Cells in most tissues reside in microenvironment surrounded with specific three-dimensional features. The extracellular matrix or substratum with which cells interact often includes topography at the nanoscale. For example, the basement membrane of many tissues displays features of pores, fibers and ridges in the nanometer range. The nanoscale topography has significant effects on cellular behavior. Knowledge of the cell-substratum interactions is crucial to the understanding of many fundamental biological questions and to regenerative medicine. Rapid advances in nanotechnology enable cellular study on engineered nanoscale surfaces. Recent findings underscore the phenomenon that mammalian cells do respond to nanosized features on a synthetic surface. This review covers the commonly used techniques of engineering nanoscale surface and the techniques which have not been adapted but are of great potential in regenerative medicine, surveys the applications of nanoscale surface in regenerative medicine including vascular, bone, neural and stem cell tissue engineering, and discusses the possible mechanisms of cellular responses to nanoscale surface. A better understanding of the interactions between cells and nanoscale surfacing will help advance the field of regenerative medicine. Copyright (c) 2010 John Wiley & Sons, Inc.For further resources related to this article, please visit the WIREs website. PMID: 20803682 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Biomimetic Nanopatterns as Enabling Tools for Analysis and Control of Live Cells. Adv Mater. 2010 Aug 27; Authors: Kim DH, Lee H, Lee YK, Nam JM, Levchenko A It is becoming increasingly evident that cell biology research can be considerably advanced through the use of bioengineered tools enabled by nanoscale technologies. Recent advances in nanopatterning techniques pave the way for engineering biomaterial surfaces that control cellular interactions from the nano- to the microscale, allowing more precise quantitative experimentation capturing multi-scale aspects of complex tissue physiology in vitro. The spatially and temporally controlled display of extracellular signaling cues on nanopatterned surfaces (e. g., cues in the form of chemical ligands, controlled stiffness, texture, etc.) that can now be achieved on biologically relevant length scales is particularly attractive enabling experimental platform for investigating fundamental mechanisms of adhesion-mediated cell signaling. Here, we present an overview of bio-nanopatterning methods, with the particular focus on the recent advances on the use of nanofabrication techniques as enabling tools for studying the effects of cell adhesion and signaling on cell function. We also highlight the impact of nanoscale engineering in controlling cell-material interfaces, which can have profound implications for future development of tissue engineering and regenerative medicine. PMID: 20803528 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | A new paradigm in cell therapy for diabetes: Turning pancreatic alpha-cells into beta-cells. Bioessays. 2010 Aug 27; Authors: Sangan CB, Tosh D Cell therapy means treating diseases with the body's own cells. One of the cell types most in demand for therapeutic purposes is the pancreatic beta-cell. This is because diabetes is one of the major healthcare problems in the world. Diabetes can be treated by islet transplantation but the major limitation is the shortage of organ donors. To overcome the shortfall in donors, alternative sources of pancreatic beta-cells must be found. Potential sources include embryonic or adult stem cells or, from existing beta-cells. There is now a startling new addition to this list of therapies: the pancreatic alpha-cell. Thorel and colleagues recently showed that under circumstances of extreme pancreatic beta-cell loss, alpha-cells may serve to replenish the insulin-producing compartment. This conversion of alpha-cells to beta-cells represents an example of transdifferentiation. Understanding the molecular basis for transdifferentiation may help to enhance the generation of beta-cells for the treatment of diabetes. PMID: 20803505 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Clinical Application of Stem Cells in the Cardiovascular System. Adv Biochem Eng Biotechnol. 2010 Aug 27; Authors: Stamm C, Klose K, Choi YH Regenerative medicine encompasses "tissue engineering" - the in vitro fabrication of tissues and/or organs using scaffold material and viable cells - and "cell therapy" - the transplantation or manipulation of cells in diseased tissue in vivo. In the cardiovascular system, tissue engineering strategies are being pursued for the development of viable replacement blood vessels, heart valves, patch material, cardiac pacemakers and contractile myocardium. Anecdotal clinical applications of such vessels, valves and patches have been described, but information on systematic studies of the performance of such implants is not available, yet. Cell therapy for cardiovascular regeneration, however, has been performed in large series of patients, and numerous clinical studies have produced sometimes conflicting results. The purpose of this chapter is to summarize the clinical experience with cell therapy for diseases of the cardiovascular system, and to analyse possible factors that may influence its outcome. PMID: 20803146 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | PROTEIN TEMPLATES IN HARD TISSUE ENGINEERING. Nano Today. 2010 Aug 1;5(4):254-266 Authors: George A, Ravindran S Biomineralization processes such as formation of bones and teeth require controlled mineral deposition and self-assembly into hierarchical biocomposites with unique mechanical properties. Ideal biomaterials for regeneration and repair of hard tissues must be biocompatible, possess micro and macroporosity for vascular invasion, provide surface chemistry and texture that facilitate cell attachment, proliferation, differentiation of lineage specific progenitor cells, and induce deposition of calcium phosphate mineral. To expect in-vivo like cellular response several investigators have used extracellular matrix proteins as templates to recreate in-vivo microenvironment for regeneration of hard tissues. Recently, several novel methods of designing tissue repair and restoration materials using bioinspired strategies are currently being formulated. Nanoscale structured materials can be fabricated via the spontaneous organization of self-assembling proteins to construct hierarchically organized nanomaterials. The advantage of such a method is that polypeptides can be specifically designed as building blocks incorporated with molecular recognition features and spatially distributed bioactive ligands that would provide a physiological environment for cells in-vitro and in-vivo. This is a rapidly evolving area and provides a promising platform for future development of nanostructured templates for hard tissue engineering. In this review we try to highlight the importance of proteins as templates for regeneration and repair of hard tissues as well as the potential of peptide based nanomaterials for regenerative therapies. PMID: 20802848 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Translation of stem cell therapy for neurological diseases. Transl Res. 2010 Sep;156(3):155-160 Authors: Schwarz SC, Schwarz J "Regenerative medicine" hopefully will provide novel therapies for diseases that remain without effective therapy. This development is also true for most neurodegenerative disorders including Alzheimer's disease, Huntington's disease, or Parkinson's disease. Transplantation of new neurons to the brain has been performed in Parkinson's disease and in Huntington's disease. The restoration of dopaminergic neurons in patients with Parkinson's disease via implantation of embryonic midbrain tissue was taken from animal experiments to clinical applications, showing a limited efficacy. Clinical trials in patients with Huntington's disease using fetal striatal tissue currently are underway. Today, it seems possible to generate functional dopaminergic or striatal neurons form a variety of stem cells including embryonic or neural stem cells as well as induced pluripotent stem cells. First clinical trials using neural stem cell or embryonic-stem-cell-derived tissue are approved or already underway. Such cells allow for extensive in vitro and in vivo testing as well as "good manufacturing production," reducing the risks in clinical application. PMID: 20801412 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bone marrow and circulating stem/progenitor cells for regenerative cardiovascular therapy. Transl Res. 2010 Sep;156(3):112-129 Authors: Alaiti MA, Ishikawa M, Costa MA Cardiovascular disease is the leading cause of death and disability in the Western world. In addition to the advancement of current therapeutic approaches to reduce the associated morbidity and mortality, regenerative medicine and cell-based therapy have been areas of continuous investigation. Circulating and bone-marrow-derived stem or endothelial progenitor cells are an attractive source for regenerative therapy in the cardiovascular field. In this review, we highlight the advantages and limitations of this approach with a focus on key observations from animal studies and clinical trials. PMID: 20801408 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Control of embryonic stem cell identity by nucleosome remodeling enzymes. Curr Opin Genet Dev. 2010 Aug 25; Authors: Fazzio TG, Panning B Embryonic stem (ES) cells are pluripotent cells that can self-renew indefinitely or be induced to differentiate into multiple cell lineages, and thus have the potential to be used in regenerative medicine. Pluripotency transcription factors (TFs), such as Oct4, Sox2, and Nanog, function in a regulatory circuit that silences the expression of key TFs required for differentiation and activates the expression of genes important for maintenance of pluripotency. In addition, proteins that remodel chromatin structure also play important roles in determining the ES cell-specific gene expression pattern. Here we review recent studies demonstrating the roles of enzymes that carry out one facet of chromatin regulation, nucleosome remodeling, in control of ES cell self-renewal and differentiation. PMID: 20800472 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Platform technologies for tubular organ regeneration. Trends Biotechnol. 2010 Aug 25; Authors: Basu J, Ludlow JW As a result of recent successes in regenerative medicine approaches to engineering multiple disparate tubular organs, methodology commonalities are emerging. Principal themes include the importance of a biodegradable scaffold seeded with a population of smooth muscle cells. Such composites trigger a regenerative response following in vivo implantation, resulting in de novo organogenesis. In this review, we examine bladder regeneration as a foundational platform technology to highlight key principles applicable to the regeneration of any tubular organ, and illustrate how these general concepts underlie current strategies to regenerate components of gastrointestinal, vascular, pulmonary and genitourinary systems. We focus on identifying the elements of this platform that have facilitated the transition of tubular organ regeneration from academic proof-of-concept to commercial viability. PMID: 20800302 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Tissue-engineered conduit using urine-derived stem cells seeded bacterial cellulose polymer in urinary reconstruction and diversion. Biomaterials. 2010 Aug 25; Authors: Bodin A, Bharadwaj S, Wu S, Gatenholm P, Atala A, Zhang Y The objective of this study was to generate bacterial cellulose (BC) scaffolds seeded with human urine-derived stem cells (USC) to form a tissue-engineered conduit for use in urinary diversion. Microporous BC scaffolds were synthesized and USC were induced to differentiate into urothelial and smooth muscle cells (SMC). Induced USC (10(6) cells/cm(2)) were seeded onto BC under static and 3D dynamic (10 or 40 RPM) conditions and cultured for 2 weeks. The urothelial cells and SMC derived from USC formed multilayers on the BC scaffold surface, and some cells infiltrated into the scaffold. The urothelium derived from USC differentiation expressed urothelial markers (uroplakin Ia and AE1/AE3) and the SMC expressed SMC markers (alpha-smooth muscle actin and desmin). In addition, USC/BC scaffold constructs were implanted into athymic mice, and the cells were tracked using immunohistochemical staining for human nuclear antigen. In vivo, the cells appeared to differentiate and express urothelial and SMC markers. In conclusion, porous BC scaffolds allow 3 dimensional growth of USC, leading to formation of a multilayered urothelium and cell-matrix infiltration. Thus, cell-seeded BC scaffolds hold promise for use in tissue-engineered urinary conduits for urinary reconstruction. PMID: 20800278 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Extraction and physico-chemical characterization of a versatile biodegradable polysaccharide obtained from green algae. Carbohydr Res. 2010 Jul 27; Authors: Alves A, Caridade SG, Mano JF, Sousa RA, Reis RL During the last years, considerable attention has been given to different marine organisms, like algae, as potential sources of valuable materials. The continuous demand for novel materials and technologies is high and research on the underexploited marine green algae, including its polysaccharidic part-ulvan, has increased accordingly. In this research work, a novel method for extraction of ulvan from green algae is proposed and demonstrated successfully. Different characterization techniques were employed to characterize the isolated algal polysaccharide, namely, on what concerns its thermal trace and crystallinity. Upon heating, ulvan behaves as a non-meltable polysaccharide that is thermally stable before degradation at 220 degrees C. Ulvan is semi-crystalline in nature and possesses high hygroscopic features, as revealed in this research work. Due to its properties, ulvan can be considered, pure or modified, as a versatile biodegradable polymer for different applications, including tissue engineering and regenerative medicine. PMID: 20800225 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fibrin Glues in Combination with Mesenchymal Stem cells to Develop a Tissue-engineered Cartilage Substitute. Tissue Eng Part A. 2010 Aug 29; Authors: Ahmed TA, Giulivi A, Griffith M, Hincke MT Damage of cartilage due to traumatic or pathological conditions results in disability and severe pain. Regenerative medicine, using tissue engineering-based constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a promising approach for restoration of structure and function. Fresh fibrin (FG) and platelet-rich fibrin (PR-FG) glues produced by the CryoSeal(R) FS System, in combination with human bone marrow-derived mesenchymal stem cells (BM-hMSCs), were evaluated in this study. We additionally tested the incorporation of heparin-based delivery system (HBDS) into these scaffolds to immobilize endogenous growth factors as well as exogenous TGF-beta2. Strongly CD90+ and CD105+ hMSCs were encapsulated into FG and PR-FG with and without HBDS. Encapsulation of hMSCs in PR-FG led to increased expression of collagen II gene at 2.5 weeks, however, no difference was observed between FG and PR-FG at 5 weeks. The incorporation of HBDS prevented the enhancement of collagen II gene expression. BM-hMSCs in FG initially displayed enhanced aggrecan gene expression and increased accumulation of Alcian blue-positive extracellular matrix (ECM); incorporation of HBDS into these glues did not improve aggrecan gene expression and ECM accumulation. The most significant effect on cartilage marker gene expression and accumulation was observed after encapsulation of hMSCs in FG. We conclude that fibrin glue is more promising than platelet-rich fibrin glue as a scaffold for chondrogenic differentiation of hMSCs; however, immobilization of growth factors inside these fibrin scaffolds with the HBDS system has a negative impact on this process. In addition, BM-hMSCs are valid and potentially superior alternatives to chondrocytes for tissue engineering of articular cartilage. PMID: 20799906 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells and hepatic cirrhosis. Panminerva Med. 2010 Jun;52(2):149-65 Authors: Chen Z, Qi LZ, Zeng R, Li HY, Dai LJ Hepatic cirrhosis is defined as the histological development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which leads to portal hypertension and end-stage liver disease. The majority of patients with hepatic cirrhosis die from life-threatening complications at early age. Liver transplantation has been the most effective treatment for patients with hepatic cirrhosis. Since liver transplantation is critically limited by the shortage of available donor livers, searching for an effective alternative therapy has attracted great interest in preclinical studies. The encouraging advances in stem cell research have paved the way towards the treatment of the end-stage of chronic liver disease. In view of the pathogenic fundamentals of hepatic cirrhosis, stem cell-based treatment should be aimed to complement or replace damaged liver cells and to correct the imbalanced extracellular matrix regeneration/degradation. This review is intended to describe the characteristics and therapeutic potential of various liver repair-related stem cells, including hepatocytes, liver progenitor cells, hematopoietic stem cells, mesenchymal stem cells, embryonic stem cells and induced pluripotent stem cells. Since autologous adult stem cells have the least number of obstacles for clinical application, their potential interventions on cirrhosis are especially illustrated in terms of the cellular and molecular mechanisms of hepatic fibrogenesis. PMID: 20517197 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cells: the building blocks to repair the injured heart. Panminerva Med. 2010 Jun;52(2):97-110 Authors: Van Oorschot AA, Smits AM, Goumans MJ Myocardial infarction is the major cause of death in western countries due to impaired function of the heart, which is the result of cardiomyocyte death and fibrotic scar formation. The endogenous regenerative capacity of the heart is unable to replenish this significant loss of tissue and conventional medical management cannot correct the underlying defects in cardiac muscle cell number. Recently, tremendous effort is being put into the development of cell transplantation protocol for heart repair, which has been put forward as an alternative therapy to reduce cell damage, cardiomyocyte death and improve tissue contraction. Unfortunately the ideal stem cell population for heart repair has not been identified to date, but several characteristics are defined which the ideal population should have namely, reduce cell damage, reduce cardiomyocyte death, induce differentiation into cardiomyocytes and endothelial cells, and improve tissue contraction. It is unclear whether this will be possible in one optimal population. Therefore the research focus is shifting towards improving the characteristics of the stem cell populations that are identified to date. In this review, we will give an overview of the different stem/progenitor cell populations and their application in cardiac repair and discuss current knowledge on issues like differentiation capacity, paracrine secretion profile, genetic modification of progenitor cells and their influence on cardiac remodeling. PMID: 20517194 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Stem cell world 2010: crucial questions from clinicians to biologists. Panminerva Med. 2010 Jun;52(2):95-6 Authors: Fagoonee S, Pellicano R, Altruda F PMID: 20517193 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | The California stem cell agency has posted its much-delayed RFA for its first foray into clinical trials – a $50 million loan/grant round that is predicted to have only three applicants.
Firms mentioned publicly as likely to seek the CIRM funds include Geron of Menlo Park, Ca.; Ipierian of South San Francisco, and Advanced Cell Technology of Santa Monica, Ca. The RFA calls for companies to | | | | | | | | | | | | | | | | | | | | | | | | | The effect of intracavernous injection of adipose tissue-derived stem cells on hyperlipidemia-associated erectile dysfunction in a rat model. J Sex Med. 2010 Apr;7(4 Pt 1):1391-400 Authors: Huang YC, Ning H, Shindel AW, Fandel TM, Lin G, Harraz AM, Lue TF, Lin CS INTRODUCTION: Hyperlipidemia has been associated with erectile dysfunction (ED) via damage to the cavernous endothelium and nerves. Adipose tissue-derived stem cells (ADSC) have been shown to differentiate into endothelial cells and secrete vasculotrophic and neurotrophic factors. AIM: To assess whether ADSC have therapeutic effects on hyperlipidemia-associated ED. METHODS: Twenty-eight male rats were induced to develop hyperlipidemia with a high-fat diet (hyperlipidemic rats, HR). Ten additional male rats were fed a normal diet to serve as controls (normal rats, NR). Five months later, all rats were subjected to ADSC isolation from paragonadal fat. The cells were cultured for 1 week, labeled with 5-ethynyl-2'-deoxyuridine (EdU), and then injected autologously into the corpus cavernosum of 18 HR. The remaining 10 HR rats were injected with phosphate buffered saline (PBS). At 2 and 14 days post-transplantation, four rats in the HR + ADSC group were sacrificed for tracking of the transplanted cells. At 28 days post-transplantation, all remaining rats were analyzed for serum biochemistry, erectile function, and penile histology. MAIN OUTCOME MEASURES: Erectile function was assessed by intracavernous pressure (ICP) measurement during electrostimulation of the cavernous nerve. Cavernous nerves, endothelium, and smooth muscle were assessed by immunohistochemistry. RESULTS: Serum total cholesterol and low-density lipoprotein levels were significantly higher in HR than in NR. High-density lipoprotein level was significantly lower in HR than in NR. Mean ICP/mean arterial pressure ratio was significantly lower in HR + PBS than in NR + PBS or HR + ADSC. Neuronal nitric oxide synthase (nNOS)-positive nerve fibers and endothelial cells were fewer in HR + PBS than in HR + ADSC. Smooth muscle content was significantly higher in both HR groups than in NR. CONCLUSIONS: Hyperlipidemia is associated with abnormalities in both the nerves and endothelium. Treatment with ADSC ameliorates these adverse effects and holds promise as a potential new therapy for ED. PMID: 20141586 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Nanoscale surfacing for regenerative medicine. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2010 Sep;2(5):478-95 Authors: Yang Y, Leong KW Cells in most tissues reside in microenvironment surrounded with specific three-dimensional features. The extracellular matrix or substratum with which cells interact often includes topography at the nanoscale. For example, the basement membrane of many tissues displays features of pores, fibers and ridges in the nanometer range. The nanoscale topography has significant effects on cellular behavior. Knowledge of the cell-substratum interactions is crucial to the understanding of many fundamental biological questions and to regenerative medicine. Rapid advances in nanotechnology enable cellular study on engineered nanoscale surfaces. Recent findings underscore the phenomenon that mammalian cells do respond to nanosized features on a synthetic surface. This review covers the commonly used techniques of engineering nanoscale surface and the techniques which have not been adapted but are of great potential in regenerative medicine, surveys the applications of nanoscale surface in regenerative medicine including vascular, bone, neural and stem cell tissue engineering, and discusses the possible mechanisms of cellular responses to nanoscale surface. A better understanding of the interactions between cells and nanoscale surfacing will help advance the field of regenerative medicine. Copyright (c) 2010 John Wiley & Sons, Inc.For further resources related to this article, please visit the WIREs website. PMID: 20803682 [PubMed - in process] | | | | | | | | | | | | | | | | | | | | | | | | | Biomimetic Nanopatterns as Enabling Tools for Analysis and Control of Live Cells. Adv Mater. 2010 Aug 27; Authors: Kim DH, Lee H, Lee YK, Nam JM, Levchenko A It is becoming increasingly evident that cell biology research can be considerably advanced through the use of bioengineered tools enabled by nanoscale technologies. Recent advances in nanopatterning techniques pave the way for engineering biomaterial surfaces that control cellular interactions from the nano- to the microscale, allowing more precise quantitative experimentation capturing multi-scale aspects of complex tissue physiology in vitro. The spatially and temporally controlled display of extracellular signaling cues on nanopatterned surfaces (e. g., cues in the form of chemical ligands, controlled stiffness, texture, etc.) that can now be achieved on biologically relevant length scales is particularly attractive enabling experimental platform for investigating fundamental mechanisms of adhesion-mediated cell signaling. Here, we present an overview of bio-nanopatterning methods, with the particular focus on the recent advances on the use of nanofabrication techniques as enabling tools for studying the effects of cell adhesion and signaling on cell function. We also highlight the impact of nanoscale engineering in controlling cell-material interfaces, which can have profound implications for future development of tissue engineering and regenerative medicine. PMID: 20803528 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Characterization of protein release from hydrolytically degradable poly(ethylene glycol) hydrogels. Biotechnol Bioeng. 2010 Aug 27; Authors: Zustiak SP, Leach JB We present a novel fully hydrophilic, hydrolytically degradable poly(ethylene glycol) (PEG) hydrogel suitable for soft tissue engineering and delivery of protein drugs. The gels were designed to overcome drawbacks associated with current PEG hydrogels (i.e., reaction mechanisms or degradation products that compromise protein stability): the highly selective and mild cross-linking reaction allowed for encapsulating proteins prior to gelation without altering their secondary structure as shown by circular dichroism experiments. Further, hydrogel degradation and structure, represented by mesh size, were correlated to protein release. It was determined that polymer density had the most profound effect on protein diffusivity, followed by the polymer molecular weight, and finally by the specific chemical structure of the cross-linker. By examining the diffusion of several model proteins, we confirmed that the protein diffusivity was dependent on protein size as smaller proteins (e.g., lysozyme) diffused faster than larger proteins (e.g., Ig). Furthermore, we demonstrated that the protein physical state was preserved upon encapsulation and subsequent release from the PEG hydrogels and contained negligible aggregation or protein-polymer adducts. These initial studies indicate that the developed PEG hydrogels are suitable for release of stable proteins in drug delivery and tissue engineering applications. (c) 2010 Wiley Periodicals, Inc. PMID: 20803477 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bone morphogenetic protein-7 promotes chondrogenesis in human amniotic epithelial cells. Int Orthop. 2010 Aug 29; Authors: Zhou J, Yu G, Cao C, Pang J, Chen X Bone morphogenetic proteins (BMPs) play important roles at multiple stages of chondrogenesis. This study was undertaken to investigate the potential role of bone morphogenetic protein-7 (BMP-7) in the differentiation of chondrocytes using tissue engineering techniques. The impact of BMP-7 on human amniotic epithelial cells (hAECs) was tested. The hAECs were treated either with recombinant human BMP-7 cDNA or with transforming growth factor beta 1 (TGF-beta1) as a positive control for three weeks in vitro. Cartilaginous differentiation and proliferation were assayed by quantitative RT-PCR, histology, and in situ hybridization. Our results were such that hAECs treated with either BMP-7 or TGF-beta1 expressed cartilage markers (aggrecan, Sox9, CEP-68, and type II and X collagens) within three weeks. Compared with a control vector, BMP-7 induced a decrease in type I collagen expression, while the transcription of the cartilage-specific type II collagen remained stable. In induction experiments, BMP-7 transgenic hAECs exhibited the largest amount of matrix synthesis. In conclusion, these data indicate that BMP-7 plays an important role in inducing the production of cartilage by hAECs in vitro. Cartilage differentiation and matrix maturation can be promoted by BMPs in a cartilage engineering paradigm. These properties make BMPs promising tools in the engineering of cartilaginous joint bio-prostheses and as candidate biological agents or genes for cartilage stabilisation. PMID: 20803292 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Clinical Application of Stem Cells in the Cardiovascular System. Adv Biochem Eng Biotechnol. 2010 Aug 27; Authors: Stamm C, Klose K, Choi YH Regenerative medicine encompasses "tissue engineering" - the in vitro fabrication of tissues and/or organs using scaffold material and viable cells - and "cell therapy" - the transplantation or manipulation of cells in diseased tissue in vivo. In the cardiovascular system, tissue engineering strategies are being pursued for the development of viable replacement blood vessels, heart valves, patch material, cardiac pacemakers and contractile myocardium. Anecdotal clinical applications of such vessels, valves and patches have been described, but information on systematic studies of the performance of such implants is not available, yet. Cell therapy for cardiovascular regeneration, however, has been performed in large series of patients, and numerous clinical studies have produced sometimes conflicting results. The purpose of this chapter is to summarize the clinical experience with cell therapy for diseases of the cardiovascular system, and to analyse possible factors that may influence its outcome. PMID: 20803146 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | PROTEIN TEMPLATES IN HARD TISSUE ENGINEERING. Nano Today. 2010 Aug 1;5(4):254-266 Authors: George A, Ravindran S Biomineralization processes such as formation of bones and teeth require controlled mineral deposition and self-assembly into hierarchical biocomposites with unique mechanical properties. Ideal biomaterials for regeneration and repair of hard tissues must be biocompatible, possess micro and macroporosity for vascular invasion, provide surface chemistry and texture that facilitate cell attachment, proliferation, differentiation of lineage specific progenitor cells, and induce deposition of calcium phosphate mineral. To expect in-vivo like cellular response several investigators have used extracellular matrix proteins as templates to recreate in-vivo microenvironment for regeneration of hard tissues. Recently, several novel methods of designing tissue repair and restoration materials using bioinspired strategies are currently being formulated. Nanoscale structured materials can be fabricated via the spontaneous organization of self-assembling proteins to construct hierarchically organized nanomaterials. The advantage of such a method is that polypeptides can be specifically designed as building blocks incorporated with molecular recognition features and spatially distributed bioactive ligands that would provide a physiological environment for cells in-vitro and in-vivo. This is a rapidly evolving area and provides a promising platform for future development of nanostructured templates for hard tissue engineering. In this review we try to highlight the importance of proteins as templates for regeneration and repair of hard tissues as well as the potential of peptide based nanomaterials for regenerative therapies. PMID: 20802848 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Concentration effect of gold nanoparticles on proliferation of keratinocytes. Colloids Surf B Biointerfaces. 2010 Jul 6; Authors: Lu S, Xia D, Huang G, Jing H, Wang Y, Gu H 34nm gold nanoparticles with good stability were synthesized and characterized and their effect (as a function of concentration) on the proliferation of keratinocytes was evaluated by means of MTT and nucleolar organizer region (AgNOR) count (silver staining). The cell morphology was observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The results demonstrate that a low concentration of gold nanoparticles enhances the proliferation of keratinocytes. Specifically, a concentration of 5.0ppm gold nanoparticle has the best effect on the promotion of cell growth. In the experiment group, the AgNOR-positive areas and AgNOR area/nuclear area ratios of keratinocytes co-cultured with 5.0ppm gold nanoparticles were greater than those in the control group (p<0.01). At a level greater than10.0ppm, gold nanoparticles were found to have a cytotoxic effect on keratinocytes. It is concluded that a low concentration of gold nanoparticles may be used as a biomedical material in skin tissue engineering. PMID: 20801623 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Helicoidal multi-lamellar features of RGD-functionalized silk biomaterials for corneal tissue engineering. Biomaterials. 2010 Aug 27; Authors: Gil ES, Mandal BB, Park SH, Marchant JK, Omenetto FG, Kaplan DL RGD-coupled silk protein-biomaterial lamellar systems were prepared and studied with human cornea fibroblasts (hCFs) to match functional requirements. A strategy for corneal tissue engineering was pursued to replicate the structural hierarchy of human corneal stroma within thin stacks of lamellae-like tissues, in this case constructed from scaffolds constructed with RGD-coupled, patterned, porous, mechanically robust and transparent silk films. The influence of RGD-coupling on the orientation, proliferation, ECM organization, and gene expression of hCFs was assessed. RGD surface modification enhanced cell attachment, proliferation, alignment and expression of both collagens (type I and V) and proteoglycans (decorin and biglycan). Confocal and histological images of the lamellar systems revealed that the bio-functionalized silk human cornea 3D constructs exhibited integrated corneal stroma tissue with helicoidal multi-lamellar alignment of collagen-rich and proteoglycan-rich extracellular matrix, with transparency of the construct. This biomimetic approach to replicate corneal stromal tissue structural hierarchy and architecture demonstrates a useful strategy for engineering human cornea. Further, this approach can be exploited for other tissue systems due to the pervasive nature of such helicoids in most human tissues. PMID: 20801503 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Covalently Immobilized Platelet Derived Growth Factor-BB Promotes Angiogenesis in Biomimetic Poly(ethylene glycol) Hydrogels. Acta Biomater. 2010 Aug 26; Authors: Saik JE, Gould DJ, Watkins EM, Dickinson ME, West JL The field of tissue engineering is severely limited by the lack of microvascularization in tissue engineered constructs. Biomimetic poly(ethylene glycol) hydrogels containing covalently immobilized platelet-derived growth factor BB (PDGF-BB) were developed to promote angiogenesis. Poly(ethylene glycol) hydrogels resist protein absorption and subsequent nonspecific cell adhesion, thus providing a "blank slate," which can be modified through the incorporation of cell adhesive ligands and growth factors. PDGF-BB is a key angiogenic protein able to support neovessel stabilization by inducing functional anastomoses and recruiting pericytes. Due to PDGF's widespread effects in the body and half life of only thirty minutes in circulating blood, immobilization of PDGF-BB may be necessary. In this work, bioactive, covalently immobilized PDGF-BB was shown to induce tubulogenesis on 2D modified surfaces, migration in 3D degradable hydrogels, and angiogenesis in a mouse cornea micropocket angiogenesis assay. Covalently immobilized PDGF-BB was also used in combination with covalently immobilized FGF-2, which led to significantly increased endothelial cell migration in 3D degradable hydrogels as compared to presentation of each factor alone. When a co-culture of endothelial cell and mouse pericyte precursor 10T1/2 cells was seeded onto modified surfaces, tubule formation was independent of surface modifications with covalently immobilized growth factors. Furthermore, the combination of soluble PDGF-BB and immobilized PDGF-BB induced a more robust vascular response as compared to soluble PDGF-BB alone when implanted into an in vivo mouse cornea micropocket angiogenesis assay. Based on these results, we believe bioactive hydrogels can be tailored to improve the formation of functional microvasculature for tissue engineering. PMID: 20801242 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | NOTCH1 and NOTCH3 coordinate esophageal squamous differentiation through a CSL-dependent transcriptional network. Gastroenterology. 2010 Aug 26; Authors: Ohashi S, Natsuizaka M, Yashiro-Ohtani Y, Kalman RA, Nakagawa M, Wu L, Klein-Szanto AJ, Herlyn M, Diehl JA, Katz JP, Pear WS, Seykora JT, Nakagawa H BACKGROUND & AIMS:: The Notch receptor family regulates cell fate through cell-cell communication. CSL (CBF-1/RBP-jkappa, Su(H), Lag-1) drives canonical Notch-mediated gene transcription during cell lineage specification, differentiation and proliferation in the hematopoietic system, the intestine, the pancreas and the skin. However, the functional roles of Notch in esophageal squamous epithelial biology remain unknown. METHODS:: Normal esophageal keratinocytes were stimulated with calcium chloride to induce terminal differentiation. The squamous epithelia were reconstituted in organotypic three-dimensional culture, a form of human tissue engineering. Notch was inhibited in culture with a gamma-secretase inhibitor or dominant negative mastermind-like1 (DNMAML1). The roles of Notch receptors were evaluated by in vitro gain-of-function and loss-of-function experiments. Additionally, DNMAML1was targeted to the mouse esophagus by cytokeratin K14promoter-driven Cre ( K14Cre) recombination of Lox - STOP - Lox-DNMAML1. Notch-regulated gene expression was determined by reporter transfection, chromatin immunoprecipitation (ChIP) assays, quantitative reverse-transcription polymerase chain reactions (RT-PCR), Western blotting, immunofluorescence and immunohistochemistry. RESULTS:: NOTCH1 (N1) was activated at the onset of squamous differentiation in the esophagus. Intracellular domain of N1 (ICN1) directly activated NOTCH3 (N3) transcription, inducing HES5 and early differentiation markers such as involucrin (IVL) and cytokeratin CK13 in a CSL-dependent fashion. N3 enhanced ICN1 activity and was required for squamous differentiation. Loss of Notch signaling in K14Cre;DNMAML1mice perturbed esophageal squamous differentiation and resulted in N3 loss and basal cell hyperplasia. CONCLUSIONS:: Notch signaling is important for esophageal epithelial homeostasis. In particular, the crosstalk of N3 with N1 during differentiation provides novel, mechanistic insights into Notch signaling and squamous epithelial biology. PMID: 20801121 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Bone marrow stromal cells as an inducer for cardiomyocyte differentiation from mouse embryonic stem cells. Ann Anat. 2010 Aug 5; Authors: Yue F, Johkura K, Tomotsune D, Shirasawa S, Yokoyama T, Nagai M, Sasaki K Bone marrow stromal cells (BMSCs) secrete soluble factors and display varied cell-biological functions. To confirm the ability and efficiency of BMSCs to induce embryonic stem cells (ESCs) into cardiomyocytes, mouse embryoid bodies (EBs) were co-cultured with rat BMSCs. After about 10 days, areas of rhythmically contracting cells in more solid aggregates became evident with bundle-like structures formed along borders between EB outgrowth and BMSC layer. ESC-derived cardiomyocytes exhibited sarcomeric striations when stained with troponin I (Trop I), organized in separated bundles. Besides, the staining for connexin 43 was detected in cell-cell junctions, which demonstrated that ESC-derived cardiomyocytes were coupled by gap junction in culture. The related genes of cardiomyocytes were found in these beating and no-beating EBs co-cultured with BMSCs. In addition, an improved efficiency of cardiomyocyte differentiation from ESC-BMSC co-culture was found in the serum-free medium: 5-fold up-regulation in the number of beating area compared with the serum medium. Effective cardiac differentiation was also recognized in transfer filter assay and in condition medium obtained from BMSC culture. A clear increase in the expression of cardiac genes and TropI protein confirmed further cardiac differentiation by BMP4 and Retinoic Acid (RA) treatment. These results demonstrate that BMSCs can induce cardiomyocyte differentiation from ESCs through soluble factors and enhance it with BMP4 or RA treatment. Serum-free ESC-BMSC co-culture represents a defined in vitro model for identifying the cardiomyocyte-inducing activity from BMSCs and, in addition, a straightforward experimental system for assessing clinical applications. PMID: 20801009 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Citric acid-derived in situ crosslinkable biodegradable polymers for cell delivery. Biomaterials. 2010 Aug 26; Authors: Gyawali D, Nair P, Zhang Y, Tran RT, Zhang C, Samchukov M, Makarov M, Kim HK, Yang J Herein, we report a first citric acid (CA)-derived in situ crosslinkable biodegradable polymer, poly(ethylene glycol) maleate citrate (PEGMC). The synthesis of PEGMC could be carried out via a one-pot polycondensation reaction without using organic solvents or catalysts. PEGMC could be in situ crosslinked into elastomeric PPEGMC hydrogels. The performance of hydrogels in terms of swelling, degradation, and mechanical properties were highly dependent on the molar ratio of monomers, crosslinker concentration, and crosslinking mechanism used in the synthesis process. Cyclic conditioning tests showed that PPEGMC hydrogels could be compressed up to 75% strain without permanent deformation and with negligible hysteresis. Water-soluble PEGMC demonstrated excellent cytocompatibilty in vitro. The degradation products of PPEGMC also showed minimal cytotoxicity in vitro. Animal studies in rats clearly demonstrated the excellent injectability of PEGMC and degradability of the in situ-formed PPEGMC. PPEGMC elicited minimal inflammation in the early stages post-injection and was completely degraded within 30 days in rats. In conclusion, the development of CA-derived injectable biodegradable PEGMC presents numerous opportunities for material innovation and offers excellent candidate materials for in situ tissue engineering and drug delivery applications. PMID: 20800893 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Dental follicle cells combined with beta-tricalcium phosphate ceramic: A novel available therapeutic strategy to restore periodontal defects. Med Hypotheses. 2010 Aug 25; Authors: Zuolin J, Hong Q, Jiali T Tissue-engineering strategies to restore the periodontal defects are being developed. It will result in the periodontal formation and growing new function tissue rather than new replacement of periodontium. Although a number of procedures have been investigated in an attempt to regenerate lost periodontal tissue, none has yet led to new cementum formation, remodeling of the periodontal ligament, and new bone formation in clinic. Dental follicle cells (DFCs), as a progenitor cell of periodontal ligament cell and stem cell, have more potential abilities than PDL-cell in formation of periodontal tissue. More researches focus on the inductive environments, such as bone morphogenetic protein-2 (BMP-2), dexamethasone, and transfer growth factor, and scaffold. We hypotheses that DFCs from Beagle's dog are isolated, induced by BMP-2, basic-fibroblast growth factor and dexamethasone, and seeded by beta-tricalcium phosphate ceramic (beta-TCP), then the complex was auto-implanted into the periodontal defects in the same Beagle's dog to observe the regeneration of periodontal tissue in vivo. The study will explore the feasibility and application of restore of periodontal defects by DFCs-beta-TCP complex. We believe it is especially helpful to future clinical study and application. PMID: 20800363 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Miscibility of choline-substituted polyphosphazenes with PLGA and osteoblast activity on resulting blends. Biomaterials. 2010 Aug 25; Authors: Weikel AL, Owens SG, Morozowich NL, Deng M, Nair LS, Laurencin CT, Allcock HR The preparation of phosphazene tissue engineering scaffolds with bioactive side groups has been accomplished using the biological buffer, choline chloride. Mixed-substituent phosphazene cyclic trimers (as model systems) and polymers with choline chloride and glycine ethyl ester, alanine ethyl ester, valine ethyl ester, or phenylalanine ethyl ester were synthesized. Two different synthetic protocols were examined. A sodium hydride mediated route resulted in polyphosphazenes with a low choline content, while a cesium carbonate mediated process produced polyphosphazenes with higher choline content. The phosphazene structures and physical properties were studied using multinuclear NMR, differential scanning calorimetry (DSC), and gel permeation chromatography (GPC) techniques. The resultant polymers were then blended with PLGA (50:50) or PLGA (85:15) and characterized by DSC analysis and scanning electron microscopy (SEM). Polymer products obtained via the sodium hydride route produced miscible blends with both ratios of PLGA, while the cesium carbonate route yielded products with reduced blend miscibility. Heterophase hydrolysis experiments in aqueous media revealed that the polymer blends hydrolyzed to near-neutral pH media ( approximately 5.8 to 6.8). The effect of different molecular structures on cellular adhesion showed osteoblast proliferation with an elevated osteoblast phenotype expression compared to PLGA over a 21-day culture period. PMID: 20800277 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Extraction and physico-chemical characterization of a versatile biodegradable polysaccharide obtained from green algae. Carbohydr Res. 2010 Jul 27; Authors: Alves A, Caridade SG, Mano JF, Sousa RA, Reis RL During the last years, considerable attention has been given to different marine organisms, like algae, as potential sources of valuable materials. The continuous demand for novel materials and technologies is high and research on the underexploited marine green algae, including its polysaccharidic part-ulvan, has increased accordingly. In this research work, a novel method for extraction of ulvan from green algae is proposed and demonstrated successfully. Different characterization techniques were employed to characterize the isolated algal polysaccharide, namely, on what concerns its thermal trace and crystallinity. Upon heating, ulvan behaves as a non-meltable polysaccharide that is thermally stable before degradation at 220 degrees C. Ulvan is semi-crystalline in nature and possesses high hygroscopic features, as revealed in this research work. Due to its properties, ulvan can be considered, pure or modified, as a versatile biodegradable polymer for different applications, including tissue engineering and regenerative medicine. PMID: 20800225 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Influence of Shear Stress in Perfusion Bioreactor Cultures for the Development of 3D Bone Tissue Constructs: a Review. Tissue Eng Part B Rev. 2010 Aug 29; Authors: McCoy RJ, O'Brien FJ Bone tissue engineering aims to generate clinically applicable bone graft substitutes in an effort to ease the demands and reduce the potential risks associated with traditional autograft and allograft bone replacement procedures. Biomechanical stimuli play an important role under physiologically relevant conditions in the normal formation, development and homeostasis of bone tissue; predominantly strain (predicted levels in vivo for humans <2000 muepsilon) caused by physical deformation, and fluid shear stress (0.8 - 3 Pa), generated by interstitial fluid movement through lacunae caused by compression and tension under loading. Therefore in vitro bone tissue cultivation strategies seek to incorporate biochemical stimuli in an effort to create more physiologically relevant constructs for grafting. This review is focused on collating information pertaining to the relationship between fluid shear stress, cellular deformation and osteogenic differentiation; providing further insight into the optimal culture conditions for the creation of bone tissue substitutes. PMID: 20799909 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Fibrin Glues in Combination with Mesenchymal Stem cells to Develop a Tissue-engineered Cartilage Substitute. Tissue Eng Part A. 2010 Aug 29; Authors: Ahmed TA, Giulivi A, Griffith M, Hincke MT Damage of cartilage due to traumatic or pathological conditions results in disability and severe pain. Regenerative medicine, using tissue engineering-based constructs to enhance cartilage repair by mobilizing chondrogenic cells, is a promising approach for restoration of structure and function. Fresh fibrin (FG) and platelet-rich fibrin (PR-FG) glues produced by the CryoSeal(R) FS System, in combination with human bone marrow-derived mesenchymal stem cells (BM-hMSCs), were evaluated in this study. We additionally tested the incorporation of heparin-based delivery system (HBDS) into these scaffolds to immobilize endogenous growth factors as well as exogenous TGF-beta2. Strongly CD90+ and CD105+ hMSCs were encapsulated into FG and PR-FG with and without HBDS. Encapsulation of hMSCs in PR-FG led to increased expression of collagen II gene at 2.5 weeks, however, no difference was observed between FG and PR-FG at 5 weeks. The incorporation of HBDS prevented the enhancement of collagen II gene expression. BM-hMSCs in FG initially displayed enhanced aggrecan gene expression and increased accumulation of Alcian blue-positive extracellular matrix (ECM); incorporation of HBDS into these glues did not improve aggrecan gene expression and ECM accumulation. The most significant effect on cartilage marker gene expression and accumulation was observed after encapsulation of hMSCs in FG. We conclude that fibrin glue is more promising than platelet-rich fibrin glue as a scaffold for chondrogenic differentiation of hMSCs; however, immobilization of growth factors inside these fibrin scaffolds with the HBDS system has a negative impact on this process. In addition, BM-hMSCs are valid and potentially superior alternatives to chondrocytes for tissue engineering of articular cartilage. PMID: 20799906 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Temporal Exposure to Chondrogenic Factors Modulates Human Mesenchymal Stem Cell Chondrogenesis in Hydrogels. Tissue Eng Part A. 2010 Aug 29; Authors: Buxton AN, Bahney CS, Yoo J, Johnstone B Tissue engineering utilizes scaffolds containing chondrogenic cells to promote cartilage development at a clinically relevant scale, yet there remains a limited understanding of the optimal conditions for inducing differentiation and matrix production. We investigated how cell density and temporal exposure to chondrogenic factors impacted chondrogenesis of human mesenchymal stem cells (hMSCs) encapsulated in poly(ethylene glycol) diacrylate hydrogels. We found maximal proteoglycan and collagen production in constructs seeded between 10 and 25 x 10;6 cells/ml. Matrix deposition was significantly less per cell in constructs seeded at either higher or lower densities, indicating that paracrine communications may remain important despite loss of direct cell-cell contact. In vitro chondrogenesis of hMSCs was first accomplished using pellet cultures and a defined medium containing TGF-beta1 and dexamethasone. The differentiation of hMSCs in hydrogels also required initial exposure to TGF-beta1, with no chondrogenic matrix produced in its absence. If TGF-beta1 was initially included for at least 7 days, its removal impacted collagen production per cell but also lead to an increase in cell number, such that total collagen deposition was equivalent to controls when TGF-beta1 was included for at least 3 weeks. Furthermore, proteoglycan content per construct was higher at 6 weeks after removal of TGF-beta1 at any time. In contrast to TGF-beta1, dexamethasone was not required for chondrogenesis of hMSCs in hydrogels: there was no difference in matrix deposition between hydrogels cultured with or without dexamethasone. Furthermore, without dexamethasone, SOX9 gene expression was higher during early chondrogenesis and there was a significant reduction in collagen I deposition, suggesting a more hyaline cartilage phenotype is achieved without dexamethasone. Collagen content at 6 weeks was lower if dexamethasone was excluded after the first 7 days, but was equivalent to control if dexamethasone was included for 2 weeks or longer. Proteoglycan deposition was unaffected by dexamethasone exclusion. These results indicate that modulating exposure to TGF-beta1 is beneficial for cell survival/proliferation and matrix production from hMSCs in hydrogels, and that dexamethasone is not only dispensable but its exclusion may be advantageous for forming hyaline cartilage. PMID: 20799905 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Porous Poly(vinyl Alcohol)-Hydrogel Matrix-Engineered Bio-Synthetic Cartilage. Tissue Eng Part A. 2010 Aug 28; Authors: Bichara DA, Zhao X, Bodugoz-Senturk H, Ballyns FP, Oral E, Randolph MA, Bonassar LJ, Gill T, Muratoglu OK The objective of this study was to fabricate hydrogel matrix-engineered bio-synthetic cartilage using poly(vinyl alcohol) (PVA-H) and articular chondrocytes. We injected chondrocytes with fibrin gel (FG) or saline carriers into porous PVA-H discs and three-layered constructs (PVA-H between devitalized cartilage). After implantation in nude mice, PVA discs were explanted at 6 weeks and subjected to creep testing for a 20 hour period. The three-layered constructs were explanted at 12 weeks and subjected to tensile testing to determine the strength of the interface between the engineered hydrogel and devitalized cartilage. Histological analysis revealed PVA-H porous channels occupied by chondrocytes. Extracellular matrix was identified by Safranin O and toluidine blue stains. Immunohistochemical analysis revealed a positive stain for COL II and only scant staining for COL I. Creep and relaxation response of PVA-FG-chondrocyte constructs was similar to that of native cartilage. The presence of cells and FG significantly enhanced the integration strength of layered constructs (p<0.05). These results demonstrate that porous PVA-H in combination with FG and chondrocytes provides a favorable microenvironment for tissue engineering of articular cartilage, creating a bio-synthetic construct that can adhere to native devitalized articular cartilage utilizing hydrogel matrix-engineered technology. PMID: 20799889 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | 3D co-cultures of osteoblasts and endothelial cells in DegraPol foam: Histological and high field MRI analyses of pre-engineered capillary networks in bone grafts. Tissue Eng Part A. 2010 Aug 28; Authors: Buschmann J, Welti M, Hemmi S, Neuenschwander P, Baltes C, Giovanoli P, Rudin M, Calcagni M Tissue engineering of bone grafts was addressed in a critical size model on the chick chorioallantoic membrane model (CAM assay), using DegraPol(R) (DP) foam as scaffold material. The scaffolds were seeded with cultures of human osteoblasts (OB) and human en notdo notthelial cells (EC), respectively, or with a co-culture of the two cell types (control: no cells). In vitro samples (7 days cultivation) and ex vivo CAM samples at incubation day 15 (ID 15) were analyzed by high field magnetic resonance imaging (MRI) and histology. The co-culture system performed best with respect to perfusion, as assessed by contrast-enhanced MRI using Gd-DTPA. The scaffold seeded by the co-culture supported an increased vascular ingrowth, which was confirmed by histological analysis. DP foam is a suitable scaffold for bone tissue engineering and the MRI technique allows for non-destructive and quantitative assessment of perfusion capability during early stages of bone forming constructs. PMID: 20799888 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
No comments:
Post a Comment