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Osteogenic potential of poly(ethylene glycol)-amorphous calcium phosphate composites on human mesenchymal stem cells.

ABSTRACT: Synthetic hydrogel-amorphous calcium phosphate composites are promising candidates to substitute biologically sourced scaffolds for bone repair. While the hydrogel matrix serves as a template for stem cell colonisation, amorphous calcium phosphate s provide mechanical integrity with the potential to stimulate osteogenic differentiation. Here, we utilise composites of poly(ethylene glycol)-based hydrogels and differently stabilised amorphous calcium phosphate to investigate potential effects on attachment and osteogenic differentiation of human mesenchymal stem cells. We found that functionalisation with integrin binding motifs in the form of RGD tripeptide was necessary to allow adhesion of large numbers of cells in spread morphology. Slow dissolution of amorphous calcium phosphate mineral in the scaffolds over at least 21 days was observed, resulting in the release of calcium and zinc ions into the cell culture medium. While we qualitatively observed an increasingly mineralised extracellular matrix along with calcium deposition in the presence of amorphous calcium phosphate-loaded scaffolds, we did not observe significant changes in the expression of selected osteogenic markers.

SUBMITTER: Chahal AS

PROVIDER: S-EPMC7268109 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Osteogenic potential of poly(ethylene glycol)-amorphous calcium phosphate composites on human mesenchymal stem cells.

Chahal Aman S AS Schweikle Manuel M Lian Aina-Mari AM Reseland Janne E JE Haugen Håvard J HJ Tiainen Hanna H

Journal of tissue engineering 20200101

Synthetic hydrogel-amorphous calcium phosphate composites are promising candidates to substitute biologically sourced scaffolds for bone repair. While the hydrogel matrix serves as a template for stem cell colonisation, amorphous calcium phosphate s provide mechanical integrity with the potential to stimulate osteogenic differentiation. Here, we utilise composites of poly(ethylene glycol)-based hydrogels and differently stabilised amorphous calcium phosphate to investigate potential effects on a ...[more]

PMID: 32537121

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Project description:Growth factors have been shown to be potent mediators of osteogenesis. However, their use in tissue-engineered scaffolds not only can be costly but also can induce undesired responses in surrounding tissues. Thus, the ability to specifically induce osteogenic differentiation in the absence of exogenous growth factors through manipulation of scaffold material properties would be desirable for bone regeneration. Previous research indicates that addition of inorganic or hydrophobic components to organic, hydrophilic scaffolds can enhance multipotent stem cell (MSC) osteogenesis. However, the combined impact of scaffold inorganic content and hydrophobicity on MSC behavior has not been systematically explored, particularly in three-dimensional (3D) culture systems. The aim of the present study was therefore to examine the effects of simultaneous increases in scaffold hydrophobicity and inorganic content on MSC osteogenic fate decisions in a 3D culture environment toward the development of intrinsically osteoinductive scaffolds. Mouse 10T½ MSCs were encapsulated in a series of novel scaffolds composed of varying levels of hydrophobic, inorganic poly(dimethylsiloxane) (PDMS) and hydrophilic, organic poly(ethylene glycol) (PEG). After 21 days of culture, increased levels of osteoblast markers, runx2 and osteocalcin, were observed in scaffolds with increased PDMS content. Bone extracellular matrix (ECM) molecules, collagen I and calcium phosphate, were also elevated in formulations with higher PDMS:PEG ratios. Importantly, this osteogenic response appeared to be specific in that markers for chondrocytic, smooth muscle cell, and adipocytic lineages were not similarly affected by variations in scaffold PDMS content. As anticipated, the increase in scaffold hydrophobicity accompanying increasing PDMS levels was associated with elevated scaffold serum protein adsorption. Thus, scaffold inorganic content combined with alterations in adsorbed serum proteins may underlie the observed cell behavior.

Project description:Our studies of amorphous calcium phosphate (ACP)-based materials over the last decade have yielded bioactive polymeric composites capable of protecting teeth from demineralization or even regenerating lost tooth mineral. The anti-cariogenic/re-mineralizing potential of these ACP composites originates from their propensity, when exposed to the oral environment, to release in a sustained manner sufficient levels of mineral-forming calcium and phosphate ions to promote formation of stable apatitic tooth mineral. However, the less than optimal ACP filler/resin matrix cohesion, excessive polymerization shrinkage and water sorption of these experimental materials can adversely affect their physicochemical and mechanical properties, and, ultimately, limit their lifespan. This study demonstrates the effects of chemical structure and composition of the methacrylate monomers used to form the matrix phase of composites on degree of vinyl conversion (DVC) and water sorption of both copolymers and composites and the release of mineral ions from the composites. Modification of ACP surface via introducing cations and/or polymers ab initio during filler synthesis failed to yield mechanically improved composites. However, moderate improvement in composite's mechanical stability without compromising its remineralization potential was achieved by silanization and/or milling of ACP filler. Using ethoxylated bisphenol A dimethacrylate or urethane dimethacrylate as base monomers and adding moderate amounts of hydrophilic 2-hydroxyethyl methacrylate or its isomer ethyl-α-hydroxymethacrylate appears to be a promising route to maximize the remineralizing ability of the filler while maintaining high DVC. Exploration of the structure/composition/property relationships of ACP fillers and polymer matrices is complex but essential for achieving a better understanding of the fundamental mechanisms that govern dissolution/re-precipitation of bioactive ACP fillers, and, ultimately, the suitability of the composites for clinical evaluation.

Dataset Information

Osteogenic potential of poly(ethylene glycol)-amorphous calcium phosphate composites on human mesenchymal stem cells.

Publications

Osteogenic potential of poly(ethylene glycol)-amorphous calcium phosphate composites on human mesenchymal stem cells.

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