Designer biomaterials for mechanobiology

Li, Linqing; Eyckmans, Jeroen; Chen, Christopher

doi:10.1038/nmat5049

Cited by 153 publications

(137 citation statements)

References 73 publications

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“…Human mesenchymal stem cells (hMSCs) are attractive candidates for tissue engineering, which can be potentially applied for bone, cartilage, fat, and tendon regeneration . In vivo, most cells are organized in tissues where they are interconnected with other cells and continuously subjected to mechanical forces including shear, compressive, and extensional forces . The homeostasis of tissues is ensured by the ability of cells to exploit traction forces to sense the physical characteristics of their microenvironment .…”

Section: Introductionmentioning

confidence: 99%

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

Zhang

Yang

Abali

et al. 2019

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Although mechanisms of how physical forces convert into biochemical signals are increasingly understood, it is still unknown how soft cues guide cell behavior. Herein, it is shown that the commitment and differentiation of encapsulating human mesenchymal stem cell (hMSC) spheroids in thermosensitive 3D hydrogels are simply altered by interpenetrating poly(N‐isopropylacrylamide‐co‐2‐hydroxyethyl methacrylate) (NIPAM‐HEMA) nanogel to a gelatin methacryloyl (GelMA) network. This cell‐laden hydrogel provides dynamic mechanics with covalent crosslinking coordinated reversible physical networks, which can regulate hMSCs in situ by reversibly stiffening soft niches via multicyclic temperature changes from 25 to 37 °C. The spreading of hMSC spheroids in the hydrogel is strongly dependent on myosin‐dependent traction stress with dynamic mechanical stimuli through focal adhesion kinase (FAK) signaling. Notably, the dynamic microenvironment gradually influences the expression and distribution from the basal to apical side of nuclear lamin A/C and increases the Yes‐associated protein (YAP) nuclear localization with cycles, which ultimately favors hMSCs undergoing osteogenesis (but not adipogenesis) in the soft microniche. Moreover, it is demonstrated that the viscoelastic behavior of the soft microniche can be guided by temperature through a nonlinear model. These findings highlight the central roles of the dynamic relationship between the biomechanical signals and mechanosensitive transcriptional regulators in cellular mechanosensing.

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Section: Introductionmentioning

confidence: 99%

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

Zhang

Yang

Abali

et al. 2019

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“…When a constant stress was exerted by stationary cells, the underlying protein nanosheets were expected to yield with larger strain . Integrin moves with the protein nanosheets and thus there is no resistance applied to integrin and the focal adhesion molecules . Subsequently, the lack of tension prevents the formation of stable adhesions.…”

mentioning

confidence: 99%

“…Myosin contractility, which drives F‐actin retrograde flow, is countered by the elastic resistance of the substrate, slowing down the flow and increasing the rate of force loading on integrin and focal adhesion molecules . On stiff substrates, the high loading rate results in the unfolding of force‐sensitive proteins like talin, binding vinculin within the adhesion sites, and triggering downstream signaling . It is tempting to speculate that hMSCs pulling on FN anchoring the protein nanosheet encounter a relatively low elastic resistance on PFD.…”

mentioning

confidence: 99%

“…[24] On stiff substrates, the high loading rate results in the unfolding of force-sensitive proteins like talin, binding vinculin within the adhesion sites, and triggering downstream signaling. [25] It is tempting to speculate that hMSCs pulling on FN anchoring the protein nanosheet encounter a relatively low elastic resistance on PFD. As was observed, this lack of tension prevents the formation of stable adhesions even when integrins can bind to abundant ligands contained within protein nanosheets.…”

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confidence: 99%

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Modulation of Mesenchymal Stem Cells Mechanosensing at Fluid Interfaces by Tailored Self‐Assembled Protein Monolayers

Jia

Minami

Uto

et al. 2019

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Mechanical cues of cellular microenvironments can modulate cell functions including cell spreading and differentiation. Most studies of cellular functions are performed using a solid substrate, and it is thought that cells cannot spread on fluid substrates because of rapid relaxation, which cannot resist against actomyosin‐based cell contractility. Here, the spreading and growth of anchorage‐dependent cells such as human mesenchymal stem cells at the liquid interface between a perfluorocarbon fluid and the culture medium are observed. It is demonstrated that a monomolecular protein nanosheet self‐assembled at a fluid interface is sufficiently rigid to support cell spreading without additional treatment. Fine tuning of the packing of these proteins at the liquid interface permits tailoring of the mechanics of the protein layer, ultimately allowing for the regulation of cell spreading. The greater stiffness of the protein nanosheets triggers cell spreading, adhesion growth, and yes‐associated protein nuclear translocation. Cell behavior at the fluid interface is explained within the framework of the molecular clutch model. In addition, the freestanding ultrathin protein nanosheets are extremely flexible, easily deformed, and perceived by cells as being much softer. The findings are expected to provide a new perspective for insights into cell–material interactions.

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“…Nevertheless, design requirements greatly vary depending on the target tissue. For further reading on these specific design requirements, we refer to excellent recent reviews . However, it is clear that these design requirements are now a next logical step for advancing bioinks toward functional and bioactive bioinks that can, at least partially, orchestrate cellular behavior postprocessing.…”

Section: Strategies To Evolve From Shape To Functionmentioning

confidence: 99%

From Shape to Function: The Next Step in Bioprinting

et al. 2020

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In 2013, the “biofabrication window” was introduced to reflect the processing challenge for the fields of biofabrication and bioprinting. At that time, the lack of printable materials that could serve as cell‐laden bioinks, as well as the limitations of printing and assembly methods, presented a major constraint. However, recent developments have now resulted in the availability of a plethora of bioinks, new printing approaches, and the technological advancement of established techniques. Nevertheless, it remains largely unknown which materials and technical parameters are essential for the fabrication of intrinsically hierarchical cell–material constructs that truly mimic biologically functional tissue. In order to achieve this, it is urged that the field now shift its focus from materials and technologies toward the biological development of the resulting constructs. Therefore, herein, the recent material and technological advances since the introduction of the biofabrication window are briefly summarized, i.e., approaches how to generate shape, to then focus the discussion on how to acquire the biological function within this context. In particular, a vision of how biological function can evolve from the possibility to determine shape is outlined.

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Designer biomaterials for mechanobiology

Cited by 153 publications

References 73 publications

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

Dynamic Mechanics‐Modulated Hydrogels to Regulate the Differentiation of Stem‐Cell Spheroids in Soft Microniches and Modeling of the Nonlinear Behavior

Modulation of Mesenchymal Stem Cells Mechanosensing at Fluid Interfaces by Tailored Self‐Assembled Protein Monolayers

From Shape to Function: The Next Step in Bioprinting

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