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

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-β1) with the goal of increasing proliferation and matrix production. Tethered TGF-β1 was found to be distributed homogenously throughout the gel, and its bioactivity was confirmed with a TGF-β1 responsive reporter cell line. Relative to solubly delivered TGF-β1, chondrocytes presented with immobilized TGF-β1 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-β1 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.