Abstract
Diabetic wounds often exhibit delayed healing due to compromised vascular function and intensified inflammation. In this study, we overexpressed Thymosin β4 (Tβ4) in Adipose-Derived Stem Cells (ADSCs) to produce Exosomes (Exos) rich in Tβ4. We then utilized a dual photopolymerizable hydrogel composed of Hyaluronic Acid Methacryloyl (HAMA) and Poly-L-lysine Methacryloyl (PLMA) for the sustained release of Tβ4-Exos on diabetic wounds. The results showed that Tβ4-Exos could stimulate angiogenesis and collagen synthesis, and mitigate inflammation in diabetic wounds by promoting the polarization of M1-type macrophages and inhibiting that of M2-type macrophages. Furthermore, Tβ4-Exos was found to activate the PI3K/AKT/mTOR/HIF-1a signaling pathway, thereby enhancing vascular proliferation. In summary, the sustained release of Tβ4-Exos in HAMA-PLMA (HP) hydrogel and the management of inflammation through the upregulation of the HIF-1a pathway and modulation of macrophage polarization in vascular proliferation significantly accelerated the healing process of diabetic wounds.