Morphology and cellular-traction of fibroblasts on 2D silk-fibroin hydrogel substrates
TL;DR: Results suggest that surface-stiffness of SF-hydrogel, rather than nature of surface-ligand, regulates both cellular morphology and cellular traction stresses.
Abstract: Development of clinically amenable bio-implants with silk-fibroin (SF) necessitates characterization of cellular-traction generated between cells and the substrate. However, studies on the biomecha...
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TL;DR: Wang et al. as mentioned in this paper describe varied building blocks of silk at different levels used in biomedical field and their effective extraction and reconstruction strategies, and present recent discoveries and research progresses on how these functional regenerated silk fibroin (RSF) biomaterials used in advanced biomedical applications, especially in the fields of cell-material interactions, soft tissue regeneration, and flexible bioelectronic devices.
Abstract: Silk fibroin has become a promising biomaterial owing to its remarkable mechanical property, biocompatibility, biodegradability, and sufficient supply. However, it is difficult to directly construct materials with other formats except for yarn, fabric and nonwoven based on natural silk. A promising bioinspired strategy is firstly extracting desired building blocks of silk, then reconstructing them into functional regenerated silk fibroin (RSF) materials with controllable formats and structures. This strategy could give it excellent processability and modifiability, thus well meet the diversified needs in biomedical applications. Recently, to engineer RSF materials with properties similar to or beyond the hierarchical structured natural silk, novel extraction and reconstruction strategies have been developed. In this review, we seek to describe varied building blocks of silk at different levels used in biomedical field and their effective extraction and reconstruction strategies. This review also present recent discoveries and research progresses on how these functional RSF biomaterials used in advanced biomedical applications, especially in the fields of cell-material interactions, soft tissue regeneration, and flexible bioelectronic devices. Finally, potential study and application for future opportunities, and current challenges for these bioinspired strategies and corresponding usage were also comprehensively discussed. In this way, it aims to provide valuable references for the design and modification of novel silk biomaterials, and further promote the high-quality-utilization of silk or other biopolymers.
17 citations
TL;DR: A review of the effects of mechanosignalling in the field of cellular mechanobiology can be found in this paper , where the authors discuss some of the interesting works wherein specific alteration of the mechanical properties of the substrates would lead to fate determination of stem cells into various differentiated cells such as osteoblasts, adipocytes, tenocytes, cardiomyocytes, and neurons, and how these properties are being utilized for the development of organoids.
Abstract: Sensing the mechanical properties of the substrates or the matrix by the cells and the tissues, the subsequent downstream responses at the cellular, nuclear and epigenetic levels and the outcomes are beginning to get unraveled more recently. There have been various instances where researchers have established the underlying connection between the cellular mechanosignalling pathways and cellular physiology, cellular differentiation, and also tissue pathology. It has been now accepted that mechanosignalling, alone or in combination with classical pathways, could play a significant role in fate determination, development, and organization of cells and tissues. Furthermore, as mechanobiology is gaining traction, so do the various techniques to ponder and gain insights into the still unraveled pathways. This review would briefly discuss some of the interesting works wherein it has been shown that specific alteration of the mechanical properties of the substrates would lead to fate determination of stem cells into various differentiated cells such as osteoblasts, adipocytes, tenocytes, cardiomyocytes, and neurons, and how these properties are being utilized for the development of organoids. This review would also cover various techniques that have been developed and employed to explore the effects of mechanosignalling, including imaging of mechanosensing proteins, atomic force microscopy (AFM), quartz crystal microbalance with dissipation measurements (QCMD), traction force microscopy (TFM), microdevice arrays, Spatio-temporal image analysis, optical tweezer force measurements, mechanoscanning ion conductance microscopy (mSICM), acoustofluidic interferometric device (AID) and so forth. This review would provide insights to the researchers who work on exploiting various mechanical properties of substrates to control the cellular and tissue functions for tissue engineering and regenerative applications, and also will shed light on the advancements of various techniques that could be utilized to unravel the unknown in the field of cellular mechanobiology.
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TL;DR: Traction stress measurements carried out using fibroblasts on polyacrylamide gels with Young's moduli suggest sustained substrate strain on soft substrates and sustained traction stress on stiff substrates may be factors governing cellular responses to substrate rigidity.
113 citations
TL;DR: Findings suggest that fibroblast activation induced by a stiff matrix is involved in mechanisms of the pathophysiology of pulmonary fibrosis.
Abstract: In patients with pulmonary diseases such as idiopathic pulmonary fibrosis and severe acute respiratory distress syndrome, progressive pulmonary fibrosis is caused by dysregulated wound healing via activation of fibroblasts after lung inflammation or severe damage Migration of fibroblasts toward the fibrotic lesions plays an important role in pulmonary fibrosis Fibrotic tissue in the lung is much stiffer than normal lung tissue Emerging evidence supports the hypothesis that the stiffness of the matrix is not only a consequence of fibrosis, but also can induce fibroblast activation Nevertheless, the effects of substrate rigidity on migration of lung fibroblasts have not been fully elucidated We evaluated the effects of substrate stiffness on the morphology, α-smooth muscle actin (α-SMA) expression, and cell migration of primary human lung fibroblasts by using polyacrylamide hydrogels with stiffnesses ranging from 1 to 50 kPa Cell motility was assessed by platelet-derived growth factor (PDGF)-induced chemotaxis and random walk migration assays As the stiffness of substrates increased, fibroblasts became spindle-shaped and spread Expression of α-SMA proteins was higher on the stiffer substrates (25 kPa gel and plastic dishes) than on the soft 2 kPa gel Both PDGF-induced chemotaxis and random walk migration of fibroblasts precultured on stiff substrates (25 kPa gel and plastic dishes) were significantly higher than those of cells precultured on 2 kPa gel Transfection of the fibroblasts with short interfering RNA for α-SMA inhibited cell migration These findings suggest that fibroblast activation induced by a stiff matrix is involved in mechanisms of the pathophysiology of pulmonary fibrosis
87 citations
TL;DR: A system is proposed that enables mechanical stimulation of human-skin-derived keratinocytes and human dermal fibroblasts that specifically interact with peptide sequences immobilized on a non-interacting but deformable substrate that enables the decoration of deformable substrates with cell-adhesion peptides in extremely defined nanostructures.
Abstract: Mechanical stress is a decisive factor for the differentiation, proliferation, and general behavior of cells. However, the specific signaling of mechanotransduction is not fully understood. One basic problem is the clear distinction between the different extracellular matrix (ECM) constituents that participate in cellular adhesion and their corresponding signaling pathways. Here, a system is proposed that enables mechanical stimulation of human-skin-derived keratinocytes and human dermal fibroblasts that specifically interact with peptide sequences immobilized on a non-interacting but deformable substrate. The peptide sequences mimic fibronectin, laminin, and collagen type IV, three major components of the ECM. To achieve this, PDMS is activated using ammonia plasma and coated with star-shaped isocyanate-terminated poly(ethylene glycol)-based prepolymers, which results in a functional coating that prevents unspecific cell adhesion. Specific cell adhesion is achieved by functionalization of the layers with the peptide sequences in different combinations. Moreover, a method that enables the decoration of deformable substrates with cell-adhesion peptides in extremely defined nanostructures is presented. The distance and clustering of cell adhesion molecules below 100 nm has been demonstrated to be of utmost importance for cell adhesion. Thus we present a new toolbox that allows for the detailed analysis of the adhesion of human-skin-derived cells on structurally and biochemically decorated deformable substrates.
84 citations
TL;DR: Results show that hyaluronic acid alters the integrin-dependent stiffness response of cells in vitro and suggests that expression of HA within the extracellular matrix (ECM) in vivo might similarly alter theresponse of cells that bind the ECM through integrins.
73 citations
TL;DR: This review is focused on the influence of surface properties of silk scaffolds (wettability, charge, elasticity and biodegradability) on the biological activity of cells cultured thereon and how the origin of silk proteins (natural source, regenerated or recombinantly produced) influence the scaffold surface properties in the context of biomedical applications.
Abstract: Polymers are often employed in tissue engineering to replace damaged extracellular matrix (ECM). During the last few decades silk proteins have been extensively investigated concerning their use as biopolymers for the generation of biocompatible, artificial scaffolds. Including the low or absence of immune-response and lack of cell toxicity, silk proteins present interesting properties useful for tissue engineering and organ repair. Since cell–matrix interactions define the behaviour of cells and posterior graft integration, this review is focused on the influence of surface properties of silk scaffolds (wettability, charge, elasticity and biodegradability) on the biological activity (adhesion, proliferation and/or migration) of cells cultured thereon. Further, it is highlighted how the origin of silk proteins (natural source, regenerated or recombinantly produced), as well as the scaffold morphology and its treatment/post-treatment influence the scaffold surface properties in the context of biomedical applications.
69 citations