Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system

Shou, Yufeng; Johnson, Sarah C.; Quek, Ying Jie; Li, Xianlei; Tay, Andy

doi:10.1016/j.mtbio.2022.100269

Cited by 15 publications

(22 citation statements)

References 313 publications

(354 reference statements)

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“…To further elucidate the mechanism underlying increased ECM stiffness and tumor progression, researchers have developed a variety of artificial ECM-like hydrogel scaffolds with tunable stiffness to mimic the mechanical profile of tumor microenvironment for studying stiffness-dependent tumor behaviors. − Nonetheless, most of these systems lack control of mechanical cues across time to recapitulate dynamic in vivo conditions, resulting in poor predictability of cellular responses from these platforms. To address this limitation, there has been increasing interest in developing platforms to provide dynamically changing mechanical stiffness through on-demand application of external stimuli (refer to Table S1 for a list).…”

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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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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“…This is useful in fabricating tissue with specific structures such as artificial skin with fibroblasts and epithelial cells (e.g., keratinocyte), or organs with different function microzones such as lymph node (i.e., T/B cell zone), which are directed by matrix stiffness and porous structure. [18,261] These artifacts in most cases are constructed by degradable bio-ink which will be gradually disintegrated and replaced by regenerated tissues and ECM components. [343] In addition to tissue engineering, by using secondary crosslinking (e.g., photochemistry and enzyme) or external stimuli (e.g., magnetic field and temperature), it is possible to modulate stiffening/softening process on specially crafted hydrogels, [26] providing researchers with a reliable drug screening platform to simulate the drug/therapeutic efficacy under stiffening/softening conditions.…”

Section: Mechano-stimulated Hydrogel To Enhance Clinical Translationmentioning

confidence: 99%

“…Generally, they are divided into three types: lymphocytes (i.e., T cells, B cells, and natural killer cells), neutrophils, and monocytes/macrophages. [ 18 ] Given the central roles of immune cells in the immune system, immense efforts have been made over the past decade to delineate immune cell biology and how to manipulate their behaviors. [ 261 ] As of December 2022, there are ≈12 000 registered clinical trials worldwide listed on ClinicalTrials.gov that use T cells for immunotherapy, especially in cancer treatment.…”

Section: Engineering Hydrogel For Cellular Mechanical Stimulationmentioning

confidence: 99%

“…Most importantly, many ECM proteins (e.g., laminin, collagen, fibronectin) and their associated protein derivatives (e.g., RGD, GFOGER, YIGSR) can be incorporated into the gel formulation to yield the gels properties that are similar to native ECM. [18][19][20] To study cell-ECM mechanocommunications using hydrogels, cells are typically cultured within gels with fixed mechanical properties. Mechanical properties include stiffness, strain, porosity, topography, and cell adhesivity have been extensively studied under static settings.…”

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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“…Conventional methods using 2D tissue culture plates or bioreactors with 2.5D microcarriers can achieve ideal cell expansion rate, but these culturing platforms reduce stem cell potency which cause inconsistent therapeutic effectiveness [ 10 ]. While culturing MSCs in 3D biomaterials such as hydogels is less scalable, this helps to reduce cellular senescence, increase cell-matrix interaction, and improve MSC self-renewal and differentiation potential [ [10] , [11] , [12] , [13] , [14] ]. To the best of our knowledge, biomaterial-based MSC manufacturing has been limited to academic interests; (2) Mechanical pre-conditioning.…”

Section: Introductionmentioning

confidence: 99%

Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

Shou

Liu

et al. 2023

Bioactive Materials

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Integrative lymph node-mimicking models created with biomaterials and computational tools to study the immune system

Cited by 15 publications

References 313 publications

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

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

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

Mechano-responsive hydrogel for direct stem cell manufacturing to therapy

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