Thermoresponsive Carboxymethyl Chitosan-Based Gel Loaded with Herbal-Derived Carbon Dots for Promoting Wound Healing

The repair of chronic and infected wounds continues to present significant clinical challenges, including prolonged inflammation, impaired angiogenesis, and imbalances in the biomechanical microenvironment. This study developed an innovative thermoresponsive gel integrating Salvia miltiorrhiza-derived carbon dots (SM-CDs), designed to accelerate wound healing through a "biochemical-mechanical" synergistic regulation strategy. First, SM-CDs were synthesized via hydrothermal method. These CDs retained the triple bioactivity of S. miltiorrhiza, encompassing antimicrobial, antioxidant, and pro-angiogenic properties, thereby enhancing their interaction with biofilms and bioavailability. Second, a multistep cross-linking strategy was employed to construct a ternary gel network (denoted PCS gel) composed of N-isopropylacrylamide (NIPAM), carboxymethyl chitosan (CMCS), and sodium alginate (SA). This system demonstrated efficient drug release (67.12% cumulative release over 72 h) and mechanical contraction (83.99% volume contraction ratio) at 37 °C. These effects are attributed to the phase transition behavior of NIPAM and the electrostatic/ionic cross-linking mechanisms of CMCS/SA. In vitro and in vivo studies revealed that the SM-CDs@PCS gel promotes wound healing through a dual mechanism: (1) Biochemical modulation: suppressing oxidative stress (91% ROS scavenging rate) and inflammatory responses (TNF-α downregulated to 16.25 ± 2.69%; IL-6 downregulated to 10.49 ± 2.04%), polarizing macrophages toward the pro-repair M2 phenotype (M2/M1 ratio = 1.69 ± 0.11), and promoting angiogenesis; (2) Mechanical modulation: enhancing collagen deposition through the gel's biomechanical contraction effect, thereby accelerating wound closure. This research provides insights into the application of herbal medicine-derived CDs materials and intelligent gels for the management of hard-to-heal wounds.