Fibrin-targeted block copolymers for the prevention of postsurgical adhesions.

Despite advances in surgical methods, postsurgical adhesions (PSA) remain a significant clinical challenge affecting millions of patients each year. These permanent fibrous connections between tissues result from the bridging of wounded internal surfaces by an extended fibrin gel matrix (FGM). Adhesion formation is a result of a systems level convergence of wound healing pathways, complicating the design of materials that could inhibit their occurrence. In this study, a systematic approach that identifies key material properties required for functional performance optimization was used to design a new fibrin-targeted PSA prevention material. A series of multifunctional polymers with varied molecular architectures was synthesized to investigate the effect of changing polymer structural parameters on the ability to disrupt the formation of an extended FGM. Initial studies in a murine adhesion model demonstrated a statistically significant reduction in the degree of PSA formation, demonstrating the potential value of this systematic approach.

Block copolymers for the rational design of self-forming postsurgical adhesion barriers.

Post-surgical adhesions, abnormal fibrous linkages between adjacent tissue surfaces, represent one of the most common and significant complications facing surgical recovery today. Physical barriers and gels have been the most successful at limiting their formation, yet are not effective in cases where the pro-adhesive site is either unknown or difficult to reach (e.g. during laparoscopic surgery). In this work, poly(methacrylic acid-co-t-butylmethacrylate)-b-poly(ethylene glycol (M(N) = 1000) methacrylate) diblock and statistical copolymers were synthesized as a platform for designing self-forming adhesion barriers, which can attach to exposed pro-adhesive sites through binding with the positively charged extracellular matrix, basement membrane proteins and deposited fibrin. An experimental model based upon a quartz crystal microbalance with dissipation was developed to test the diblock copolymers ability (i) to adsorb to an amine-terminated self-assembled monolayer, and (ii) to inhibit subsequent protein adsorption. These results were also confirmed using an in vitro cell attachment model. As the mole fraction of methacrylic acid content increased, polymer adsorption increased. All synthesized diblock copolymers investigated provided high resistance to protein adsorption, with blockade ranging from 55% to 81%. Except for the uncharged control polymers, the ability of these materials to resist cellular attachment showed similar trends, with the suppression of attachment approaching 75%. Energy dissipation analysis and variable-angle spectroscopic ellipsometry revealed two competing adsorption mechanisms depending on the molecular properties of the polymer.