Regenerative engineered vascularized bone mediated by calcium peroxide
Regenerative engineered vascularized bone mediated by calcium peroxide
复制标题
DOI：
10.1002/jbm.a.36879
复制
发表时间：
2020-01-22
影响因子：
4.9
通讯作者：
Laurencin, Cato T.
中科院分区：
文献类型：
--
作者：
Daneshmandi, Leila;Laurencin, Cato T.
阻碍骨组织工程支架临床移植的主要挑战之一是缺乏功能性血管的建立。血管化不足和氧气供应不足限制了支架内细胞的存活，导致与宿主组织的骨结合不良，最终导致骨再生不足。受发育生物学提示的启发，我们通过将过氧化钙(CaO2)加入到聚丙交酯-乙交酯(PLGA)微球基质中来再生工程复合基质，并试图评估CaO2分解的副产物O-2、Ca~(2+)和H_2O_2是否可以促进血管化骨组织的再生。采用水包油乳化法成功制备了复合微球。通过扫描电子显微镜、X射线能谱、热重分析、X射线粉末衍射等手段证实了CaO2的存在和包覆。微球被进一步热烧结成三维多孔支架，并对其降解和释放副产物进行了表征。使用人类脂肪干细胞证实了基质的体外细胞相容性及其支持成骨分化的能力。最后，在小鼠临界大小的颅骨缺损模型中进行了体内研究，以评估这些基质支持血管化骨再生的能力。结果表明，CaO2的存在增加了基质的细胞化和生物活性。8周后，宿主细胞向基质内部迁移较多，供体细胞存活率和持久性较高，与复合基质协同作用可促进血管化骨再生。
One of the main challenges hindering the clinical translation of bone tissue engineering scaffolds is the lack of establishment of functional vasculature. Insufficient vascularization and poor oxygen supply limit cell survival within the constructs resulting in poor osseointegration with the host tissue and eventually leading to inadequate bone regeneration. Inspired by cues from developmental biology, we regenerative engineered a composite matrix by incorporating calcium peroxide (CaO2) into poly(lactide-co-glycolide) (PLGA) microsphere-based matrices and sought to assess whether the delivery of the byproducts of CaO2 decomposition, namely O-2, Ca2+, and H2O2 could enhance the regeneration of vascularized bone tissue. The composite microspheres were successfully fabricated via the oil-in-water emulsion method. The presence and encapsulation of CaO2 was confirmed using scanning electron microscopy, energy dispersive x-ray spectroscopy, thermogravimetric analysis, and X-ray powder diffraction. The microspheres were further heat sintered into three-dimensional porous scaffolds and characterized for their degradation and release of byproducts. The in vitro cytocompatibility of the matrices and their ability to support osteogenic differentiation was confirmed using human adipose-derived stem cells. Lastly, an in vivo study was performed in a mouse critical-sized calvarial defect model to evaluate the capacity of these matrices in supporting vascularized bone regeneration. Results demonstrated that the presence of CaO2 increased cellularization and biological activity throughout the matrices. There was greater migration of host cells to the interior of the matrices and greater survival and persistence of donor cells after 8 weeks, which in synergy with the composite matrices led to enhanced vascularized bone regeneration.