Unlocking the future of osteoarthritis: Material engineering and drug delivery confluence for advanced therapeutic approaches

The limited regeneration capacity of articular cartilage (AC) is attributed to the hypocellular nature of the cartilage tissue and the absence of vascularization. On the other hand, degenerative joint disease, such as osteoarthritis (OA), is characterized by irreversible AC degeneration and synovial inflammation, leading to pain, discomfort, and restricted joint mobility. The existing treatment options for OA mostly provide symptomatic relief. Therefore, it is vital to explore several approaches, such as cartilage regeneration and maintenance of cartilage homeostasis. During OA pathogenesis, significant changes are observed in the gene expression and phenotype of articular chondrocytes. Some of these changes include chondrocyte hypertrophy, expansion of the endoplasmic reticulum-Golgi apparatus, secretion of stiffer collagen matrix like collagen type X, increased matrix metalloproteinases (MMPs)-3, -9, and -13 and alkaline phosphatase levels; and decrease of SOX9, proteoglycans, and collagen type II. The changes seen in chondrocytes are similar to those observed during endochondral ossification. Therefore, modulating key molecular players like bone morphogenetic protein (BMP) and wingless-related integration site (Wnt) Wnt/beta-catenin signaling pathways using their antagonists and agonists, respectively, has been shown to effectively inhibit OA progression. These advancements have been further explored in the context of cartilage tissue engineering to design artificial AC-like scaffolds that mimic former physicochemical properties and can be applied as a substitute for damaged cartilage. However, modern science still has unaccomplished objectives that can completely translate our understanding of AC maintenance into the complete restoration of healthy joints. Therefore, in this review, we looked at how understanding the cellular and molecular behavior of articular chondrocytes may be used in confluence with other existing non-surgical therapeutic approaches, such as nanomedicines, regenerative biology, and tissue engineering combined, to find a cure for OA.