Microenvironment-responsive injectable dynamic hydrogel for sequential antioxidant and tissue regeneration therapy of radiation-induced skin injury.
This study developed a multifunctional injectable hydrogel called HCG@CDs designed to treat radiation-induced skin injury (RISI), a common complication of cancer radiotherapy. The hydrogel was constructed by cross-linking carboxymethyl chitosan (CMCS) with oxidized hyaluronic acid (OHA) conjugated to a Glycyl-L-Histidyl-L-Lysine-Copper(II) complex (GHK-Cu²⁺) via dynamic Schiff-base bonds, with carbon dots (CDs) possessing superoxide dismutase (SOD)-like activity dispersed throughout the network. The system was designed for sequential, pH-responsive drug release: CDs are rapidly released in the acidic wound environment to scavenge reactive oxygen species (ROS) and reduce early oxidative stress, while GHK-Cu²⁺ is released more gradually to promote inflammation modulation, cell migration, proliferation, and collagen deposition. Both in vitro cell-based assays and in vivo animal model experiments were conducted, with results reportedly showing reduced oxidative damage, attenuated inflammatory responses, and accelerated wound healing. Limitations include reliance on preclinical models (cell culture and animal studies), with no human clinical data presented. The translational relevance to human RISI treatment remains to be established through further clinical investigation.
Why this grade: Evidence is based entirely on in vitro cell assays and in vivo animal models, with no human subjects enrolled, limiting direct applicability to clinical conclusions.
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 2+ ) 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 2+ 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.
Educational summary of published research — not medical advice. License: cc by-nc-nd. Full text is shown only where licensing permits.