Department of General-, Visceral-, and Transplantation Surgery, University Hospital Heidelberg, D-69120 Heidelberg, Germany.
Institute for BioMedical Printing Technology, Technical University Darmstadt, D-64289 Darmstadt, Germany.
Int J Mol Sci. 2022 Aug 2;23(15):8589. doi: 10.3390/ijms23158589.
Among advanced therapy medicinal products, tissue-engineered products have the potential to address the current critical shortage of donor organs and provide future alternative options in organ replacement therapy. The clinically available tissue-engineered products comprise bradytrophic tissue such as skin, cornea, and cartilage. A sufficient macro- and microvascular network to support the viability and function of effector cells has been identified as one of the main challenges in developing bioartificial parenchymal tissue. Three-dimensional bioprinting is an emerging technology that might overcome this challenge by precise spatial bioink deposition for the generation of a predefined architecture. Bioinks are printing substrates that may contain cells, matrix compounds, and signaling molecules within support materials such as hydrogels. Bioinks can provide cues to promote vascularization, including proangiogenic signaling molecules and cocultured cells. Both of these strategies are reported to enhance vascularization. We review pre-, intra-, and postprinting strategies such as bioink composition, bioprinting platforms, and material deposition strategies for building vascularized tissue. In addition, bioconvergence approaches such as computer simulation and artificial intelligence can support current experimental designs. Imaging-derived vascular trees can serve as blueprints. While acknowledging that a lack of structured evidence inhibits further meta-analysis, this review discusses an end-to-end process for the fabrication of vascularized, parenchymal tissue.
在先进治疗药物产品中，组织工程产品有可能解决当前供体器官严重短缺的问题，并为器官替代治疗提供未来的替代选择。临床上可获得的组织工程产品包括组织如皮肤、角膜和软骨等。人们已经认识到，为支持效应细胞的存活和功能而建立充足的宏观和微观血管网络是开发生物人造实质组织的主要挑战之一。三维生物打印是一种新兴技术，通过精确的空间生物墨水沉积来生成预定的结构，从而克服这一挑战。生物墨水是一种打印基质，其中可能包含细胞、基质化合物和信号分子，以及支持材料如水凝胶。生物墨水可以提供促进血管生成的线索，包括促血管生成的信号分子和共培养细胞。这两种策略都被报道可以增强血管生成。我们综述了构建血管化组织的预打印、打印中和后打印策略，例如生物墨水的组成、生物打印平台和材料沉积策略。此外，生物融合方法，如计算机模拟和人工智能，可以支持当前的实验设计。成像衍生的血管树可以作为蓝图。尽管承认缺乏结构化证据会抑制进一步的荟萃分析，但本综述讨论了血管化实质组织制造的端到端过程。
