Bioengineered bone designed to heal large defects requires concomitant development of osseous and vascular tissue to ensure engraftment and survival. Adult human mesenchymal stromal cells (MSC) are promising in this application because they have demonstrated both osteogenic and vasculogenic potential. This study employed a modular approach in which cells were encapsulated in biomaterial carriers (microtissues) designed to support tissue-specific function. Osteogenic microtissues consisting of MSC embedded in a collagen-chitosan matrix; vasculogenic (VAS) microtissues consisted of endothelial cells and MSC in a fibrin matrix. Microtissues were precultured under differentiation conditions to induce appropriate MSC lineage commitment, and were then combined in a surrounding fibrin hydrogel to create a multimodular construct. Results demonstrated the ability of microtissues to support lineage commitment, and that preculture primes the microtissues for the desired function. Combination of osteogenic and vasculogenic microtissues into multimodular constructs demonstrated that osteogenic priming resulted in sustained osteogenic activity even when cultured in vasculogenic medium, and that vasculogenic priming induced a pericyte-like phenotype that resulted in development of a primitive vessel network in the constructs. The modular approach allows microtissues to be separately precultured to harness the dual differentiation potential of MSC to support both bone and blood vessel formation in a unified construct.

中文翻译：

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由血管生成和成骨微组织组成的多模块血管化骨结构

旨在治愈大缺损的生物工程骨需要骨和血管组织的同时发育，以确保植入和存活。成人间充质基质细胞（MSC）在这一应用中很有前景，因为它们已表现出成骨和血管生成的潜力。这项研究采用了模块化方法，其中细胞被封装在旨在支持组织特异性功能的生物材料载体（微组织）中。由嵌入胶原-壳聚糖基质中的 MSC 组成的成骨微组织；血管生成 (VAS) 微组织由纤维蛋白基质中的内皮细胞和 MSC 组成。在分化条件下预培养微组织以诱导适当的 MSC 谱系定型，然后与周围的纤维蛋白水凝胶组合以创建多模块构建体。结果证明了微组织支持谱系定型的能力，并且预培养为微组织提供了所需的功能。将成骨和血管生成微组织组合成多模块构建体表明，即使在血管生成培养基中培养，成骨启动也会导致持续的成骨活性，并且血管生成启动诱导周细胞样表型，从而导致构建体中原始血管网络的发育。模块化方法允许单独预培养微组织，以利用 MSC 的双重分化潜力，支持统一结构中的骨和血管形成。