Xie Wanqing, Xing Yuan, Xiao Li, Zhang Pu, Oh Richard, Zhang Yangpu, Yu Xiaoyu, He Yi, Oh Eunha G, Cao Ruofan, Ramasubramanian Melur K, Wang Yong, Jin Li, Oberhozler Jose, Li Xudong
Department of Orthopaedic Surgery, University of Virginia, Charlottesville, VA 22908, USA.
Department of Surgery, University of Virginia, 345 Cripell Drive, Charlottesville, VA 22908, USA.
Adv Mater Technol. 2023 Nov 10;8(21). doi: 10.1002/admt.202300606. Epub 2023 Aug 27.
This study aims to develop an organ-on-a-chip model, intervertebral Disc-on-a-Chip, to investigate integrated effects of mechanical loading and nutrition on disc health. The system consists of a detachable multilayer microfluidic chip, a Computer-Arduino-based control system, and a mechanical loading unit, which were optimized for accurate axial force measurement and the maintenance of a 21-day disc culture. To ensure accuracy of axial force, we optimized the axial mechanical loading regimen, used the Computer-Arduino-based system and low-profile force sensors (LPFS) to control the mechanical loading unit, and modeled the force distribution by using computational simulation. A 21-day disc culture was demonstrated using the Disc-on-a-Chip system, with optimized mechanical loading (0.02 MPa at 1Hz, 1.5 hr/day) and flow rate (1 μL/min). The structural integrity, collagen breakdown, catabolic enzyme activities, and disc cell and collagen alignment revealed that the on-chip cultured discs exhibited a preferred disc health similar to that of native discs for up to 21 days, while discs in a static culture showed detrimental degenerative changes. The mouse Disc-on-a-Chip system mimics disc microenvironment and provides a valuable platform for studying the effects of various factors on disc health and degeneration and testing new therapies.
本研究旨在开发一种芯片上的器官模型——芯片上的椎间盘，以研究机械负荷和营养对椎间盘健康的综合影响。该系统由一个可拆卸的多层微流控芯片、一个基于计算机- Arduino的控制系统和一个机械加载单元组成，这些组件经过优化，可实现精确的轴向力测量和维持21天的椎间盘培养。为确保轴向力的准确性，我们优化了轴向机械加载方案，使用基于计算机- Arduino的系统和薄型力传感器（LPFS）来控制机械加载单元，并通过计算模拟对力分布进行建模。使用芯片上的椎间盘系统进行了21天的椎间盘培养，采用了优化的机械负荷（1Hz下0.02MPa，每天1.5小时）和流速（1μL/分钟）。结构完整性、胶原蛋白分解、分解代谢酶活性以及椎间盘细胞和胶原蛋白排列表明，芯片上培养的椎间盘在长达21天的时间内表现出与天然椎间盘相似的良好椎间盘健康状况，而静态培养的椎间盘则出现了有害的退行性变化。小鼠芯片上的椎间盘系统模拟了椎间盘微环境，为研究各种因素对椎间盘健康和退变的影响以及测试新疗法提供了一个有价值的平台。
