Chirality-Dependent Supramolecular Biomaterials Remodeling of Scar Microenvironment via Integrin-Mediated Regulation for Hypertrophic Scars Therapy

Hypertrophic scars, characterized by excessive fibroblast activation, present significant clinical challenges. Current treatments (e.g., laser, surgery, steroids) face limitations: Surgery is costly and associated with high recurrence rates, while pharmacological interventions often induce pain and exhibit low bioavailability or efficacy. To address this, we engineered a novel chiral supramolecular biomaterial derived from L-/D-phenylalanine and D-phenylalanine (L/DP) with well-defined nanostructure and optical activity. L/DP achieved biomimetic integration and stereoselective regulating of integrin β1 (ITGβ1) in scar tissue. In vitro, LP suppressed fibroblast proliferation by downregulating ITGβ1 (72%), inhibiting FAK/PI3K/AKT signaling and TGF-β1. In vivo (rabbit ear HS model), LP reduced scar thickness (54%), collagen deposition (39%), and α-SMA expression (45%), outperforming conventional drugs by 23%. This chirality-directed strategy provides a drug-free, painless, and highly effective HS therapy via integrin-mediated remodeling of the scar microenvironment and holds substantial clinical promise.