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Modular multifunctional poly(ethylene glycol) hydrogels for stem cell differentiation.

ABSTRACT: Synthetic polymers are employed to create highly defined microenvironments with controlled biochemical and biophysical properties for cell culture and tissue engineering. Chemical modification is required to input biological or chemical ligands, which often changes the fundamental structural properties of the material. Here, we report on a simple modular biomaterial design strategy that employs functional cyclodextrin nanobeads threaded onto poly(ethylene glycol) polymer necklaces to form multifunctional hydrogels. Nanobeads with desired chemical or biological functionalities can be simply threaded onto the PEG chains to form hydrogels, creating an accessible platform for users. We describe the design and synthesis of these multifunctional hydrogels, elucidate structure-property relationships, and demonstrate applications ranging from stem cell culture and differentiation to tissue engineering.

SUBMITTER: Singh A

PROVIDER: S-EPMC7021251 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Modular multifunctional poly(ethylene glycol) hydrogels for stem cell differentiation.

Singh Anirudha A Zhan Jianan J Ye Zhaoyang Z Elisseeff Jennifer H JH

Advanced functional materials 20120913 5

Synthetic polymers are employed to create highly defined microenvironments with controlled biochemical and biophysical properties for cell culture and tissue engineering. Chemical modification is required to input biological or chemical ligands, which often changes the fundamental structural properties of the material. Here, we report on a simple modular biomaterial design strategy that employs functional cyclodextrin nanobeads threaded onto poly(ethylene glycol) polymer necklaces to form multif ...[more]

PMID: 32063822

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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:Human mesenchymal stem cells (hMSCs) are motile cells that migrate from their native niche to wounded sites where they regulate inflammation during healing. New materials are being developed as hMSC delivery platforms to enhance wound healing. To act as an effective wound healing material, the hydrogel must degrade at the same rate as tissue regeneration, while maintaining a high cell viability. This work determines the kinetics and mechanism of cell-mediated degradation in hMSC-laden poly(ethylene glycol) (PEG) hydrogels. We use a well-established hydrogel scaffold that is composed of a backbone of four-arm star PEG functionalized with norbornene that is cross-linked with a matrix metalloproteinase (MMP) degradable peptide. This peptide sequence is cleaved by cell-secreted MMPs, which allow hMSCs to actively degrade the hydrogel during motility. Three mechanisms of degradation are characterized: hydrolytic, noncellular enzymatic and cell-mediated degradation. We use bulk rheology to characterize hydrogel material properties and quantify degradation throughout the entire reaction. Hydrolysis and noncellular enzymatic degradation are first characterized in hydrogels without hMSCs, and follow first-order and Michaelis-Menten kinetics, respectively. A high cell viability is measured in hMSC-laden hydrogels, even after shearing on the rheometer. After confirming hMSC viability, bulk rheology characterizes cell-mediated degradation. When comparing cell-mediated degradation to noncellular degradation mechanisms, cell-mediated degradation is dominated by enzymatic degradation. This indicates hydrogels with hMSCs are degraded primarily due to cell-secreted MMPs and very little network structure is lost due to hydrolysis. Modeling cell-mediated degradation provides an estimate of the initial concentration of MMPs secreted by hMSCs. By changing the concentration of hMSCs, we determine the initial MMP concentration increases with increasing hMSC concentration. This work characterizes the rate and mechanism of scaffold degradation, giving new insight into the design of these materials as implantable scaffolds.

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Modular multifunctional poly(ethylene glycol) hydrogels for stem cell differentiation.

Publications

Modular multifunctional poly(ethylene glycol) hydrogels for stem cell differentiation.

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