Controlled in vivo Bone Formation and Vascularization Using Ultrasound-Triggered Release of Recombinant Vascular Endothelial Growth Factor From Poly(D,L-lactic-co-glycolicacid) Microbubbles
Controlled in vivo Bone Formation and Vascularization Using Ultrasound-Triggered Release of Recombinant Vascular Endothelial Growth Factor From Poly(D,L-lactic-co-glycolicacid) Microbubbles
复制标题
利用超声触发从聚（D,L-乳酸-乙醇酸）微泡中释放重组血管内皮生长因子来控制体内骨形成和血管化
DOI：
10.3389/fphar.2019.00413
复制
发表时间：
2019-04-24
影响因子：
5.6
通讯作者：
Yu, Bo
中科院分区：
文献类型：
--
作者：
Gong, Yong;Li, Songjian;Yu, Bo
由于缺乏血管化，肌肉骨骼系统的骨缺损很难治疗。具有内部血管化能力和骨诱导生物活性的生物材料是骨科应用的有前途的策略。血管内皮生长因子（VEGF）已广泛用于血管生成和成骨。在这里，我们开发了负载 VEGF 的 PLGA 微泡 (MB)，与超声靶向微泡破坏 (UTMD) 相结合，用于改善骨缺损修复中的血管生成和成骨。释放曲线显示 UTMD 促进 PLGA MB 中 VEGF 的爆发释放。我们随后研究了超声应用与 VEGF MB 的组合用于体外成骨。结果表明，VEGF MB 联合 UTMD 增加了成骨相关基因的表达和钙沉积。术后 4 周和 8 周进行显微计算机断层扫描 (micro-CT) 和组织学分析。体内结果表明，在大鼠颅骨缺损模型中，VEGF MB 联合 UTMD 可以显着增强缺损部位的新骨形成和血管向内生长。总之，VEGF MB 与 UTMD 相结合可以增强颅骨骨缺损的骨再生和血管化，并具有巨大的临床转化潜力。
Bone defects are challenging to treat in musculoskeletal system due to the lack of vascularization. Biomaterials with internal vascularization ability and osteoinduction bioactivity are promising strategies for orthopedic applications. Vascular endothelial growth factor (VEGF) has been widely used for angiogenesis and osteogenesis. Here, we developed VEGF-loaded PLGA microbubbles (MBs) for improvement of angiogenesis and osteogenesis in bone defect repair in combination with ultrasound-targeted microbubble destruction (UTMD). Release profile showed UTMD promoted the burst release of VEGF from PLGA MBs. We subsequently investigated the combination of ultrasound application with VEGF MBs for in vitro osteogenesis. The results demonstrated that the expression of osteogenesis-related genes and calcium deposits were increased by VEGF MBs in combination of UTMD. Micro-computed tomography (micro-CT) and histological analysis were conducted 4 and 8 weeks post-surgery. In vivo results show that VEGF MBs in combination of UTMD could significantly enhance new bone formation and vascular ingrowth at the defect site in a rat calvarial defect model. In summary, VEGF MBs in combination of UTMD could augment bone regeneration and vascularization at calvarial bone defects and hold huge potential for clinical translation.