Delayed healing and nonunion formation are major challenges in orthopedic surgery, which require the development of novel treatment strategies. Vascularization is considered one of the major prerequisites for successful bone healing, providing an adequate nutrient supply and allowing the infiltration of progenitor cells to the fracture site. Hence, during the last decade, a considerable number of studies have focused on the evaluation of vascularization strategies to prevent or to treat nonunion formation. These involve (1) biophysical applications, (2) systemic pharmacological interventions, and (3) tissue engineering, including sophisticated scaffold materials, local growth factor delivery systems, cell-based techniques, and surgical vascularization approaches. Accumulating evidence indicates that in nonunions, these strategies are indeed capable of improving the process of bone healing. The major challenge for the future will now be the translation of these strategies into clinical practice to make them accessible for the majority of patients. If this succeeds, these vascularization strategies may markedly reduce the incidence of nonunion formation. Impact statement Delayed healing and nonunion formation are a major clinical problem in orthopedic surgery. This review provides an overview of vascularization strategies for the prevention and treatment of nonunions. The successful translation of these strategies in clinical practice is of major importance to achieve adequate bone healing.
Keywords: VEGF; angiogenesis; bone formation; bone healing; cell therapy; delayed healing; nonunion; scaffold; tissue engineering; vascularization.