(395a) Injectable Hydrogels for Tandem Cell/Gene Transplantation
Cell transplantation by direct injection is a minimally invasive approach for the treatment of many ischemic diseases including stroke, peripheral arterial disease, and myocardial infarct. For example, adipose-derived stromal cells (ASCs) have been shown to promote neovascularization in preclinical models of ischemic tissues. Unfortunately, the direct injection of ASCs into ischemic tissue is limited by low cell viability and poor cell function. The transplanted cells are exposed to strong mechanical forces during injection (which results in cell damage) and low oxygen levels after injection (which results in further cell death and compromises cell function). To overcome these challenges, we have developed a family of injectable hydrogels that protects cells from mechanical forces during injection and provides mechanical scaffolding and biochemical cues to promote long-term cell survival and potency within ischemic tissues. At room temperature, all gel formulations are weak hydrogels (Gâ?? <50 Pa) that form due to peptide-peptide heteroassembly to form a supramolecular network. These weak hydrogels undergo rapid shear-thinning to be easily hand injectable and rapid self-healing to localize transplanted cargo at the desired target site. Upon heating to 37Â°C, the hydrogels undergo a secondary crosslinking mechanism due to lower critical solution temperature (LCST) behavior. Simply tuning the weight fraction of the LCST polymer from 0-5 wt% results in hydrogels with tunable stiffness, Gâ?? ~ 100 - 1000 Pa. Current research efforts focus on tuning the biochemical and mechanical cues provided by this delivery platform to optimize the hydrogel for tandem delivery of ASCs and therapeutic gene vectors to significantly enhance the angiogenic potential of transplanted cells.