Musculoskeletal tissue engineering: Regional gene therapy for bone repair

Bone loss associated with fracture nonunion, revision total joint arthroplasty (TJA), and pseudoarthrosis of the spine presents a challenging clinical scenario for the orthopaedic surgeon. Current treatment options including autograft, allograft, bone graft substitutes, and bone transport techniques are associated with significant morbidity, high costs, and prolonged treatment regimens. Unfortunately, these treatment strategies have proven insufficient to safely and consistently heal bone defects in the stringent biological environments often encountered in clinical cases of bone loss. The application of tissue engineering (TE) to musculoskeletal pathology has uncovered exciting potential treatment strategies for challenging bone loss scenarios in orthopaedic surgery. Regional gene therapy involves the local implantation of nucleic acids or genetically modified cells to direct specific protein expression, and has shown promise as a potential TE technique for the regeneration of bone. Preclinical studies in animal models have demonstrated the ability of regional gene therapy to safely and effectively heal critical sized bone defects which otherwise do not heal. The purpose of the present review is to provide a comprehensive overview of the current status of gene therapy applications for TE in challenging bone loss scenarios, with an emphasis on gene delivery methods and models, scaffold biomaterials, preclinical results, and future directions.