Differently charged polypeptides and their impact on peritoneal and pleural postoperative adhesion formation

Abstract: Organization LUND UNIVERSITY Department of Surgery, Clinical Sciences Skånes University Hospital Lund SE-221 85 Lund Sweden Document name DOCTORAL DISSERTATION Date of issue: November 8, 2013 Author(s): Daniel Åkerberg Sponsoring organization Title and subtitle: Differently charged polypeptides and their impact on peritoneal and pleural postoperative adhesion formation Abstract: Abdominal adhesions are formed after previous peritoneal traumas where previous surgery poses the most frequent cause. An increasing number of clinical complications due to adhesions have been detected such as small bowel obstructions, female infertility, and pain. Postoperative adhesions also form in pleura and pericardium after thoracic surgery. Complications include risk of bleeding, organ perforation and prolonged surgery, both in the thorax and abdomen, during reoperations. Previous reports have shown increased healthcare expenditures due to complications of abdominal adhesions. Several prophylactic anti-adhesion devices exist on the market, but none of them are sufficient in every aspect, such as being able to be used during abdominal infections, bleeding and in case of an intestinal anastomosis. The use of two differently charged polypeptides covering the peritoneal wounds during surgery has, in previous studies, shown promising anti-adhesion effects. The aim of this study was to investigate whether the polypeptides in any way affected different important healing aspects of the peritoneum and if the polypeptides may be administered as a spray in an animal study (I). Furthermore, the aim was to elucidate if the administered polypeptides affected important aspects of the healing process during an extended time dynamic pattern (II). It was also investigated whether the polypeptides reduced adhesions after adhesiolysis in the abdomen (III) and pleura (IV), and if there was an impact on peritoneal/pleural healing. In order to investigate the impact of polypeptides, an in vitro cell model was set up (V). A significant decrease in adhesions was seen both in the abdomen and pleura using the polypeptides. A significant decrease in adhesion reformation was seen after adhesiolysis and polypeptide administration. Despite some variation, no significant impact on key parameters of peritoneal and pleural resolving processes were seen after administration of the polypeptides. It was feasible to administer the polypeptides with a spray atomizer. Cell proliferation was decreased when higher concentrations of the polypeptides were administered, indicating a dose response relationship relying on the configuration and amount of charges of the polypeptides. In conclusion, the use of the two differently charged polypeptides to prevent abdominal and pleural adhesions was feasible, reducing adhesions after primary surgery and relaparotomy, without affecting key parameters of the resolving process investigated. Key words: Abdominal adhesions, small bowel obstructions, pain, female infertility, pleural adhesions, peritoneal, pleural, resolving process and key substances. Classification system and/or index terms (if any) Supplementary bibliographical information Language English ISSN and key title 1652-8220 ISBN978-91-87651-18-2 Recipient’s notes Number of pages 150 Price Security classification