摘要
Vascular networks inside organs provide the means for metabolic exchange and adequate nutrition.Similarly,vascular or nutrient networks are needed when building tissue constructs>500μm in vitro due to the hydrogel compact pore size of bioinks.As the hydrogel used in bioinks is rather soft,it is a great challenge to reconstruct effective vascular networks.Recently,coaxial 3 D bioprinting was developed to print tissue constructs directly using hollow hydrogel fibers,which can be treated as built-in microchannels for nutrient delivery.Furthermore,vascular networks could be printed directly through coaxial 3 D bioprinting.This review summarizes recent advances in coaxial bioprinting for the fabrication of complex vascularized tissue constructs including methods,the effectiveness of varying strategies,and the use of sacrificial bioink.The limitations and challenges of coaxial 3 D bioprinting are also summarized.
组织/器官内的血供系统,为组织提供了必要的营养及代谢交换。而在体外构造组织/器官原型时,如何在大尺寸结构中构建营养网络,是长期以来的技术难题。近年来,同轴生物3D打印技术为该问题提供了一种极具潜力的解决方案。同轴生物3D打印技术的基本原理是:使用同轴喷头将外层的水凝胶材料和内层的牺牲材料共同挤出,打印为所需的复杂结构,内层的牺牲材料去除后形成的中空通路即成为后续培养中的营养网络。该技术结合了传统生物打印方法和牺牲组分3D打印方法的优点,能够一步构造内置营养网络的大尺寸仿生结构,在组织工程和器官重建等领域具有突出的优势。本文结合课题组近年围绕同轴生物3D打印技术所做的一些工作,梳理和总结了该技术的最新研究进展。主要关注以下几点:(1)在同轴3D打印血管时必须考虑的因素;(2)首选生物材料清单;(3)内皮化通道的制造原理及其潜在机制;(4)同轴生物3D打印技术的最近进展;(5)未来的挑战。首先,本文概述了当前生物3D打印中常用的水凝胶材料,包括海藻酸钠(Alginate)、明胶/甲基丙烯酸酐化明胶(Gelatin/Gel MA)和胶原(Collagen)等,介绍了这些材料的生物相容性、可打印性和打印原理等生物3D打印技术中重点关注的因素。随后,论文详述了同轴生物3D打印技术的基本原理、技术特点以及使用该技术构造内含营养网络(特别是血管化)的大尺寸结构的最新尝试。最后,论文展望了同轴生物3D技术未来可能的发展方向。最新的研究进展表明,该技术为快速制造血管化的组织/器官原型提供了可能。
基金
the National Key Research and Development Program of China(No.2018YFA0703000)
the Science Fund for Creative Research Groups of the National Natural Science Foundation of China(No.51521064)。
