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Poly (ethylene glycol) hydrogel elasticity influences human mesenchymal stem cell behavior.

ABSTRACT: Coordinated investigations into the interactions between biologically mimicking (biomimetic) material constructs and stem cells advance the potential for the regeneration and possible direct replacement of diseased cells and tissues. Any clinically relevant therapies will require the development and optimization of methods that mass produce fully functional cells and tissues. Despite advances in the design and synthesis of biomaterial scaffolds, one of the biggest obstacles facing tissue engineering is understanding how specific extracellular cues produced by biomaterial scaffolds influence the proliferation and differentiation of various cell sources. Matrix elasticity is one such tailorable property of synthetic scaffolds that is known to differ between tissues. Here, we investigate the interactions between an elastically tailorable polyethylene glycol (PEG)-based hydrogel platform and human bone marrow-derived mesenchymal stem cells (hMSCs). For these studies, two different hydrogel compositions with elastic moduli in the ranges of 50-60?kPa and 8-10?kPa were implemented. Our findings demonstrate that the different elasticities in this platform can produce changes in hMSC morphology and proliferation, indicating that the platform can be implemented to produce changes in hMSC behavior and cell state for a broad range of tissue engineering and regenerative applications. Furthermore, we show that the platform's different elasticities influence stem cell differentiation potential, particularly when promoting stem cell differentiation toward cell types from tissues with stiffer elasticity. These findings add to the evolving and expanding library of information on stem cell-biomaterial interactions and opens the door for continued exploration into PEG-based hydrogel scaffolds for tissue engineering and regenerative medicine applications.

SUBMITTER: Whitehead AK

PROVIDER: S-EPMC6007362 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Poly (ethylene glycol) hydrogel elasticity influences human mesenchymal stem cell behavior.

Whitehead Anna K AK Barnett Haley H HH Caldorera-Moore Mary E ME Newman Jamie J JJ

Regenerative biomaterials 20180424 3

Coordinated investigations into the interactions between biologically mimicking (biomimetic) material constructs and stem cells advance the potential for the regeneration and possible direct replacement of diseased cells and tissues. Any clinically relevant therapies will require the development and optimization of methods that mass produce fully functional cells and tissues. Despite advances in the design and synthesis of biomaterial scaffolds, one of the biggest obstacles facing tissue enginee ...[more]

PMID: 29942649

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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.

Dataset Information

Poly (ethylene glycol) hydrogel elasticity influences human mesenchymal stem cell behavior.

Publications

Poly (ethylene glycol) hydrogel elasticity influences human mesenchymal stem cell behavior.

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