Novel hydrogel-based strategies to prevent surgical adhesions

Post-operative, or ’surgical’, adhesions can cause chronic abdominal pain and life-threatening gut obstruction; they may also render women infertile. Hospital readmissions for surgical adhesion-related complications occur in one third of patients over the 10 years after open surgery, with an estimated annual NHS cost of £67 million. There is therefore an urgent need for therapies to prevent surgical adhesions. Existing physical strategies, such as degradable membranes and gel barriers, show limited efficacy. Although several drugs prevent or reduce surgical adhesions in animal models, intraperitoneal delivery of such agents in patients faces major challenges regarding agent stability and delivery to and retention at the site of injury.

In Manchester, we have developed a novel peptide hydrogel technology as well as a robust experimental model of surgical adhesions. This project will bring together these two technologies to test the hypothesis that intraperitoneal application of hydrogels that topically will prevent adhesion formation and improve peritoneal repair. We will generate hydrogel/drug formulations and test their efficacy using our in vivo model. Adhesion morphology, inflammatory response and tissue regeneration will be scored. We will work alongside our surgical collaborators in the Transplant Unit at Manchester Royal Infirmary and our industrial collaborator.

Training will be provided in advanced in vivo sciences as the student will use a surgical adhesion model already established in the principle supervisor’s laboratory. Adhesions will be characterised by immunohistochemistry and inflammation by FACs. RT-PCR to analyses gene expression and western blotting/ ELISA will be performed to determine the fibrogenic response. Furthermore, the student will receive training in preparing hydrogels and assessing in vitro release kinetics and gel-degradation profiles. Through collaboration with our industrial collaborator and surgical colleagues, training will be provided in translating ideas into clinical practice.

Candidates must hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in a subject relevant to cell/developmental biology, immunology and/or matrix biology. Prior laboratory experience and/or an MSc in an appropriate subject area would be an advantage.