文献类型：期刊文献

英文题名：Accelerated Bone Regenerative Efficiency by Regulating Sequential Release of BMP-2 and VEGF and Synergism with Sulfated Chitosan

作者：Zhang, Shuang[2];Chen, Jie[3];Yu, Yuanman[1];Dai, Kai[2];Wang, Jing[1];Liu, Changsheng[2]

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

年份：2019

卷号：5

期号：4

起止页码：1944

外文期刊名：ACS BIOMATERIALS SCIENCE & ENGINEERING

收录：;EI(收录号：20191106634277);WOS:【SCI-EXPANDED(收录号:WOS:000464241400027)】；

基金：The authors wish to express their gratitude for the financial support from the National Natural Science Foundation of China (Nos. 31330028, 31470923, and 31870953), National Natural Science Foundation of China for Innovative Research Groups (No. 51621002), and International Cooperation Project and Research Project of Shanghai Science and Technique Committee (15520711100, 15DZ1942502). This study is also supported by the 111 Project (B14018).

语种：英文

外文关键词：BMP-2; VEGF; sulfated chitosan; spatiotemporal delivery; osteogenesis; angiogenesis

摘要：Emerging evidence suggests that successful healing of bone substitutes depends on the osteogenesis angiogenesis interplay. Bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) have been identified as key regulators of osteogenesis and angiogenesis during bone regeneration. While the importance of growth factors is now widely accepted, the impact and mechanisms of different releasing sequences on bone repair have not been fully understood. Here, a composite vehicle (Gel/PMs), constructed with hydrogels and microspheres, was developed, which is capable of achieving two distinct releasing modes: BMP-2 first release followed by VEGF release (B/V) and VEGF first release followed by BMP-2 release (V/B). In our results, the B/V mode exhibited more extensive vascular network formation by up-regulating angiogenic genes during the bone remolding, thus facilitating rapid bone transformation which was confirmed by radiography. Further histological and immune-staining analysis revealed that fast release of BMP-2 made for rapidly initiating osteogenesis, while later VEGF release promoted persistent angiogenesis and mature bone formation. Moreover, interest arises from the introduction of 2-N,6-O-sulfated chitosan (SCS), a sulfonated heparin-like polysaccharide. It has synergistic effects with both BMP-2 and VEGF, which can further accelerate bone healing by efficiently improving osteogenesis and angiogenesis. The results demonstrated that disparate releasing sequence of growth factors might influence regenerative efficiency. Such a strategy may provide insights toward designing bioactive materials and give promising application in tissue regeneration.