Abstract

Objective: Adhesions develop after 95% of operations, represent a major clinical challenge, and cost the U.S healthcare system $2.5B annually. In cardiac surgery, adhesions are problematic during re-operations, increasing operative times and posing risks of hemorrhage and injury to the heart and lungs during sternal reentry and cardiac dissection. We hypothesized that shear-thinning, self-healing polymer nanoparticle hydrogels (PNP) would provide a viscoelastic barrier, effectively preventing adhesion formation (Fig 1A). Methods: Multiple PNP formulations underwent rheologic characterization. Male Sprague Dawley rats (n=52) underwent permanent ligation of the LAD to induce robust postinfarct adhesions, followed by epicardial application of PNP (200L), Seprafilm®(1cm 2 ), or no treatment. Male Dorset sheep (n=8) underwent an anterolateral epicardial abrasion followed by application of PNP (25mL), Seprafilm® (12 cm 2 ), or no treatment. Degree of adhesion formation, standardized dissection time, heart function, and immune response were assessed 4-weeks following surgery. Results: PNP exhibited formulation-dependent mechanical properties indicating the effect of hydrogel stiffness on adhesion barrier efficacy (Fig 1B). Infarct size and heart function were controlled to ensure similar inflammatory responses contributing to adhesion formation across treatment groups. Treatment with certain PNP formulations significantly reduced the development of adhesions compared to controls (Fig 1C). Ovine hearts treated with the PNP 1:10 revealed a pristine epicardial surface (Fig 1D, 1E, and 1F) and resulted in a shorter dissection time relative to the controls (Fig 1G). Conclusion: Administration of a shear-thinning, self-healing hydrogel reduces the extent of adhesion formation in the thoracic cavity following surgery in small and large animal models. PNP provides an easily delivered, scalable solution for post-operative adhesion prevention.

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