Chondrocyte colonisation of a tissue-engineered cartilage substitute under a mechanical stimulus

Abstract

Cell-free collagen scaffolds as cartilage substitute for small focal defects show promising results in first clinical studies. However, chondrocyte migration between scaffolds and the colonisation process of a cell-free implant is yet to be fully understood. We here focus on mechanobiological interdependencies between cell migration and mechanical stimulus in a 3D environment. We develop an in vitro model composed of a human chondrocyte-seeded collagen base and adjacent cell-free collagen type I scaffolds of varying collagen concentrations. Constructs are either cultured statically or dynamically under the influence of a physiological compression (0.5Hz, 0.5% initial strain). After 20 days we identify vital chondrocytes inside all collagen implants, proving that chondrocytes migrated from the underlying scaffold into the implants. Chondrocytes have not colonised the entire sample and are predominantly found in the bottom of the implant. In static culture conditions, a nearly equal cell number is found inside of all collagen scaffolds. In dynamic culture, the total amount of cells is increased by 30% to 320%, with the highest population in a commercial implant. Differences in cell population between the materials in dynamic culturing can be referred to differences in mechanical properties of the scaffolds, such as strain-rate insensitivity fostering the colonisation process.

Keywords: Bioreactor system; Cartilage; Human chondrocyte migration; Mechanobiology; Tissue engineering.