文献类型：期刊文献

英文题名：Supercritical CO2 foamed composite scaffolds incorporating bioactive lipids promote vascularized bone regeneration via Hif-1α upregulation and enhanced type H vessel formation

作者：Li, Shuang[1];Song, Chaobo[2];Yang, Shengbing[4];Yu, Weijun[3];Zhang, Weiqi[1];Zhang, Guohua[1];Xi, Zhenhao[2];Lu, Eryi[1]

机构：[1]Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Stomatol, 160 Pujian Rd, Shanghai, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab Multiphase Mat Chem Engn, 130 Meilong Rd, Shanghai, Peoples R China;[3]Shanghai Jiao Tong Univ, Sch Med, Coll Stomatol, 390 Yanqiao Rd, Shanghai, Peoples R China;[4]Shanghai Jiao Tong Univ, Shanghai Key Lab Orthoped Implants, Shanghai Peoples Hosp 9, Dept Orthoped Surg,Sch Med, 639 Zhizaoju Rd, Shanghai, Peoples R China

年份：2019

卷号：94

起止页码：253

外文期刊名：ACTA BIOMATERIALIA

收录：;EI(收录号：20215111342975);WOS:【SCI-EXPANDED(收录号:WOS:000479020900021)】；

基金：This work received funding from the National Natural Science Foundation of China (No 81570948, No 21676083), the Science and Technology Commission of Shanghai Municipality (No 17140903400), the Shanghai Rising-Star Program (No 16QB140130) and the Opening Project of the Shanghai Key Laboratory of Orthopaedic Implants (KFKT2017001).

语种：英文

外文关键词：Supercritical CO2 foaming; Scaffold; Bioactive lipid; Vascularization; Bone regeneration

摘要：Bone tissue engineering has substantial potential for the treatment of massive bone defects; however, efficient vascularization coupled with bone regeneration still remains a challenge in this field. In the current study, supercritical carbon dioxide (scCO(2)) foaming technique was adopted to fabricate mesoporous bioactive glasses (MBGs) particle-poly (lactic-co-glycolic acid) (PLGA) composite scaffolds with appropriate mechanical and degradation properties as well as in vitro bioactivity. The MBG-PLGA scaffolds incorporating the bioactive lipid FTY720 (designated as FTY/MBG-PLGA) exhibited simultaneously sustained release of the bioactive lipid and ions. In addition to providing a favorable microenvironment for cellular adhesion and proliferation, FTY/MBG-PLGA scaffolds significantly facilitated the in vitro osteogenic differentiation of rBMSCs and also markedly stimulated the upregulation of Hif-1 alpha expression via the activation of the Erk1/2 pathway, which mediated the osteogenic and pro-angiogenic effects on rBMSCs. Furthermore, FTY/MBG-PLGA extracts induced superior in vitro angiogenic performance of HUVECs. In vivo evaluation of critical-sized rat calvarial bone defects indicated that FTY/MBG-PLGA scaffolds potently promoted vascularized bone regeneration. Notably, the significantly enhanced formation of type H vessels (CD31 (hi)Emcn(hi) neo-vessels) was observed in newly formed bone tissue in FTY/MBG-PLGA group, strongly suggesting that FTY720 and therapeutic ions released from the scaffolds synergistically induced more type H vessel formation, which indicated the coupling of angiogenesis and osteogenesis to achieve efficiently vascularized bone regeneration. Overall, the results indicated that the foamed porous MBG-PLGA scaffolds incorporating bioactive lipids achieved desirable vascularization-coupled bone formation and could be a promising strategy for bone regenerative medicine. Statement of Significance Efficacious coupling of vascularization and bone formation is critical for the restoration of large bone defects. A novel technique was used to fabricate composite scaffolds incorporating bioactive lipids which possessed synergistic cues of bioactive lipids and therapeutic ions to potently promote bone regeneration as well as vascularization. The underlying molecular mechanism for the osteogenic and pro-angiogenic effects of the composite scaffolds was unveiled. Interestingly, the scaffolds were further found to enhance the formation of type H capillaries within the bone healing microenvironment to couple angiogenesis to osteogenesis to achieve satisfying vascularized bone regeneration. These findings provide a novel strategy to develop efficiently vascularized engineering constructs to treat massive bone defects. (C) 2019 Acta Materialia Inc. Published by Elsevier Ltd.