文献类型：期刊文献

英文题名：Treatment of heterotopic ossification via inhibiting the MMP-2/CDH5 axis through oral delivery of network pharmacology-predicted Chinese medicine

作者：Huang, Junchao[1];An, Jinxi[1];He, Le[2];Wang, Huajun[3];Hong, Jiachang[1];Bu, Ziheng[1];Zhang, Xudong[1];Liu, Wei[1];Wu, Tingyu[1];Wang, Seng[4];Zhu, Wei[1];Li, Yuhui[4];Wan, Jixian[4];Sun, Min[2];Du, Jianzhong[1,2];Wu, Peng[1]

机构：[1]Tongji Univ, Shanghai East Hosp, Sch Med, Dept Sports Med, Shanghai 200120, Peoples R China;[2]East China Univ Sci & Technol, Sch Mat Sci & Engn, Shanghai 200237, Peoples R China;[3]Jinan Univ, Affiliated Hosp 1, Guangzhou Key Lab Precis Orthoped & Regenerat Med, Dept Sports Med,Guangdong Prov Key Lab Speed Capab, Guangzhou 510630, Guangdong, Peoples R China;[4]Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Dept Orthoped, Shanghai 200072, Peoples R China

年份：2026

卷号：38

外文期刊名：MATERIALS TODAY BIO

收录：;EI(收录号：20261820617746);WOS:【SCI-EXPANDED(收录号:WOS:001759875700001)】；

基金：The authors acknowledge the financial support from National Natural Science Foundation of China (22335005, 22305177) , Shanghai Rising-Star Program (Sailing, 23YF1433000) , Postdoctoral Fellowship Program of CPSF (GZC20250042) , China University Industry-University-Research Innovation Fund (2024hr012) , the Shanghai Science and Technology Commission Science and Technology Innovation Action Plan Domestic Science and Technology Cooperation Project (24010701900) , Shanghai Hospital Development Center Foundation (SHDC22024242) , Jiangxi Province Natural Science Foundation General Project (20252BAC240483) , Program for Research-oriented Physician of Shanghai Tenth People's Hospital (2023YJXYSA004) , the Fundamental Research Funds for the Cornell University. We thank Fig-draw for supporting the preparation of some figures.

语种：英文

外文关键词：Oral hydrogel; Heterotopic ossification; Matrix Metalloproteinase-2; Forsythoside A; Network pharmacology

摘要：Heterotopic ossification (HO) is characterized by ectopic bone formation in soft tissues such as tendons, with an incidence exceeding 30% in high-risk populations. Currently, no targeted therapeutic options are available. In this study, matrix metalloproteinase-2 (MMP-2) was identified as a critical promoter of HO by mediating the degradation of vascular endothelial Cadherin 5 (CDH5), thereby enhancing vascular permeability and facilitating inflammatory cell infiltration. Through network pharmacology analysis, Forsythoside A (FA), a compound derived from the traditional Chinese medicine Forsythia, was predicted to act as a potential MMP-2 inhibitor. However, the clinical application of FA is hindered by its narrow therapeutic window. To overcome this limitation, we developed an intestinal enzyme-responsive hydrogel (FA@SD-hydrogel) for targeted delivery of FA. This delivery system significantly improved the bioavailability of FA and enabled sustained release, thereby reducing the required dosage and associated toxicity. Comprehensive in vivo and in vitro experiments demonstrated that FA@SD-hydrogel achieved superior therapeutic efficacy against HO with reduced toxicity. By inhibiting MMP-2, the hydrogel effectively suppressed ectopic bone formation, reduced local vascular permeability, and reversed the inflammatory microenvironment driven by M1 macrophages, ultimately reprogramming the osteogenic niche. Together, these findings underscore the critical role of the MMP-2/CDH5 axis in HO pathogenesis and establish a targeted therapeutic strategy via FA@SD-hydrogel through the integration of network pharmacology and biomaterial engineering.