Continuous cyclic compressive loading modulates biological and mechanical properties of collagen hydrogels seeded with human chondrocytes

Abstract

Purpose: This study investigated the potential of cyclic compressive loading in the generation of in vitro engineered cartilaginous tissue with the aim of contributing to a better understanding of mechanical preconditioning and its possible role in further optimizing existing matrix-associated cartilage replacement procedures.

Methods: Human chondrocytes were harvested from 12 osteoarthritic knee joints and seeded into a type I collagen (col-I) hydrogel at low density (2×10⁵ cells/ml gel). The cell-seeded hydrogel was condensed and cultivated under continuous cyclic compressive loading (frequency: 0.3 Hz; strain: 10%) for 14 days under standardized conditions. After retrieval, specimens were subject to staining, histomorphometric evaluation, gene expression analysis and biomechanical testing.

Results: Cellular morphology was altered by both stimulation and control conditions as was staining for collagen II (col-II). Gene expression measurements revealed a significant increase for col-II under either cultivation condition. No significant differences in col-I, aggrecan and MMP-13 gene expression profiles were found. The col-II/col-I mRNA ratio significantly increased under stimulation, whereas the biomechanical properties deteriorated under either cultivation method.

Conclusions: Although the effects observed are small, mechanical preconditioning has demonstrated its potential to modulate biological properties of collagen hydrogels seeded with human chondrocytes.