The development of natural polymer scaffold-based therapeutics for osteochondral repair

Due to the limited regenerative capacity of cartilage, untreated joint defects can advance to more extensive degenerative conditions such as osteoarthritis. While some biomaterial-based tissue-engineered scaffolds have shown promise in treating such defects, no scaffold has been widely accepted by clinicians to date. Multi-layered natural polymer scaffolds that mimic native osteochondral tissue and facilitate the regeneration of both articular cartilage (AC) and subchondral bone (SCB) in spatially distinct regions have recently entered clinical use, while the transient localized delivery of growth factors and even therapeutic genes has also been proposed to better regulate and promote new tissue formation. Furthermore, new manufacturing methods such as 3D bioprinting have made it possible to precisely tailor scaffold micro-architectures and/or to control the spatial deposition of cells in requisite layers of an implant. In this way, natural and synthetic polymers can be combined to yield bioactive, yet mechanically robust, cell-laden scaffolds suitable for the osteochondral environment. This mini-review discusses recent advances in scaffolds for osteochondral repair, with particular focus on the role of natural polymers in providing regenerative templates for treatment of both AC and SCB in articular joint defects.