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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Stem Cells. Aug 26, 2026; 18(8): 121713
Published online Aug 26, 2026. doi: 10.4252/wjsc.121713
Applying microfluidic techniques for biomaterial and mechanical regulation of mesenchymal stem cells
Bing-Qi Song, Jing Du, Xiao-Ming Li
Bing-Qi Song, Jing Du, Xiao-Ming Li, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Key Laboratory of Innovation and Transformation of Advanced Medical Devices of Ministry of Industry and Information Technology, National Medical Innovation Platform for Industry-Education Integration in Advanced Medical Devices (Interdiscipline of Medicine and Engineering), Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
Co-corresponding authors: Jing Du and Xiao-Ming Li.
Author contributions: Song BQ investigated the literatures, wrote the original draft, prepared the illustrations, and reviewed and edited the manuscript; Li XM and Du J contributed equally to this work as co-corresponding authors, responsible for funding acquisition, conceptualization, study design, supervision, and critical revision of the manuscript.
AI contribution statement: This manuscript only used AI tools (specifically ChatGPT) for language polishing and formatting assistance. The AI tool did not participate in the entire process of research data generation, result interpretation, conclusion writing, literature selection, or figure generation. All content generated by artificial intelligence has been strictly reviewed and revised by the author.
Supported by Beijing Natural Science Foundation, No. L251086 and No. L248028; and the National Natural Science Foundation of China, No. 32571560 and No. 82273500.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Xiao-Ming Li, PhD, Professor, Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Key Laboratory of Innovation and Transformation of Advanced Medical Devices of Ministry of Industry and Information Technology, National Medical Innovation Platform for Industry-Education Integration in Advanced Medical Devices (Interdiscipline of Medicine and Engineering), Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, No. 37 Xueyuan Road, Haidian District, Beijing 100191, China. x.m.li@hotmail.com
Received: April 1, 2026
Revised: May 7, 2026
Accepted: June 4, 2026
Published online: August 26, 2026
Processing time: 142 Days and 1 Hours
Abstract

Mesenchymal stem cells (MSCs) hold great promise for tissue repair and regeneration. The therapeutic efficacy of MSCs depends on the precise regulation of their proliferation and differentiation. In vivo, this process is synergistically modulated by extracellular matrix-derived biochemical cues and mechanical stress-dominated biophysical stimuli. However, traditional two-dimensional culture systems fail to replicate the complex three-dimensional microenvironment. In addition, population-averaged assays are often confounded by cellular heterogeneity and paracrine effects, which notably limits our mechanistic understanding of MSC fate determination. Microfluidic techniques, with high throughput, high accuracy and integration, provide powerful tools to overcome these limitations. In this review, we summarize recent research progress in the use of microfluidic techniques to investigate the mechanisms of MSC regulation. We outline the roles of biomaterials and mechanical stress in MSC-mediated repair processes, and highlight typical applications of microfluidic techniques in cell sorting and heterogeneity analysis, precise loading of biomaterials and mechanical stress, and dynamic phenotypic tracking of MSCs. We then discuss the current challenges and future directions in stem cell therapy, providing a methodological framework for MSC investigation and accelerating clinical translation.

Keywords: Microfluidic techniques; Mesenchymal stem cells; Biomaterials; Mechanical stress; Single-cell analysis; Three-dimensional cell culture

Core Tip: This review organizes microfluidic applications for mesenchymal stem cell research into three sequential stages: Cell quality control to acquire pure subpopulations, microenvironment engineering to replicate the physiological microenvironment, and phenotypic monitoring to track real-time responses. These continuous stages consequently link raw cell preparation to functional readout. To accelerate the clinical adoption of stem cell therapies, we propose that integration, intelligence, and scalable manufacturing are crucial directions for microfluidic systems.

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