Stem cell migration is a tightly regulated process in vivo, orchestrated by a collection of mechanical and chemotactic cues via concentration gradients. A variety of in vitro assays have been developed to facilitate cell migration studies; however, very few assays allow the investigation of both matrix stiffness and chemotactic cues on cell migration within a single device, especially in a three-dimensional (3D) environment. Here, we develop a microfluidic device that can produce 3D orthogonal gradients of matrix stiffness and chemotactic cues with varied steepness in a suspended array of hydrogel cylinders. The device's working principle is the formation of diffusion-driven concentration gradients within a suspended array of hydrogel cylinders between a source and a sink. Device fabrication is based on poly(dimethylsiloxane) (PDMS) replica molding, followed by assembly on a glass substrate. To validate this device, we study the migration of human mesenchymal stem cells (hMSCs) in response to orthogonal gradients of matrix stiffness and stromal cell-derived factor 1 alpha (SDF-1α). This technology has the potential to be applied to various cell types, facilitating exploration in different cellular contexts.
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http://dx.doi.org/10.1021/acssensors.4c02793 | DOI Listing |
Mater Today Bio
April 2025
Shanghai Clinical Research and Trial Center, Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai, 201210, China.
The mechanical properties and physical confinement of the extracellular matrix (ECM) are crucial roles in regulating tumor growth and progression. Extensive efforts have been dedicated to replicating the physical characteristics of tumor tissue by developing two-dimensional (2D) and three-dimensional (3D) models. However, it remains a significant challenge to modulate the local microenvironment around the specific cells according to the culture progress.
View Article and Find Full Text PDFFront Pharmacol
February 2025
Department of Biochemistry, Faculty of Pharmacy, Menoufia University, Shebin EL-Kom, Menoufia, Egypt.
Introduction: Understanding the molecular mechanism underlying the pathogenesis of knee osteoarthritis (KOA) may be beneficial in fetching new therapeutics. Our study aims to investigate the implication of Wnt/ β-catenin pathway in development of KOA by detection of the downstream target genes and their crosstalk with miR-214 in patients with KOA and to correlate that with the clinical findings.
Methods: Sixty participants were involved in the study.
Differentiation
March 2025
Department of Biological Sciences, University of Delaware, Newark, DE, USA; Department of Biomedical Engineering, University of Delaware, Newark, DE, USA. Electronic address:
Articular cartilage is an avascular tissue that allows for frictionless mobility of joints. Unfortunately, cartilage is incapable of self-repair and any damage leads to degradation in osteoarthritis (OA). Autologous chondrocyte implantation therapies are currently being used to treat focal cartilage defects caused by post-traumatic OA (PTOA).
View Article and Find Full Text PDFAm J Physiol Heart Circ Physiol
March 2025
Biomedical Engineering Program, College of Engineering and Computing, University of South Carolina, Columbia, SC 29201.
Endothelial dysfunction, defined as a reduction in the bioavailability of nitric oxide (NO), is a risk factor for the occurrence and progression of various vascular diseases. This study investigates the effect of endothelial dysfunction on age-related changes in aortic extracellular matrix (ECM) microstructure and the relationship between microstructural adaptation and the mechanical response. Here, we used groups of NOS3 knockout (KO), NOS3 heterozygotes (Het), and wild type (WT) B6 mice (controls) to study changes in hemodynamic parameters, collagen fiber organization, and both active and passive aortic mechanics using biaxial pressure myography over a time course from 1.
View Article and Find Full Text PDFJ Gen Physiol
May 2025
Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
Marfan syndrome (MFS) is an autosomal dominant disease caused by mutations in the gene (FBN1) of fibrillin-1, a major determinant of the extracellular matrix (ECM). Functional impairment in the cardiac left ventricle (LV) of these patients is usually a consequence of aortic valve disease. However, LV passive stiffness may also be affected by chronic changes in mechanical load and ECM dysfunction.
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