Shah Mohammadi Maziar, Buchen Jack T, Pasquina Paul F, Niklason Laura E, Alvarez Luis M, Jariwala Shailly H
The Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland, USA.
Department of Physical Medicine and Rehabilitation, The Center for Rehabilitation Sciences Research, Uniformed Services University of Health Sciences, Bethesda, Maryland, USA.
Tissue Eng Part B Rev. 2021 Aug;27(4):366-381. doi: 10.1089/ten.TEB.2020.0223. Epub 2020 Dec 3.
Effective vascularization is vital for survival and functionality of complex tissue-engineered organs. The formation of the microvasculature, composed of endothelial cells (ECs) alone, has been mostly used to restore the vascular networks in organs. However, recent heterocellular studies demonstrate that co-culturing is a more effective approach in revascularization of engineered organs. This review presents key considerations for manufacturing of artificial vascularized composite tissues. We summarize the importance of co-cultures and the multicellular interactions with ECs, as well as design and use of bioreactors, as critical considerations for tissue vascularization. In addition, as an emerging scaffolding technique, this review also highlights the current caveats and hurdles associated with three-dimensional bioprinting and discusses recent developments in bioprinting strategies such as four-dimensional bioprinting and its future outlook for manufacturing of vascularized tissue constructs. Finally, the review concludes with addressing the critical challenges in the regulatory pathway and clinical translation of artificial composite tissue grafts. Impact statement Regeneration of composite tissues is critical as biophysical and biochemical characteristics differ between various types of tissues. Engineering a vascularized composite tissue has remained unresolved and requires additional evaluations along with optimization of methodologies and standard operating procedures. To this end, the main hurdle is creating a viable vascular endothelium that remains functional for a longer duration postimplantation, and can be manufactured using clinically appropriate source of cell lines that are scalable for the fabrication of human-scale organs. This review presents key considerations for regeneration and manufacturing of vascularized composite tissues as the field advances.
有效的血管化对于复杂组织工程器官的存活和功能至关重要。仅由内皮细胞（ECs）组成的微血管形成，大多用于恢复器官中的血管网络。然而，最近的异细胞研究表明，共培养是工程器官血管再生中更有效的方法。本综述提出了制造人工血管化复合组织的关键考虑因素。我们总结了共培养以及与内皮细胞的多细胞相互作用的重要性，以及生物反应器的设计和使用，作为组织血管化的关键考虑因素。此外，作为一种新兴的支架技术，本综述还强调了与三维生物打印相关的当前注意事项和障碍，并讨论了生物打印策略（如四维生物打印）的最新进展及其在制造血管化组织构建体方面的未来前景。最后，综述总结了人工复合组织移植物在监管途径和临床转化方面的关键挑战。影响声明复合组织的再生至关重要，因为不同类型组织的生物物理和生化特征不同。工程化血管化复合组织仍未得到解决，需要进一步评估，并优化方法和标准操作程序。为此，主要障碍是创建一个可行的血管内皮，使其在植入后能在更长时间内保持功能，并能用临床上合适的可扩展细胞系制造，以用于制造人体规模的器官。随着该领域的发展，本综述提出了血管化复合组织再生和制造的关键考虑因素。
