Inflammatory Responses and Healing in the Injured Abdomen

UoM administered thesis: Doctor of Medicine

  • Authors:
  • Steven Pengelly

Abstract

Abdominal surgery itself, and implants used in abdominal wall reconstruction, are associated with intra-abdominal inflammation that can go on to cause complications such as adhesions, fistulae or failure of the implant. The pathophysiology of these complications is not fully understood but it would be desirable to produce an in vitro model that can reliably study these peritoneal responses. The use of ‘temporary abdominal closure’ (TAC) systems following laparotomy for abdominal trauma is increasing, and can lead to the requirement for abdominal wall reconstruction using an implant. It was hypothesised that many Servicemen injured in the Iraq and Afghanistan campaigns would subsequently suffer inflammatory complications as a result of these reconstructions, and so these patients’ hospital and primary care records were searched to find evidence of this. Very few of these patients required abdominal wall reconstruction, and no evidence was found that TAC was associated with an increased frequency of complications when compared to early closure of the abdominal fascia. In order to develop an in vitro model of peritoneal inflammation that can be used to study cytokine responses to various stimuli, donated human peritoneum was incubated with and without LPS in the presence of implants used for abdominal wall reconstruction. Incubation with Biodesign® and Strattice™, non-crosslinked biological implants, was associated with significant reductions in supernatant IL-6, IL-1β and TNFα concentrations when compared to control. As generally this was matched by drops in mRNA for these cytokines, this seemed to be a true effect on the tissues rather than an artefact of the experiment, such as cell death or cytokine adsorption by the implant. This effect may be mediated by glycoproteins in these implants binding growth factors in the supernatant. This model, although a long way off direct clinical application, shows promise in further studying peritoneal inflammatory responses.

Details

Original languageEnglish
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Award date1 Aug 2018