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首页> 外文期刊>Acta biomaterialia >Supercritical CO2 foamed composite scaffolds incorporating bioactive lipids promote vascularized bone regeneration via Hif-1α upregulation and enhanced type H vessel formation
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Supercritical CO2 foamed composite scaffolds incorporating bioactive lipids promote vascularized bone regeneration via Hif-1α upregulation and enhanced type H vessel formation

机译：掺入生物活性脂质的超临界CO2发泡复合支架通过HIF-1α上调促进血管化骨再生和增强的H血管形成

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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 (scCO2) 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-1α 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 (CD31hiEmcnhi 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
机译：骨组织工程具有巨大骨缺陷的实质性潜力;然而，与骨再生相结合的有效血管形成仍然是该领域的挑战。在目前的研究中，采用超临界二氧化碳（SCCO2）发泡技术制造介孔生物活性玻璃（MBG）颗粒 - 聚（乳酸二乙醇酸）（PLGGA）复合支架，具有适当的机械和降解性能以及体外生物活性。包含生物活性脂质FTY720的MBG-PLGA支架（指定为FTY / MBG-PLGG），同时持续释放生物活性脂质和离子。除了为细胞粘附和增殖提供有利的微环境外，FTY / MBG-PLGGA支架显着促进了RBMSC的体外骨质发生分化，并且还通过ERK1 / 2途径的激活显着刺激了HIF-1α表达的上调，介导对RBMSCs的成骨和促血管生成作用。此外，FTY / MBG-PLGA提取物诱导出高于HUVEC的体外血管生成性能。体内评估临界大鼠颅骨骨缺损表明，FTY / MBG-PLGA支架有效地促进了血管化骨再生。值得注意的是，在FTY / MBG-PLGA组的新形成的骨组织中观察到H血管（CD31HIEMCNHI新血管）的显着增强的形成，强烈表明，来自支架释放的FTY720和治疗离子协同诱导更多类型的H血管形成，这表明血管生成和骨肉发生的偶联，以实现有效的血管化骨再生。总体而言，结果表明，掺入生物活性脂质的发泡多孔MBG-PLGA支架达到了所需的血管化耦合骨形成，并且可能是骨再生医学的有希望的策略

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