Magnetic nanocomposite hydrogel with tunable stiffness for probing cellular responses to matrix stiffening

Yan, Tianhao; Rao, Depeng; Chen, Ye; Wang, Yu; Zhang, Qingchuan; Wu, Shangquan

doi:10.1016/j.actbio.2021.11.001

Cited by 24 publications

(24 citation statements)

References 52 publications

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“…MSCs under stronger DMS were elongated and polygonal, with ∼2.2-fold increase in cell area and larger cell shape factors (i.e., larger cell aspect ratio and smaller circularity) than MSCs under static cultivation which were smaller and spherical ( Fig. 2 e,f and S16 ) likely attributing to focal adhesion maturation and cytoskeleton assembly as demonstrated in previous works [ [62] , [63] , [64] , [65] ]. As shown in Fig.…”

Section: Resultssupporting

confidence: 72%

“…2 d and S16 , stronger DMS resulted in more pronounced actin stress fibers (i.e., F-actin) and punctuated vinculin accumulation (a key component of focal adhesion site) in MSCs. The enhanced expression of vinculin likely connected the F-actin bundle to focal adhesion site, leading to stronger cell adhesion and ultimately influenced cell morphology [ 64 , 66 ].…”

Section: Resultsmentioning

confidence: 99%

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Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Shou

Liu

et al. 2023

Bioactive Materials

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Section: Resultssupporting

confidence: 72%

Section: Resultsmentioning

confidence: 99%

Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Shou

Liu

et al. 2023

Bioactive Materials

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“…The recent development of magnetically actuated hydrogels provides an alternative to study dynamic cancer behaviors, and it has been found that magneto-induced strain-stiffening of hydrogels can significantly influence cancer cell morphology and activities through increased cell-ECM interaction, matrix solid stress, and cytoskeleton assembly. 16,27,32,33 A major advantage using remote magnetic fields to control matrix stiffness is that magnetic materials can be modulated wirelessly without physical contact and any magnetically induced changes in ECM mechanical properties are completely reversible.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, long duration exposure to enzyme and light irradiation also heightens the risks of undesirable mitochondrial DNA damage, protein denaturation, and cell apoptosis which can alter experimental outcomes. ,, Methods using pH and temperature can achieve reversible stiffness variation (i.e., both stiffening and softening processes) multiple times, but they are likely to affect cell fate and activity, , making it challenging to distinguish cellular response to dynamic matrix changes from pH/temperature influences. The recent development of magnetically actuated hydrogels provides an alternative to study dynamic cancer behaviors, and it has been found that magneto-induced strain-stiffening of hydrogels can significantly influence cancer cell morphology and activities through increased cell-ECM interaction, matrix solid stress, and cytoskeleton assembly. ,,, A major advantage using remote magnetic fields to control matrix stiffness is that magnetic materials can be modulated wirelessly without physical contact and any magnetically induced changes in ECM mechanical properties are completely reversible.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Magneto-Softening of 3D Hydrogel Reverses Malignant Transformation of Cancer Cells and Enhances Drug Efficacy

Shou

Teo

et al. 2023

ACS Nano

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High extracellular matrix stiffness is a prominent feature of malignant tumors associated with poor clinical prognosis. To elucidate mechanistic connections between increased matrix stiffness and tumor progression, a variety of hydrogel scaffolds with dynamic changes in stiffness have been developed. These approaches, however, are not biocompatible at high temperature, strong irradiation, and acidic/basic pH, often lack reversibility (can only stiffen and not soften), and do not allow study on the same cell population longitudinally. In this work, we develop a dynamic 3D magnetic hydrogel whose matrix stiffness can be wirelessly and reversibly stiffened and softened multiple times with different rates of change using an external magnet. With this platform, we found that matrix stiffness increased tumor malignancy including denser cell organization, epithelial-to-mesenchymal transition and hypoxia. More interestingly, these malignant transformations could be halted or reversed with matrix softening (i.e., mechanical rescue), to potentiate drug efficacy attributing to reduced solid stress from matrix and downregulation of cell mechanotransductors including YAP1. We propose that our platform can be used to deepen understanding of the impact of matrix softening on cancer biology, an important but rarely studied phenomenon.

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“…Mesenchymal stem cells (MSCs) are a promising source of regenerative medicine for tissue engineering and regenerative therapeutics. Biophysical cues, such as matrix stiffness [3,4], surface topography [5][6][7], ligand spacing [8,9], and ligand dynamics [10][11][12][13], are shown to regulate cellular behaviors and cell fates. In particular, MSCs can sense and respond to matrix stiffness, which is indicated by Young's modulus and represents the elasticity of the matrix [2].…”

Section: Introductionmentioning

confidence: 99%

Integrating Soft Hydrogel with Nanostructures Reinforces Stem Cell Adhesion and Differentiation

Yin

Yang

2022

J. Compos. Sci.

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Biophysical cues can regulate stem cell behaviours and have been considered as critical parameters of synthetic biomaterials for tissue engineering. In particular, hydrogels have been utilized as promising biomimetic and biocompatible materials to emulate the microenvironment. Therefore, well-defined mechanical properties of a hydrogel are important to direct desirable phenotypes of cells. Yet, limited research pays attention to engineering soft hydrogel with improved cell adhesive property, which is crucial for stem cell differentiation. Herein, we introduce silica nanoparticles (SiO2 NPs) onto the surface of methacrylated hyaluronic (MeHA) hydrogel to manipulate the presentation of cell adhesive ligands (RGD) clusters, while remaining similar bulk mechanical properties (2.79 ± 0.31 kPa) to that of MeHA hydrogel (3.08 ± 0.68 kPa). RGD peptides are either randomly decorated in the MeHA hydrogel network or on the immobilized SiO2 NPs (forming MeHA–SiO2). Our results showed that human mesenchymal stem cells exhibited a ~1.3-fold increase in the percentage of initial cell attachment, a ~2-fold increase in cell spreading area, and enhanced expressions of early-stage osteogenic markers (RUNX2 and alkaline phosphatase) for cells undergoing osteogenic differentiation with the osteogenic medium on MeHA–SiO2 hydrogel, compared to those cultured on MeHA hydrogel. Importantly, the cells cultivated on MeHA–SiO2 expressed a ~5-fold increase in nuclear localization ratio of the yes-associated protein, which is known to be mechanosensory in stem cells, compared to the cells cultured on MeHA hydrogel, thereby promoting osteogenic differentiation of stem cells. These findings demonstrate the potential use of nanomaterials into a soft polymeric matrix for enhanced cell adhesion and provide valuable guidance for the rational design of biomaterials for implantation.

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Magnetic nanocomposite hydrogel with tunable stiffness for probing cellular responses to matrix stiffening

Cited by 24 publications

References 52 publications

Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Dynamic Magneto-Softening of 3D Hydrogel Reverses Malignant Transformation of Cancer Cells and Enhances Drug Efficacy

Integrating Soft Hydrogel with Nanostructures Reinforces Stem Cell Adhesion and Differentiation

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