A 3R (remove-remodel-repair)-Integrated Self-Assembled Chlorella-Gelatin-PEG Hydrogel for Diabetic Wound Healing

Diabetic wound healing remains a critical clinical challenge due to persistent bacterial infections, oxidative stress, and chronic inflammation. Inspired by the principles of traditional Chinese medicine, we developed a multifunctional hydrogel (CPGel) via solvent-driven self-assembly of bioactive Chlorella extracts, gelatin, and polyethylene glycol (PEG). The CPGel synergizes the 3R strategy: (1) Remove-complete eradication of E. coli and S. aureus via intrinsic antibacterial activity; (2) Remodel-65 % ROS scavenging and immunomodulation by polarizing macrophages from proinflammatory M1 to anti-inflammatory M2 phenotypes to resolve chronic inflammation; and (3) Repair-accelerated tissue regeneration via 9-fold angiogenesis (α-SMA) and 2-fold collagen I deposition. Mechanically robust (compressive strength: 4.16 MPa; tensile strength: 627 kPa) and antifreezing (-100 °C), CPGel demonstrated exceptional transparency and adhesion, ensuring seamless integration with wound sites. In diabetic mice, CPGel achieved 100 % wound closure within 21 days, surpassing controls (73 %), while promoting neovascularization and hair follicle regeneration. This study bridges traditional herbal medicine with advanced biomaterial engineering, offering a scalable, toxin-free platform that addresses the triad of diabetic wound pathogenesis. By harmonizing the 3R strategy-Remove, Remodel, and Repair-CPGel represents a paradigm shift in chronic wound management, with high potential for clinical translation and sustainable therapeutic design.