Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics

Yang, Boguang; Wei, Kongchang; Loebel, Claudia; Zhang, Kunyu; Qian, Feng; Li, Rui; Wong, Siu Hong Dexter; Xu, Xiayi; Lau, Chunhon; Chen, Xiaoyu; Zhao, Pengchao; Yin, Chao; Burdick, Jason A.; Wang, Yi; Bian, Liming

doi:10.1038/s41467-021-23120-0

Cited by 129 publications

(113 citation statements)

References 54 publications

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“…Accumulative evidences have shown that the harbored cells can in real time perceive and respond to the surrounding microenvironment changes induced by external stimuli in a spatial- and temporal-controlled manner. 35 – 39 By adjusting intracellular signaling events such as dynamical integrin clustering regulation, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, environmental cues-responsive proteins (e.g., Yes-associated protein (YAP), transcriptional co-activator with a PDZ-binding motif (TAZ), catenin, etc.) activation, gene expression, etc., cells displayed different biological characteristics and behaviors.…”

Section: Introductionmentioning

confidence: 99%

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Cao

Duan

Yan

et al. 2021

Sig Transduct Target Ther

480

256

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Hydrogel is a type of versatile platform with various biomedical applications after rational structure and functional design that leverages on material engineering to modulate its physicochemical properties (e.g., stiffness, pore size, viscoelasticity, microarchitecture, degradability, ligand presentation, stimulus-responsive properties, etc.) and influence cell signaling cascades and fate. In the past few decades, a plethora of pioneering studies have been implemented to explore the cell–hydrogel matrix interactions and figure out the underlying mechanisms, paving the way to the lab-to-clinic translation of hydrogel-based therapies. In this review, we first introduced the physicochemical properties of hydrogels and their fabrication approaches concisely. Subsequently, the comprehensive description and deep discussion were elucidated, wherein the influences of different hydrogels properties on cell behaviors and cellular signaling events were highlighted. These behaviors or events included integrin clustering, focal adhesion (FA) complex accumulation and activation, cytoskeleton rearrangement, protein cyto-nuclei shuttling and activation (e.g., Yes-associated protein (YAP), catenin, etc.), cellular compartment reorganization, gene expression, and further cell biology modulation (e.g., spreading, migration, proliferation, lineage commitment, etc.). Based on them, current in vitro and in vivo hydrogel applications that mainly covered diseases models, various cell delivery protocols for tissue regeneration and disease therapy, smart drug carrier, bioimaging, biosensor, and conductive wearable/implantable biodevices, etc. were further summarized and discussed. More significantly, the clinical translation potential and trials of hydrogels were presented, accompanied with which the remaining challenges and future perspectives in this field were emphasized. Collectively, the comprehensive and deep insights in this review will shed light on the design principles of new biomedical hydrogels to understand and modulate cellular processes, which are available for providing significant indications for future hydrogel design and serving for a broad range of biomedical applications.

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Section: Introductionmentioning

confidence: 99%

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Cao

Duan

Yan

et al. 2021

Sig Transduct Target Ther

480

256

View full text Add to dashboard Cite

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“…In this context, hydrogels with dynamic characteristics, which are accomplished either through the integration of degradable structural compounds or reversible dynamic cross-links, permit efficient accommodation of cells to the matrix and aid in the achievement of the connected cellular specific functions (B. Yang et al, 2021 ). Since, it is well known that cancer cells can alter their extracellular matrix environment by secreting of molecules ( Dhar et al, 2018 ; Kano, 2015 ), release of exosomes ( Hoshino et al, 2015 ), degrading ( Stephens et al, 2019 ), re-orientating (aligning) (B.…”

Section: Environmental Matrix Viscoelasticity Acts On Cellsmentioning

confidence: 99%

Viscoelasticity Acts as a Marker for Tumor Extracellular Matrix Characteristics

Mierke

2021

Front. Cell Dev. Biol.

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Biological materials such as extracellular matrix scaffolds, cancer cells, and tissues are often assumed to respond elastically for simplicity; the viscoelastic response is quite commonly ignored. Extracellular matrix mechanics including the viscoelasticity has turned out to be a key feature of cellular behavior and the entire shape and function of healthy and diseased tissues, such as cancer. The interference of cells with their local microenvironment and the interaction among different cell types relies both on the mechanical phenotype of each involved element. However, there is still not yet clearly understood how viscoelasticity alters the functional phenotype of the tumor extracellular matrix environment. Especially the biophysical technologies are still under ongoing improvement and further development. In addition, the effect of matrix mechanics in the progression of cancer is the subject of discussion. Hence, the topic of this review is especially attractive to collect the existing endeavors to characterize the viscoelastic features of tumor extracellular matrices and to briefly highlight the present frontiers in cancer progression and escape of cancers from therapy. Finally, this review article illustrates the importance of the tumor extracellular matrix mechano-phenotype, including the phenomenon viscoelasticity in identifying, characterizing, and treating specific cancer types.

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“…Hydrogels containing more crosslinks promote osteogenic differentiation of the encapsulated cells. Bian et al demonstrated better spreading and osteogenic differentiation of encapsulated cells in hydrogels with large dissociation rate constants than those of hydrogels with low dissociation rate constants, which was dependent on the concerted action of the cell adhesion structures containing β1 integrins ( Yang et al, 2021 ). This indicates that the biofunctionalization of hydrogels also crucial for realizing ECM mimetic effects.…”

Section: Dynamic Biomaterial-mediated Stem Cell Fate Modulationmentioning

confidence: 99%

Mechanobiological Strategies to Enhance Stem Cell Functionality for Regenerative Medicine and Tissue Engineering

Shafiq

Ali

Han

et al. 2021

Front. Cell Dev. Biol.

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Stem cells have been extensively used in regenerative medicine and tissue engineering; however, they often lose their functionality because of the inflammatory microenvironment. This leads to their poor survival, retention, and engraftment at transplantation sites. Considering the rapid loss of transplanted cells due to poor cell-cell and cell-extracellular matrix (ECM) interactions during transplantation, it has been reasoned that stem cells mainly mediate reparative responses via paracrine mechanisms, including the secretion of extracellular vesicles (EVs). Ameliorating poor cell-cell and cell-ECM interactions may obviate the limitations associated with the poor retention and engraftment of transplanted cells and enable them to mediate tissue repair through the sustained and localized presentation of secreted bioactive cues. Biomaterial-mediated strategies may be leveraged to confer stem cells enhanced immunomodulatory properties, as well as better engraftment and retention at the target site. In these approaches, biomaterials have been exploited to spatiotemporally present bioactive cues to stem cell-laden platforms (e.g., aggregates, microtissues, and tissue-engineered constructs). An array of biomaterials, such as nanoparticles, hydrogels, and scaffolds, has been exploited to facilitate stem cells function at the target site. Additionally, biomaterials can be harnessed to suppress the inflammatory microenvironment to induce enhanced tissue repair. In this review, we summarize biomaterial-based platforms that impact stem cell function for better tissue repair that may have broader implications for the treatment of various diseases as well as tissue regeneration.

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Enhanced mechanosensing of cells in synthetic 3D matrix with controlled biophysical dynamics

Cited by 129 publications

References 54 publications

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Current hydrogel advances in physicochemical and biological response-driven biomedical application diversity

Viscoelasticity Acts as a Marker for Tumor Extracellular Matrix Characteristics

Mechanobiological Strategies to Enhance Stem Cell Functionality for Regenerative Medicine and Tissue Engineering

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