Bone fracture healing: Cell therapy in delayed unions and nonunions

- We reviewed the current concepts of impaired bone fracture healing in nonunions.
- Atrophic bone nonunions are difficult to heal due to cellular insufficiency.
- Cell therapy solutions provide MSCs intended to enhance osteogenesis and healing.
- We review clinical data, insufficient to prove enhanced bone healing with MSCs.
- More and better clinical trials are required to confirm or refute the role of MSC.

Bone fracture healing impairment related to mechanical problems has been largely corrected by advances in fracture management. Better protocols, more strict controls of time and function, and hardware and surgical technique evolution have contributed to better prognosis, even in complex fractures. However, atrophic nonunion persists in clinical cases where, for different reasons, the osteogenic capability is impaired. When this is the case, a better understanding of the basic mechanisms under bone repair and augmentation techniques may put in perspective the current possibilities and future opportunities. Among those, cell therapy particularly aims to correct this insufficient osteogenesis. However, the launching of safe and efficacious cell therapies still requires substantial amount of research, especially clinical trials. This review will envisage the current clinical trials on bone healing augmentation based on cell therapy, with the experience provided by the REBORNE Project, and the insight from investigator-driven clinical trials on advanced therapies towards the future. This article is part of a Special Issue entitled Stem Cells and Bone.