Scaling strategies for bioink manufacturing in bone and cartilage bioprinting: Challenges, innovations, and future perspectives

Bioprinting has emerged as a transformative platform for engineering bone and cartilage tissues; however, its clinical translation is currently limited by the lack of scalable, reproducible, and regulatory-compliant bioink manufacturing. This review provides a comprehensive evaluation of current challenges, advancements, and strategies for the scale-up of bioink manufacturing, with a specific focus on bone and cartilage bioprinting applications. The key topics addressed include mechanical performance, cell viability preservation, reproducibility, batch-to-batch consistency, sterility assurance, and regulatory compliance. Emerging methods, including bioreactor-based cell expansion, continuous bioprocessing, and hybrid biomaterials, are critically assessed for their potential to enhance scalability while maintaining biological functionality and manufacturing reproducibility. Future directions for industrial-scale bioink manufacturing are discussed with particular emphasis on manufacturing-critical requirements, including sterility assurance, endotoxin control, batch-to-batch consistency, and clearly defined release criteria, each of which is essential for regulatory approval and clinical translation. Collectively, these developments reflect a shift from manual bioink preparation toward automated, validated, and scalable manufacturing pipelines that advance the clinical deployment of patient-specific regenerative therapies for musculoskeletal applications.