文献类型：期刊文献

英文题名：A triple-coated ligament graft to facilitate ligament-bone healing by inhibiting fibrogenesis and promoting osteogenesis

作者：Li, Yamin[1];Guo, Ximeng[2];Dong, Shikui[1];Zhu, Tonghe[1];Chen, Yunsu[3];Zhao, Song[1];Xie, Guoming[1];Jiang, Jia[1];He, Hongyan[2];Liu, Changsheng[2];Zhao, Jinzhong[1]

机构：[1]Shanghai Jiao Tong Univ, Dept Sports Med, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China;[2]East China Univ Sci & Technol, Engn Res Ctr Biomed Mat, Minist Educ, Shanghai 200237, Peoples R China;[3]Shanghai Jiao Tong Univ, Dept Joint Surg, Affiliated Peoples Hosp 6, 600 Yishan Rd, Shanghai 200233, Peoples R China

年份：2020

卷号：115

起止页码：160

外文期刊名：ACTA BIOMATERIALIA

收录：;EI(收录号：20215111341473);WOS:【SCI-EXPANDED(收录号:WOS:000577511200012)】；

基金：This study was supported by National Key Research and Development Program of China (Grant No. 2018YFC1106200, 2018YFC1106202), the National Natural Science Foundation of China (Grant No. 81871753, 81772341, 31570971), the New Frontier Multi-center Project of Shenkang Hospital Development Center of Shanghai (Grant No. SHDC12017121), the Collaborative Innovation Transformation Project of Shanghai Jiao Tong University School of Medicine (Grant No. TM201726), Shanghai International S&T Cooperation Project (Grant No. 18520710100), and the Doctor Innovation Project of Shanghai Jiao Tong University School of Medicine (BXJ201839).

语种：英文

外文关键词：Nano-coating; Macrophage polarization; Anti-fibrogenesis; Osteogenesis; Ligament-bone healing

摘要：Absence of ligament-bone healing due to poor bioactivity and hyperplasia of fibrous tissue caused by immune response severely impairs ligament grafts' functional duration in anterior cruciate ligament (ACL) reconstruction. While osteogenic modification is a popular technique for promoting ligament-bone integration, inadequate osseointegration remains a common experience, due to occupying fibrous hyperplasia and impaired osteogenesis potential. In the present study, a triple-nano-coating polyethylene terephthalate (PET) graft was developed by polydopamine self-assembly, chondroitin sulfate (CS) chemical-grafting and BMP-2 physical-immobilization to facilitate robust ligament-bone healing, The CS/polydopaminemodified PET (C-pPET) graft was demonstrated to inhibit fibrogenesis by regulating polarization of macrophages and promoting the secretion of anti-inflammatory factors. Moreover, the immunoregulatory function of CS cooperated with BMP-2 to facilitate osteogenic differentiation of stem cells, promoting the expression of ALP, Runx2, OCN and COL I. Bone regeneration was significantly enhanced at early-middle stage in the BMP-loaded pPET (B/pPET) group, while occurring at middle-late stage in the C-pPET group. Continuous new bone formation and optimal ligament-bone healing were observed in the B/C-pPET group via sequential and synergistic immune osteogenesis by CS and cytokine osteogenesis by BMP-2. Thus, the present study revealed a practical avenue for the promotion of ligament-bone healing through the development of a triple-nano-coating engineered ligament combining immunoregulatory anti-fibrogenesis and sequential-synergistic osteogenesis, which holds a great potential for improving the clinical efficacy of ligament graft in ACL reconstruction. Statement of Significance A triple-nano-coating polyethylene terephthalate (PET) graft was developed by polydopamine self-assembly, chondroitin sulfate (CS) chemical-grafting and BMP-2 physical-immobilization to facilitate robust ligament-bone healing. This study demonstrated that the multifunctional ligament grafts could reshape the local immune microenvironment by regulating macrophage phenotype and immune cytokine secretion to inhibit the fibrous hyperplasia and regulate stem cell towards osteogenic differentiation to promote bone regeneration. The present study demonstrates that efficient ligament-bone healing is achieved via the combination of immunoregulatory anti-fibrogenesis and dual osteogenesis of immunoregulation and cytokine induction. (C) 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.