Selenium‐Albumin Nanoaccelerator Hydrogel Promotes Wound Healing by Antibacterial, Anti‐Inflammatory and Antioxidant along with Inhibits Scar Formation via Downregulating CD36

Abstract Wounds repairing after skin damage or diabetes remain a vast medical challenge, which often faces infection, inflammation, oxidative stress, and skin scarring. Herein, a multifunctional selenium‐albumin nanoaccelerator hydrogel (H‐Se NPs‐Gel) is constructed based on the self‐assembly of human serum albumin (HSA) with selenium nanoparticles (Se NPs) using carbomer as the carrier, it has remarkable antibacterial, anti‐inflammatory, antioxidant and inhibits scarring properties than Se NPs for wound healing. Compared with Se NPs, H‐Se NPs exhibit smaller particle sizes, exceptional stability, better antibacterial activity against common bacteria and MRSA, and superior antioxidant and anti‐inflammatory capabilities in vitro without remarkable toxicity on skin cells. Importantly, it exhibits superior efficacy to Se NPs‐Gel in accelerating the healing of full‐thickness skin defects and diabetic wounds in mice. Interestingly, in a hypertrophic scar (HTS) model, H‐Se NPs‐Gel is more effective than Se NPs‐Gel in inhibiting collagen formation to suppress scarring, which is mediated by the inhibition of CD36. The antagonistic effect of H‐Se NPs on CD36 is also proved with the CD36 overexpression model. Furthermore, H‐Se NPs‐Gel demonstrates excellent safety in mice without systemic toxicity. H‐Se NPs‐Gel is an effective and safe therapy strategy for promoting wound healing and reducing scar formation in clinic.