Controllable ligand spacing stimulates cellular mechanotransduction and promotes stem cell osteogenic differentiation on soft hydrogels

Zhang, Man; Sun, Qian; Liu, Yiling; Chu, Zhiqin; Yu, Leixiao; Hou, Yong; Kang, Heemin; Wei, Qiang; Zhao, Weifeng; Spatz, Joachim P.; Zhao, Changsheng; Cavalcanti‐Adam, Elisabetta Ada

doi:10.1016/j.biomaterials.2020.120543

Cited by 49 publications

(47 citation statements)

References 68 publications

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“…Since the size of a single gold nanodot is smaller than the size of integrin, each single gold nanodot can only bind to one integrin in principle [ 72 ]. This well-designed ligand spacing initiates cell mechanotransduction and leads to the osteogenic differentiation of mesenchymal stem cell [ 73 ].…”

Section: Deformable Materialsmentioning

confidence: 99%

Soft overcomes the hard: Flexible materials adapt to cell adhesion to promote cell mechanotransduction

Sun

Hou

Chu

et al. 2022

Bioactive Materials

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Cell behaviors and functions show distinct contrast in different mechanical microenvironment. Numerous materials with varied rigidity have been developed to mimic the interactions between cells and their surroundings. However, the conventional static materials cannot fully capture the dynamic alterations at the bio-interface, especially for the molecular motion and the local mechanical changes in nanoscale. As an alternative, flexible materials have great potential to sense and adapt to mechanical changes in such complex microenvironment. The flexible materials could promote the cellular mechanosensing by dynamically adjusting their local mechanics, topography and ligand presentation to adapt to intracellular force generation. This process enables the cells to exhibit comparable or even higher level of mechanotransduction and the downstream ‘hard’ phenotypes compared to the conventional stiff or rigid ones. Here, we highlight the relevant studies regarding the development of such adaptive materials to mediate cell behaviors across the rigidity limitation on soft substrates. The concept of ‘soft overcomes the hard’ will guide the future development and application of biological materials.

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Section: Deformable Materialsmentioning

confidence: 99%

Soft overcomes the hard: Flexible materials adapt to cell adhesion to promote cell mechanotransduction

Sun

Hou

Chu

et al. 2022

Bioactive Materials

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“…Likewise, a similar cytoskeletal arrangement was observed in HUVECs after culturing on different scaffolds for 3 days (Figure 4h). The effects of cell morphology on regulating cell phenotype and cell function have been well documented by several researchers, [42] and a spindle-shaped morphology has been proven to enhance cell behaviors by targeting cell proliferation and differentiation. [43] Further study also showed that a highly expanded cytoskeletal structure tended to be closely correlated with the differentiation of BMSCs toward an osteogenic lineage.…”

Section: Evaluation Of In Vitro Cytocompatibilitymentioning

confidence: 99%

Bioinspired Redwood‐Like Scaffolds Coordinated by In Situ‐Generated Silica‐Containing Hybrid Nanocoatings Promote Angiogenesis and Osteogenesis both In Vitro and In Vivo

Chen

et al. 2021

Adv Healthcare Materials

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Inspired by natural redwood and bone, a biomimetic strategy is presented to develop a highly bioactive redwood-like nanocomposite via radial freeze casting of biocompatible hydrogels followed by the in situ coprecipitation of a Si-containing CaP hybrid nanocoating (SCPN). The engineered material displays radially aligned macrochannels and a porous network structure similar to those of natural redwood. In addition to acting as a mechanical reinforcement, introducing SCPNs into the weak redwood-like scaffold yields not only a nanoroughened surface topography, a low swelling ratio, retarded enzymatic degradation, and enhanced protein absorption abilities but also the sustained sequential release of Si and Ca ions, thereby providing essential biophysical and biochemical cues for effective bone regeneration. Benefiting from the redwood-like structures and bioactive SCPNs, the biomimetic materials create a favorable microenvironment for promoting the initial adhesion, spreading, proliferation, and migration of bone marrow-derived mesenchymal stem cells and human umbilical vein endothelial cells. Furthermore, the in vitro and in vivo data showed that the biocompatible redwood-like scaffold with precipitated SCPN can synergistically promote osteogenesis and angiogenesis in their aligned direction. Collectively, this work presents a novel bioinspired redwood-like material with multifunctional properties that provides new insight into bone defect repair.

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“…[162,163] Zhang et al have studied the influence of ordered ligand spacing, superimposed on gels, on stem cell differentiation. [164] To produce ordered ligand spacing, the authors first used block copolymers loaded with gold nanoparticles to obtain ordered gold nanoarrays of spacings 70, 150, and 230 nm between the gold nanoparticles on glass coverslips. Then, PAAm gels were cast on these glass coverslips consisting of the gold nanopatterns to enable pattern transfer to gels.…”

Section: Ligand Presentation and Stiffnessmentioning

confidence: 99%

Hydrogels with Tunable Physical Cues and Their Emerging Roles in Studies of Cellular Mechanotransduction

Narasimhan

Horrocks

Malmström

2021

Advanced NanoBiomed Research

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The extracellular matrix provides complex biophysical cues to cells which respond to these signals with signaling cascades that determine various cellular processes including fate. Many material systems have been explored to mimic the mechanical properties of the extracellular matrix to determine the cell responses to mechanical cues. While stiffness has emerged as an important regulator of cell behavior, recently, other mechanical properties such as strain stiffening and viscoelasticity have also emerged as potent regulators. This review explores the substrates used for studying mechanotransduction and strategies adopted to impart more complex mechanical cues including spatiotemporal control of mechanical properties. In addition, practical considerations for designing hydrogels for cell culture are discussed and the response of cells to viscoelastic cues in particular is discussed in depth. Recent mechanotransduction studies of combinations of mechanical and other cues are finally reviewed. It is anticipated that such multiphysical cues will further the understanding of mechanotransduction involved in complex processes such as migration and mechanical memory and provide a framework in controlling cell behavior.

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Controllable ligand spacing stimulates cellular mechanotransduction and promotes stem cell osteogenic differentiation on soft hydrogels

Cited by 49 publications

References 68 publications

Soft overcomes the hard: Flexible materials adapt to cell adhesion to promote cell mechanotransduction

Soft overcomes the hard: Flexible materials adapt to cell adhesion to promote cell mechanotransduction

Bioinspired Redwood‐Like Scaffolds Coordinated by In Situ‐Generated Silica‐Containing Hybrid Nanocoatings Promote Angiogenesis and Osteogenesis both In Vitro and In Vivo

Hydrogels with Tunable Physical Cues and Their Emerging Roles in Studies of Cellular Mechanotransduction

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