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揭示力学生物学:一种用于在纳米纤维基质上进行单轴机械刺激的紧凑型装置及其对细胞行为和纳米颗粒分布的影响。

Unveiling Mechanobiology: A Compact Device for Uniaxial Mechanical Stimulation on Nanofiber Substrates and Its Impact on Cellular Behavior and Nanoparticle Distribution.

作者信息

Basak Soumyadeep, Tiwari Ayush, Sharma Deepanshu, Packirisamy Gopinath

机构信息

Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee, Haridwar, Uttarakhand 247667, India.

Centre for Nanotechnology, Indian Institute of Technology Roorkee, Roorkee, Haridwar, Uttarakhand 247667, India.

出版信息

ACS Appl Bio Mater. 2024 Apr 15;7(4):2283-2298. doi: 10.1021/acsabm.3c01285. Epub 2024 Mar 11.

Abstract

Biotechnology and its allied sectors, such as tissue culture, regenerative medicine, and personalized medicine, primarily rely upon extensive studies on cellular behavior and their molecular pathways for generating essential knowledge and innovative strategies for human survival. Most such studies are performed on flat, adherent, plastic-based surfaces and use nanofiber and hydrogel-like soft matrices from the past few decades. However, such static culture conditions cannot mimic the immediate cellular microenvironment, where they perceive or generate a myriad of different mechanical forces that substantially affect their downstream molecular pathways. Including such mechanical forces, still limited to specialized laboratories, using a few commercially available or noncommercial technologies are gathering increasing attention worldwide. However, large-scale consideration and adaptation by developing nations have yet to be achieved due to the lack of a cost-effective, reliable, and accessible solution. Moreover, investigations on cellular response upon uniaxial mechanical stretch cycles under more in vivo mimetic conditions are yet to be studied comprehensively. In order to tackle these obstacles, we have prepared a compact, 3D-printed device using a microcontroller, batteries, sensors, and a stepper motor assembly that operates wirelessly and provides cyclic mechanical attrition to any thin substrate. We have fabricated water-stable and stretchable nanofiber substrates with different fiber orientations by using the electrospinning technique to investigate the impact of mechanical stretch cycles on the morphology and orientation of C2C12 myoblast-like cells. Additionally, we have examined the uptake and distribution properties of BSA-epirubicin nanoparticles within cells under mechanical stimulation, which could act as fluorescently active drug-delivery agents for future therapeutic applications. Consequently, our research offers a comprehensive analysis of cellular behavior when cells are subjected to uniaxial stretching on various nanofiber mat architectures. Furthermore, we present a cost-effective alternative solution that addresses the long-standing requirement for a compact, user-friendly, and tunable device, enabling more insightful outcomes in mechanobiology.

摘要

生物技术及其相关领域,如组织培养、再生医学和个性化医学,主要依靠对细胞行为及其分子途径的广泛研究,以生成人类生存所需的基本知识和创新策略。在过去几十年中,大多数此类研究是在基于塑料的平坦、贴壁表面上进行的,并使用纳米纤维和水凝胶状的软基质。然而,这种静态培养条件无法模拟细胞的直接微环境,在该环境中,细胞感知或产生无数不同的机械力,这些力会极大地影响其下游分子途径。包括此类机械力的研究,仍局限于专业实验室,使用一些商业上可用或非商业技术,在全球范围内正受到越来越多的关注。然而,由于缺乏具有成本效益、可靠且易于使用的解决方案,发展中国家尚未实现大规模的考虑和应用。此外,在更接近体内模拟条件下,关于单轴机械拉伸循环对细胞反应的研究尚未得到全面开展。为了克服这些障碍,我们制备了一种紧凑的3D打印设备,该设备使用微控制器、电池、传感器和步进电机组件,可无线操作并为任何薄基板提供循环机械磨损。我们通过静电纺丝技术制造了具有不同纤维取向的水稳定且可拉伸的纳米纤维基板,以研究机械拉伸循环对C2C12成肌样细胞形态和取向的影响。此外,我们研究了在机械刺激下细胞内BSA-表柔比星纳米颗粒的摄取和分布特性,这些纳米颗粒可作为未来治疗应用中的荧光活性药物递送剂。因此,我们的研究提供了对细胞在各种纳米纤维垫结构上进行单轴拉伸时细胞行为的全面分析。此外,我们提出了一种具有成本效益的替代解决方案,满足了对紧凑、用户友好且可调谐设备的长期需求,能够在机械生物学中获得更有洞察力的结果。

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