Encapsulating multiple growth factors within a scaffold enhances the regenerative capacity of engineered bone grafts through their localization and controls the spatiotemporal release profile. In this study, we bioprinted hybrid bone grafts with an inherent built-in controlled growth factor delivery system, which would contribute to vascularized bone formation using a single stem cell source, human adipose-derived stem/stromal cells (ASCs) in vitro. The strategy was to provide precise control over the ASC-derived osteogenesis and angiogenesis at certain regions of the graft through the activity of spatially positioned microencapsulated BMP-2 and VEGF within the osteogenic and angiogenic bioink during bioprinting. The 3D-bioprinted vascularized bone grafts were cultured in a perfusion bioreactor. Results proved localized expression of osteopontin and CD31 by the ASCs, which was made possible through the localized delivery activity of the built-in delivery system. In conclusion, this approach provided a methodology for generating off-the-shelf constructs for vascularized bone regeneration and has the potential to enable single-step, in situ bioprinting procedures for creating vascularized bone implants when applied to bone defects.

中文翻译：

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使用脂肪干细胞/基质细胞作为单细胞来源进行血管化骨 3D 生物打印的空间生长因子传递

将多种生长因子封装在支架内，可以通过其定位增强工程骨移植物的再生能力，并控制时空释放曲线。在这项研究中，我们生物打印了具有固有的内置受控生长因子输送系统的混合骨移植物，这将有助于在体外使用单一干细胞来源、人类脂肪干细胞/基质细胞（ASC）形成血管化骨。该策略是通过生物打印过程中成骨和血管生成生物墨水中空间定位的微囊 BMP-2 和 VEGF 的活性，对移植物某些区域的 ASC 衍生的成骨和血管生成进行精确控制。3D生物打印的血管化骨移植物在灌注生物反应器中培养。结果证明，ASC 可以局部表达骨桥蛋白和 CD31，这是通过内置递送系统的局部递送活性实现的。总之，这种方法提供了一种生成用于血管化骨再生的现成结构的方法，并且有潜力实现单步原位生物打印程序，用于在应用于骨缺损时创建血管化骨植入物。