biostudies-literatureUnknown31Yu HWenzhou Municipal Science and Technology BureauZhejiang Provincial Health CommissionDiabetic 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 suMaterials today. Bio101585https://www.ebi.ac.uk/biostudies/studies/S-EPMC11893380biostudies-literatureTβ4-exosome-loaded hemostatic and antibacterial hydrogel to improve vascular regeneration and modulate macrophage polarization for diabetic wound treatment.PMC11893380Liu KZhang DWang BWang GChen HZhou YWang JLi LYu HLai YLi ZZhao SWang QHe YPan CChen WNi BChen YfalseTβ4-exosome-loaded hemostatic and antibacterial hydrogel to improve vascular regeneration and modulate macrophage polarization for diabetic wound treatment.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 su2025-01-01T00:00:00Z2025 Apr2025-04-26T02:50:08.112Z2025-04-06T10:34:57.827ZS-EPMC118933804007086910.1016/j.mtbio.2025.101585