He Yijun, Wang Wenhao, Lin Shaozhang, Yang Yixi, Song Lizhi, Jing Yihan, Chen Lihao, He Zaopeng, Li Wei, Xiong Ao, Yeung Kelvin W K, Zhao Qi, Jiang Yuan, Li Zijie, Pei Guoxian, Zhang Zhi-Yong
Translational Research Centre of Regenerative Medicine and 3D Printing of Guangzhou Medical University, Guangdong Province Engineering Research Center for Biomedical Engineering, State Key Laboratory of Respiratory Disease, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, PR China.
Hand and Foot Surgery & Plastic Surgery, Affiliated Shunde Hospital of Guangzhou Medical University, Foshan, 528315, PR China.
Bioact Mater. 2021 Aug 12;9:491-507. doi: 10.1016/j.bioactmat.2021.07.030. eCollection 2022 Mar.
The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) - osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a rat femoral bone defect, the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography (μ-AG) and micro-computational tomography (μ-CT). Based on the immunofluorescence studies, PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors. In addition, superior osseointegration was observed by a direct host bone-PCL interface, which was likely attributed to the formation of type H vessels. The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration. It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels, which could compensate for the inherent biological inertness of synthetic polymers.
生物惰性聚合物支架作为骨替代物的潜在应用受到植入后缺乏新血管形成以及随后宿主骨向内生长减少的限制，这很可能是由于无法复制细胞间适当的内源性相互作用所致。人脐静脉内皮细胞衍生的脱细胞细胞外基质（HdECM）含有一系列血管生成生物分子，最近已被证明可介导内皮细胞（ECs） - 骨祖细胞（OPs）之间的相互作用。我们使用HdECM创建了一种聚己内酯（PCL）/纤维蛋白/HdECM（PFE）混合支架。我们假设PFE支架可以重建一个具有生物指导作用的微环境，重新引入这种相互作用，从而实现血管化骨再生。在大鼠股骨骨缺损处植入后，通过微血管造影（μ-AG）和微计算机断层扫描（μ-CT）显示PFE支架具有早期血管浸润并增强了骨再生。基于免疫荧光研究，PFE通过大量的H型血管和骨祖细胞介导了内源性血管生成和成骨作用。此外，在宿主骨与PCL的直接界面处观察到了优异的骨整合，这可能归因于H型血管的形成。我们创新的PFE支架所创建的具有生物指导作用的微环境使得优异的骨整合和与H型血管相关的骨再生成为可能。借助诱导生成的H型血管，它可以成为改善骨替代物骨整合的一种替代解决方案，这可以弥补合成聚合物固有的生物惰性。
