Stiffness memory of indirectly 3D-printed elastomer nanohybrid regulates chondrogenesis and osteogenesis of human mesenchymal stem cells

Wu, Linxiao; Magaz, Adrián; Wang, Tao; Liu, Chaozong; Darbyshire, Arnold; Loizidou, Marilena; Emberton, Mark; Birchall, Martin A.; Song, Wenhui

doi:10.1016/j.biomaterials.2018.09.013

Cited by 53 publications

(63 citation statements)

References 48 publications

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“…The initial high stiffness of the CC membranes appeared to slow down chondrogenic differentiation compared to CC+H (p < 0.01) in the beginning. As more MSCs grew on the surface and inside of the porous scaffold (Figure ), their differentiation potential was improved and regulated by the ECM‐derived microenvironment generated by earlier differentiated cells on the substrate with on‐going stiffness softening, a similar trend to the MSCs on reversely 3D‐printed scaffolds made by 3D‐TIPS . Therefore, CC membranes remained efficient chondrogenic differentiation during stiffness softening, significantly higher than RTC+H and both the TCP and positive controls.…”

Section: Resultsmentioning

confidence: 90%

“…In this case, a gradual shift from the original mechanosensing toward de novo cell‐derived matrix sensing in a more physiologically microenvironment niche generated by the cells themselves may have occurred. While differences in the associated bone gene expression in the CC+H and RTC+H membranes remained, the effect of the micro‐/nanoporous structure is again noticeable (p < 0.05), but more significant than those in the scaffolds made by 3D‐TIPS with digitally printed macropores . Therefore, the influence of the initial stiffness and subsequent stiffness softening of the CC scaffold on modulating osteogenesis is overriding its porosity.…”

Section: Resultsmentioning

confidence: 94%

“…In addition, the production of Osteocalcin and Collagen I analyzed by ELISA over a 3 week period (Figure L–M) was significantly higher from the CC membranes than the rest ( p < 0.0001), in consistence with the results by qPCR. Compared to membranes with 3D digitally printed macropores, such differences are even higher, indicating the stiffness softening as a predominant drive for promoting osteogenesis.…”

Section: Resultsmentioning

confidence: 96%

“…A bicinchoninic acid (BCA) assay kit (Pierce, USA) was used to evaluate protein adsorption on the membranes ( n = 3) using bovine serum albumin (BSA) as standard in phosphate buffered saline (PBS), following ref. ; membranes in serum‐free medium were used as blank. Tissue culture plate (TCP) coverslips (Thermonax, USA) were used as control.…”

Section: Methodsmentioning

confidence: 99%

“…A family of nondegradable scaffolds based on poly (urea–urethane) (PUU) nanohybrids terminated by polyhedral oligomeric silsesquioxane (PUU‐POSS) produced by 3D‐TIPS showed stiffness softening at body temperature . These 3D‐TIPS constructs were found to promote cellular proliferation of dermal fibroblasts and differentiation of mesenchymal stem cells in vitro, and guide vascularization and modulate macrophage polarization in vivo . The hyperelasticity, promotion, and regulation of chondrogenesis and osteogenesis of MSCs on PUU‐POSS scaffolds by 3D‐TIPS show promise for the repair and regeneration of cartilage and its interface with bone.…”

Section: Introductionmentioning

confidence: 99%

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Thermoresponsive Stiffness Softening of Hierarchically Porous Nanohybrid Membranes Promotes Niches for Mesenchymal Stem Cell Differentiation

Magaz

Darbyshire

et al. 2019

Adv Healthcare Materials

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Despite the attention given to the development of novel responsive implants for regenerative medicine applications, the lack of integration with the surrounding tissues and the mismatch with the dynamic mechanobiological nature of native soft tissues remain in the current products. Hierarchical porous membranes based on a poly (urea–urethane) (PUU) nanohybrid have been fabricated by thermally induced phase separation (TIPS) of the polymer solution at different temperatures. Thermoresponsive stiffness softening of the membranes through phase transition from the semicrystalline phase to rubber phase and reverse self‐assembly of the quasi‐random nanophase structure is characterized at body temperature near the melting point of the crystalline domains of soft segments. The effects of the porous structure and stiffness softening on proliferation and differentiation of human bone‐marrow mesenchymal stem cells (hBM‐MSCs) are investigated. The results of immunohistochemistry, histological, ELISA, and qPCR demonstrate that hBM‐MSCs maintain their lineage commitment during stiffness relaxation; chondrogenic differentiation is favored on the soft and porous scaffold, while osteogenic differentiation is more prominent on the initial stiff one. Stiffness relaxation stimulates more osteogenic activity than chondrogenesis, the latter being more influenced by the synergetic coupling effect of softness and porosity.

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 96%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Thermoresponsive Stiffness Softening of Hierarchically Porous Nanohybrid Membranes Promotes Niches for Mesenchymal Stem Cell Differentiation

Magaz

Darbyshire

et al. 2019

Adv Healthcare Materials

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Materials‐Mediated In Situ Physical Cues for Bone Regeneration

Liu,

Zhang,

et al. 2023

Adv Funct Materials

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Physical cues like morphology, light, electric signal, mechanic signal, magnetic signal, and heat can be used as alternative regulators for expensive but short‐acting growth factors in bone tissue engineering to promote osteogenic differentiation and bone regeneration. As physical stimulation applied directly to the tissue cannot be focused on the bone defect area to regulate the cell behaviors and fate in situ, this limits the efficiency of precise bone regeneration. Biomaterials‐mediated in situ physical cues, as an effective strategy combining the synergistic effect of materials themselves, are put forward and studied widely to promote osteogenic differentiation and bone repair efficiently and precisely. Different types of physical cues provide different choices to better satisfy the requirements for targeted bone defect repair. In this review, the recent research about different biomaterials‐mediated physical cues accelerating osteogenesis in vitro and promoting in situ bone formation in vivo is introduced. Meanwhile, the corresponding possible mechanisms of various physical cues regulating cell responses are also discussed. This review provides useful and enlightening guidance for the utilization of intrinsically physical properties of functional materials to achieve efficient bone regeneration, leading to the design and construction of smart biomaterials for practical applications, and eventually promoting clinical translation.

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Osteogenic and Adipogenic Differentiation of Mesenchymal Stem Cells in Gelatin Solutions of Different Viscosities

Lee

Chen

Yoshitomi

et al. 2020

Adv Healthcare Materials

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Accumulating evidence indicates that stem cell fate can be regulated by mechanical properties of the extracellular matrix. Most studies have focused onthe influence of matrix elasticity and viscoelasticity on stem cell differentiation. However, how matrix viscosity affects stem cell differentiation has been overlooked. In this study, a biphasic gelatin solution/hydrogel system is used for 3D culture of human bone marrow-derived mesenchymal stem cells (MSCs) to investigate the influence of gelatin solution viscosity on simultaneous osteogenic and adipogenic differentiation at the same culture condition. Gelatin solution promotes cell proliferation, while its promotive effect decreases with the increase of viscosity. The influence of viscosity on osteogenic and adipogenic differentiation of MSCs shows opposite trends. A high-viscosity gelatin solution results in an increase of alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenesis-related genes. On the other hand, in a low-viscosity gelatin solution, a lot of lipid vacuoles are formed and adipogenesis-related genes are highly expressed. The results indicate high viscosity is beneficial for osteogenic differentiation, while low viscosity is beneficial for adipogenic differentiation. These findings suggest the importance of matrix viscosity on stem cell differentiation in 3D microenvironments.

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Stiffness memory of indirectly 3D-printed elastomer nanohybrid regulates chondrogenesis and osteogenesis of human mesenchymal stem cells

Cited by 53 publications

References 48 publications

Thermoresponsive Stiffness Softening of Hierarchically Porous Nanohybrid Membranes Promotes Niches for Mesenchymal Stem Cell Differentiation

Thermoresponsive Stiffness Softening of Hierarchically Porous Nanohybrid Membranes Promotes Niches for Mesenchymal Stem Cell Differentiation

Materials‐Mediated In Situ Physical Cues for Bone Regeneration

Osteogenic and Adipogenic Differentiation of Mesenchymal Stem Cells in Gelatin Solutions of Different Viscosities

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