Bispecific antibody engineered extracellular vesicles redirect T cells to prevent postoperative epidural fibrosis
- Shanwei Ye
- Qian Xu
- Yong Xu
- Hui Lu
- Zhenfeng Liu
- Jianfeng Guo
- Yichuan Li
- Wei Wang
- Jun Ran
- Xiaohua Zhu
- Dongling Zhu
- Wei Wu
- Zechuan Yang
- Shiqi Gu
- Feng Li
- Lugui Qiu
- Ellen Puré
- Vijay G. Bhoj
- Liang Huang
- Wei Xiong
- Zheng Zhang
2026-06-27
Epidural fibrosis (EF) is a frequent and debilitating complication that impairs recovery following spinal surgery, yet effective targeted therapies are lacking. Here we observe enrichment of FAP⁺ fibroblasts at surgical sites in patients after laminectomy. To therapeutically target this subset, we develop bispecific antibody–decorated extracellular vesicles (BsAb EVs), which redirect endogenous T cells to eliminate FAP⁺ fibroblasts in situ. In a preclinical model, BsAb EVs selectively eliminate pathogenic fibroblasts, reduce fibrotic collagen accumulation, and prevent the development of postoperative epidural fibrosis without detectable systemic toxicity under the tested conditions. Single-cell RNA sequencing reveals that FAP⁺ fibroblasts represent a transcriptionally distinct subset from α-SMA⁺ myofibroblasts, characterized by enhanced extracellular matrix remodeling and TGF-β production. Together, these findings highlight a critical stromal subset in EF pathogenesis and position BsAb EVs as a promising immunotherapeutic strategy for targeting pathogenic stromal cells in fibrotic and tissue-remodeling disorders.