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

Thymosin β4 (Tβ4) is a peptide with multiple biological functions. Here, we focus on the role of Tβ4 in vascularization, and review our studies of the controlled delivery of Tβ4 through its incorporation in biomaterials. Tβ4 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 Tβ4 over 28 days. In vitro, the Tβ4-encapsulated hydrogel increased migration of endothelial cells and tube formation from epicardial explants that were cultivated on top of the hydrogel, compared to Tβ4-free hydrogel and soluble Tβ4 in the culture medium. In vivo, subcutaneously injected Tβ4-containing collagen-chitosan hydrogel in rats led to enhanced vascularization compared to Tβ4-free hydrogel and collagen hydrogel with Tβ4. Furthermore, the injection of the Tβ4-encapsulated hydrogel in the infarct region improved angiogenesis, reduced tissue loss, and retained left ventricular wall thickness after myocardial infarction in rats.