Freeman Fiona E, Pitacco Pierluca, Van Dommelen Lieke H A, Nulty Jessica, Browe David C, Shin Jung-Youn, Alsberg Eben, Kelly Daniel J
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.
Bio Protoc. 2021 Nov 5;11(21):e4219. doi: 10.21769/BioProtoc.4219.
The local delivery of growth factors such as BMP-2 is a well-established strategy for the repair of bone defects. The limitations of such approaches clinically are well documented and can be linked to the need for supraphysiological doses and poor spatio-temporal control of growth factor release . Using bioprinting techniques, it is possible to generate implants that can deliver cytokines or growth factors with distinct spatiotemporal release profiles and patterns to enhance bone regeneration. Specifically, for bone healing, several growth factors, including vascular endothelial growth factor (VEGF) and bone morphogenic proteins (BMPs), have been shown to be expressed at different phases of the process. This protocol aims to outline how to use bioprinting strategies to deliver growth factors, both alone or in combination, to the site of injury at physiologically relevant dosages such that repair is induced without adverse effects. Here we describe: the printing parameters to generate the polymer mechanical backbone; instructions to generate the different bioinks and allow for the temporal control of both growth factors; and the printing process to develop implants with spatially defined patterns of growth factors for bone regeneration. The novelty of this protocol is the use of multiple-tool fabrication techniques to develop an implant with spatio-temporal control of growth factor delivery for bone regeneration. While the overall aim of this protocol was to develop an implant for bone regeneration, the technique can be modified and used for a variety of regenerative purposes. Graphic abstract: 3D Bioprinting Spatio-Temporally Defined Patterns of Growth Factors to Tightly Control Bone Tissue Regeneration.
局部递送诸如骨形态发生蛋白-2（BMP-2）等生长因子是修复骨缺损的一种成熟策略。此类方法在临床上的局限性已有充分记录，并且可能与需要超生理剂量以及生长因子释放的时空控制不佳有关。利用生物打印技术，可以制造出能够以独特的时空释放曲线和模式递送细胞因子或生长因子以促进骨再生的植入物。具体而言，对于骨愈合，包括血管内皮生长因子（VEGF）和骨形态发生蛋白（BMPs）在内的几种生长因子已被证明在该过程的不同阶段表达。本方案旨在概述如何使用生物打印策略，以生理相关剂量单独或联合递送生长因子至损伤部位，从而诱导修复且无不良影响。在此我们描述：生成聚合物机械骨架的打印参数；生成不同生物墨水并实现对两种生长因子的时间控制的说明；以及开发具有空间定义的生长因子模式以促进骨再生的植入物的打印过程。本方案的新颖之处在于使用多工具制造技术来开发一种对生长因子递送具有时空控制的用于骨再生的植入物。虽然本方案的总体目标是开发一种用于骨再生的植入物，但该技术可以进行修改并用于多种再生目的。图形摘要：3D生物打印生长因子的时空定义模式以严格控制骨组织再生。
