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 O₂, 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.

中文翻译：

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由过氧化钙介导的再生工程血管化骨。

阻碍骨组织工程支架临床转化的主要挑战之一是缺乏功能性脉管系统的建立。血管化不足和氧气供应不足限制了结构内的细胞存活，导致与宿主组织的骨整合不良，最终导致骨再生不足。受发育生物学线索的启发，我们通过将过氧化钙 (CaO ₂ ) 结合到基于聚(丙交酯-共-乙交酯) (PLGA) 微球的基质中来再生设计一种复合基质，并试图评估 CaO ₂副产物的传递分解，即 O ₂、Ca ²⁺和 H ₂ O ₂可以促进血管化骨组织的再生。通过水包油乳液法成功制备了复合微球。CaO ₂的存在和包封使用扫描电子显微镜、能量色散 X 射线光谱、热重分析和 X 射线粉末衍射证实。微球被进一步热烧结成三维多孔支架，并表征其降解和副产物的释放。使用人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，在小鼠临界尺寸颅骨缺损模型中进行了一项体内研究，以评估这些基质支持血管化骨再生的能力。结果表明，CaO ₂的存在在整个基质中增加细胞化和生物活性。8 周后，宿主细胞更多地迁移到基质内部，供体细胞的存活率和持久性更高，这与复合基质协同导致血管化骨再生增强。