Fatemeh Zabihi, Siamak Beyranvand, Zahra Mohammadi, Zahra Mohammadi, Mahtab Zeinivand, Omid Dezfoulian, Ghasem Farjanikish, Katharina Achazi, Cheng Chong, Fiorenza Rancan, Annika Vogt, Sarah Hedtrich, Hamid Reza Mohammadi, Rainer Haag, Mohsen Adeli
Diabetic wounds remain a major clinical challenge due to persistent inflammation and impaired tissue regeneration. In this study, we report the scalable synthesis of hyperbranched polyglycerol-b-poly(2-ethyl-2-oxazoline) star copolymers bearing terminal arginine groups (hPG-b-PEO-Arg), designed to self-assemble into nanoscale hydrocolloids (70-200 nm) in aqueous media, driven by the distinct hydrophilicity of the polymer blocks. These hydrophilic nanoparticles penetrate damaged wound tissue, facilitating in vivo healing of diabetic wounds in rats (n = 10). The copolymers were synthesized on a 300 g scale via ring-opening polymerization and demonstrated excellent cytocompatibility with primary human fibroblasts and keratinocytes at concentrations up to 15 mg/mL. In vivo, hPG-b-PEO-Arg treatment accelerated wound closure and promoted collagen-rich tissue regeneration without evidence of systemic toxicity, oxidative stress, or skin irritation. The combination of scalable synthesis, high biocompatibility, and intrinsic hydrocolloid-forming capability positions hPG-b-PEO-Arg as a promising platform for chronic wound management and broader biomedical applications.