Stimuli Responsive Delivery Vehicles for Cardiac Microtissue Transplantation

Cell transplantation has emerged as the most promising therapy for restoring the scarred myocardium in the treatment of heart failure. However, clinical efficacy of (stem) cell therapies is still limited by poor retention rate and survival of injected cells in the ischemic tissue. Here we present a new strategy to deliver microtissues in the treatment of heart dysfunction in order to improve the retention, survival, and integration of the delivered cells. For this purpose, we developed stimuli responsive biodegradable polymer constructs consisting of a thin film of thermosensitive hydrogel coupled to a thin film of non-responsive polymer. Due to the temperature responsive swelling behavior of the hydrogel layer, the bilayer polymer constructs can roll or unroll at will. Therefore they can potentially be used for efficient encapsulation and protection of cell clusters during delivery, while under physiological conditions, the constructs, named cell wraps, can unroll and expose the delivered microtissue to the ischemic tissue.