Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; Department of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland.
Trinity Centre for Biomedical Engineering, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland; Department of Mechanical, Manufacturing and Biomedical Engineering, School of Engineering, Trinity College Dublin, Dublin, Ireland; Advanced Materials and Bioengineering Research Centre (AMBER), Royal College of Surgeons in Ireland and Trinity College Dublin, Dublin, Ireland.
Acta Biomater. 2021 May;126:154-169. doi: 10.1016/j.actbio.2021.03.003. Epub 2021 Mar 8.
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. Micro-computed 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.
为了使 3D 生物打印组织能够扩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，并通过去除相关的废物副产物。本研究旨在开发一种生物打印策略，以体外工程化预血管化组织，并研究这些构建体在体内增强大骨缺损血管化和再生的能力。通过对不同生物墨水的筛选，发现纤维蛋白基水凝胶最适合支持人脐静脉内皮细胞（HUVEC）发芽和微血管网络的建立。当这种生物墨水与 HUVEC 和支持人骨髓基质/干细胞（hBMSC）结合时，这些微血管网络在体外得以维持。此外，只有包含 HUVEC 和 hBMSC 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生成。为了评估这种生物打印策略的治疗效用，将这些生物墨水用于预血管化 3D 打印的聚己内酯（PCL）支架，随后将其植入大鼠临界尺寸股骨缺损中。微计算机断层扫描（µCT）血管造影显示体内血管化水平增加，这与新骨形成水平的提高相关。这种预血管化的构建体可用于增强一系列大组织缺损的血管化，为多种新的生物打印治疗方法奠定基础。 意义声明：本文展示了一种多功能的 3D 生物打印技术，可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中，以改善大鼠股骨缺损模型中的血管化。
