Year 1
This study aims to develop technologies to promote in vivo survival and differentiation of transplanted cells. We developed a hybrid biomaterial consisting of hyaluronic acid (HA) grafted with 6-aminocaproic acid (6ACA) moieties to improve the function of hESC-derived progenitor cells into cardiotoxin-injured skeletal muscles of NOD/SCID. The biomaterial significantly improved the survival and engraftment of transplanted cells in a dose-dependent manner. The donor cells were found to contribute to the regeneration of damaged muscle fibers and to the satellite cell (muscle specific stem cells) compartment. In another study, we have developed a cell responsive material. Specifically, we have synthesized a modified poly(ethylene glycol) (PEG) hydrogel that undergoes degradation responding to cell-secreted molecules by incorporating disulfide moieties onto the backbone of the hydrogel precursor. Our results show the disulfide-modified PEG hydrogels disintegrate seamlessly into solution in presence of cells without any external stimuli. The rate of hydrogel degradation, which ranges from hours to months, is found to be dependent upon the type of encapsulated cells, cell number, and fraction of disulfide moieties present in the hydrogel backbone. The in vivo analysis of these cell-laden hydrogels, through a dorsal window chamber and intramuscular implantation, demonstrated autonomous release of cells to the host environment.