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

Shou, Yufeng; Teo, Xin Yong; Li, Xianlei; Le, Zhicheng; Liu, Ling; Sun, Xinhong; Jonhson, Win; Ding, Jun; Lim, Chwee Teck; Tay, Andy

doi:10.1021/acsnano.2c11278

Cited by 24 publications

(18 citation statements)

References 103 publications

(177 reference statements)

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“…[118] Readers are encouraged to refer to published papers for the advantages and limitations of these approaches. [25,26]…”

Section: Stiffnessmentioning

confidence: 99%

“…[23,24] These stimuli-responsive hydrogels have been shown in proofof-concept studies to direct targeted cellular responses, and some have even led to appreciable outcomes for disease treatment. [25] There are significant technical obstacles to replicate the native ECM in vitro. One of the major difficulties is simulating the native dynamic structural remodeling of ECM.…”

Section: Introductionmentioning

confidence: 99%

“…[ 23,24 ] These stimuli‐responsive hydrogels have been shown in proof‐of‐concept studies to direct targeted cellular responses, and some have even led to appreciable outcomes for disease treatment. [ 25 ]…”

Section: Introductionmentioning

confidence: 99%

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Dynamic Stimulations with Bioengineered Extracellular Matrix‐Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy

Shou

Teo

et al. 2023

Advanced Science

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Cells interact with their surrounding environment through a combination of static and dynamic mechanical signals that vary over stimulus types, intensity, space, and time. Compared to static mechanical signals such as stiffness, porosity, and topography, the current understanding on the effects of dynamic mechanical stimulations on cells remains limited, attributing to a lack of access to devices, the complexity of experimental set-up, and data interpretation. Yet, in the pursuit of emerging translational applications (e.g., cell manufacturing for clinical treatment), it is crucial to understand how cells respond to a variety of dynamic forces that are omnipresent in vivo so that they can be exploited to enhance manufacturing and therapeutic outcomes. With a rising appreciation of the extracellular matrix (ECM) as a key regulator of biofunctions, researchers have bioengineered a suite of ECM-mimicking hydrogels, which can be fine-tuned with spatiotemporal mechanical cues to model complex static and dynamic mechanical profiles. This review first discusses how mechanical stimuli may impact different cellular components and the various mechanobiology pathways involved. Then, how hydrogels can be designed to incorporate static and dynamic mechanical parameters to influence cell behaviors are described. The Scopus database is also used to analyze the relative strength in evidence, ranging from strong to weak, based on number of published literatures, associated citations, and treatment significance. Additionally, the impacts of static and dynamic mechanical stimulations on clinically relevant cell types including mesenchymal stem cells, fibroblasts, and immune cells, are evaluated. The aim is to draw attention to the paucity of studies on the effects of dynamic mechanical stimuli on cells, as well as to highlight the potential of using a cocktail of various types and intensities of mechanical stimulations to influence cell fates (similar to the concept of biochemical cocktail to direct cell fate). It is envisioned that this progress report will inspire more exciting translational development of mechanoresponsive hydrogels for biomedical applications.

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“…[118] Readers are encouraged to refer to published papers for the advantages and limitations of these approaches. [25,26]…”

Section: Stiffnessmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Dynamic Stimulations with Bioengineered Extracellular Matrix‐Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy

Shou

Teo

et al. 2023

Advanced Science

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“…Their findings revealed that matrix stiffening promoted malignancies, while matrix softening downregulated the expression of mechano-transductors. 24 While, in that study, the whole matrix stiffness could be rapidly altered to measure downstream effects, the influence of dynamic mechanical compression and strain of the network generated from individual point sources, like individual cells, remains to be studied. This work applies magnetically controlled microscale actuation of 3D tumor invasion assays over several days of culture.…”

Section: Introductionmentioning

confidence: 99%

Magnetically Controlled Cyclic Microscale Deformation ofIn VitroCancer Invasion Models

Asgeirsson

Mehta

Hesse

et al. 2023

Preprint

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Mechanical cues play an important role in the metastatic cascade of cancer. Three-dimensional (3D) tissue matrices with tunable stiffness have been extensively used as model systems of the tumor microenvironment for physiologically relevant studies. Tumor-associated cells actively deform these matrices, providing mechanical cues to other cancer cells residing in the tissue. Mimicking such dynamic deformation in the surrounding tumor matrix may help clarify the effect of local strain on cancer cell invasion. Remotely controlled microscale magnetic actuation of such 3D in vitro systems is a promising approach, offering a non-invasive means for in situ interrogation. Here, we investigate the influence of cyclic deformation on tumor spheroids embedded in matrices, continuously exerted for days by cell-sized anisotropic magnetic probes, referred to as uRods. Particle velocimetry analysis revealed the spatial extent of matrix deformation produced in response to a magnetic field, which was found to be on the order of 200 um, resembling strain fields reported to originate from contracting cells. Intracellular calcium influx was observed in response to cyclic actuation, as well as an influence on cancer cell invasion from 3D spheroids, as compared to unactuated controls. Localized actuation at one side of a tumor spheroid tended to result in anisotropic invasion toward the uRods causing the deformation. In summary, our approach offers a strategy to test and control the influence of non-invasive micromechanical cues on cancer cell invasion and metastasis.

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“…Their findings revealed that matrix stiffening promoted malignancies, while matrix softening downregulated the expression of mechano-transductors. 26 While, in that study, the whole matrix stiffness could be rapidly altered to measure downstream effects, the influence of dynamic mechanical compression and strain of the network generated from individual point sources, like individual cells, remains to be studied.…”

Section: Introductionmentioning

confidence: 99%

Magnetically controlled cyclic microscale deformation of in vitro cancer invasion models

Asgeirsson,

Mehta,

Scheeder

et al. 2023

Biomater. Sci.

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

Cited by 24 publications

References 103 publications

Dynamic Stimulations with Bioengineered Extracellular Matrix‐Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy

Dynamic Stimulations with Bioengineered Extracellular Matrix‐Mimicking Hydrogels for Mechano Cell Reprogramming and Therapy

Magnetically Controlled Cyclic Microscale Deformation ofIn VitroCancer Invasion Models

Magnetically controlled cyclic microscale deformation of in vitro cancer invasion models

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