**1. Background**

Healing of the bone fracture is a biological process that restores its continuity, mechanical properties, and structure. It bases on various cell lineages recruited, activated and regulated by molecular mediators, namely chemokines, growth factors, and cytokines, cooperating in a cascade of events aimed to fill the fracture gap with callus, which later on is remodeled into

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

mature bone. Thus, this process is, in fact, a regeneration, not healing, as its goal is to restore not only the bone's continuity but also its structure.

under unfavorable conditions, they may differentiate into, unwanted from the point of view of the fracture healing, cellular population forming cartilaginous or fibrous pseudoarthrosis. Hypoxia, hypercapnia, and acidosis that characterize deprived of vasculature posttraumatic hematoma, promote their differentiation into chondrocytes, whereas higher oxygen tension

Fracture Repair: Its Pathomechanism and Disturbances http://dx.doi.org/10.5772/intechopen.76252 5

Four sources of molecular stimulators and regulators of bone healing could be distinguished:

Platelets are the abundant source of molecular substances of blood origin. Released from granules into a posttraumatic hematoma, those substances activate, together with mediators

Platelets participate in various reparative processes, being involved in the restoration of traumatized mucous and epithelia, healing various soft tissues (i.e. muscle) and the bone, and restoration of the vascularity in the process of angiogenesis. An influence of other hematoma products, including fibrin clot and activated clotting factors, hemoglobin, complement cascade and subcellular structures such as subcellular fragments of blood cells increases, giving

Traumatized tissues provide molecular stimuli that are released in response to injury. Damage - associated molecular pattern molecules (DAMPs) are the most potent activators of the sterile, traumatic inflammation ("first hit"), whereas the later one ("second hit") mostly dependents on molecules provided by the inflowing immune cells. Those molecules activate immune system directly through toll-like receptors (TLRs) [8]. So far, several DAMPs have been distinguished, including heat-shock proteins (HSPs), high-mobility group box 1 (HMGB-1), monosodium urate, heparan sulfate, adenosine triphosphate (ATP), polysaccharides, proteoglycan, phospholipids, and deoxyribonucleic acid (DNA). Similar capabilities possess hyaluronian

Nerve endings provide neuromediators that participate in fracture repair, including calcitonin gene - related peptide and neuropeptide-Y [11]. Released in response to mechanical (injury) and physicochemical (hypoxia, acidosis) stimuli, they participate in the molecular regulation of cellular events during the reparative phase and callus mineralization [12]. However, they

The later abundant source of molecular stimulators are leukocytes originating from the bloodforming hematoma and inflowing from the peripheral circulation. Granulocytes are the first

released from nerve endings, and cellular events proceeding in the fracture gap.

an insight into a complex role of several hematoma compounds in the healing [7].

and reduced acidosis-into osteoblasts [6].

**3. Molecular stimulators of fracture repair**

**2.** Traumatized bone and tissues neighboring it

fragments released from disintegrated ECM [9, 10].

were also found to control remodeling [13].

**3.** Nerve endings at the adjacent tissues

**4.** Inflowing inflammatory cells

**1.** Extravagated blood forming the posttraumatic hematoma

Clinically, healing manifests with remission of pain corresponding with gradually increasing stiffness enabling transduction of mechanical loads. Radiographically-with formation and remodeling of the callus in-between its gap. Monitoring of this process indicates the advance of the reparative processes.
