Salehi Sara, Lippert Lozano Ernesto, Zhang Yichuan, Guo Yinan, Liu Renee, Tran Kenny, Messner Franka, Brandacher Gerald, Grayson Warren L
Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, 400 N. Broadway, Smith 5023, Baltimore, MD 21231, USA.
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21218, USA.
Bioengineering (Basel). 2024 Mar 25;11(4):307. doi: 10.3390/bioengineering11040307.
Static cold storage (SCS), the current clinical gold standard for organ preservation, provides surgeons with a limited window of time between procurement and transplantation. In vascularized composite allotransplantation (VCA), this time limitation prevents many viable allografts from being designated to the best-matched recipients. Machine perfusion (MP) systems hold significant promise for extending and improving organ preservation. Most of the prior MP systems for VCA have been built and tested for large animal models. However, small animal models are beneficial for high-throughput biomolecular investigations. This study describes the design and development of a multiparametric bioreactor with a circuit customized to perfuse rat abdominal wall VCAs. To demonstrate its concept and functionality, this bioreactor system was employed in a small-scale demonstrative study in which biomolecular metrics pertaining to graft viability were evaluated non-invasively and in real time. We additionally report a low incidence of cell death from ischemic necrosis as well as minimal interstitial edema in machine perfused grafts. After up to 12 h of continuous perfusion, grafts were shown to survive transplantation and reperfusion, successfully integrating with recipient tissues and vasculature. Our multiparametric bioreactor system for rat abdominal wall VCA provides an advanced framework to test novel techniques to enhance normothermic and sub-normothermic VCA preservations in small animal models.
静态冷藏(SCS)是目前器官保存的临床金标准,它为外科医生提供了从器官获取到移植之间有限的时间窗口。在血管化复合组织异体移植(VCA)中,这种时间限制使得许多有活力的异体移植物无法分配给最匹配的受者。机器灌注(MP)系统在延长和改善器官保存方面具有巨大潜力。大多数先前用于VCA的MP系统都是针对大型动物模型构建和测试的。然而,小型动物模型有利于高通量生物分子研究。本研究描述了一种多参数生物反应器的设计与开发,该生物反应器带有一个定制的回路,用于灌注大鼠腹壁VCA。为了证明其概念和功能,该生物反应器系统被用于一项小规模的示范研究,在该研究中,对与移植物活力相关的生物分子指标进行了非侵入性实时评估。我们还报告了机器灌注移植物中缺血性坏死导致的细胞死亡发生率较低以及间质水肿最小。在持续灌注长达12小时后,移植物显示能够在移植和再灌注后存活,成功地与受体组织和血管系统整合。我们用于大鼠腹壁VCA的多参数生物反应器系统提供了一个先进的框架,用于测试在小型动物模型中增强常温及亚常温VCA保存的新技术。