Paradigm Shifts in Regenerative Medicine for Bone and Joint Surgery: From Mechanical Repair to Intelligent Biological...

Orthopedic surgery is transitioning from a mechanical repair paradigm to intelligent biological restoration driven by advances in regenerative medicine and artificial intelligence (AI). This review synthesizes the science and clinical translation of stem cell therapies, bioactive and 'smart' scaffolds, growth factor strategies, and AI-enabled planning and delivery systems.

We conducted a narrative review of peer-reviewed literature (2013-2025) on regenerative orthopedics, including stem cells, platelet concentrates, tissue engineering, biofabrication/bioprinting, AI/robotics, and translational frameworks, with an emphasis on musculoskeletal applications and regional experiences.

Evidence supports mesenchymal stem cells (MSCs), platelet-rich plasma (PRP), and bone marrow aspirate concentrate (BMAC) for selected indications, augmented by biomimetic scaffolds and controlled growth factor delivery. Biofabrication enables defect-specific constructs including three-dimensional bioprinting sheet, while AI assists scaffold/matrix optimization through machine learning-based design algorithms, supports imaging-based healing prediction via deep learning models, and enhances precision in robotic-assisted biologic delivery. Regulatory hurdles such as variable stem cell approval pathways, ethical concerns over cell sourcing and patient data use, and high production costs remain major barriers to clinical adoption, alongside the need for surgeon training in biologic and AI-integrated systems.

The convergence of biologics, smart materials, and AI is redefining bone and joint surgery from replacement to restoration. Future systems will pair digital twins and wearables with bioprinting, living implants and precision robotics for closed-loop, adaptive regenerative care.