Covalently tethered TGF-?1 with encapsulated chondrocytes in a PEG hydrogel system enhances extracellular matrix production.
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ABSTRACT: Healing articular cartilage defects remains a significant clinical challenge because of its limited capacity for self-repair. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with growth factor delivery that can locally signal cells and promote their function is often advantageous. We have previously shown that PEG thiol-ene hydrogels permit covalent attachment of growth factors. However, it is not well known if embedded chondrocytes respond to tethered signals over a long period. Here, chondrocytes were encapsulated in PEG hydrogels functionalized with transforming growth factor-beta 1 (TGF-?1) with the goal of increasing proliferation and matrix production. Tethered TGF-?1 was found to be distributed homogenously throughout the gel, and its bioactivity was confirmed with a TGF-?1 responsive reporter cell line. Relative to solubly delivered TGF-?1, chondrocytes presented with immobilized TGF-?1 showed significantly increased DNA content, and GAG and collagen production over 28 days, while maintaining markers of articular cartilage. These results indicate the potential of thiol-ene chemistry to covalently conjugate TGF-?1 to PEG to locally influence chondrocyte function over 4 weeks. Scaffolds with other or multiple tethered growth factors may prove broadly useful in the design of chondrocyte delivery vehicles for cartilage tissue engineering applications.
SUBMITTER: Sridhar BV
PROVIDER: S-EPMC4145048 | biostudies-literature | 2014 Dec
REPOSITORIES: biostudies-literature
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