Dynamic Compression Improves Chondrogenesis in the Tissue Engineered Model of Cartilage

Hyaline cartilage is a dense avascular tissue with low regenerative potential, present at the ends of the diarthrodial joints and in the cartilage growth plate. Skeletal diseases often result from extracellular changes in this tissue; however, studies of these are hindered by the tissue complexity, the difficulty in obtaining human material, and the cost of generating animal models. Recent developments in tissue engineering are opening possibilities to develop mechanoresponsive zonally stratified models of cartilage in vitro. In this study, we optimized a 3D model of cartilage using chondroprogenitor cells cultured for 21 days in 2% agarose hydrogel constructs with daily dynamic compression. Our hydrogel constructs developed pericellular matrices with nanostiffness comparable with native murine tissue and showed increased production of extracellular matrix components and expression of chondrogenic and differentiation markers. Daily dynamic compression resulted in progressive increase in mechanoresponsive gene expression and promoted a juvenile cartilage phenotype, decreasing expression of dedifferentiation and cartilage degradation markers. Our study highlights the potential of hydrogel-enhanced chondrogenesis and proposes an adaptable and scalable in vitro model to study mechanoresponses, intracellular signals, and pericellular matrix involvement in cartilage development and disease.