Mechanically Reinforced In Situ Injectable Hydrogels Integrating MXene Nanosheet-Driven Photothermal Antibacterial and Immunomodulatory Capacities for Enhanced Diabetic Wound Healing
Yiyu Wang, Chunqing Niu, Yushan Li, Hangqi Shu, Jian Shi, Ick Soo Kim, Xin Zheng, Xinyu Wang, Kai Zhao
Abstract
Recently, injectable hydrogels with synergistic antioxidant and antimicrobial properties have emerged as promising candidates for diabetic wound treatment. However, the outstanding flowability of injectable hydrogels often compromises their mechanical properties, and few systems provide the multiple synergistic cues needed for rapid healing. Here, we designed an injectable dual-cross-linked hydrogel (SCO@M) that integrated MXene nanosheets (NNs) to furnish simultaneous photothermal antibacterial activity and intrinsic immunomodulation. At first, a dynamic network was formed in situ through reversible Schiff-base and hydrogen bonds among oxidized hyaluronic acid, carboxymethyl chitosan, and methacrylated silk fibroin (SF-MA), endowing the precursor with shear-thinning behavior and easy injectability. Brief UV exposure then photo-cross-linked residual SF-MA to form a covalent secondary network, markedly reinforcing mechanical strength without sacrificing injectability. Importantly, the incorporation of MXene NNs not only enhanced the mechanical properties but also imparted robust photothermal antibacterial activity under near-infrared irradiation alongside excellent reactive oxygen species (ROS) scavenging capacity. Both in vitro and in vivo results demonstrated that SCO@M normalized the inflammatory response by modulating the M1/M2 macrophage balance via IL-17/MAPK/TNF-α pathways, enhanced angiogenesis and cell migration, and accelerated wound closure in diabetic rats, representing a promising strategy for chronic wound healing.