M2 macrophage-derived exosome-encapsulated microneedles with mild photothermal therapy for accelerated diabetic wound healing

Due to local overactive inflammatory response and impaired angiogenesis, current treatments for diabetic wounds remain unsatisfactory. M2 macrophage-derived exosomes (MEs) have shown considerable potential in biomedical applications, especially since they have anti-inflammatory properties that modulate macrophage phenotypes. However, exosome-based strategies still have limitations, such as short half-lives and instability. Herein, we develop a double-layer microneedle-based wound dressing system ( [email protected] ) by encapsulating MEs in the needle tips and polydopamine (PDA) nanoparticles in backing layer to simultaneously suppress inflammation and improve angiogenesis at the wound site. In vitro , released MEs increased macrophage polarization towards the M2 phenotype. In addition, mild heat (40 ​°C) generated by the photosensitive PMN backing layer contributed to improved angiogenesis. More importantly, [email protected] also showed promising effects in diabetic rats. The uncontrolled inflammatory response at the wound site was inhibited by [email protected] during a 14-day period; in addition, MEs and the photothermal effects produced by PMN provided a combined proangiogenic effect by improving the expression of CD31 and vWF. Collectively, this study provides a simple and efficient cell-free strategy for suppressing inflammation and promoting vascular regeneration to treat diabetic wounds.