Development of a multifunctional uniaxial bioreactor with real-time monitoring of culture conditions and tissue health  

具有培养条件和组织健康实时监测功能的多功能单轴生物反应器的开发

作　　者：Adit Mehta Po-Feng Lee Eric Renteria Frank C.Marini Ji Hyun Kim Tracy Criswell Thomas D.Shupe Anthony Atala Metin N.Gurcan Shay Soker Joshua Hunsberger James J.Yoo Young Min Ju Adit Mehta;Po-Feng Lee;Eric Renteria;Frank C.Marini;Ji Hyun Kim;Tracy Criswell;Thomas D.Shupe;Anthony Atala;Metin N.Gurcan;Shay Soker;Joshua Hunsberger;James J.Yoo;Young Min Ju(维克森林大学医学院维克森林再生医学研究所,美国温斯顿-塞勒姆市,NC 27157;维克森林大学医学院人工智能中心,美国温斯顿-塞勒姆市,NC 27157;再生医学发展组织(ReMDO),美国温斯顿-塞勒姆市,NC 27106)

机构地区：[1]Wake Forest Institute for Regenerative Medicine,Wake Forest School of Medicine,Winston-Salem,NC 27157,USA [2]Center for Artificial Intelligence,Wake Forest School of Medicine,Winston-Salem,NC 27157,USA [3]RegenMed Development Organization(ReMDO),Winston-Salem,NC 27106,USA

出　　处：《Bio-Design and Manufacturing》2025年第2期310-330,I0012-I0015,共25页生物设计与制造(英文)

基　　金：possible by the US Army Medical Research and Development Command through the Medical Technology Enterprise Consortium under Contract#W81XWH-15-9-0001.

摘　　要：Bioreactors are used to dynamically condition engineered tissues to achieve the required degree of maturation before in vivo implantation.Integrating sensors and imaging capabilities into bioreactors can help us understand how the culture environment influences tissue maturation and growth.Additionally,this enables the monitoring of tissue constructs and provides critical information for quality control.This study aimed to develop a standardized,self-contained,uniaxial bioreactor module for the clinical manufacturing of tissue constructs;this system would benefit from unidirectional mechanical or electrical stimulation,or both.We achieved this goal by integrating stimulation and sensing components that provide an optimal culture environment and monitoring capabilities to improve tissue manufacturing.The uniaxial bioreactor module included integrated,user-friendly mechanical and electrical stimulations with force measurement to enhance the preconditioning of the engineered tissues.Also,a sensor loop and media exchange system were integrated to monitor the culture environment and cellular metabolites over time,and the camera system above the tissue construct enabled the macroscopic visualization of tissue maturation.Furthermore,the onboard media exchange system was programmed into the module to maintain aseptic culture conditions in the long term.Subsequently,using native skeletal muscle tissue and tissue-engineered skeletal muscle constructs,the performance of the uniaxial bioreactor module was validated for its application in preconditioning and enhancing tissue maturation.生物反应器通过动态调控工程化组织,使其在体内植入前达到所需的成熟度。将传感器和成像功能整合至生物反应器中有助于理解培养环境如何影响组织成熟与生长,同时为组织构建体提供监测和质量控制的关键信息。本研究旨在开发一种标准化、自包含的单轴生物反应器模块,用于临床组织构建体的制造;该系统通过单向机械或电刺激(或两者结合)优化培养环境并提升组织制造效率。该单轴生物反应器模块集成了用户友好的机械与电刺激功能及力测量系统,以增强工程化组织的预处理能力。此外,传感器环路和培养基交换系统可实时监测培养环境及细胞代谢物,且位于组织构建体上方的摄像头系统可实现组织成熟的宏观可视化。系统内置的培养基交换程序可长期维持无菌培养条件。通过使用天然骨骼肌组织和组织工程化的骨骼肌构建体,验证了该单轴生物反应器模块在预处理和促进组织成熟方面的性能。

关 键 词：BIOREACTOR Manufacturing Monitoring sensors and automation Regenerative medicine Tissue engineering 

分 类 号：G63[文化科学—教育学]