Dynamic compression modulates anabolic and catabolic activity in chondrocyte seeded agarose constructs

Abstract

Mechanical stimulation is a widely used technique in the development of tissue engineered cartilage. While various regimes can enhance tissue growth and improve construct mechanical properties, existing outcome measures predominantly assess the anabolic effect of mechanical stimuli. Catabolic responses are generally overlooked, and a critical gap remains in how mechanical loading simultaneously affects both anabolic and catabolic processes. In this study, full-thickness articular cartilage was aseptically harvested from the metacarpal-phalangeal joints of skeletally mature bovine. Isolated chondrocytes were encapsulated in agarose gels and subjected to dynamic compressive strains from 0 % to 15 % for either 20 or 60 min using a custom-built mechanical stimulation device. Anabolism was assessed by [³H]-proline and [³⁵S]-sulfate incorporation, while catabolism was evaluated by MMP-13 enzymatic activity. Long-term effects of dynamic loading were assessed through biochemical analyses and histological evaluation. Results showed that low-to-moderate strains (2.5 % and 5 %) induced high anabolic activity relative to control with minimal catabolic response. In contrast, high strains (15 %) resulted in elevated catabolic and reduced anabolic activity relative to control. The application of mechanical stimuli over the long-term elicited comparable responses with lower compressive stains leading to improved cartilaginous extracellular matrix accumulation. This study provides valuable insights into the complex interplay between anabolic and catabolic metabolism in chondrocyte-seeded agarose constructs subjected to dynamic compression. This research underscores the necessity of evaluating both responses to optimize the growth and properties of tissue-engineered cartilage.