Fracture healing: mechanisms and interventions

Abstract

Fractures are the most common large-organ, traumatic injuries to humans. The repair of bone fractures is a postnatal regenerative process that recapitulates many of the ontological events of embryonic skeletal development. Although fracture repair usually restores the damaged skeletal organ to its pre-injury cellular composition, structure and biomechanical function, about 10% of fractures will not heal normally. This article reviews the developmental progression of fracture healing at the tissue, cellular and molecular levels. Innate and adaptive immune processes are discussed as a component of the injury response, as are environmental factors, such as the extent of injury to the bone and surrounding tissue, fixation and the contribution of vascular tissues. We also present strategies for fracture treatment that have been tested in animal models and in clinical trials or case series. The biophysical and biological basis of the molecular actions of various therapeutic approaches, including recombinant human bone morphogenetic proteins and parathyroid hormone therapy, are also discussed.

Valence State Manipulation of Cerium Oxide Nanoparticles on a Titanium Surface for Modulating Cell Fate and Bone Formation

“…Manipulating the surface Ce 4+ /Ce 3+ ratio of CeONPs can modulate macrophage polarization and cytokine secretion, and facilitate appropriate immune reactions that balance antiinflammation and pro‐inflammation, which lead to the satisfactory outcomes of new bone formation and bone–biomaterial integration. The introduction of a biomaterial into the body initiates an inflammatory cascade due to cell and tissue damage, and this cascade persists for roughly 4 d 13. This early inflammatory response is highly beneficial to the host, it must subsequently be terminated to avoid tissue damage and to promote tissue regeneration 14.…”

“…[[qv: 11f,12]] Introduction of an implant into the body initiates an inflammatory cascade due to cell and tissue damage, and this cascade persists for roughly 4 d 13. This early inflammatory response is beneficial to the host, but termination of subsequent inflammation is critical for blocking tissue damage and promoting tissue regeneration 14.…”

Intramedullary Mg2Ag nails augment callus formation during fracture healing in mice

“…Fractures of the femoral and tibia shaft often occur in response to high energy trauma and are preferentially treated by an intramedullary nail that supports the fracture zone and facilitates bone healing [1][2][3]. The intramedullary stabilization usually remains since implant removal in general and extraction of a nail in particular can be very time-consuming, cumbersome and may cause further tissue damage, refracture and other subsequent problems [4][5][6].…”

Modeling the effects of inflammation in bone fracture healing

“…These two stages occur within the first 21 days after the trauma [3]. The acute inflammatory expressions are usually observed in the first 4 to 24 hours and callus production occurs in the first 3 days [13].…”

“…The simulation time is set to 21 days after the trauma which is the approximate time for the inflammation and repairing steps of fracture healing both in humans and animals [3]. During this time, the cartilage density is being replaced by woven bone which eventually fills completely the fracture gap [1].…”