Dataset Information

Understanding the host response to cell-laden poly(ethylene glycol)-based hydrogels.

ABSTRACT: Poly(ethylene glycol) (PEG)-based hydrogels are promising in situ cell carriers for tissue engineering. However, their success in vivo will in part depend upon the foreign body reaction (FBR). This study tests the hypothesis that the FBR affects cells encapsulated within PEG hydrogels, and in turn influences the severity of the FBR. Fibroblasts were encapsulated within PEG hydrogels containing RGD to support cell attachment. Macrophages were seeded on top of cell-laden hydrogels to mimic in vivo macrophage interrogation and treated with lipopolysaccharide to induce an inflammatory phenotype. The presence of activated macrophages reduced fibroblast gene expression for extracellular matrix molecules and remodeling, but stimulated VEGF and IL-1? gene expression. Fibroblasts impacted macrophage phenotype leading to increased iNOS, IL-1? and TNF-? expressions. Syngeneic cell-laden and acellular hydrogels were also implanted subcutaneously into C57bl/6 mice for 2, 7 and 28 days. Encapsulated fibroblasts secreted collagen type I during the first week, but tissue deposition and cellularity decreased by 28 days. The presence of encapsulated fibroblasts led to greater acute inflammation, but did not influence the fibrotic response. In summary, this work emphasizes the importance of the host response in tissue engineering, and the potentially deleterious impact it may have on cell-laden synthetic scaffolds.

SUBMITTER: Swartzlander MD

PROVIDER: S-EPMC3683297 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Understanding the host response to cell-laden poly(ethylene glycol)-based hydrogels.

Swartzlander Mark D MD Lynn Aaron D AD Blakney Anna K AK Kyriakides Themis R TR Bryant Stephanie J SJ

Biomaterials 20121110 4

Poly(ethylene glycol) (PEG)-based hydrogels are promising in situ cell carriers for tissue engineering. However, their success in vivo will in part depend upon the foreign body reaction (FBR). This study tests the hypothesis that the FBR affects cells encapsulated within PEG hydrogels, and in turn influences the severity of the FBR. Fibroblasts were encapsulated within PEG hydrogels containing RGD to support cell attachment. Macrophages were seeded on top of cell-laden hydrogels to mimic in vivo ...[more]

PMID: 23149012

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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

Understanding the host response to cell-laden poly(ethylene glycol)-based hydrogels.

Publications

Understanding the host response to cell-laden poly(ethylene glycol)-based hydrogels.

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