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Mechanically tunable, human mesenchymal stem cell viable poly(ethylene glycol)-oxime hydrogels with invariant precursor composition, concentration, and stoichiometry.

ABSTRACT: Hydrogels are used widely for exploratory tissue engineering studies. However, currently no hydrogel systems have been reported that exhibit a wide range of elastic modulus without changing precursor concentration, identity, or stoichiometry. Herein, ester and amide-based PEG-oxime hydrogels with tunable moduli (~5-30 kPa) were synthesized with identical precursor mass fraction, stoichiometry, and concentration by varying the pH and buffer concentration of the gelation solution, exploiting the kinetics of oxime bond formation. The observed modulus range can be attributed to increasing amounts of network defects in slower forming gels, as confirmed by equilibrium swelling and small angle neutron scattering (SANS) experiments. Finally, hMSC viability was confirmed in these materials in a 24 h assay. While only an initial demonstration of the potential utility, the controlled variation in defect density and modulus is an important step forward in isolating system variables for hypothesis-driven biological investigations.

SUBMITTER: Dilla RA

PROVIDER: S-EPMC6820350 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Mechanically tunable, human mesenchymal stem cell viable poly(ethylene glycol)-oxime hydrogels with invariant precursor composition, concentration, and stoichiometry.

Dilla Rodger A RA Xu Yanyi Y Zander Zachary K ZK Bernard Neil N Wiener Clinton G CG Vogt Bryan D BD Becker Matthew L ML

Materials today. Chemistry 20181215

Hydrogels are used widely for exploratory tissue engineering studies. However, currently no hydrogel systems have been reported that exhibit a wide range of elastic modulus without changing precursor concentration, identity, or stoichiometry. Herein, ester and amide-based PEG-oxime hydrogels with tunable moduli (~5-30 kPa) were synthesized with identical precursor mass fraction, stoichiometry, and concentration by varying the pH and buffer concentration of the gelation solution, exploiting the k ...[more]

PMID: 31667447

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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.

Dataset Information

Mechanically tunable, human mesenchymal stem cell viable poly(ethylene glycol)-oxime hydrogels with invariant precursor composition, concentration, and stoichiometry.

Publications

Mechanically tunable, human mesenchymal stem cell viable poly(ethylene glycol)-oxime hydrogels with invariant precursor composition, concentration, and stoichiometry.

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