Hyaluronic acid and alginate blend hydrogel films for the prevention of postsurgical adhesions

Postoperative adhesions form as the body's natural response to injury in an effort to temporarily protect and supply nutrients to these tissues. However, adhesions can remain permanent, and fail otherwise successful surgeries by tethering tissues together that are normally separated. An ideal anti-adhesive device reduces unwanted adhesions and leaves the patient in a state most similar to before surgery. This dissertation introduces a novel, robust hydrogel film consisting of two hydrophilic polydisaccharides, hyaluronic acid (HA) and alginate. To address the challenge of retaining HA in alginate-rich hydrogels, we methacrylated the HA (GMHA), creating hydrophobic moieties. These hydrophobic interactions shift the percolation threshold, allowing for greater concentrations of GMHA to be retained in resulting films. UV crosslinking retains GMHA beyond the percolation threshold and widens the possibilities of usable films. To enhance the mechanical properties of these alginate/GMHA films, we employed a previously developed method for creating thin, branched, interconnected fibers using urea crystal templating. Templated films are softer and, yet, tougher than films that have not been templated. This toughness is a result of increased density of polymer in the fibers. These films were selected as most conformable and most robust by surgeons in a blinded handling study. In a rat peritoneal abrasion model for adhesion formation, the films successfully prevented adhesions with statistical equivalence to the leading anti-adhesion device commercially available. Finally, future recommendations are suggested for the development of a bilayer construct with a collagen/alginate blend bound to an alginate/HA layer for an anti-adhesive and regenerative strategy. This construct addresses the need for opposing strategies in the dynamic environment of wound healing. Further research is needed to develop the usefulness of this bilayer system, as preventing unwanted adhesions is merely a first step in achieving a blemish-free healed wound.