|  |  |  | | | | | TE-RegenMed-StemCell feed | | | | | | | | | | | | | | | | | | The California stem cell agency and the NIH have some things in common. They both give away billions of dollars, and they both generally work outside the view of the general public.
But major differences do exist. CIRM operates on borrowed money. The NIH does not – at least nominally. CIRM operates free of legislative or meddling by the state's top official(the governor). The NIH does not. | | | | | | | | | | | | | | | | | | | | | | | | | [Nanobiotechnologies in medicine: nanodiagnostics and nanodrugs]. Biomed Khim. 2010 Jan-Feb;56(1):7-25 Authors: Archakov AI PMID: 21328908 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Cell responses and hemocompatibility of g-HA/PLA composites. Sci China Life Sci. 2011 Mar 17; Authors: Li J, Zheng W, Zheng Y, Lou X The objective of this study was to investigate the hemocompatibility and cell responses to some novel poly(L-lactide) (PLA) composites containing surface modified hydroxyapatite particles for potential applications as a bone substitute material. The surface of hydroxyapatite (HA) particles was first grafted with L-lactic acid oligomers to form grafted HA (g-HA) particles. The g-HA particles were further blended with PLA to prepare g-HA/PLA composites. Our previous study has shown significant improvement in tensile properties of these materials due to the enhanced interfacial adhesion between the polymer matrix and HA particles. To further investigate the potential applications of these composites in bone repair and other orthopedic surgeries, a series of in vitro and in vivo experiments were conducted to examine the cell responses and hemocompatibility of the materials. In vitro experiments showed that the g-HA/PLA composites were well tolerated by the L-929 cells. Hemolysis of the composites was lower than that of pure PLA. Subcutaneous implantation demonstrated that the g-HA/PLA composites were more favorable than the control materials for soft tissue responses. The results suggested that the g-HA/PLA composites are promising and safe materials with potential applications in tissue engineering. PMID: 21416229 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | The use of whole organ decellularization for the generation of a vascularized liver organoid. Hepatology. 2011 Feb;53(2):604-17 Authors: Baptista PM, Siddiqui MM, Lozier G, Rodriguez SR, Atala A, Soker S A major roadblock to successful organ bioengineering is the need for a functional vascular network within the engineered tissue. Here, we describe the fabrication of three-dimensional, naturally derived scaffolds with an intact vascular tree. Livers from different species were perfused with detergent to selectively remove the cellular components of the tissue while preserving the extracellular matrix components and the intact vascular network. The decellularized vascular network was able to withstand fluid flow that entered through a central inlet vessel, branched into an extensive capillary bed, and coalesced into a single outlet vessel. The vascular network was used to reseed the scaffolds with human fetal liver and endothelial cells. These cells engrafted in their putative native locations within the decellularized organ and displayed typical endothelial, hepatic, and biliary epithelial markers, thus creating a liver-like tissue in vitro. CONCLUSION: These results represent a significant advancement in the bioengineering of whole organs. This technology may provide the necessary tools to produce the first fully functional bioengineered livers for organ transplantation and drug discovery. PMID: 21274881 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Influence of PDGF-AB on Tissue Development in Autologous Platelet-Rich Plasma Gels. Tissue Eng Part A. 2011 Mar 17; Authors: Wirz S, Dietrich M, Flanagan TC, Bokermann G, Wagner W, Schmitz-Rode T, Jockenhoevel S Fibrin-based scaffolds are widely used in tissue engineering. We postulated that the use of platelet-rich plasma (PRP) in contrast to platelet-poor plasma (PPP) and pure fibrinogen as the basic material leads to an increased release of autologous PDGF-AB (platelet-derived growth factor), which may have a consequent positive effect on tissue development. Therefore, we evaluated the release of PDGF-AB during the production process and the course of PDGF release during cultivation of plasma gels with and w/o platelets. The influence of PDGF-AB on the proliferation rate of human umbilical cord artery smooth muscle cells (HUASMCs) was studied using XTT assay. The synthesis of extracellular matrix (ECM) by HUASMCs in plasma- and fibrin gels was measured using hydroxyproline assay. The use of PRP led to an increase in autologous PDGF-AB release. Furthermore, the platelet-containing plasma gels showed a prolonged release of growth factor during cultivation. Both PRP and PPP gels had a positive effect on the production of collagen. However, PDGF-AB as a supplement in medium and in pure fibrin gel had neither an effect on cell proliferation nor on the collagen synthesis rate. This observation may be due to an absence of PDGF receptors in HUASMCs as determined by flow cytometry. In conclusion, although the prolonged autologous production of PDGF-AB in PRP gels is possible, the enhanced tissue development by HUASMCs within such gels is not PDGF-related. PMID: 21413900 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Designing a tubular matrix of oriented collagen fibrils for tissue engineering. Acta Biomater. 2011 Mar 14; Authors: Lai ES, Anderson CM, Fuller GG A scaffold composed entirely of an extracellular matrix component, such as collagen, with cellular level control can be highly desirable for applications in tissue engineering. In this article, we introduce a novel, straightforward flow processing technique that fabricates a small-diameter tubular matrix constructed of anisotropic collagen fibrils. Scanning electron microscopy confirmed the uniformed alignment of the collagen fibrils and subsequent matrix-induced alignment of human fibroblasts. The uniform alignment of the fibroblasts along the collagen fibrils demonstrated the ability of the aligned fibrils to successfully dictate the directional growth of human fibroblasts through contact guidance. Various non-cytotoxic cross-linking techniques were also conducted on the collagen conduit to enhance the conduit's mechanical properties. Tensile testing and burst pressure were the two types of measurements performed to characterize the mechanical integrity of the conduit. The mechanical characterization of the cross-linked collagen conduits identified the 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride cross-linking as the most promising technique to reinforce the native collagen's mechanical properties. An oriented conduit of biocompatible material has been fabricated with decent mechanical strength and at a small-diameter scale, which is especially applicable in engineering cardiovascular tissues and nerve grafts. PMID: 21414424 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Multilayered Microspheres for the Controlled Release of Growth Factors in Tissue Engineering. Biomacromolecules. 2011 Mar 17; Authors: Go DP, Gras SL, Mitra D, Nguyen TH, Stevens GW, Cooper-White JJ, O'Connor AJ Tissue regeneration may be stimulated by growth factors but to be effective, this delivery must be sustained and requires delivery vehicles that overcome the short half-life of these molecules in vivo. One promising approach is to couple growth factors to the biomaterial surface so that they are readily bioavailable. Here the layer-by-layer process was used to construct a multilayered polyelectrolyte delivery system on the surface of poly(lactic-co-glycolic) acid constructs. The system was first optimized on a planar surface before translation to a 3D microsphere system. The layers incorporated heparin to facilitate the loading of basic fibroblast growth factor and increase growth factor stability. Cross-linked capping layers also reduced any burst release. The model growth factor was released in a sustained manner and stimulated significantly higher cell proliferation in vitro on release compared with the addition of the growth factor heparin complex free in solution, demonstrating the promise of this approach. PMID: 21413682 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates. Eur Heart J. 2011 Mar 17; Authors: Weber B, Scherman J, Emmert MY, Gruenenfelder J, Verbeek R, Bracher M, Black M, Kortsmit J, Franz T, Schoenauer R, Baumgartner L, Brokopp C, Agarkova I, Wolint P, Zund G, Falk V, Zilla P, Hoerstrup SP Aims A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. Methods and results Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 ± 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue. Conclusion Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prostheses. PMID: 21415068 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Highly Extensible, Tough, and Elastomeric Nanocomposite Hydrogels from Poly(ethylene glycol) and Hydroxyapatite Nanoparticles. Biomacromolecules. 2011 Mar 17; Authors: Gaharwar AK, Dammu SA, Canter JM, Wu CJ, Schmidt G Unique combinations of hard and soft components found in biological tissues have inspired researchers to design and develop synthetic nanocomposite gels and hydrogels with elastomeric properties. These elastic materials can potentially be used as synthetic mimics for diverse tissue engineering applications. Here we present a set of elastomeric nanocomposite hydrogels made from poly(ethylene glycol) (PEG) and hydroxyapatite nanoparticles (nHAp). The aqueous nanocomposite PEG-nHAp precursor solutions can be injected and then covalently cross-linked via photopolymerization. The resulting PEG-nHAp hydrogels have interconnected pore sizes ranging from 100 to 300 nm. They have higher extensibilities, fracture stresses, compressive strengths, and toughness when compared with conventional PEO hydrogels. The enhanced mechanical properties are a result of polymer nanoparticle interactions that interfere with the permanent cross-linking of PEG during photopolymerization. The effect of nHAp concentration and temperature on hydrogel swelling kinetics was evaluated under physiological conditions. An increase in nHAp concentration decreased the hydrogel saturated swelling degree. The combination of PEG and nHAp nanoparticles significantly improved the physical and chemical hydrogel properties as well as some biological characteristics such as osteoblast cell adhesion. Further development of these elastomeric materials can potentially lead to use as a matrix for drug delivery and tissue repair especially for orthopedic applications. PMID: 21413708 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Hypoxia and adipose-derived stem cell-based tissue regeneration and engineering. Expert Opin Biol Ther. 2011 Mar 18; Authors: Zachar V, Duroux M, Emmersen J, Rasmussen JG, Pennisi CP, Yang S, Fink T Introduction: Realization that oxygen is one of the key regulators of development and differentiation has a profound significance on how current cell-based and tissue engineering applications using adipose-derived stem cells (ASCs) can be further improved. Areas covered: The article provides an overview of mechanisms of hypoxic responses during physiological adaptations and development. Furthermore, a synopsis of the hypoxic responses of ASCs is provided, and this information is presented in context of their utility as a major source of stem cells across the regenerative applications explored to date. Expert opinion: The reader will obtain insight into a highly specific area of stem cell research focusing on ASCs and hypoxia. In order to enhance the level of comprehension, a broader context with other stem cell and experimental systems is provided. It is emphasized that the pericellular oxygen tension is a critical regulatory factor that should be taken into account when devising novel stem cell-based therapeutic applications along with other parameters, such as biochemical soluble factors and the growth substrates. PMID: 21413910 [PubMed - as supplied by publisher] | | | | | | | | | | | | | | | | | | | | | | | | | Vitamin E triggers poly(2-hydroxyethyl methacrylate) (PHEMA) embolic potential: a proposed application for endovascular surgery. J Biomater Sci Polym Ed. 2011;22(4-6):641-50 Authors: Renò F, Traina V, Gatti S, Cannas M Poly(2-hydroxyethyl methacrylate) (PHEMA) is a biocompatible polymer used as embolizing agent for endovascular surgery. Blending of PHEMA with a hydrophobic and anti-oxidant agent, Vitamin E (Vit.E, 0.1-10%, w/v), modified PHEMA's haemocombatibility, evaluated measuring wettability, plasma protein adsorption along with whole blood coagulation time. The presence of Vit.E increases PHEMA's hydrophobicity and plasma protein adsorption (in particular albumin and Immunoglobulin G), while it also accelerates blood clot formation. These effects are developed due to a combination of issues such as surface hydrophobicity and plasma protein adsorption induced by the presence of Vit.E, suggesting that Vit.E blending could improve the use of PHEMA as embolizing agent. PMID: 20566049 [PubMed - indexed for MEDLINE] | | | | | | | | | | | | | | | | | | | | | | | | | Cell-laden microengineered pullulan methacrylate hydrogels promote cell proliferation and 3D cluster formation. Soft Matter. 2011 Jan 1;7(5):1903-1911 Authors: Bae H, Ahari AF, Shin H, Nichol JW, Hutson CB, Masaeli M, Kim SH, Aubin H, Yamanlar S, Khademhosseini A The ability to encapsulate cells in three-dimensional (3D) environments is potentially of benefit for tissue engineering and regenerative medicine. In this paper, we introduce pullulan methacrylate (PulMA) as a promising hydrogel platform for creating cell-laden microscale tissues. The hydration and mechanical properties of PulMA were demonstrated to be tunable through modulation of the degree of methacrylation and gel concentration. Cells encapsulated in PulMA exhibited excellent viability. Interestingly, while cells did not elongate in PulMA hydrogels, cells proliferated and organized into clusters, the size of which could be controlled by the hydrogel composition. By mixing with gelatin methacrylate (GelMA), the biological properties of PulMA could be enhanced as demonstrated by cells readily attaching to, proliferating, and elongating within the PulMA/GelMA composite hydrogels. These data suggest that PulMA hydrogels could be useful for creating complex, cell-responsive microtissues, especially for applications that require controlled cell clustering and proliferation. PMID: 21415929 [PubMed - as supplied by publisher] | | | | | | | | | |  | |  | |  |
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