Degradation rate affords a dynamic cue to regulate stem cells beyond varied matrix stiffness

Peng, Yuanmeng; Liu, Qiong‐Jie; He, Tianlei; Yang, Kai; Yao, Xiang; Ding, Jiandong

doi:10.1016/j.biomaterials.2018.04.021

Cited by 127 publications

(90 citation statements)

References 78 publications

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“…[ 14 ] Dynamic matrix remodeling is essential for cell adhesion and homeostatic function. [ 15,16 ] Time‐variant matrix mechanical properties including creep, [ 17 ] stress relaxation, [ 18,19 ] stress‐stiffening, [ 20 ] and degradation [ 21,22 ] have all been shown to regulate cell adhesion and stem cell fate specification. While these studies and others have highlighted the importance of dynamic mechanical properties for cellular mechanotransduction, the molecular mechanisms underlying dynamic mechanosensing have yet to be fully described.…”

Section: Figurementioning

confidence: 99%

Ligand Diffusion Enables Force‐Independent Cell Adhesion via Activating α5β1 Integrin and Initiating Rac and RhoA Signaling

Hou

Xie

et al. 2020

Advanced Materials

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Cells reside in a dynamic microenvironment in which adhesive ligand availability, density, and diffusivity are key factors regulating cellular behavior. Here, the cellular response to integrin‐binding ligand dynamics by directly controlling ligand diffusivity via tunable ligand–surface interactions is investigated. Interestingly, cell spread on the surfaces with fast ligand diffusion is independent of myosin‐based force generation. Fast ligand diffusion enhances α5β1 but not αvβ3 integrin activation and initiates Rac and RhoA but not ROCK signaling, resulting in lamellipodium‐based fast cell spreading. Meanwhile, on surfaces with immobile ligands, αvβ3 and α5β1 integrins synergistically initiate intracellular‐force‐based canonical mechanotransduction pathways to enhance cell adhesion and osteogenic differentiation of stem cells. These results indicate the presence of heretofore‐unrecognized pathways, distinct from canonical actomyosin‐driven mechanisms, that are capable of promoting cell adhesion.

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Section: Figurementioning

confidence: 99%

Ligand Diffusion Enables Force‐Independent Cell Adhesion via Activating α5β1 Integrin and Initiating Rac and RhoA Signaling

Hou

Xie

et al. 2020

Advanced Materials

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“…As the degradation rate was vital to cell adhesion and differentiation, the degradation rate of SCS/P is of possible benefit to bone differentiation. 38 International Journal of Nanomedicine downloaded from https://www.dovepress.com/ by 44.224.250.200 on 12-Aug-2020 For personal use only.…”

Section: Physical Characterizationmentioning

confidence: 99%

<p>Delivery vehicle of muscle-derived irisin based on silk/calcium silicate/sodium alginate composite scaffold for bone regeneration</p>

Xin

et al. 2019

IJN

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Background: Irisin is a cytokine produced by skeletal muscle and usually plays a pivotal role in inducing fat browning and regulating energy expenditure. In recent years, it was found that irisin might be the molecular entity responsible for muscle-bone connectivity and is useful in osteogenesis induction. Materials and methods: To study its effect on bone regeneration, we developed silk/calcium silicate/sodium alginate (SCS) composite scaffold based on an interpenetrating network hydrogel containing silk fibroin, calcium silicate, sodium alginate. Then we loaded irisin on the SCS before coating it with polyvinyl alcohol (PVA). The SCS/P scaffold was physically characterized and some in vitro and in vivo experiments were carried out to evaluate the scaffold effect on bone regeneration. Results: The SCS/P scaffold was showed a porous sponge structure pursuant to scanning electron microscopy analysis. The release kinetics assay demonstrated that irisin was stably released from the irisin-loaded hybrid system (i/SCS/P system) to 50% within 7 days. Moreover, osteoinductive studies using bone marrow stem cells (BMSCs) in vitro exhibited the i/ SCS/P system improved the activity of alkaline phosphatase (ALP) and enhanced the expression levels of a series of osteogenic markers containing Runx-2, ALP, BMP2, Osterix, OCN, and OPN. Alizarin red staining also demonstrated the promotion of osteogenesis induced by i/SCS/P scaffolds. In addition, in vivo studies showed that increased bone regeneration with better mineralization and higher quality was found during the repair of rat calvarial defects through utilizing the i/SCS/P system. Conclusion: These data provided strong evidence that the composite i/SCS/P would be a promising substitute for bone tissue engineering.

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“…Engineering dynamic substrates that replicate the variations of biomechanical properties of ECM in vitro would be of high interest to better understand cell mechanotransduction, as well as develop strategies for understanding and controlling pathophysiological processes. There are few examples reported in the literature that uses external triggers to control biomaterial variations of stiffness in time and amplitude, with examples of decreasing elastic moduli due to hydrolysis or enzymatic remodeling of biodegradable polymers (Peng et al, 2018) or to exposure of photocleavable hydrogels to light exposure (Kloxin et al, 2010;Yao et al, 2017). Other examples of increasing elastic moduli use more biomimetic approaches incubating poly(ethylene glycol) (PEG)-fibrinogen with thrombin (Kesselman et al, 2013) or after light exposure of modified PEG polymers (Mabry et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Functionalized Enzyme-Responsive Biomaterials to Model Tissue Stiffening in vitro

Mattei

Marca

Ahluwalia

et al. 2020

Front. Bioeng. Biotechnol.

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The mechanical properties of the cellular microenvironment play a crucial role in modulating cell function, and many pathophysiological processes are accompanied by variations in extracellular matrix (ECM) stiffness. Lysyl oxidase (LOx) is one of the enzymes involved in several ECM-stiffening processes. Here, we engineered poly(ethylene glycol) (PEG)-based hydrogels with controlled mechanical properties in the range typical of soft tissues. These hydrogels were functionalized featuring free primary amines, which allows an additional chemical LOx-responsive behavior with increase in crosslinks and hydrogel elastic modulus, mimicking biological ECMstiffening mechanisms. Hydrogels with elastic moduli in the range of 0.5-4 kPa were obtained after a first photopolymerization step. The increase in elastic modulus of the functionalized and enzyme-responsive hydrogels was also characterized after the second-step enzymatic reaction, recording an increase in hydrogel stiffness up to 0.5 kPa after incubation with LOx. Finally, hydrogel precursors containing HepG2 (bioinks) were used to form three-dimensional (3D) in vitro models to mimic hepatic tissue and test PEG-based hydrogel biocompatibility. Hepatic functional markers were measured up to 7 days of culture, suggesting further use of such 3D models to study cell mechanobiology and response to dynamic variation of hydrogels stiffness. The results show that the functionalized hydrogels presented in this work match the mechanical properties of soft tissues, allow dynamic variations of hydrogel stiffness, and can be used to mimic changes in the microenvironment properties of soft tissues typical of inflammation and pathological changes at early stages (e.g., fibrosis, cancer).

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Degradation rate affords a dynamic cue to regulate stem cells beyond varied matrix stiffness

Cited by 127 publications

References 78 publications

Ligand Diffusion Enables Force‐Independent Cell Adhesion via Activating α5β1 Integrin and Initiating Rac and RhoA Signaling

Ligand Diffusion Enables Force‐Independent Cell Adhesion via Activating α5β1 Integrin and Initiating Rac and RhoA Signaling

<p>Delivery vehicle of muscle-derived irisin based on silk/calcium silicate/sodium alginate composite scaffold for bone regeneration</p>

Functionalized Enzyme-Responsive Biomaterials to Model Tissue Stiffening in vitro

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