Glucopeptide Superstructure Hydrogel Promotes Surgical Wound Healing Following Neoadjuvant Radiotherapy by Producing NO and Anti‐cellular Senescence

Abstract Neoadjuvant radiotherapy (NAC), a preoperative intervention regimen for reducing the stage of primary tumors and surgical margins, has gained increasing attention in the past decade. However, radiation‐induced skin damage during neoadjuvant radiotherapy exacerbates surgical injury, remarkably increasing the risk of refractory wounds and compromising the therapeutic effects. Radiation impedes wound healing by increasing the production of reactive oxygen species (ROS) and inducing cell apoptosis and senescence. In this study, we prepared a self‐assembling peptide (R‐peptide) and hyaluronic acid (HA)‐based and cordycepin (Cor)‐loaded superstructure hydrogel (CHRgel) for surgical incision healing after neoadjuvant radiotherapy. Results showed that (i) R‐peptide co‐assembled with HA to form biomimetic fiber bundle microstructure, in which R‐peptide drives the assembly of single fiber through π‐π stacking and other forces and HA, as a single fiber adhesive, facilitates bunching through electrostatic interactions. (ii) The biomimetic superstructure contributes to the adhesion and proliferation of cells in the surgical wound. (iii) Aldehyde‐modified HA provides dynamic covalent binding sites for cordycepin to achieve responsive release, inhibiting radiation‐induced cellular senescence. (iv) Arginine in the peptides provides antioxidant capacity and a substrate for the endogenous production of nitric oxide (NO) to promote wound healing and angiogenesis of surgical wounds after neoadjuvant radiotherapy. This article is protected by copyright. All rights reserved