Controlled delivery of thymosin ?4 for tissue engineering and cardiac regenerative medicine
Thymosin ?4 (T?4) is a peptide with multiple biological functions. Here, we focus on the role of T?4 in vascularization, and review our studies of the controlled delivery of T?4 through its incorporation in biomaterials. T?4 promotes vascularization through VEGF induction and AcSDKP-induced migration and differentiation of endothelial cells. We developed a collagenchitosan hydrogel for the controlled release of T?4 over 28 days. In vitro, the T?4-encapsulated hydrogel increased migration of endothelial cells and tube formation from epicardial explants that were cultivated on top of the hydrogel, compared to T?4-free hydrogel and soluble T?4 in the culture medium. In vivo, subcutaneously injected T?4-containing collagenchitosan hydrogel in rats led to enhanced vascularization compared to T?4-free hydrogel and collagen hydrogel with T?4. Furthermore, the injection of the T?4-encapsulated hydrogel in the infarct region improved angiogenesis, reduced tissue loss, and retained left ventricular wall thickness after myocardial infarction in rats.
thymosin ?4 peptide hydrogel angiogenesis heart