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| Tracking CIRM Grants: "Thin Ice" Lurking?
June 23, 2010 at 5:06 PM
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| Directors of the California stem cell agency today approved a $15.7 million operating budget for next fiscal year – 28 percent higher than this year's spending – and requested a report from its staff concerning its critical grants management system.
The report was sought after CIRM Director Michael Friedman, CEO of the City of Hope, said he wanted to "express in the strongest possible terms my | | |
| Fresh Joy from Cyberspace
June 23, 2010 at 2:57 PM
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| | We have a new connection to the CIRM audiocast. Directors are taking up the strategic financing report now. CIRM VP John Robson is speaking. | | |
| Joys of Cyberspace
June 23, 2010 at 2:53 PM
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| | We have lost the audiocast connection to the CIRM board meeting so reports may be limited. The broadcast disappeared entirely, resumed with one side of someone's phone conversation and then provided a steady electronic hiss. | | |
| 'Troubling' Trend: Is CIRM Playing Field Level for Business?
June 23, 2010 at 2:30 PM
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| A longtime observer of California stem cell matters today said he is troubled by a trend at CIRM that appears to give short shrift to research at biotech businesses in the Golden State.
John M. Simpson has been watching the California stem cell agency since late 2005, along with participating in its affairs, most notably development of its IP policies.
Simpson, stem cell project director for | | |
| Mystery Item No. 16 Revealed
June 23, 2010 at 1:50 PM
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| | Here is a link to Mystery Item No. 16. It involves an overview of CIRM's current grant portfolio and is designed to "facilitate programmatic decision-making." Pat Olson, executive director of scientific activities, is presenting the assessment as we write. Her Power Point presentation appears to have been posted by CIRM yesterday afternoon. We reported incorrectly earlier today that the material | | |
| CIRM Directors Discuss Strategic Financing Plans
June 23, 2010 at 1:41 PM
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| | Directors of the California stem cell this morning began their meeting with a discussion of strategic financing plans. The scenarios being examined would mean different end dates for funding more research. Under one possibility, no grants would be approved after 2014. Another would see funding end in 2017. Both scenarios do not envision funding beyond the remaining $2 billion that CIRM has. | | |
| More Live Coverage Today: CIRM Budget, Financial Projections and Mystery Item No. 16 on Tap
June 23, 2010 at 9:59 AM
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| The California stem cell agency begins its board meeting at 10:30 a.m. PDT this morning, and we will be filing stories as warranted.
Today's matters include the proposed $15.7 million operational budget for the fiscal year that begins one week from tomorrow. The spending plan is a 28 percent increase over its current expenditures. Also on tap are strategic financial projections and a | | |
| Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases.
June 23, 2010 at 8:22 AM
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| | Treatment of diabetic impotence with umbilical cord blood stem cell intracavernosal transplant: preliminary report of 7 cases. Exp Clin Transplant. 2010 Jun;8(2):150-60 Authors: Bahk JY, Jung JH, Han H, Min SK, Lee YS Objectives: Stem cells are characterized by self renewal and multipotent differentiation.We report the effects of intracavernosal transplant of human umbilical cord blood stem cells on diabetic erectile dysfunction. Materials and Methods: Seven type 2 diabetics who had failed to achieve an erection for at least 6 months despite medications, and who are currently awaiting penile prostheses, participated. All laboratory results were normal, except for impotence and diabetes mellitus. A total of 1.5 x 107 human umbilical cord blood stem cells were infused into the corpus cavernosum. No immunosuppressive measures were taken in any of the patients. International index of erectile function-5, SEP, GAQ, erection diary, blood glucose diary, and medication dosage were followed for 9 months. Results: The mean age was 69.5 years (range, 57-87 years). Morning erections were regained in 3 participants within 1 month, and for all except 1 by the third month, and maintained for more than 6 months. Rigidity increased as the result of stem cell therapy alone, but was insufficient for penetration. With the addition of PDE5 inhibitor before coitus, 2 achieved penetration and experienced orgasm, and maintained for more than 6 months; however, 1 participant could not achieved penetration at ninth month. All but 1 reported increased desire. During follow-up, 2 returned for prosthesis, 4 returned to a nonerectile condition at 9 months, and 1 maintained erection sufficient for coitus with medication until the 11th month. Blood glucose levels decreased by 2 weeks, and medication dosages were reduced in all but 1 subject for 4 to 7 months. Glycosylated hemoglobin levels improved after treatment for up to 3 to 4 months. Conclusions: Human umbilical cord blood stem cell therapy has positive effects on erectile dysfunction and diabetes mellitus. Stem cells and unknown humoral factors of human umbilical cord blood stem cells mediate mechanism may contribute to these positive effects. PMID: 20565373 [PubMed - in process] | | |
| Toward an understanding of the role of notochordal cells in the adult intervertebral disc: From discord to accord.
June 23, 2010 at 6:41 AM
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| | Toward an understanding of the role of notochordal cells in the adult intervertebral disc: From discord to accord. Dev Dyn. 2010 Jun 21; Authors: Risbud MV, Schaer TP, Shapiro IM The goal of this mini-review is to address the long standing argument that the pathogenesis of disc disease is due to the loss and/or the replacement of the notochordal cells by other cell types. We contend that, although cells of different size and morphology exist, there is no strong evidence to support the view that the nucleus pulposus contains cells of distinct lineages. Based on lineage mapping studies and studies of other notochordal markers, we hypothesize that in all animals, including human, nucleus pulposus retains notochordal cells throughout life. Moreover, all cells including chondrocyte-like cells are derived from notochordal precursors, and variations in morphology and size are representative of different stages of maturation, and or, function. Thus, the most critical choice for a suitable animal model should relate more to the anatomical and mechanical characteristics of the motion segment than concerns of cell loss and replacement by non-notochordal cells. Developmental Dynamics, 2010. (c) 2010 Wiley-Liss, Inc. PMID: 20568241 [PubMed - as supplied by publisher] | | |
| Ovine bone- and marrow-derived progenitor cells and their potential for scaffold-based bone tissue engineering applications in vitro and in vivo.
June 23, 2010 at 6:41 AM
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| | Ovine bone- and marrow-derived progenitor cells and their potential for scaffold-based bone tissue engineering applications in vitro and in vivo. J Tissue Eng Regen Med. 2010 Jun 21; Authors: Reichert JC, Woodruff MA, Friis T, Quent VM, Gronthos S, Duda GN, Schütz MA, Hutmacher DW Recently, research has focused on bone marrow derived multipotent mesenchymal precursor cells (MPC) and osteoblasts (OB) for clinical use in bone engineering. Prior to clinical application, cell based treatment concepts need to be evaluated in preclinical, large animal models. Sheep in particular are considered a valid model for orthopaedic and trauma related research. However, only sheep aged > 6 years show secondary osteon formation characteristic of human bone. Osteogenic cells isolated from animals of this age group remain poorly characterized. In the present study, ex vivo expanded MPC isolated from ovine bone marrow proliferated at a higher rate than OB derived from tibial compact bone as assessed in standard 2D cultures. MPC expressed the respective phenotypic profile typical for different mesenchymal cell populations (CD14(-)/CD31(-)/CD45(-)/CD29(+)/CD44(+)/CD166(+)) and showed a multilineage differentiation potential. When compared to OB, MPC had a higher mineralization potential under standard osteogenic culture conditions and expressed typical bone related markers such as osteocalcin, osteonectin and type I collagen at the mRNA and protein level. After 4 weeks in 3D culture, MPC constructs demonstrated higher cell density and mineralization, whilst cell viability on the scaffolds was assessed > 90%. Cells displayed a spindle-like morphology and formed interconnected networks. In contrast, when implanted subcutaneously into NOD/SCID mice, MPC presented a lower osteogenic potential than OB. In summary, this study provides a detailed characterisation of ovine MPC and OB from a bone engineering perspective and suggests that MPC and OB provide promising means for future bone disease related treatment applications. Copyright (c) 2010 John Wiley & Sons, Ltd. PMID: 20568083 [PubMed - as supplied by publisher] | | |
| Functionalization of electrospun fibers of poly(epsilon-caprolactone) with star shaped NCO-poly(ethylene glycol)-stat-poly(propylene glycol) for neuronal cell guidance.
June 23, 2010 at 6:41 AM
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| | Functionalization of electrospun fibers of poly(epsilon-caprolactone) with star shaped NCO-poly(ethylene glycol)-stat-poly(propylene glycol) for neuronal cell guidance. J Mater Sci Mater Med. 2010 Jun 22; Authors: Klinkhammer K, Bockelmann J, Simitzis C, Brook GA, Grafahrend D, Groll J, Möller M, Mey J, Klee D Microfibers produced with electrospinning have recently been used in tissue engineering. In the development of artificial implants for nerve regeneration they are of particular interest as guidance structures for cell migration and axonal growth. Using electrospinning we produced parallel-orientated biocompatible fibers in the submicron range consisting of poly(epsilon-caprolactone) (PCL) and star shaped NCO-poly(ethylene glycol)-stat-poly(propylene glycol) (sPEG). Addition of the bioactive peptide sequence glycine-arginine-glycine-aspartate-serine (GRGDS) or the extracellular matrix protein fibronectin to the electrospinning solution resulted in functionalized fibers. Surface characteristics and biological properties of functionalized and non-functionalised fibers were investigated. Polymer solutions and electrospinning process parameters were varied to obtain high quality orientated fibers. A polymer mixture containing high molecular weight PCL, PCL-diol, and sPEG permitted a chemical reaction between hydroxyl groups of the diol and isocyanante groups of the sPEG. Surface analysis demonstrated that sPEG at the fiber surface minimized protein adhesion. In vitro experiments using dorsal root ganglia explants showed that the cell repellent property of pure PCL/sPEG fibers was overcome by functionalization either with GRGDS peptide or fibronectin. In this way cell migration and axonal outgrowth along fibers were significantly increased. Thus, functionalized electrospun PCL/sPEG fibers, while preventing non-specific protein adsorption, are a suitable substrate for biological and medical applications. PMID: 20567886 [PubMed - as supplied by publisher] | | |
| Gelatine and Gelatine/Elastin Nanocomposites for Vascular Grafts: Processing and Characterization.
June 23, 2010 at 6:41 AM
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| | Gelatine and Gelatine/Elastin Nanocomposites for Vascular Grafts: Processing and Characterization. J Biomater Appl. 2010 Jun 21; Authors: Lamprou D, Zhdan P, Labeed F, Lekakou C This study involves the preparation, microstructural, physical, mechanical, and biological characterization of novel gelatine and gelatine/elastin gels for their use in the tissue engineering of vascular grafts. Gelatine and gelatine/elastin nanocomposite gels were prepared via a sol-gel process, using soluble gelatine. Gelatine was subsequently cross-linked by leaving the gels in 1% glutaraldehyde. The cross-linking time was optimized by assessing the mass loss of the cross-linked gels in water and examining their mechanical properties in dynamic mechanical tests. Atomic force microscopy (AFM) studies revealed elastin nanodomains, homogeneously distributed and embedded in a bed of gelatine nanofibrils in the 30/70 elastin/gelatine gel. It was concluded that the manufactured nanocomposite gels resembled natural arteries in terms of microstructure and stiffness. The biological characterization involved the culture of rat smooth muscle cells (SMCs) on tubular gelatine and gelatine/elastin nanocomposite gels, and measurements of the scaffold diameter and the cell density as a function of time. PMID: 20566658 [PubMed - as supplied by publisher] | | |
| Three-Dimensional Scaffolds as a Model System for Neural and Endothelial 'In Vitro' Culture.
June 23, 2010 at 6:41 AM
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| | Three-Dimensional Scaffolds as a Model System for Neural and Endothelial 'In Vitro' Culture. J Biomater Appl. 2010 Jun 21; Authors: Veiga DD, Antunes JC, Gómez RG, Mano JF, Ribelles JL, Soria JM Biomaterials based on the hydrophobic homopolymer poly(ethyl acrylate), PEA, and its copolymers with hydroxyethyl acrylate, p(EA-co-HEA) and methacrylic acid, p(EA-co-MAAc) were prepared as polymeric scaffolds with interconnected pores of 90 microns and tested in vitro as culture substrates and compared for their impact on the differentiation of neural stem cells (NSC) obtained from the subventricular zone (SVZ) of postnatal rats and human endothelial cells (HUVEC). Immunocytochemical staining assay for specific markers show that p(EA-co-MAAc) scaffolds were suitable substrates to promote cell attachment and differentiation of adult NSC and HUVEC cells. PMID: 20566656 [PubMed - as supplied by publisher] | | |
| Resorbable Glass-Ceramic Phosphate-based Scaffolds for Bone Tissue Engineering: Synthesis, Properties and, In Vitro Effects on Human Marrow Stromal Cells.
June 23, 2010 at 6:41 AM
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| | Resorbable Glass-Ceramic Phosphate-based Scaffolds for Bone Tissue Engineering: Synthesis, Properties and, In Vitro Effects on Human Marrow Stromal Cells. J Biomater Appl. 2010 Jun 21; Authors: Vitale-Brovarone C, Ciapetti G, Leonardi E, Baldini N, Bretcanu O, Verné E, Baino F Highly porous bioresorbable glass-ceramic scaffolds were prepared via sponge replication method by using an open-cell polyurethane foam as a template and phosphate-based glass powders. The glass, belonging to the P2O5-SiO2-CaO-MgO-Na2O-K2O system, was synthesized by a melting-quenching route, ground, and sieved to obtain powders with a grain size of less than 30 microm. A slurry containing glass powders, polyvinyl alcohol, and water was prepared to coat the polymeric template. The removal of the polymer and the sintering of the glass powders were performed by a thermal treatment, in order to obtain an inorganic replica of the template structure. The structure and properties of the scaffold were investigated from structural, morphological, and mechanical viewpoints by means of X-ray diffraction, scanning electron microscopy, density measurements, image analysis, and compressive tests. The scaffolds exhibited a trabecular architecture that closely mimics the structure of a natural spongy bone. The solubility of the porous structures was assessed by soaking the samples in acellular simulated body fluid (SBF) and Tris-HCl for different time frames and then by assessing the scaffold weight loss. As far as the test in SBF is concerned, the nucleation of hydroxyapatite on the scaffold trabeculae demonstrates the bioactivity of the material. Biological tests were carried out using human bone marrow stromal cells to test the osteoconductivity of the material. The cells adhered to the scaffold struts and were metabolically active; it was found that cell differentiation over proliferation occurred. Therefore, the produced scaffolds, being biocompatible, bioactive, resorbable, and structurally similar to a spongy bone, can be proposed as interesting candidates for bone grafting. PMID: 20566654 [PubMed - as supplied by publisher] | | |
| Improving the compressive strength of bioceramic robocast scaffolds by polymer infiltration.
June 23, 2010 at 6:41 AM
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| | Improving the compressive strength of bioceramic robocast scaffolds by polymer infiltration. Acta Biomater. 2010 May 31; Authors: MartÃnez-Vázquez FJ, Perera FH, Miranda P, Pajares A, Guiberteau F The effect of polymer infiltration on the compressive strength of beta-tricalcium phosphate (TCP) scaffolds fabricated by robocasting (direct write assembly) is analyzed in this work. Porous structures consisting of a tetragonal three-dimensional mesh of interpenetrating rods were fabricated from concentrated TCP inks with suitable viscoelastic properties. Biodegradable polymers (polylactic acid (PLA) and poly(epsilon-caprolactone) (PCL)) were infiltrated into selected scaffolds by immersion of the structure in a polymer melt. Infiltration increased the uniaxial compressive strength of these model scaffolds by a factor of three (PCL) or six (PLA). It also considerably improved the mechanical integrity of the structures after initial cracking, with the infiltrated structure retaining a significant load-bearing capacity after fracture of the ceramic rods. The strength improvement in the infiltrated scaffolds was attributed to two different contributions: the sealing of precursor flaws in the ceramic rod surfaces and the partial transfer of stress to the polymer, as confirmed by finite element analysis. The implications of these results for the mechanical optimization of scaffolds for bone tissue engineering applications are discussed. PMID: 20566307 [PubMed - as supplied by publisher] | | |
| The use of human mesenchymal stem cells encapsulated in RGD modified alginate microspheres in the repair of myocardial infarction in the rat.
June 23, 2010 at 6:41 AM
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| | The use of human mesenchymal stem cells encapsulated in RGD modified alginate microspheres in the repair of myocardial infarction in the rat. Biomaterials. 2010 Jun 19; Authors: Yu J, Du KT, Fang Q, Gu Y, Mihardja SS, Sievers RE, Wu JC, Lee RJ The combination of scaffold material and cell transplantation therapy has been extensively investigated in cardiac tissue engineering. However, many polymers are difficult to administer or lack the structural integrity to restore LV function. Additionally, polymers need to be biological friendly, favorably influence the microenvironment and increase stem cell retention and survival. This study determined whether human mesenchymal stem cells (hMSCs) encapsulated in RGD modified alginate microspheres are capable of facilitating myocardial repair. The in vitro study of hMSCs demonstrated that the RGD modified alginate can improve cell attachment, growth and increase angiogenic growth factor expression. Alginate microbeads and hMSCs encapsulated in microbeads successfully maintained LV shape and prevented negative LV remodeling after an MI. Cell survival was significantly increased in the encapsulated hMSC group compared with PBS control or cells alone. Microspheres, hMSCs, and hMSCs in microspheres groups reduced infarct area and enhanced arteriole formation. In summary, surface modification and microencapsulation techniques can be combined with cell transplantation leading to the maintenance of LV geometry, preservation of LV function, increase of angiogenesis and improvement of cell survival. PMID: 20566215 [PubMed - as supplied by publisher] | | |
| Fabrication, Surface Properties and Protein Encapsulation/Release Studies of Electrospun Gelatin Nanofibers.
June 23, 2010 at 6:41 AM
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| | Fabrication, Surface Properties and Protein Encapsulation/Release Studies of Electrospun Gelatin Nanofibers. J Biomater Sci Polym Ed. 2010 Jun 21; Authors: Liu S, Su Y, Chen Y The aim of this study was to fabricate gelatin nanofibers by electrospinning and investigate the characteristics of these nanofibers. It has been reported that composite nanofibrous mats with drug impregnated in biocompatible and biodegradable polymer nanofibers can serve as tissue-engineering scaffolds with desired and controllable drug-release properties. The composite nanofibrous mats electrospun from a solution consisting of gelatin, bovine serum albumin (BSA, a model compound to simulate proteins), poly(ethylene glycol) sorbitan monolaurate (Tween-20) and 2,2,2-trifluoroethanol (TFE) were prepared and characterized. The BSA release profile in phosphate-buffered saline (PBS, pH 7.4) was recorded and analyzed. For comparison, nanofibrous mats electrospun from the solution containing gelatin and BSA were also prepared and assessed. The morphologies of the nanofibrous mats were examined by scanning electron microscopy; the surface hydrophilicity was measured by water contact angle method; and the protein-release profiles were recorded by analyzing BSA amount after immersing the electrospun nanofibrous mats in PBS for various time periods. The results indicated that the composite nanofibrous mats electrospun from the gelatin emulsion and/or solution had controllable protein-release behavior and they could be utilized as tissue-engineering scaffolds with protein encapsulated. PMID: 20566066 [PubMed - as supplied by publisher] | | |
| Proliferation of Mesenchymal Stem Cell on Chitosan Films Associated with Convex Micro-topography.
June 23, 2010 at 6:41 AM
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| | Proliferation of Mesenchymal Stem Cell on Chitosan Films Associated with Convex Micro-topography. J Biomater Sci Polym Ed. 2010 Jun 21; Authors: Yang J, Liu A, Zhou C Topographical micro-structures of material surfaces are known to influence cell behavior. In this study, alignment and proliferation of mesenchymal stem cells (MSCs) on chitosan (CS) films with different micro-topography was investigated. A modified solvent-non-solvent method was used to produce micro-well polystyrene films which were used as templates for preparation of micro-hilled CS films. The alignment and proliferation of MSCs on CS films were characterized by scanning electron microscopy and the MTT assay, respectively. Polystyrene films with different micro-well diameters were produced under different conditions. We successfully produced CS films with micro-hills of 10 mum (CS10) and 5-30 mum (CS5-30) by a molding approach. MSCs cultured on CS10 covered the tightly packed micro-hills and flattened polygonally. In contrast, MSCs on CS5-30 mostly adhered between loosely packed micro-hills and demonstrated elongated extensions. The proliferation rate of MSCs on CS5-30 was highest on day 4 (66% on CS5-30 versus 46% on CS10 and 24% on smooth CS) and day 8 (106% on CS5-30 versus 38% on CS10 and 72% on smooth CS). It is reasonable to suggest that spatially and dimensionally dispersed micro-hills on CS films facilitate the alignment and proliferation of MSCs. This may be used to physically modify CS for tissue-engineering applications. PMID: 20566064 [PubMed - as supplied by publisher] | | |
| Preparation of Biocompatible, UV-Cured Fumarated Poly(ether-ester)-Based Tissue-Engineering Hydrogels.
June 23, 2010 at 6:41 AM
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| | Preparation of Biocompatible, UV-Cured Fumarated Poly(ether-ester)-Based Tissue-Engineering Hydrogels. J Biomater Sci Polym Ed. 2010 Jun 21; Authors: Akdemir ZS, Kayaman-Apohan N, Kahraman MV, Kuruca SE, Güngör A, Karadenizli S The aim of this study was to develop biodegradable, photo-polymerizable in situ gel-forming systems prepared from a fumaric acid monoethyl ester (FAME) modified poly(lactide-co-glycolide) (PLGA) co-polymer. By reacting lactide and glycolide in the presence of stannous octoate as a catalyst and 2-ethyl,2-hydroxymethyl 1,3-propanediol as an initiator, hydroxyl terminated branched PLGA was synthesized. Afterwards, at room temperature hydroxyl terminated branched PLGA was reacted with fumaric acid monoethyl ester (FAME). N,N'-dicyclohexylcarbodiimide and triethylamine were used as a coupling agent and catalyst, respectively. The gel percentage, equilibrium mass swelling, degradation profile and polymerization kinetics of the hydrogels were investigated. All of the results were influenced by the amount of FAME modified PLGA co-polymer. Biocompatibility of the hydrogels was examined by using MTT cytotoxicity assay. According to the results, hydrogels are biocompatible and cell viability percentage depends on the amount of PLGA co-polymer. While the amount was 15% in hydrogel composition, cell viability was 100%, but after increasing the PLGA co-polymer amount to 30% the viability reduced to 78%. PMID: 20566062 [PubMed - as supplied by publisher] | | |
| Novel Melt-Processable Chitosan-Polybutylene Succinate Fibre Scaffolds for Cartilage Tissue Engineering.
June 23, 2010 at 6:41 AM
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| | Novel Melt-Processable Chitosan-Polybutylene Succinate Fibre Scaffolds for Cartilage Tissue Engineering. J Biomater Sci Polym Ed. 2010 Jun 21; Authors: Oliveira JT, Crawford A, Mundy JL, Sol PC, Correlo VM, Bhattacharya M, Neves NM, Hatton PV, Reis RL Novel chitosan/polybutylene succinate fibre-based scaffolds (C-PBS) were seeded with bovine articular chondrocytes in order to assess their suitability for cartilage tissue engineering. Chondrocytes were seeded onto C-PBS scaffolds using spinner flasks under dynamic conditions, and cultured under orbital rotation for a total of 6 weeks. Non-woven polyglycolic acid (PGA) felts were used as reference materials. Tissue-engineered constructs were characterized by scanning electron microscopy (SEM), hematoxylin-eosin (H&E), toluidine blue and alcian blue staining, immunolocalization of collagen types I and II, and dimethylmethylene blue (DMB) assay for glycosaminoglycans (GAG) quantification at different time points. SEM showed the chondrocytes' typical morphology, with colonization at the surface and within the pores of the C-PBS scaffolds. These observations were supported by routine histology. Toluidine blue and alcian blue stains, as well as immunohistochemistry for collagen types I and II, provided qualitative information on the composition of the engineered extracellular matrix. More pronounced staining was observed for collagen type II than collagen type I. Similar results were observed with constructs engineered on PGA scaffolds. These also exhibited higher amounts of matrix glycosaminoglycans and presented a central region which contained fewer cells and little matrix, a feature that was not detected with C-PBS constructs. PMID: 20566057 [PubMed - as supplied by publisher] | | |
| Effects of Chitosan-Coated Fibers as a Scaffold for Three-Dimensional Cultures of Rabbit Fibroblasts for Ligament Tissue Engineering.
June 23, 2010 at 6:41 AM
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| | Effects of Chitosan-Coated Fibers as a Scaffold for Three-Dimensional Cultures of Rabbit Fibroblasts for Ligament Tissue Engineering. J Biomater Sci Polym Ed. 2010 Jun 21; Authors: Sarukawa J, Takahashi M, Abe M, Suzuki D, Tokura S, Furuike T, Tamura H Material selection in tissue-engineering scaffolds is one of the primary factors defining cellular response and matrix formation. In this study, we fabricated chitosan-coated poly(lactic acid) (PLA) fiber scaffolds to test our hypothesis that PLA fibers coated with chitosan highly promoted cell supporting properties compared to those without chitosan. Both PLA fibers (PLA group) and chitosan-coated PLA fibers (PLA-chitosan group) were fabricated for this study. Anterior cruciate ligament (ACL) fibroblasts were isolated from Japanese white rabbits and cultured on scaffolds consisting of each type of fiber. The effects of cell adhesivity, proliferation, and synthesis of the extracellular matrix (ECM) for each fiber were analyzed by cell counting, hydroxyproline assay, scanning electron microscopy and quantitative RT-PCR. Cell adhesivity, proliferation, hydroxyproline content and the expression of type-I collagen mRNA were significantly higher in the PLA-chitosan group than in the PLA group. Scanning electron microscopic observation showed that fibroblasts proliferated with a high level of ECM synthesis around the cells. Chitosan coating improved ACL fibroblast adhesion and proliferation, and had a positive effect on matrix production. Thus, the advantages of chitosan-coated PLA fibers show them to be a suitable biomaterial for ACL tissue-engineering scaffolds. PMID: 20566054 [PubMed - as supplied by publisher] | | |
| Polylysine-Modified PEG-Based Hydrogels to Enhance the Neuro-Electrode Interface.
June 23, 2010 at 6:41 AM
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| | Polylysine-Modified PEG-Based Hydrogels to Enhance the Neuro-Electrode Interface. J Biomater Sci Polym Ed. 2010 Jun 21; Authors: Rao SS, Han N, Winter JO Neural prostheses are a promising technology in the treatment of lost neural function. However, poor biocompatibility of these devices inhibits the formation of a robust neuro-electrode interface. Several factors including mechanical mismatch between the device and tissue, inflammation at the implantation site, and possible electrical damage contribute to this response. Many researchers are investigating polymeric brain mimetic coatings as a means to improve integration with nervous tissue. Specifically, hydrogels, constructs also employed in tissue engineering, have been explored because of their structural and mechanical similarity to native tissue. However, many hydrogel materials (e.g., poly(ethylene glycol) (PEG)) do not support cell adhesion. In this work, we report a technique to enhance the interface between polymeric brain mimetic coatings and neural tissue using adhesion molecules. In particular, polylysine-modified PEG-based hydrogels were synthesized, characterized and shown to promote neural adhesion using a PC12 cell line. In addition, we examined adhesion behavior of a PEG-co-polymer and found that these materials adhere to electrodes for at least 4 weeks. These results suggest that polylysine-PEG hydrogel biomaterials are biocompatible and can enhance stability of chronic neural interfaces. PMID: 20566048 [PubMed - as supplied by publisher] | | |
| Preparation and Characterization of a Composite of Demineralized Bone Matrix Fragments and Polylactide Beads for Bone Tissue Engineering.
June 23, 2010 at 6:41 AM
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| | Preparation and Characterization of a Composite of Demineralized Bone Matrix Fragments and Polylactide Beads for Bone Tissue Engineering. J Biomater Sci Polym Ed. 2010 Jun 21; Authors: Thomas CB, Maxson S, Burg KJ A composite that utilizes the osteoinductivity of demineralized bone matrix (DBM) and the attractive characteristics of polylactide (PL) may be useful as a tissue-engineered bone substitute. The objective of this study was to investigate the potential of a composite system consisting of DBM fragments and PL beads to support the attachment and proliferation of multipotent mouse marrow stromal cells and to provide a structure for the cells' differentiation into the osteoblast lineage. Furthermore, the overarching goal was to provide a preliminary assessment of the DBM/PL cultures in order to facilitate the development of injectable composite DBM/PL systems in the long term. Demineralized bone matrix fragments were produced from bovine femurs and polylactide beads were produced by a single emulsion process. Differential scanning calorimetry and gel-permeation chromatography were used to characterize the PL samples. Multipotent mouse marrow stromal cells were cultured on several different substrate mixtures including 100% DBM, 70% DBM:30% PL, 50% DBM:50% PL and 100% PL. Cells were analyzed using a LIVE/DEAD((R)) Viability/Cytotoxicity kit as well as scanning electron microscopy. Lactic acid and glucose levels were measured throughout the study. Osteogenic differentiation of the MSCs was assessed with an alkaline phosphatase activity (ALP) assay and RT-PCR for expression of bone sialoprotein, osteocalcin and runt-related transcription factor 2. All cell types attached more readily to DBM fragments than PL beads resulting in more lactic acid production in the samples containing mostly DBM. The ALP activity and gene expression results indicate that the optimal mixture for the D1 line of multipotent mouse marrow stromal cells differentiation into osteoblasts is 100% PL. However, it is likely that the decreased pH in the DBM containing samples resulted in an environment that was not very conducive for osteogenic differentiation. PMID: 20566047 [PubMed - as supplied by publisher] | | |
| Neural Progenitor Cells Survival and Neuronal Differentiation in Peptide-Based Hydrogels.
June 23, 2010 at 6:41 AM
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| | Neural Progenitor Cells Survival and Neuronal Differentiation in Peptide-Based Hydrogels. J Biomater Sci Polym Ed. 2010 Jun 21; Authors: Song Y, Li Y, Zheng Q, Wu K, Guo X, Wu Y, Yin M, Wu Q, Fu X We designed nanofibrous hydrogels as 2-D and 3-D scaffolds for anchorage-dependent cells. The IKVAV-containing peptide amphiphile molecules spontaneously self-assembled into higher-order nanofiber hydrogels under cell-containing media. Neural progenitor cells (NPCs) were incubated in peptide-based hydrogels. Effects of self-assembling hydrogels on survival and neural differentiation of NPCs were observed. Peptide was synthesized using a solid-phase method. TEM study of the hydrogel revealed a network of nanofibers. Phase-contrast light micrographs showed that the described hydrogel had no observable cytotoxicity to NPCs. Additionally this hydrogel could induce cells to differentiate into neuron-like cells and glial-like cells. Moreover, the cells encapsulated within hydrogel had a higher neuronal differentiation rate than in the surface of the hydrogel. This self-assembled hydrogel might serve as nerve tissue-engineering scaffold. PMID: 20566041 [PubMed - as supplied by publisher] | | |
| A low-cost, rapid deposition method for "smart" films: applications in mammalian cell release.
June 23, 2010 at 6:41 AM
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| | A low-cost, rapid deposition method for "smart" films: applications in mammalian cell release. ACS Appl Mater Interfaces. 2010 Apr;2(4):1048-51 Authors: Reed JA, Lucero AE, Hu S, Ista LK, Bore MT, López GP, Canavan HE The "smart" polymer poly (N-isopropyl acrylamide), or pNIPAM, has been studied for bioengineering applications. The polymer's abrupt change in hydrophobicity near physiologic temperatures makes it ideal for use as a substrate in many applications, including protein separation and prevention of biofouling. To tether pNIPAM, many techniques such as plasma deposition, have been utilized, but most are expensive and require long equipment calibration or fabrication periods. Recently, a novel method for codepositing this smart polymer with a sol-gel, tetraethyl orthosilicate (TEOS), was developed. In this work, we adapt this technique for applications in mammalian cell attachment/detachment. In addition, we compare the effects of the pNIPAM/TEOS ratio to functionality using surface analysis techniques (XPS and contact angles). We found the optimal ratio to be 0.35 wt % pNIPAM/TEOS. Cell detachment from these substrates indicate that they would be ideal for applications that do not require intact cell sheets, such as biofouling prevention and protein separation, as this technique is a simple and affordable technique for pNIPAM deposition. PMID: 20423125 [PubMed - indexed for MEDLINE] | | |
| Developing an articular cartilage decellularization process toward facet joint cartilage replacement.
June 23, 2010 at 6:41 AM
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| | Developing an articular cartilage decellularization process toward facet joint cartilage replacement. Neurosurgery. 2010 Apr;66(4):722-7; discussion 727 Authors: Elder BD, Kim DH, Athanasiou KA OBJECTIVE: The facet joint has been identified as a significant source of morbidity in lower back pain. In general, treatments have focused on reducing the pain associated with facet joint osteoarthritis, and no treatments have targeted the development of a replacement tissue for arthritic facet articular cartilage. Therefore, the objective of this study was to develop a nonimmunogenic decellularized articular cartilage replacement tissue while maintaining functional properties similar to native facet cartilage tissue. METHODS: In vitro testing was performed on bovine articular cartilage explants. The effects of 2% sodium dodecyl sulfate (SDS), a detergent used for cell and nuclear membrane solubilization, on cartilage cellularity, biochemical, and biomechanical properties, were examined. Compressive biomechanical properties were determined using creep indentation, and the tensile biomechanical properties were obtained with uniaxial tensile testing. Biochemical assessment involved determination of the DNA content, glycosaminoglycan (GAG) content, and collagen content. Histological examination included hematoxylin and eosin staining for tissue cellularity, as well as staining for collagen and GAG. RESULTS: Treatment with 2% SDS for 2 hours maintained the compressive and tensile biomechanical properties, as well as the GAG and collagen content while resulting in a decrease in cell nuclei and a 4% decrease in DNA content. Additionally, treatment for 8 hours resulted in complete histological decellularization and a 40% decrease in DNA content while maintaining collagen content and tensile properties. However, a significant decrease in compressive properties and GAG content was observed. Similar results were observed with 4 hours of treatment, although the decrease in DNA content was not as great as with 8 hours of treatment. CONCLUSION: Treatment with 2% SDS for 8 hours resulted in complete histological decellularization with decreased mechanical properties, whereas treatment for 2 hours maintained mechanical properties, but had a minimal effect on DNA content. Therefore, future studies must be performed to optimize a treatment for decellularization while maintaining mechanical properties close to those of facet joint cartilage. This study served as a step in creating a decellularized articular cartilage replacement tissue that could be used as a treatment for facet cartilage osteoarthritis. PMID: 20305493 [PubMed - indexed for MEDLINE] | | |
| Toward an understanding of the role of notochordal cells in the adult intervertebral disc: From discord to accord.
June 23, 2010 at 6:16 AM
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| | Toward an understanding of the role of notochordal cells in the adult intervertebral disc: From discord to accord. Dev Dyn. 2010 Jun 21; Authors: Risbud MV, Schaer TP, Shapiro IM The goal of this mini-review is to address the long standing argument that the pathogenesis of disc disease is due to the loss and/or the replacement of the notochordal cells by other cell types. We contend that, although cells of different size and morphology exist, there is no strong evidence to support the view that the nucleus pulposus contains cells of distinct lineages. Based on lineage mapping studies and studies of other notochordal markers, we hypothesize that in all animals, including human, nucleus pulposus retains notochordal cells throughout life. Moreover, all cells including chondrocyte-like cells are derived from notochordal precursors, and variations in morphology and size are representative of different stages of maturation, and or, function. Thus, the most critical choice for a suitable animal model should relate more to the anatomical and mechanical characteristics of the motion segment than concerns of cell loss and replacement by non-notochordal cells. Developmental Dynamics, 2010. (c) 2010 Wiley-Liss, Inc. PMID: 20568241 [PubMed - as supplied by publisher] | | | | 
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