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Vol. 18 (2026)

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

https://doi.org/10.1007/s40820-026-02180-1
Xueqian Wang
State Key Lab of Metal Matrix Composites, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Chengyao Han
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
Hongrui Shan
Research Center of Precision Sensing and Control, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, People’s Republic of China
Jinjin Li
National Key Laboratory of Advanced Micro and Nano Manufacture Technology, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Beibei Wu
State Key Lab of Metal Matrix Composites, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China
Yixin Zhang
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
Ke Li
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China
Chuanliang Feng
State Key Lab of Metal Matrix Composites, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, People’s Republic of China

Corresponding Author: Chuanliang Feng

clfeng@sjtu.edu.cn

Nano-Micro Letters, Vol. 18 (2026), Article Number: 343

Abstract

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.


Highlights:
1 A chiral supramolecular biomaterial (L-/D-phenylalanine and D-phenylalanine, L/DP) is rationally designed with defined chiral nanostructure and optical activity for hypertrophic scars (HS) therapy.
2 The LP biomaterial significantly inhibited excessive fibroblast proliferation by downregulating ITGβ1 by 72%, suppressing downstream FAK/PI3K/AKT signaling and TGF-β1 activation.
3 In rabbit HS models, LP outperforms drug and DP, reducing scar thickness by 54%, collagen deposition by 39%, and α-SMA expression by 45%, offering an effective, painless, drug-free HS therapy strategy.

Keywords

Chirality Biomaterial Hypertrophic scars Integrin Fibroblasts
Wang, Xueqian, Chengyao Han, Hongrui Shan, Jinjin Li, Beibei Wu, Yixin Zhang, Ke Li, and Chuanliang Feng. 2026. “Chirality-Dependent Supramolecular Biomaterials Remodeling of Scar Microenvironment via Integrin-Mediated Regulation for Hypertrophic Scars Therapy”. Nano-Micro Letters 18 (April):343. https://doi.org/10.1007/s40820-026-02180-1.
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