Microenvironment-responsive injectable dynamic hydrogel for sequential antioxidant and tissue regeneration therapy of radiation-induced skin injury.

Yu, Xiaorui; Yang, Tingyu; Bei, Zhongwu; Liu, Jie; Song, Ying; Wang, Qiang; Li, Jianan; Liang, Shiyu et al. · Bioact Mater · 2026

basic_science · Level V

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Abstract

Radiotherapy is essential for cancer treatment, yet radiation-induced skin injury (RISI) remains a major clinical challenge due to reactive oxygen species (ROS) accumulation, metabolic dysregulation, and the limited efficacy of single-modality therapies in modulating the oxidative-inflammatory microenvironment. To overcome this limitation, we have developed a multifunctional injectable hydrogel, HCG@CDs, by cross-linking biocompatible carboxymethyl chitosan (CMCS) with oxidized hyaluronic acid (OHA) conjugated to the Glycyl-L-Histidyl-L-Lysine-Copper(II) complex (GHK-Cu <math xmlns="http://www.w3.org/1998/Math/MathML"><msup><mrow></mrow> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </math> ) via dynamic Schiff-base linkages. Carbon dots (CDs) possessing superoxide dismutase (SOD)-like activity are uniformly dispersed within this three-dimensional dynamic network, creating an integrated platform for full-cycle therapy. The system exhibits intelligent, pH-responsive release behavior, whereby CDs are rapidly liberated in the acidic wound microenvironment to efficiently scavenge ROS and mitigate early-stage oxidative stress. Subsequently, GHK-Cu <math xmlns="http://www.w3.org/1998/Math/MathML"><msup><mrow></mrow> <mrow><mn>2</mn> <mo>+</mo></mrow> </msup> </math> is released in a sustained manner to synergistically promote tissue repair by modulating inflammation, enhancing cell migration and proliferation, and facilitating collagen deposition. In vitro and in vivo evaluations have confirmed that the HCG@CDs hydrogel effectively alleviates radiation-induced oxidative damage and inflammatory responses, significantly accelerating the healing of skin wounds. Overall, this multifunctional hydrogel demonstrates great potential in accelerating the healing of RISI through multi-target synergistic regulation, highlighting its significant promise for clinical wound management and skin regeneration.