(603f) Targeted Block Copolymers for the Prevention of Post-Surgical Adhesions

Following abdominal surgery, the internal wound healing can result in fibrous tissue deposits that connect adjacent tissues, resulting in formations called post-surgical adhesions (PSAs)[1, 2]. While often asymptomatic, these adhesions can lead to serious problems including bowel obstructions, chronic pain, and infertility. In the United States, an estimated 440,000 adhesiolysis surgeries are conducted annually to correct issues arising from the formation of PSAs [3].

To date, no satisfactory method has been developed to prevent all PSA types. While improvements in surgical techniques have reduced instances of PSA for some procedures, the most successful methods to prevent adhesions have relied on physical barriers that separate damaged tissue surfaces[4]. Current barriers methods are limited by the fact that the barriers must be applied directly to the area of damage. This limitation precludes their application in laparoscopic surgeries and limits their effectiveness, as the damaged tissue cannot necessarily be identified or accessed by the physician during surgery.

We have previously demonstrated the ability of block copolymers to adsorb to model surfaces based on charge affinity and inhibit the non-specific adsorption of proteins from solution. Since this protein adsorption event is important in the biochemical cascade that leads to postsurgical adhesion formation, this approach shows great promise as a method to reduce PSA formation. Such an approach overcomes some of the limitations of current treatments; specifically, since the polymer can is applied as a solution and self-assembles at the site of injury, this technique is readily adaptable to laparoscopic procedures and can be employed to treat damaged inaccessible or unidentified tissue damage.

We have extended the power of this method by incorporating peptide domains which have specific binding affinity for damaged tissue protein markers. By controlling the polymer architecture and optimizing the targeting moieties, the function of the material can be controlled. Using a Quartz Crystal Microbalance with Dissipation (QCM-D), the adsorption to model surfaces has been investigated. This technique allows the simultaneous evaluation of binding kinetics, protein blockade, and adsorbate conformation.

References

1. Ellis, H., et al., Adhesion-related hospital readmissions after abdominal and pelvic surgery: a retrospective cohort study. Lancet, 1999. 353(9163): p. 1476-80.

2. Risberg, B., Adhesions: preventive strategies. Eur J Surg Suppl, 1997(577): p. 32-9.

3. Matthews, B.D., et al., Assessment of adhesion formation to intra-abdominal polypropylene mesh and polytetrafluoroethylene mesh. J Surg Res, 2003. 114(2): p. 126-32.

4. Boland, G.M. and R.J. Weigel, Formation and prevention of postoperative abdominal adhesions. J Surg Res, 2006. 132(1): p. 3-12.