Synthesis And Characterization Of Hydrophilic Anionic-Neutral Block Copolymers For The Prevention Of Post-Surgical Adhesions
John M. Medley1, Eugene Kaplan2 and Thomas D. Dziubla1, (1)Chemical and Materials Engineering, University of Kentucky, 177 F. Paul Anderson Tower, Lexington, KY 40506, (2)Urology & Pelvic Reconstructive Surgery, Center for Advanced Gynecologic Surgery and Pelvic Floor Medicine, 120 La Casa Via, Suite 209, Walnut Creek, CA 94598

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.

Here we hypothesize the development of a self-assembled polymer barrier based upon charge affinity for the site of exposed damaged tissue. Since it will be applied as an aqueous solution, it is not necessary to know precisely the exact location of all damaged tissue areas and could potentially be used in both laparoscopic and the more invasive procedures. In this study, we have synthesized a copolymer of methacrylic acid and PEGylated methacrylic acid for investigation as an adhesion barrier. Since this polymer includes ester linkages and relatively short chain segments (MW<10,000 g/mol), it will be bioerodible and readily cleared from the body.

Employing ionic interactions, the material targets the unique environment presented by damaged tissue and, by self-assembling at the site of injury, is expected to form a surface coating. Since polyethylene glycol is known to resist the adsorption of proteins and cells, this surface protection is anticipated to prevent the formation of post-surgical adhesions and facilitate normal healing of damaged tissues. After this polymer is fully characterized using NMR, GPC, and FTIR, surface adhesion and affinity will be investigated using a quartz crystal microbalance. The degradation kinetics will also be tailored by the incorporation of cross-linking functionality.

References

1. Risberg, B., Adhesions: Preventive Strategies. European Journal of Surgery, Supplement, 1997. 577: p. 32-39.

2. Ellis, H., et al., Adhesion-related Hospital Readmissions after Abdominal and Pelvic Surgery: A Retrospective Cohort Study. Lancet, 1996. 353.

3. Matthews, B.D., el at, Assessment of Adhesion Formation to Intra-abdominal Polypropylene Mesh and Polytetrafluoroethylene Mesh. Journal of Surgical Research, 2003. 114(126-132).

4. Boland, B.A.a.R.J.W., Formation and Prevention of Postoperative Abdominal Adhesions. Journal of Surgical Research, 2006. 132: p. 3-12.

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Self-Assembled Biomaterials I

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