Vascular restoration through local delivery of angiogenic factors stimulates bone regeneration in critical size defects  

作　　者：Liang Fang Zhongting Liu Cuicui Wang Meng Shi Yonghua He Aiwu Lu Xiaofei Li Tiandao Li Donghui Zhu Bo Zhang Jianjun Guan Jie Shen 

机构地区：[1]Department of Orthopaedic Surgery,School of Medicine,Washington University,St.Louis,MO,63110,USA [2]Department of Mechanical Engineering&Materials Sciences,School of Engineering,Washington University,St.Louis,MO,63110,USA [3]Department of Developmental Biology,Center of Regenerative Medicine,Washington University,St.Louis,MO,63110,USA [4]Department of Biomedical Engineering,School of Medicine,Stony Brook University,Stony Brook,NY,11794,USA

出　　处：《Bioactive Materials》2024年第6期580-594,共15页生物活性材料（英文）

基　　金：supported by the following NIH grants:R01 grants(AR075860,AR077616,and AR083900 to JS;HL138175,HL164062,and DK133949 to JG)and a R21 grant(AR077226 to JS);a P30 Core Center grant(AR074992 to the Musculoskeletal Research Center at Washington University in St.Louis).

摘　　要：Critical size bone defects represent a significant challenge worldwide,often leading to persistent pain and physical disability that profoundly impact patients’quality of life and mental well-being.To address the intricate and complex repair processes involved in these defects,we performed single-cell RNA sequencing and revealed notable shifts in cellular populations within regenerative tissue.Specifically,we observed a decrease in progenitor lineage cells and endothelial cells,coupled with an increase in fibrotic lineage cells and pro-inflammatory cells within regenerative tissue.Furthermore,our analysis of differentially expressed genes and associated signaling pathway at the single-cell level highlighted impaired angiogenesis as a central pathway in critical size bone defects,notably influenced by reduction of Spp1 and Cxcl12 expression.This deficiency was particularly pronounced in progenitor lineage cells and myeloid lineage cells,underscoring its significance in the regeneration process.In response to these findings,we developed an innovative approach to enhance bone regeneration in critical size bone defects.Our fabrication process involves the integration of electrospun PCL fibers with electrosprayed PLGA microspheres carrying Spp1 and Cxcl12.This design allows for the gradual release of Spp1 and Cxcl12 in vitro and in vivo.To evaluate the efficacy of our approach,we locally applied PCL scaffolds loaded with Spp1 and Cxcl12 in a murine model of critical size bone defects.Our results demonstrated restored angiogenesis,accelerated bone regeneration,alleviated pain responses and improved mobility in treated mice.

关 键 词：Critical size bone defects ANGIOGENESIS Spp1 CXCL12 Polycaprolactone scaffold 

分 类 号：R318[医药卫生—生物医学工程]