Influence of the Temporal Deposition of Extracellular Matrix on the Mechanical Properties of Tissue-Engineered Cartilage

Abstract

Enhancement of the load-bearing capacity of tissue-engineered (TE) cartilage is expected to improve the clinical outcome of implantations. Generally, cartilage TE studies aim to increase the total extracellular matrix (ECM) content to improve implant mechanical properties. Besides the ECM content, however, temporal variations in deposition rate of ECM components during culture may also have an effect. Using a computational approach, the present study aims to quantify possible effects of temporal variations in the deposition of glycosaminoglycan (GAG) at given collagen synthesis rates on the mechanical stiffness of cartilage TE constructs. Maturation of a cylindrical cartilage TE construct over 42 days of culture was simulated using a composition-based finite element model that accounted for the transient deposition of GAG and collagen. Results showed an effect of GAG deposition rate on the swelling behavior and the collagen network strain, which resulted in significant changes in the compressive stiffness of cartilage TE constructs. When collagen deposition was first allowed in the constructs while the GAG deposition was delayed for the first 2 or 4 weeks, the collagen more effectively restricted tissue swelling later during the culture. Consequently, while the ultimate amount of ECM at day 42 was identical between the constructs, those with delayed GAG deposition contained elevated internal osmotic swelling pressure (up to 48%). This increased the compressive stiffness (up to 60%) of cartilage TE constructs at day 42. These findings clarify similar, yet unexplained, experimental observations. By providing further insights into mechanical effects inside cartilage TE constructs, these analyses are expected to help in designing culture regimes for engineering TE cartilage with improved load-bearing properties.