Enhancing fracture repair: cell-based approaches

Fracture repair is based both on the macrolevel modulation of fracture fragments and the subsequent cellular activity. Surgeons have also long recognized other influences on cellular behavior: the effect of the fracture or subsequent surgery on the available pool of cells present locally in the periosteum, the interrelated effects of fragment displacement, and construct stiffness on healing potential, patient pathophysiology and systemic disease conditions (such as diabetes), and external regulators of the skeletal repair (such as smoking or effect of medications). A wide variety of approaches have been applied to enhancing fracture repair by manipulation of cellular biology. Many of these approaches reflect our growing understanding of the cellular physiology that underlies skeletal regeneration. This review focuses on approaches to manipulating cell lineages, influencing paracrine and autocrine cell signaling, or applying other strategies to influence cell surface receptors and subsequent behavior. Scientists continue to evolve new approaches to pharmacologically enhancing the fracture repair process.