Heparan sulfate co-immobilized with cRGD ligands and BMP2 on biomimetic platforms promotes BMP2-mediated osteogenic differentiation

Sefkow-Werner, Julius; Machillot, Paul; Sales, Adrià; Castro-Ramirez, Elaine; Degardin, Mélissa; Boturyn, Didier; Cavalcanti‐Adam, Elisabetta Ada; Albigès-Rizo, Corinne; Picart, Catherine; Migliorini, Elisa

doi:10.1016/j.actbio.2020.07.015

“…We have also shown that bBMP-2 presented from a soft film was sufficient to trigger cell spreading and migration 26 , overriding the response to film stiffness. The same effect has been shown on rigid surfaces with a low cRGD surface density 27 and on surfaces presenting peptides specific for α5β1 integrins 28 . This process on soft films involved 3 integrins and BMP receptors that worked together to control SMAD signaling and tensional homeostasis 26 , thereby coupling cell adhesion and fate commitment.…”

Section: Introductionsupporting

confidence: 71%

Differential bioactivity of four BMP-family members as function of biomaterial stiffness

Sales¹,

Khodr²,

Machillot³

et al. 2022

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Whereas soft biomaterial is not able to induce cell spreading, BMP-2 presented by a soft film has been described to be sufficient to trigger cell spreading, migration and downstream BMP-2 signaling. Based on thin polyelectrolyte films of controlled stiffness, we investigated whether the presentation of four BMP members (2, 4, 7, 9) in a matrix-bound manner may differentially impact cell adhesion and bone differentiation of skeletal progenitors. We performed high content and automated screening of cellular responses, including cell number, cell spreading area, SMAD phosphorylation and alkaline phosphatase activity. The basolateral presentation of the different BMPs allowed us to discriminate the specificity of cellular response and the role of BMP receptors type I, type II, as well as three β integrins, in a BMP type and stiffness-dependent manner..

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“…We have also shown that bBMP-2 presented from a soft film was sufficient to trigger cell spreading and migration 26 , overriding the response to film stiffness. The same effect has been shown on rigid surfaces with a low cRGD surface density 27 and on surfaces presenting peptides specific for α5β1 integrins 28 . This process on soft films involved β3 integrins and BMP receptors that worked together to control SMAD signaling and tensional homeostasis 26 , thereby coupling cell adhesion and fate commitment.…”

Section: Introductionsupporting

confidence: 71%

“…The role of 1 integrin in osteoblastic differentiation is recognized, but appears to depend on the cell type and on the context. Previously in our group, Sefkow-Werner et al found an activator role of 1 integrin with sBMP-2 and BMP-2 bound to heparan sulphate, by using also C2C12 cells 27 . Many data have shown that 1 integrin plays an important role in osteoblast differentiation and function [56][57][58] .…”

Section: Identification Of Integrins In Bmp-induced Cell Adhesion Andmentioning

confidence: 71%

Differential bioactivity of four BMP-family members as function of biomaterial stiffness

A

¹

,

Khodr

²

,

Machillot

³

et al. 2021

Preprint

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Whereas soft biomaterial is not able to induce cell spreading, BMP-2 presented by a soft film has been described to be sufficient to trigger cell spreading, migration and downstream BMP-2 signaling. Based on thin polyelectrolyte films of controlled stiffness, we investigated whether the presentation of four BMP members (2, 4, 7, 9) in a matrix-bound manner may differentially impact cell adhesion and bone differentiation of skeletal progenitors. We performed high content and automated screening of cellular responses, including cell number, cell spreading area, SMAD phosphorylation and alkaline phosphatase activity. The basolateral presentation of the different BMPs allowed us to discriminate the specificity of cellular response and the role of BMP receptors type I, type II, as well as three β integrins, in a BMP type and stiffness-dependent manner.

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“…It is commonly known that some behaviors and functions of cells are related to the performances of proteins absorption on implantable materials [ 36 ]. These adsorbed proteins could serve as ligands to bind to cell membrane protein receptors (integrins) leading to cell/materials adhesion [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is commonly known that some behaviors and functions of cells are related to the performances of proteins absorption on implantable materials [ 36 ]. These adsorbed proteins could serve as ligands to bind to cell membrane protein receptors (integrins) leading to cell/materials adhesion [ 36 ]. For example, Fn plays a vital role in the initial cell adhesion and spreading on materials, because it can specially bind to integrins on cell membranes [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Implantable PEKK/tantalum microparticles composite with improved surface performances for regulating cell behaviors, promoting bone formation and osseointegration

Hu

¹

,

Mei

²

,

Qian

³

et al. 2021

Bioactive Materials

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Polyetherketoneketone (PEKK) exhibits admirable biocompatibility and mechanical performances but bioinert while tantalum (Ta) possesses excellent osteogenesis and osseointegration but high elastic modulus and density, and processing is too difficult and expensive. In the present study, combining of the advantages of both PEKK and Ta, implantable composites of PEKK/Ta were fabricated by blending PEKK with Ta microparticles of 20 v% (PT20) and 40 v% (PT40) content. In comparison with PT20 and PEKK, the surface hydrophilicity, surface energy, roughness and proteins adsorption as well as mechanical performances of PT40 significantly increased because of the higher Ta particles content in PEKK. Furthermore, PT40 exhibited the mechanical performances (e.g., compressive strength and modulus of elasticity) close to the cortical bone of human. Compared with PT20 and PEKK, PT40 with higher Ta content remarkably enhanced the responses (including adhesion, proliferation and osteogenic differentiation) of MC3T3-E1 cells in vitro . Moreover, PT40 markedly improved bone formation as well as osseointegration in vivo . In short, incorporation of Ta microparticles into PEKK created implantable composites with improved surface performances, which played key roles in stimulating cell responses/bone formation as well as promoting osseointegration. PT40 might have great potential for bear-loading bone substitute.

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Heparan sulfate co-immobilized with cRGD ligands and BMP2 on biomimetic platforms promotes BMP2-mediated osteogenic differentiation

Abstract: Heparan sulfate co-immobilized with cRGD ligands and BMP2 on biomimetic platforms promotes BMP2mediated osteogenic differentiation

Cited by 24 publications

References 77 publications

Differential bioactivity of four BMP-family members as function of biomaterial stiffness

Differential bioactivity of four BMP-family members as function of biomaterial stiffness

Differential bioactivity of four BMP-family members as function of biomaterial stiffness

Implantable PEKK/tantalum microparticles composite with improved surface performances for regulating cell behaviors, promoting bone formation and osseointegration

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