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Design of novel biomaterials for stem cell differentiation and transplantation Stem cells differentiate along different lineages in the context of complex three-dimensional (3D) tissue constructs, where the extracellular matrix (ECM) and different growth factors play an important role in this process. The 3D ECM provides structural support for higher level of tissue organization and remodeling. Recent data show significant differences in the differentiation profile of stem cells cultured in a 3D versus 2D system. We are designing biomaterials which provide several different types of information to stem cells, with the purpose of controlling their differentiation. In this platform we are developing or modifying natural or synthetic polymers and to characterize their physico-chemical and biological properties. The major goal of this research is to identify biomaterials that will improve the differentiation of stem cells in a specific cell lineage and to obtain fundamental knowledge regarding the effect of chemistry, mechanics and three-dimensional organization of the scaffold in terms of stem cell differentiation. Another area of interest in the group is to create 3D matrices (scaffolds) to improve the grafting and functionality of the delivered stem cells in vivo.
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Biomaterials with antimicrobial properties A major problem associated with the implantation of biomedical devices in the human body is the inherent risk of microbial infections. We are developing novel and more effective strategies to control microbial infections by developing coating technologies to immobilize antimicrobial agents. Recently, we reported an antifungal material, termed amphogel, formed by a hydrogel and an antifungal agent-amphotericin B- physically adsorbed that was able to kill fungi within 2 h of contact and could be reused for at least 53 days without losing its effectiveness against Candida albicans (Zumbuhel et al., PNAS 2007). |
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Endothelial-like cells isolated from human embryonic stem cells (hESCs) and cultured on matrigel form cord-like structures before (A) and after implantation in nude mice (B). Expression of endothelial marker CD31 (C) on hESC aggregates encapsulated in dextran-based hydrogels containing the cell-adhesion peptide RGD. |
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Biological activity of Amphogel. SEM photographs from the surface of amphogel (A), or dextran gel without amphotericin B (B) incubated with C. albicans that were implanted into mice and then removed after 5 days. Amphogels did not have Candida biofilm (A), while dextran gels without AmB (B) were covered with a large number of Candida cells (yellow) mixed with white blood cells (magenta). |
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Biomaterials and Stem Cell-Based Therapeutics |