Isoreactive Manipulation of Bioadhesive Polymers Impacts Tissue-Specific Interactions

Jannatul Ferdous ,Mark J Uline,Eva Romito,Tarek Shazly,Francis G Spinale,Heather Doviak,Alexandra Moreira

doi:10.4236/jbise.2017.105022

Jannatul Ferdous , Mark J Uline + Show 5 more

Open Access

https://doi.org/10.4236/jbise.2017.105022

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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.

Highlights

Bioadhesive polymeric materials have an established history of medical use, with utilities ranging from acute induction of hemostasis in cases of trauma to augmentation of wound closure in surgical applications. [1] [2] [3] Irrespective of specific use, the safety and efficacy of these materials largely depend on sufficient adherence to soft tissue surfaces, adequate residence time at the site of application, and acceptable biocompatibility. [4] Clearly, the required bioadhesive strength, material degradation/erosion kinetics, and tolerable immune/inflammatory response will all vary by application, with internal application sites subjected to high mechanical loads presenting the greatest challenge.Bioadhesive materials can be loosely divided into two categories which exemplify the current state of sealant technologies
Results show that while bioadhesion to a range of soft tissue surfaces varies with isoreactive manipulation, general indicators of material biocompatibility remain constant. Together these findings suggest that isoreactive tuning of polymeric systems is a promising strategy to circumvent current challenges in surgical sealant applications
The dextran aldehyde components of these formulations were endowed with equivalent total aldehyde content (2.3 × 1020 groups/mL), but differed in terms of oxidation states/solid content

Summary

Introduction

Bioadhesive polymeric materials have an established history of medical use, with utilities ranging from acute induction of hemostasis in cases of trauma to augmentation of wound closure in surgical applications. [1] [2] [3] Irrespective of specific use, the safety and efficacy of these materials largely depend on sufficient adherence to soft tissue surfaces, adequate residence time at the site of application, and acceptable biocompatibility. [4] Clearly, the required bioadhesive strength, material degradation/erosion kinetics, and tolerable immune/inflammatory response will all vary by application, with internal application sites subjected to high mechanical loads presenting the greatest challenge.Bioadhesive materials can be loosely divided into two categories which exemplify the current state of sealant technologies. There are numerous synthetic materials which adhere vigorously to the full range of soft tissues and persist at the site of application for long periods of time. Many of these materials are based on cyanoacrylate and its derivatives, wherein adhesive bonds with soft tissues are rapidly formed in the presence of trace water. While cyanoacrylate- and fibrin-based materials are only a small fraction of proposed technologies, their inherent limitations/tradeoffs persist to various degrees across all materials considered for soft tissue sealant applications (Table 1) [13] [14]

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