Controlled release of thymosin β4 from injected collagen-chitosan hydrogels promotes angiogenesis and prevents tissue loss after myocardial infarction

Aims: Acute myocardial infarction (MI) leads to fibrosis and severe left ventricular wall thinning. Enhancing vascularization within the infarct reduces cell death and maintains a thick left ventricular wall, which is essential for proper cardiac function. Here, we evaluated the controlled delivery of thymosin beta 4 (T beta 4), which supports cardiomyocyte survival by inducing vascularization and upregulating Akt activity, in the treatment of MI. Materials & methods: We injected collagen chitosan hydrogel with controlled release of T beta 4 into the infarct after performing left anterior descending artery ligation in rats. Results: T beta 4-encapsulated hydrogel (thymosin) significantly reduced tissue loss post-MI (13 +/- 4%), compared with 58 +/- 3% and 30 +/- 8% tissue loss for no treatment (MI only) and T beta 4-free hydrogel (control). Significantly more Factor VIII-positive blood vessels with diameter >50 mu m were in the thymosin group compared with both MI only and control (p < 0.0001), showing T beta 4-induced vascularization. Wall thickness was positively correlated with the mature blood vessel density (r = 0.9319; p < 0.0001). Conclusion: Controlled release of T beta 4 within the infarct enhances angiogenesis and presence of cardiomyocytes that are necessary for cardiac repair.