Isoreactive Manipulation of Bioadhesive Polymers Impacts Tissue-Specific Interactions

Abstract

Bioadhesive polymers can serve as surgical sealants with a wide range of potential clinical applications, including augmentation of wound closure and acute induction of hemostasis. Key determinants of sealant efficacy include the strength and duration of tissue-material adhesion, as well as material biocompatibility. Canonical bioadhesive materials, however, are limited by a tradeoff among performance criteria that is largely governed by the efficiency of tissue-material interactions. In general, increasingly bioreactive materials are endowed with greater bioadhesive potential and protracted residence time, but incite more tissue damage and localized inflammation. One emergent strategy to improve sealant clinical performance is application-specific material design, with the goal of leveraging both local soft tissue surface chemistry and environmental factors to promote adhesive tissue-material interactions. We hypothesize that copolymer systems with equivalent bioreactive group densities (isoreactive) but different amounts/oxidation states of constituent polymers will exhibit differential interactions across soft tissue types. We synthesized an isoreactive family of aldehyde-mediated co-polymers, and subjected these materials to physical (gelation time), mechanical (bulk modulus and adhesion strength), and biological (in-vitro cytotoxicity and in-vivo biocompatibility) assays indicative of sealant performance. Results show that while bioadhesion to a range of soft tissue surfaces (porcine aortic adventitia, renal artery adventitia, renal cortex, and pericardium) varies with isoreactive manipulation, general indicators of material biocompatibility remain constant. Together these findings suggest that isore-active tuning of polymeric systems is a promising strategy to circumvent current challenges in surgical sealant applications.