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Abstract
Emerging medical technologies for effective and lasting repair of articular cartilage include delivery of cells or cell-seeded scaffolds to a defect site to initiate de novo tissue regeneration. Biocompatible scaffolds assist in providing a template for cell distribution and extracellular matrix accumulation in a three-dimensional geometry. In these studies, a self-assembling peptide hydrogel is evaluated as a potential scaffold for cartilage repair using a model bovine cell source. A seeding technique is developed for 3-D encapsulation of chondrocytes in a peptide hydrogel. The chondrocyte-seeded peptide hydrogel was then evaluated cellular activities in vitro under standard culture conditions and also when subjected to dynamic compression.
During 4 weeks of culture in vitro, chondrocytes seeded within the peptide hydrogel retained their morphology and developed a cartilage-like ECM rich in proteoglycans and type II collagen, indicative of a stable chondrocyte phenotype. Time dependent accumulation of this ECM was paralleled by increases in material stiffness, indicative of deposition of mechanically-functional neo-tissue.
The effects of dynamic compression of chondrocyte-seeded peptide hydrogels were evaluated over long-term culture. A non-continuous loading protocol was identified in which proteoglycan, but not protein, synthesis increased over static, free-swelling culture. Increases in GAG matrix accumulation were observed after at least 8 days of loading, while hydroxyproline accumulation was unaffected by dynamic compression. These data demonstrated dynamic compression differentially regulated the synthesis of proteoglycans.
These results demonstrate the potential of a self-assembling peptide hydrogel as a scaffold for the synthesis and accumulation of a true cartilage-like extracellular matrix, as well as dynamic compression as a means of stimulating extracellular matrix synthesis and accumulation. Such studies may serve as a baseline for development of a clinical strategy of cartilage repair using the self-assembling peptide hydrogel while also demonstrating novel aspects of chondrocyte behavior in 3-D culture. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.) (Abstract shortened by UMI.)
