(67b) Preventing Post Surgical Tissue Adhesion Using Hydrogels Based On Dihydroxyacetone-Polyethylene Glycol Diblock Copolymer

Post surgical tissue adhesion is a complex inflammatory disorder in which tissues that normally remain separated in the body attach to each other. Adhesions occur most commonly after surgery, and are a major cause of infertility, bowel perforation, chronic abdominal and pelvic pain, small bowel obstruction, and in some cases patient mortality. Up to 75% of abdominal surgery patients require secondary surgery to correct complications directly related to adhesion formation. The economic ramifications of abdominal tissue adhesion exceed $2.1 billion annually in the United States.

There is an ongoing effort in our lab to synthesize polymeric biomaterials that can prevent tissue adhesion formation. We have previously described the synthesis and characterization of diblock copolymers composed of a poly(ethylene glycol) (PEG, V) block, and a polycarbonate block based on the glucolytic intermediate dihydroxyacetone (DHA, I) (Scheme 1). The resulting block copolymer (MPEG-pDHA, VII) incorporates some of the physical, chemical, and biological properties of both its constituting blocks. The pDHA hompolymer is insoluble in water, but is hydrophilic based on contact angle measurements. This, coupled with PEG's hydrophilicity and water solubility, allows the block copolymers to form a gel when hydrated. The gels exhibit tissue adhesive behavior, as well as the ability to form Schiff bases with primary amines. They also display a range of interesting rheological properties, including: shear thinning, rapid network relaxation, tunable viscosity, and the ability to be extruded through various gauged needles. These characteristics indicate that the gel can be applied to raw or injured surfaces via syringes, and act as a localized physical barrier for post surgical tissue adhesion prevention. The gel's performance in a rat adhesion model was comparable to that of an anti-adhesion product currently used in humans. The purpose of this work is to present the physical and rheological characterization of the gel, to illustrate how these properties are influenced by changes in the polymer composition, and investigate the ability of these gels to prevent tissue adhesion in an animal model.