Controlled delivery of thymosin β4 for tissue engineering and cardiac regenerative medicine

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