Gene Therapy to Enhance Bone and Cartilage Repair in Orthopaedic Surgery

摘要

Musculoskeletal conditions are a major public health problem. Approximately 66 millionindividuals seek medical attention for a musculoskeletal injury in the United States, with currentmedical costs being estimated at $873 billion annually. Despite advances in pharmaceuticals, implantmaterials and surgical techniques, there remains an unmet clinical need for successful treatment ofchallenging musculoskeletal injuries and pathologic conditions, particularly in the setting of compromisedbiological environments. Tissue engineering via gene therapy attempts to provide an alternativetreatment strategy to address the deficits associated with conventional approaches. The transfer of specifictarget genes coding for proteins with therapeutic or regenerative properties to target cells and tissuesin the disease environment allows for their sustained production and release specifically at thesite of interest. The increasing reports of success with gene therapy-based treatments in the clinicalmanagement of a variety of diseases provide genuine optimism that similar methods can be adaptedfor mainstream clinical application in musculoskeletal disorders. In preclinical studies, gene therapyhas been successfully used to treat cartilaginous, bone, skeletal muscle, tendon, ligament and intervertebraldisk injuries. In addition, gene therapy is being assessed in clinical trials for its safety and therapeuticpotential in osteoarthritis. This review will specifically address the clinical potential, preclinicaldata and future hurdles for gene therapy to be a viable clinical entity for the treatment of fracture nonunionand difficult bone repair scenarios, articular cartilage repair and osteoarthritis.