The roles of cellular and molecular components of a hematoma at early stage of bone healing

Abstract

Bone healing is a complex repair process that commences with the formation of a blood clot at the injured bone, termed hematoma. It has evidenced that a lack of a stable hematoma causes delayed bone healing or non-union. The hematoma at the injured bone constitutes the early healing microenvironment. It appears to dictate healing pathways that ends in a regenerative bone. However, the hematoma is often clinically removed from the damaged site. Conversely, blood-derived products have been used in bone tissue engineering for treating critical sized defects, including fibrin gels and platelet-rich plasma. A second generation of platelet concentrate that is based on leukocyte and fibrin content has also been developed and introduced in market. Conflicting effect of these products in bone repair are reported. We propose that the bone healing response becomes dysregulated if the blood response and subsequent formation and properties of a hematoma are altered. This review focuses on the central structural, cellular, and molecular components of a fracture hematoma, with a major emphasis on their roles in regulating bone healing mechanism, and their interactions with mesenchymal stem cells. New angles towards a better understanding of these factors and relevant mechanisms involved at the beginning of bone healing may help to clarify limited or adverse effects of blood-derived products on bone repair. We emphasize that the recreation of an early hematoma niche with critical compositions might emerge as a viable therapeutic strategy for enhanced skeletal tissue engineering.

Fracture Repair: Its Pathomechanism and Disturbances

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

“…Second of all, removal or drainage of hematoma or cellular infiltrates from the fracture, especially, when performed repeatedly, deprives it of molecular regulators [7].…”

Healing Processes in Cancellous Bone

“…This observation, that inflammatory and mesenchymal cells appear simultaneously, differs from how shaft fracture healing is described in the literature; the common description is that accumulation of mesenchymal cells usually appears after the initial inflammation from inflammatory cells. [6][7][8][9][10][11][12] Inflammation and bone healing…”

“…Bone is a dynamic tissue which constantly remodels itself, and with the unique ability to heal without any scar formation. [1][2][3][4][5][6] Bone tissue can be distinguished into two types: cortical bonedense and compact in structure, forming an outer hard shell around bones; and cancellous bone -spongy and porous in structure, located in the ends of long bones, the hip, and the vertebrae.…”

“…Fracture healing is described in the literature as a sequential process with overlapping phases: inflammation -accumulation of inflammatory cells; soft callus formation -cartilage formation; hard callus formation -the cartilage is mineralized and becomes new woven bone; and bone remodeling -the woven bone is replaced by lamellar bone which is more organized and stronger. 2,4,13,[5][6][7][8][9][10][11][12] This process mainly concerns cortical bone healing in so called shaft fractures. Much is known about these types of fractures because they are relatively easy to study in animal models.…”