Can Normal Fracture Healing Be Achieved When the Implant Is Retained on the Basis of Infection? An Experimental Animal Model

Abstract

Background Infection after open fractures is a common complication. Treatment options for infections developed after intramedullary nailing surgery remain a topic of controversy. We therefore used a rat fracture model to evaluate the effects of infection on osseous union when the implant was maintained.Questions/purposes In a rat model, (1) does infection alter callus strength; (2) does infection alter the radiographic appearance of callus; and (3) does infection alter the histological properties of callus? Methods An open femoral fracture was created and fixed with an intramedullary Kirschner wire in 72 adult male Sprague-Dawley rats, which were divided into two study groups. In the infection group, the fracture site was contaminated with Staphylococcus aureus (36 animals), whereas in the control group, there was no bacterial contamination (36 animals). No antibiotics were used either for prophylaxis or for treatment. We performed biomechanical (maximum torque causing failure and stiffness), radiographic (Lane and Sandhu scoring for callus formation), and histologic (scoring for callus maturity) assessments at 3 and 6 weeks. The number of bacteria colonies on the femur, wire, and soft tissue inside knee were compared to validate that we successfully created an infection model. The number of bacteria colonies in the soft tissue inside the knee was higher in the infection group after 6 weeks than after the third week, demonstrating the presence of locally aggressive infection. Results Infection decreased callus strength at 6 weeks. Torque to failure (299.07 ± 65.53 Nmm versus 107.20 ± 88.81, mean difference with 95% confidence interval, 192 [43-340]; p = 0.007) and stiffness at 6 weeks (11.28 ± 2.67 Nmm versus 2.03 ± 1.68, mean difference with 95% confidence interval, 9 [3-16]; p = 0.004) both were greater in the control group than in the group with infection.

Impact of Bacterial Infections on Osteogenesis: Evidence From In Vivo Studies

“…Neutrophils are normally only short‐lived (hours‐days), and are quickly replaced by macrophages in the fracture hematoma . In osteomyelitis, they remain present in high numbers both locally and systemically, outnumbering monocytes and lymphocytes . Recent reports have shed light on possible mechanisms by which neutrophils could inhibit callus formation.…”

“…The radiographic or micro‐CT outcomes of the studies show that the defects generally bridge uneventfully under aseptic conditions. Strikingly, in spite of the relatively small defects that are often created, many studies report non‐union at follow‐up once a chronic infection is established . This negative influence of bacterial infection on healing depends on the severity of infection, and correlates with the initial bacterial inoculation dose .…”

“…In contrast to noninfected controls, active inflammation is always observed in infection animals, irrespective of the time point of evaluation. 21,22,25,33,34,44,[64][65][66][67][68] Whereas neutrophils and monocytes normally only play a role in the acute phase of healing, they remain predominant cell populations in infected defects even after weeks to months. 43,68,69 The total absence of hyaline cartilage in the defects of severely-infected animals compared with lowgrade 44,65 or non-infected 43,44 animals, leads to the suggestion that bacterial contamination already disrupts the early stages of callus formation.…”

“…Animal experiments also offer the advantage that callus formation can be more easily monitored [21][22][23] and quantified with high-resolution imaging techniques, 23,24 and that the impact on biomechanics can be assessed. [24][25][26] From a basic point of view, the current review summarizes how bacterial infection affects the radiographic and histological appearance of bone tissue in the context of fracture healing, and whether this is related to changes in mechanical stability and callus formation. Whereas bone fracture healing normally is a wellorchestrated event, it is unclear if, and to what extent, the sequential stages of fracture healing (i.e., inflammation, repair, and remodeling) are disturbed following bacterial contamination.…”

Toll-like receptor-4-dependence of the lipopolysaccharide-mediated inhibition of osteoblast differentiation

“…On the other hand, the stability provided by implant retention has also been shown to reduce the likelihood of infection after fixation (Merritt and Dowd, 1987;Worlock et al, 1994;Schmidt and Swiontkowski, 2000). Implant retention in the presence of an underlying infection and in the absence of antibiotic treatment leads to a weaker callus and impedes callus maturation in a rat model, compared to non-infected controls (Bilgili et al, 2015). Lipopolysaccharide (LPS) is an important pathogenic factor affecting bone fracture healing.…”