Cartilage tissue engineering for obesity-induced osteoarthritis: Physiology, challenges, and future prospects

Abstract

Osteoarthritis (OA) is a multifactorial joint disease with pathological changes that affect whole joint tissue. Obesity is acknowledged as the most influential risk factor for both the initiation and progression of OA in weight-bearing and non-weight-bearing joints. Obesity-induced OA is a newly defined phenotypic group in which chronic low-grade inflammation has a central role. Aside from persistent chronic inflammation, abnormal mechanical loading due to increased body weight on weight-bearing joints is accountable for the initiation and progression of obesity-induced OA. The current therapeutic approaches for OA are still evolving. Tissue-engineering-based strategy for cartilage regeneration is one of the most promising treatment breakthroughs in recent years. However, patients with obesity-induced OA are often excluded from cartilage repair attempts due to the abnormal mechanical demands, altered biomechanical and biochemical activities of cells, persistent chronic inflammation, and other obesity-associated factors. With the alarming increase in the number of obese populations globally, the need for an innovative therapeutic approach that could effectively repair and restore the damaged synovial joints is of significant importance for this sub-population of patients. In this review, we discuss the involvement of the systemic and localized inflammatory response in obesity-induced OA and the impact of altered mechanical loading on pathological changes in the synovial joint. Moreover, we examine the current strategies in cartilage tissue engineering and address the critical challenges of cell-based therapies for OA. Besides, we provide examples of innovative ways and potential strategies to overcome the obstacles in the treatment of obesity-induced OA.

The translational potential of this article: Altogether, this review delivers insight into obesity-induced OA and offers future research direction on the creation of tissue engineering-based therapies for obesity-induced OA.

Keywords: Articular cartilage regeneration; Biomaterials; Inflammation; Obesity; Osteoarthritis.

Graphical abstract

Figure 1

Obesity and OA. Obesity induces systemic chronic low-grade inflammation that is able to increase risk of OA by inducing local inflammation within the synovial joint (i.e. synovitis). The inflamed synovium induces increased infiltration of pro-inflammatory M1 macrophages that causes overexpression of pro-inflammatory cytokines and matrix metalloproteinase. This inflammation contributes to progressive cartilage loss by increasing the production of degradative and proteolytic enzymes. Cartilage degradation fragments induce further degradation of the cartilage by converting the phenotype of chondrocytes and further increases secretion of macrophage-like synoviocytes. Altered mechanical loading gives rise to disturbed tissue homeostasis and cartilage/bone integrity in the articular joints.

Figure 2

Potential approach of tissue engineering-based treatment for obesity-induced cartilage degradation.