Bioengineering Human Cartilage-Bone Tissues for Modeling of Osteoarthritis.

Osteoarthritis (OA) is the most common joint disease worldwide, yet we continue to lack an understanding of disease etiology and pathology and effective treatment options. Essential to tissue homeostasis, disease pathogenesis, and therapeutic responses are the stratified organization of cartilage and cross talk at the osteochondral junction. Animal models may capture some of these features, but to establish clinically consistent therapeutics, there remains a need for high-fidelity models of OA that meet all the above requirements in a human patient-specific manner. In vitro bioengineered cartilage-bone tissue models could be developed to recapitulate physiological interactions with human cells and disease-initiating factors. In this study, we highlight human induced pluripotent stem cells (hiPSCs) as the advantageous cell source for these models and review approaches for chondrogenic fate specification from hiPSCs. To achieve native-like stratified cartilage organization with cartilage-bone interactions, spatiotemporal cues mimicking development can be delivered to engineered tissues by patterning of the cells, scaffold, and environment. Once healthy and native-like cartilage-bone tissues are established, an OA-like state can be induced through cytokine challenge or injurious loading. Bioengineered cartilage-bone tissues fall short of recapitulating the full complexity of native tissues, but have demonstrated utility in elucidating some mechanisms of OA progression and enabled screening of candidate therapeutics in patient-specific models. With rapid progress in stem cells, tissue engineering, imaging, and high-throughput omics research in recent years, we propose that advanced human tissue models will soon offer valuable contributions to our understanding and treatment of OA.