Spatial Growth Factor Delivery for 3D Bioprinting of Vascularized Bone with Adipose-Derived Stem/Stromal Cells as a Single Cell Source

以脂肪来源的干细胞/基质细胞作为单细胞源,进行血管化骨 3D 生物打印的空间生长因子输送

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作者:Meric Goker, Utku Serhat Derici, Seyda Gokyer, Mehmet Goktug Parmaksiz, Burak Kaya, Alp Can, Pinar Yilgor

Abstract

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.

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