Modern Approaches and Emerging Biological Therapies to Treat Fracture Nonunion

Fracture nonunion remains an unresolved complication after extremity fracture, with notable costs to patient quality of life and health systems. Nonunion is defined by the inability of fracture ends to unite without evidence of progressive healing over time. Approximately 2 to 10% of all fractures go onto nonunion, with increased rates observed in specific fracture locations and patient populations. Despite advances in fixation techniques and bone grafting, current treatments remain limited and frequently fail to restore durable bone healing. In this review, the current state of emerging biologic and bioengineering therapies for nonunion will be summarized, with a focus on how these advances may shift treatment from palliative reconstruction toward durable healing. Biological therapies such as growth factors, stem cells, and gene-modified constructs show promise but face challenges of short half-life, inconsistent efficacy, and safety concerns. Emerging approaches, including controlled-release scaffolds, immunomodulatory materials, stem cell-derived exosomes, and gene therapy platforms, offer opportunities to more precisely restore the osteogenic, angiogenic, and immunologic environment required for union.