The haematoma and its role in bone healing

Abstract

Fracture treatment is an old endeavour intended to promote bone healing and to also enable early loading and regain of function in the injured limb. However, in today's clinical routine the healing potential of the initial fracture haematoma is still not fully recognized. The Arbeitsgemeinschaft für Osteosynthesefragen (AO) formed in Switzerland in 1956 formulated four AO principles of fracture treatment which are still valid today. Fracture treatment strategies have continued to evolve further, as for example the relatively new concept of minimally invasive plate osteosynthesis (MIPO). This MIPO treatment strategy harbours the benefit of an undisturbed original fracture haematoma that supports the healing process. The extent of the supportive effect of this haematoma for the bone healing process has not been considered in clinical practice so far. The rising importance of osteoimmunological aspects in bone healing supports the essential role of the initial haematoma as a source for inflammatory cells that release the cytokine pattern that directs cell recruitment towards the injured tissue. In reviewing the potential benefits of the fracture haematoma, the early development of angiogenic and osteogenic potentials within the haematoma are striking. Removing the haematoma during surgery could negatively influence the fracture healing process. In an ovine open tibial fracture model the haematoma was removed 4 or 7 days after injury and the bone that formed during the first two weeks of healing was significantly reduced in comparison with an undisturbed control. These findings indicate that whenever possible the original haematoma formed upon injury should be conserved during clinical fracture treatment to benefit from the inherent healing potential.

Keywords: Bone healing; Fracture treatment; Haematoma; Regeneration.

Fig. 1

In a comminuted fracture of the fibula and a medial malleolus avulsion fracture the standard of care would include an internal plate fixation of the fibula fracture without the elimination of the fracture haematoma. The bone fragments would remain embedded in the ensuing haematoma while the plate fixation would ensure maintenance of the correct axis and length of the healing fibula. On the other hand leaving the haematoma in the medial malleolar fracture depicted here is not feasible. Here the fracture ends have to be repositioned through an anatomical reduction and this includes the removal of the haematoma. This is of special importance as a joint is involved in the fracture and the correct realignment of the bones of the joint has to be ensured

Fig. 2

The different tissues involved in bone regeneration are shown above with the two important revascularization steps during tissue development. In the lower line the 5 consecutive phases of bone healing are depicted

Fig. 3

a Upon injury the cytokine expression changes in the periosteum directly adjacent to the bone injury: C = uninjured control, IB = injured bone 60 h after injury. HIF1a, HMOX1, and PDGF, three factors highly relevant for revascularization are significantly upregulated in the periosteum upon injury. b Tissues involved in bone healing, periosteum, haematoma, and bone marrow were investigated under normal and delayed healing conditions. The cytokine expression and also the cellular composition in all compartments was significantly altered under mechanically induced delayed healing conditions. For detailed information please refer to: (Schmidt-Bleek et al. ; Schmidt-Bleek et al. 2012b). For statistical analyses of data, medians were calculated for each group per time point. Statistical comparisons between the groups were performed using the Mann–Whitney U-test (SPSS 22; SPSS, Inc., Chicago, IL)

Fig. 4

The expression profile of factors involved in inflammation, angiogenesis and osteogenesis change with the progression of healing, e.g. from 4 to 7 days, in the fracture haematoma and is also dependent of the healing progression. The cytokine pattern in a normal, undisturbed healing differs from one in a mechanically induced delayed healing. For statistical analyses of data, medians were calculated for each group per time point. Statistical comparisons between the groups were performed using the Mann–Whitney U-test (SPSS 22; SPSS, Inc., Chicago, IL). (For a detailed description of these experiments please consult (Lienau et al. ; Lienau et al. ; Schmidt-Bleek et al. ; Schmidt-Bleek et al. 2012b))

Fig. 5

Movat Pentachrome staining 14 days post surgery of the control group and the haematoma removal groups (D4, D7). The control group shows the physiological healing pattern (1) while group D4 (2) and group D7 (3) are characterized by prominent haematoma remnants and a delayed periosteal callus formation (overview top). The squares in the overview indicate locations of magnifications shown below for each group. a, c, and e depict a comparison of the haematoma remnants in the osteotomy gap. Note the progressed organization of the haematoma remnants (HR) in the control group (a), where connective tissue (CoT) predominates in the osteotomy gap. At the two weeks time point this connective tissue represents the normal bone healing development and indicated the maturation of the haematoma towards the soft callus phase. In groups D4 and D7 the haematoma is still unorganized with dominating erythrocytes and only a small amount of fibrin fibers without noticeable orientation (c, e). b, d, and f show the progression of the periosteal callus (PC) with respect to the osteotomy gap. While the newly formed woven bone in the control group (b) developed along the cortical bone (CtB) up to the original gap, this is neither seen in group D4 (d) nor in group D7 (f)

Fig. 6

Haematoma and woven bone fraction in the periosteal callus area. Note the reverse ratio of haematoma and woven bone tissue in the control group and the treated groups with a significantly higher fraction of bone and a significantly lower fraction of haematoma in the control group