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用于加速工程器官临床转化的牺牲模板法。

Sacrificial Templating for Accelerating Clinical Translation of Engineered Organs.

作者信息

Malkani Sherina, Prado Olivia, Stevens Kelly R

机构信息

Department of Bioengineering, University of Washington, Seattle, Washington 98195, United States.

Department of Bioengineering, Rice University, Houston, Texas 77005, United States.

出版信息

ACS Biomater Sci Eng. 2025 Jan 13;11(1):1-12. doi: 10.1021/acsbiomaterials.4c01824. Epub 2024 Dec 19.

Abstract

Transplantable engineered organs could one day be used to treat patients suffering from end-stage organ failure. Yet, producing hierarchical vascular networks that sustain the viability and function of cells within human-scale organs remains a major challenge. Sacrificial templating has emerged as a promising biofabrication method that could overcome this challenge. Here, we explore and evaluate various strategies and materials that have been used for sacrificial templating. First, we emphasize fabrication approaches that use highly biocompatible sacrificial reagents and minimize the duration that cells spend in fabrication conditions without oxygen and nutrients. We then discuss strategies to create continuous, hierarchical vascular networks, both using biofabrication alone and using hybrid methods that integrate biologically driven vascular self-assembly into sacrificial templating workflows. Finally, we address the importance of structurally reinforcing engineered vessel walls to achieve stable blood flow , so that engineered organs remain perfused and functional long after implantation. Together, these sacrificial templating strategies have the potential to overcome many current limitations in biofabrication and accelerate clinical translation of transplantable, fully functional engineered organs to rescue patients from organ failure.

摘要

可移植的工程器官有朝一日可能用于治疗终末期器官衰竭患者。然而,构建能够维持人体尺度器官内细胞活力和功能的分级血管网络仍然是一项重大挑战。牺牲模板法已成为一种有前景的生物制造方法,有望克服这一挑战。在此,我们探索并评估了用于牺牲模板法的各种策略和材料。首先,我们强调使用高度生物相容性牺牲试剂的制造方法,并尽量缩短细胞在无氧和无营养物质制造条件下的停留时间。然后,我们讨论了创建连续分级血管网络的策略,包括单独使用生物制造方法以及使用将生物驱动的血管自组装整合到牺牲模板工作流程中的混合方法。最后,我们阐述了在结构上加强工程血管壁以实现稳定血流的重要性,以便工程器官在植入后很长时间内仍能保持灌注和功能。总之,这些牺牲模板策略有可能克服生物制造目前的许多局限性,并加速可移植、功能齐全的工程器官的临床转化,从而将患者从器官衰竭中拯救出来。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bc9/11733865/2b4fac9dd1c9/ab4c01824_0001.jpg

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