3D Bioprinting of Prevascularised Implants for the Repair of Critically Sized Bone Defects

J. Nulty, Fiona E. Freeman, David C. Browe, Ross Burdis, D. Ahern, Pierluca Pitacco, Yu Bin Lee, E. Alsberg, D. Kelly
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引用次数: 59

Abstract

For 3D bioprinted tissues to be scaled-up to clinically relevant sizes, effective prevascularisation strategies are required to provide the necessary nutrients for normal metabolism and to remove associated waste by-products. The aim of this study was to develop a bioprinting strategy to engineer prevascularised tissues in vitro and to investigate the capacity of such constructs to enhance the vascularisation and regeneration of large bone defects in vivo. From a screen of different bioinks, a fibrin-based hydrogel was found to best support human umbilical vein endothelial cell (HUVEC) sprouting and the establishment of a microvessel network. When this bioink was combined with HUVECs and supporting human bone marrow stem/stromal cells (hBMSCs), these microvessel networks persisted in vitro. Furthermore, only bioprinted tissues containing both HUVECs and hBMSCs, that were first allowed to mature in vitro, supported robust blood vessel development in vivo. To assess the therapeutic utility of this bioprinting strategy, these bioinks were used to prevascularise 3D printed polycaprolactone (PCL) scaffolds, which were subsequently implanted into critically-sized femoral bone defects in rats. Microcomputed tomography (µCT) angiography revealed increased levels of vascularisation in vivo, which correlated with higher levels of new bone formation. Such prevascularised constructs could be used to enhance the vascularisation of a range of large tissue defects, forming the basis of multiple new bioprinted therapeutics. STATEMENT OF SIGNIFICANCE: This paper demonstrates a versatile 3D bioprinting technique to improve the vascularisation of tissue engineered constructs and further demonstrates how this method can be incorporated into a bone tissue engineering strategy to improve vascularisation in a rat femoral defect model.
三维生物打印预血管植入物用于修复临界大小的骨缺损
为了将3D生物打印组织放大到临床相关的尺寸,需要有效的预血管化策略来提供正常代谢所需的营养物质,并去除相关的废物副产品。本研究的目的是开发一种生物打印策略,在体外设计预血管化组织,并研究这种结构的能力,以增强体内大骨缺损的血管化和再生。从不同生物墨水的筛选中,发现基于纤维蛋白的水凝胶最能支持人脐静脉内皮细胞(HUVEC)的发芽和微血管网络的建立。当这种生物链接与HUVECs和支持的人骨髓干细胞(hBMSCs)结合时,这些微血管网络在体外持续存在。此外,只有同时含有HUVECs和hBMSCs的生物打印组织,首先在体外成熟,才能在体内支持强大的血管发育。为了评估这种生物打印策略的治疗效用,这些生物墨水被用于预血管化3D打印聚己内酯(PCL)支架,随后将其植入大鼠临界大小的股骨缺损。微计算机断层扫描(µCT)血管造影显示体内血管化水平增加,这与更高水平的新骨形成相关。这种预血管化结构可用于增强一系列大组织缺陷的血管化,形成多种新的生物打印疗法的基础。重要意义:本文展示了一种通用的3D生物打印技术,以改善组织工程构建体的血管化,并进一步展示了如何将该方法纳入骨组织工程策略,以改善大鼠股骨缺损模型的血管化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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