Experimental blunt chest trauma impairs fracture healing in rats

Abstract

In poly-traumatic patients a blunt chest trauma is an important trigger of the posttraumatic systemic inflammatory response. There is clinical evidence that fracture healing is delayed in such patients, however, experimental data are lacking. Therefore, we investigated the influence of a thoracic trauma on fracture healing in a rat model. Male Wistar rats received either a blunt chest trauma combined with a femur osteotomy or an isolated osteotomy. A more rigid or a more flexible external fixator was used for fracture stabilization to analyze whether the thoracic trauma influences regular healing and mechanically induced delayed bone healing differently. The blunt chest trauma induced a significant increase of IL-6 serum levels after 6 and 24 h, suggesting the induction of a systemic inflammation, whereas the isolated fracture had no effect. Under a more rigid fixation the thoracic trauma considerably impaired fracture healing after 35 days, reflected by a significantly reduced flexural rigidity (three-point-bending test), as well as a significantly diminished callus volume, moment of inertia, and relative bone surface (mCT analysis). In confirming the clinical evidence, this study reports for the first time that a blunt chest trauma considerably impaired bone healing, possibly via the interaction of the induced systemic inflammation with local inflammatory processes. ß

Systemic mesenchymal stem cell administration enhances bone formation in fracture repair but not load-induced bone formation

“…We did not expect to detect an alteration in the serum cytokine levels, because our previous and on-going studies show that an isolated femur osteotomy is unable to induce any considerable systemic inflammatory response even 6 h after osteotomy and that the initial post-traumatic systemic inflammatory response is down-regulated to physiological levels within 24 h of osteotomy in rodents. To achieve a considerable systemic inflammation, a second trauma is necessary (Recknagel et al, 2011). However, whether the applied MSC have an immunomodulatory effect cannot be fully answered by the present study, earlier time-points after fracture would be necessary to investigate this.…”

NF-κB inhibits osteogenic differentiation of mesenchymal stem cells by promoting β-catenin degradation

“…However, most of these studies were performed under optimized surgical conditions with minimal tissue inflammation. In the realm of therapeutic bone regeneration, the defective or injured tissues are frequently inflamed with an abnormal expression of inflammatory mediators (14)(15)(16)(17). Growing evidence suggests that proinflammatory cytokines inhibit osteogenic differentiation and bone formation (18)(19)(20)(21)(22)(23)(24).…”

Unraveling macrophage contributions to bone repair

“…41 It is possible that one of the mechanisms underlying increased rates of delayed or failed fracture healing in compound fractures is the increased pathogen load in these open wounds resulting in inappropriate or extreme polarization of macrophages. Experimentally, elevated systemic inflammation due to additional soft-tissue trauma injuries impairs fracture healing, 42,43 confirming that persistence of a proinflammatory environment is one mechanism responsible for detrimental fracture healing. 44 Interestingly, low-dose TNF administered to the fracture site at the time of surgery and 1 day post surgery improved fracture healing in mice, 45 suggesting that TNF, and potentially macrophage activation, has complex dose-and time-dependent outcomes on bone healing.…”