文献类型：期刊文献

英文题名：Sulfated chitosan enhances BMP-2-mediated spinal fusion via skeletal stem cell rejuvenation in aging

作者：Wang, Xiaogang[1,3];Huang, Dongao[1,3];Ji, Luli[1,3];Yu, Yuanman[1,3];Zhu, Fuwei[1,3];Wang, Jing[1,2];Liu, Changsheng[1,3,4]

机构：[1]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Key Lab Ultrafine Mat, Minist Educ, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Engn Res Ctr Biomed Mat, Minist Educ, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai 200237, Peoples R China

年份：2025

卷号：54

起止页码：797

外文期刊名：BIOACTIVE MATERIALS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001575693600001)】；

基金：This study was supported by the Basic Science Center Program (T2288102) , the Key Program of the National Natural Science Foundation of China (32230059) , the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry (JKVD1211002) , the National Natural Science Foundation of China (32401128) , the Postdoctoral Fellowship Program of CPSF (GZC20230793) , Shanghai Post-doctoral Excellence Program (2023251) , and Shandong Province key research and development project 2023CXPT103. We greatly thank Han guo from the Shanghai Synchrotron Radiation Facility BL13HB, for the technical support and assistance in data collection and analysis. We thank the staff members of the Integrated Laser Microscopy System (https://cstr.cn/31129.02.NFPS.CLMIS) at the National Facility for Protein Science in Shanghai (https://cstr.cn/31129.02.NFPS) , for providing technical support and assistance in data collection and analysis.

语种：英文

外文关键词：Spinal fusion; BMP-2; Osteoclast; Sulfated chitosan; Skeletal stem cell

摘要：Spinal degenerative diseases in elderly patients often require spinal fusion, but outcomes are limited by an aging microenvironment and stem cell dysfunction or depletion. In this study, we developed a bone morphogenetic protein-2 (BMP-2)/sulfated chitosan (SCS)/calcium phosphate cement (CPC) composite scaffold to enhance spinal fusion in aged mice. BMP-2/SCS significantly improved spinal fusion success rates (83.3 %) compared to BMP-2 alone (16.7 %) and high-dose BMP-2 (50 %). The BMP-2/SCS group promoted robust new bone formation and H-type vessel development, facilitating vascular-bone coupling in the fusion region. Mechanistically, SCS suppressed BMP-2-induced osteoclast overactivation and reduced MMP-9 secretion, leading to vertebral skeletal stem cell (vSSC) rejuvenation. Rejuvenated vSSCs primarily differentiated into the osteogenic bone/cartilage lineage while stromal lineage differentiation was suppressed. In contrast, co-administration of BMP-2 and alendronate sodium abolished BMP-2-mediated increases in vSSC numbers, vSSC rejuvenation, and bone integration, highlighting the indispensable role of osteoclast activity in BMP-2-induced bone regeneration. Collectively, this study demonstrates that BMP-2/SCS scaffolds effectively reverse age-related deficiencies by creating a rejuvenated bone microenvironment, promoting vascular-bone coupling, and enhancing osteogenesis, offering a promising strategy to improve spinal fusion outcomes in elderly patients.