Cell-free adipose extracellular vesicle glue ameliorates hypertrophic scars by suppressing engrailed-1 expression

作者：Dan Jin, Zerou Zhang, Bingshuai Jing, Xin Zhao, Zhiye Li, Jin Shi, Shanluo Zhou, Weiwei Guo, Yilong Tian, Liang Kong, Wenhao Zhou, Fuwei Liu, Yunpeng Li · 发表于：Materials & Design · 年份：2026 · DOI：10.1016/j.matdes.2026.116722 · 研究领域：Dermatologic Treatments and Research、Wound Healing and Treatments、Extracellular vesicles in disease

Hypertrophic scars remain a major clinical challenge because of excessive fibroblast activation and aberrant extracellular matrix deposition. Although adipose-derived extracellular vesicles (EVs) have shown therapeutic promise, their clinical translation is limited by complex cell expansion and purification procedures. Here, we report an injectable, viscoelastic, cell-free adipose-derived extracellular vesicle-rich glue (cfAEG) fabricated through mechanical emulsification and low-speed centrifugation, enabling rapid preparation without in vitro cell culture or ultracentrifugation. Rheological analyses demonstrated that cfAEG possesses favorable injectability and gel-like mechanical properties suitable for local administration. In vitro, cfAEG markedly inhibited the proliferation and myofibroblastic differentiation of human dermal fibroblasts, accompanied by reduced expression of fibrotic markers. In vivo, local injection of cfAEG significantly attenuated hypertrophic scar formation in both the rabbit ear and minipig skin models, outperforming saline controls and showing efficacy comparable to that of triamcinolone acetonide. Mechanistically, cfAEG consistently suppressed the expression of Engrailed-1 (EN1), a key transcriptional regulator of profibrotic fibroblast activation, thereby reducing collagen deposition and α–SMA expression. Collectively, this study presents cfAEG as a clinically feasible, injectable, EV-rich biomaterial that modulates fibroblast fate and scar remode...