Eight-Arm Cage-Like Nano-Unit-Based Mechanoresponsive Hydrogel Integrating Natural Pigment Probes and Nanovesicles for Promoting Wound Contraction and Healing.

Abstract

A gelatin-based hydrogel system (GPND@RP) integrating active mechanical contraction, pH-visualized monitoring, and sustained drug delivery was developed for synergistic wound healing. The hydrogel features a rigid-flexible dual-network structure, in which an eight-arm cage-like nano-unit (Octavinyl polyhedral oligomeric silsesquioxane, OV-POSS) serves as a rigid framework to restrict excessive swelling, while a thermoresponsive flexible network comprising by gelatin methacrylate, N-isopropylacrylamide, and OV-POSS undergoes sustained contraction driven by body temperature, enabling active traction and centripetal closure of wound margins. This design achieves a significant shift from traditional passive healing to an active mechanical strategy in the management of wounds. Purple cabbage-derived anthocyanins (PCA) function as a natural visual probe for real-time monitoring of wound pH (2-10), and resveratrol-loaded nanovesicles (RNVs, average particle size was 95.81 ± 5.28 nm) are released in a sustained manner to promote angiogenesis and mitigate excessive inflammation. In vivo animal experiments demonstrated that this multifunctional octahedral cage-architectured gelatin-based hydrogel achieved a 94.89% wound healing rate by day 10, versus 51.08% in the control group. Therefore, with favorable biocompatibility, adhesiveness, and photothermal properties, the GPND@RP hydrogel is a promising strategy for active wound closure and healing.