Novel model of peripheral tissue trauma‐induced inflammation and gastrointestinal dysmotility

Background Trauma is a leading cause of death and although the gut is recognized as the ‘motor’ of post‐traumatic systemic inflammatory response syndrome and multiple organ failure, studies on the gastrointestinal (GI) tract are few. Our objectives were to create a precisely controllable tissue injury model in which GI motility, systemic inflammation and wound fluid can be analyzed. Methods A non‐narcotic murine trauma model was developed by the subcutaneous dorsal trans‐implantation of a devitalized donor syngeneic harvested tissue–bone matrix (TBX), which was precisely adjusted to % total body weight and studied after 21 h. Gastrointestinal transit histograms were plotted after the oral administration of non‐digestible FITC‐dextran and geometric centers calculated. Organ bath evaluated jejunal circular muscle contractility. Multiplex electrochemiluminescence measurements of serum and TBX wound fluid inflammatory mediators were performed. Key Results Increasing TBX amounts progressively delayed transit, whereas TBX heat denaturation or decellularization prevented ileus and death. In the TBX17.5% model, jejunal muscle contractility was suppressed and a systemic inflammatory response developed as significant serum elevations in IL‐6, keratinocyte cytokine and IL‐10 compared to sham. In addition, inflammatory responses within the wound fluid showed elevated levels of preformed IL‐1β and TNF‐α, whereas, 21 h after implantation IL‐1β, IL‐6 and keratinocyte cytokine were significantly increased in the wound. Conclusions & Inferences A novel donor tissue–bone matrix trauma model was developed that is precisely adjustable and recapitulates important clinical phenomena. The non‐narcotic model demonstrated that increasing tissue injury progressively caused ileus, initiated a systemic inflammatory response and developed inflammatory changes within the wound.