Light-controlled sequential nanoregulators for antibacterial and anti-inflammatory effects on promoting chronic wound healing.

The wound microenvironment (WME) of sustained immune inflammatory response and bacterial infection notably impede the process of tissue repair in chronic wound healing. Herein, the sequential nanoregulator (TiC@MnO-EPL/TA, TMPT) consisting of photothermal-catalytic heterostructure grafted with positive-potential antimicrobial peptides and inflammation-suppressing polyphenols were engineered. In WME, positively charged TMPT nanoregulator adhere to bacteria and mineralize them. Under near-infrared laser triggering, TMPT efficiently generates photothermal-catalytic effect to eradicate bacteria and release anti-inflammatory drugs effectively. Subsequently, TMPT can eliminate the excessive accumulation of reactive oxygen species in WME over a long period of time and actively inhibit bacterial and inflammatory responses through drug release, thereby achieving controllable regulation of chronic WME. Based on the above superior properties and unique advantage, the sequential nanoregulator accelerated the chronic wound healing process by improving the WME to promote the proliferation and migration of fibroblasts, up-regulating vascular growth factor, and remodeling immunosuppressive cells, and maintaining the normal activity of cellular mediators. As envisioned, this work implements a comprehensive programmatic-regulatory strategy that maintains the oxidative and antioxidant homeostasis of WME while achieving efficient antibacterial and long-term anti-inflammatory properties for chronic wounds.