Engineering the biomechanical microenvironment of chondrocytes towards articular cartilage tissue engineering

Tissue engineering holds great promise in the generation of cartilage analogues for cartilage injury repair and replacement. However, for a long time, a variety of issues have remained unsolved in articular cartilage tissue engineering concerning immunogenicity, stability, and mechanical strength, among others. One of the most remarkable reasons lies in the lack or insufficiency of recapitulating the chondrocyte biomechanical microenvironment (BME) in the articular cartilage tissue engineering. In recent years, an increasing number of studies have disclosed the crucial role of the BME in chondrocyte phenotype and cartilage functions, which has inspired more precise and individualized research in articular cartilage tissue engineering by engineering the chondrocyte BME. This review first takes an in-depth look into the chondrocyte BME and its crucial effects on chondrocytes and articular cartilage tissues. Then, as the core of this work, the principal strategies and their approaches of engineering the chondrocyte BME towards articular cartilage tissue engineering were comprehensively discussed, from the perspectives of simulating the main characteristics of chondrocyte BME including engineering the heterogeneous matrix and the dynamic mechanical stimulation. The current limitations in this emerging area and potential strategies were also proposed to shed some light on the future directions in this field. Although there are still challenges to obtaining engineered articular cartilages with desired performance, the road ahead is bright under the constant efforts in engineering the chondrocyte BME at higher levels towards articular cartilage tissue engineering.