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基于明胶甲基丙烯酸酯的可生物降解磁性微机器人,具有大规模生产能力,可精确递送达干细胞。

A Biodegradable Magnetic Microrobot Based on Gelatin Methacrylate for Precise Delivery of Stem Cells with Mass Production Capability.

机构信息

Department of Robotics Engineering, DGIST-ETH Microrobotics Research Center Daegu Gyeong-buk Institute of Science and Technology (DGIST), Daegu, 42988, Republic of Korea.

IMsystem Co., Ltd., Daegu, 42988, Republic of Korea.

出版信息

Small. 2022 Jun;18(25):e2107888. doi: 10.1002/smll.202107888. Epub 2022 May 23.

DOI:10.1002/smll.202107888
PMID:35607749
Abstract

A great deal of research has focused on small-scale robots for biomedical applications and minimally invasive delivery of therapeutics (e.g., cells, drugs, and genes) to a target area. Conventional fabrication methods, such as two-photon polymerization, can be used to build sophisticated micro- and nanorobots, but the long fabrication cycle for a single microrobot has limited its practical use. This study proposes a biodegradable spherical gelatin methacrylate (GelMA) microrobot for mass production in a microfluidic channel. The proposed microrobot is fabricated in a flow-focusing droplet generator by shearing a mixture of GelMA, photoinitiator, and superparamagnetic iron oxide nanoparticles (SPIONs) with a mixture of oil and surfactant. Human nasal turbinate stem cells (hNTSCs) are loaded on the GelMA microrobot, and the hNTSC-loaded microrobot shows precise rolling motion in response to an external rotating magnetic field. The microrobot is enzymatically degraded by collagenase, and released hNTSCs are proliferated and differentiated into neuronal cells. In addition, the feasibility of the GelMA microrobot as a cell therapeutic delivery system is investigated by measuring electrophysiological activity on a multielectrode array. Such a versatile and fully biodegradable microrobot has the potential for targeted stem cell delivery, proliferation, and differentiation for stem cell-based therapy.

摘要

大量研究集中在用于生物医学应用的小型机器人以及用于将治疗剂(例如细胞、药物和基因)递送到靶区的微创输送。传统的制造方法,如双光子聚合,可以用于构建复杂的微纳米机器人,但单个微机器人的长制造周期限制了其实际应用。本研究提出了一种可生物降解的球形甲基丙烯酸明胶(GelMA)微机器人,用于在微流道中进行大规模生产。所提出的微机器人是在流聚焦式液滴发生器中制造的,通过将 GelMA、光引发剂和超顺磁性氧化铁纳米颗粒(SPIONs)的混合物与油和表面活性剂的混合物进行剪切。人鼻甲骨干细胞(hNTSCs)被加载到 GelMA 微机器人上,并且 hNTSC 加载的微机器人在外旋转磁场的作用下表现出精确的滚动运动。微机器人通过胶原酶进行酶降解,并且释放的 hNTSCs 增殖并分化为神经元细胞。此外,通过在多电极阵列上测量电生理活性来研究 GelMA 微机器人作为细胞治疗输送系统的可行性。这种多功能且完全可生物降解的微机器人具有用于靶向干细胞输送、增殖和分化的潜力,用于基于干细胞的治疗。

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