Programmed cell delivery from biodegradable microcapsules for tissue repair

Abstract

Injectable and resorbable hydrogels are an extremely attractive class of biomaterials. They make it possible to fill tissue defects accurately with an undoubtedly minimally invasive approach and to locally deliver cells that support repair or regeneration processes. However, their use as a cell carrier is often hindered by inadequate diffusion in bulk. A possible strategy for overcoming this transport limitation might be represented by injection of rapidly degradable cell-loaded microcapsules, so that maximum material thickness is limited by sphere radius. Here, the possibility of achieving programmable release of viable cells from alginate-based microcapsules was explored in vitro, by evaluating variations in material stability resulting from changes in hydrogel composition and assessing cell viability after encapsulation and in vitro release from microcapsules. Degradation of pure alginate microspheres was varied from a few days to several weeks by varying sodium alginate and calcium chloride concentrations. The addition of poloxamer was also found to accelerate degradation significantly, with capsule breakdown almost complete by two weeks, while chitosan was confirmed to strengthen alginate cross-linking. The presence of viable cells inside microspheres was revealed after encapsulation, and released cells were observed for all the formulations tested after a time interval dependent on bead degradation speed. These findings suggest that it may be possible to fine tune capsule breakdown by means of simple changes in material formulation and regulate, and eventually optimize, cell release for tissue repair.