Open-source hybrid 3D-bioprinter for simultaneous printing of thermoplastics and hydrogels

3D-bioprinting is a promising technology applicable in areas such as regenerative medicine or in vitro organ model development. Various 3D-bioprinting technologies and systems have been developed and are partly commercially available. Here, we present the construction and characterization of an open-source low-cost 3D-bioprinter that allows the alternated microextrusion of hydrogel and fused deposition modeling (FDM) of thermoplastic filaments. The presented 3D-bioprinter is based on a conventional Prusa i3 MK3 printer and features two independent printheads: the original FDM-head and a piston-driven microextrusion system for soft materials. Modifications were designed modularly to fit various syringe formats or heating elements to the device. The bioprinter is the first hybrid DIY 3D-bioprinter that allows switching between materials as often as required during a print run to produce complex multi-material constructs with arbitrary patterns in each layer. For validation of the printer, two designs suitable for relevant bioprinting applications were realized. First, a porous plastic construct filled with hydrogel was printed, serving as a mechanically stable bone replacement tissue model. Second, a plastic chamber, which might be used in organ-on-a-chip applications, was printed with an extruded silicone sealing that enables the liquid-tight attachment of glass slides to the top and bottom of the chamber.

三维生物打印（3D-bioprinting）是一项极具应用前景的技术，可应用于再生医学（regenerative medicine）、体外器官模型（in vitro organ model）开发等领域。目前已有多种三维生物打印技术与系统被研发出来，且部分已实现商业化落地。本文介绍一款开源低成本三维生物打印机（3D-bioprinter）的搭建与表征方案，该设备可实现水凝胶（hydrogel）的交替微挤出与热塑性丝材（thermoplastic filaments）的熔融沉积建模（fused deposition modeling, FDM）打印。

本款三维生物打印机基于常规Prusa i3 MK3型打印机（Prusa i3 MK3 printer）打造，配备两个独立打印头（printheads）：原厂熔融沉积建模打印头，以及适配软质材料的活塞驱动微挤出系统（piston-driven microextrusion system）。其改造设计采用模块化思路，可适配多种注射器规格（syringe formats）或加装加热元件（heating elements）至设备中。本生物打印机为首款可在打印过程中按需频繁切换打印材料的混合式自制三维生物打印机（hybrid DIY 3D-bioprinter），能够在每层以任意图案制备复杂多材料结构（multi-material constructs）。

为验证该打印机的打印性能，本文实现了两款适配实际生物打印应用的设计方案。其一为填充水凝胶的多孔塑料结构，可作为力学性能稳定的骨替代组织模型；其二为可应用于器官芯片（organ-on-a-chip）领域的塑料腔室，该腔室搭配挤出成型的硅橡胶密封结构，可实现载玻片（glass slides）与腔室上下表面的液密连接。