Engineering gene-activated bioprinted scaffolds for enhancing articular cartilage repair

Untreated articular cartilage injuries often result in severe chronic pain and dyskinesia. Current repair strategies have limitations in effectively promoting articular cartilage repair, underscoring the need for innovative therapeutic approaches. A gene-activated matrix (GAM) is a promising and comprehensive therapeutic strategy that integrates tissue-engineered scaffold-guided gene therapy to promote long-term articular cartilage repair by enhancing gene retention, reducing gene loss, and regulating gene release. However, for effective articular cartilage repair, the GAM scaffold must mimic the complex gradient structure of natural articular cartilage. Three-dimensional (3D) bioprinting technology has emerged as a compelling solution, offering the ability to precisely create complex microstructures that mimic the natural articular cartilage. In this review, we summarize the recent research progress on GAM and 3D bioprinted scaffolds in articular cartilage tissue engineering (CTE), while also exploring future challenges and development directions. This review aims to provide new ideas and concepts for the development of gene-activated bioprinted scaffolds with specific properties tailored to meet the stringent requirements of articular cartilage repair.