Covalently tethered TGF-β1 with encapsulated chondrocytes in a PEG hydrogel system enhances extracellular matrix production

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. (c) 2014 The Authors. Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.: 102A: 4464-4472, 2014.