TISSUE ADHESIVE, SPRAYABLE POLYMER BLENDS AS ADJUVANT SURGICAL TOOLS

Abstract

Commercial materials deployed in surgery for treatment of high-impact clinical pathologies suffer from shortcomings stemming from a combination of poor mechanical properties, difficulty in precise application, and non-specific prevention mechanisms. Work in this dissertation seeks to counteract these concerns through a multitude of blending approaches with biodegradable polymers and therapeutic agents for improved outcomes following traumatic tissue injury. The polymer blends were spray deposited using solution blow spinning, a method of fiber production where material rapidly accumulates onto target tissue substrate and forms a stable interface.

The first thrust of this dissertation hones on deposition of a biocompatible, wet tissue adhesive. These tissue adhesives were fabricated through molecular weight ratio blends of poly(lactide-co-caprolactone) (PLCL), a synthetic, biodegradable copolymer with viscoelastic properties fostering pressure-dependent adhesion. High molecular weight PLCL endowed the composite material with rigidity and inherent cohesive strength, while low molecular weight PLCL induced spreadability and adhesive strength. Such optimized material behavior presented an ability to not only adhere to hydrophilic surfaces, but also demonstrated an ability to act as a media for biocompatible and complete wound healing. Efficacy as an adhesive in wound dressings was exhibited through spray deposition of blend adhesives to bandage substrates in a porcine partial thickness burn wound model and comparison with a poly(urethane)-based clinical control material.

The second thrust of this dissertation focuses on development of an effectively applied barrier material for prevention of post-operative fibrotic scar tissue termed as adhesions. Rapid generation of tissue-conformal polymer fibers through solution blow spinning yields a material that is inherently flexible, thereby counteracting the brittle architecture of a sheet-like film currently deployed in surgery. Prevention of asymmetric fibrosis was accomplished through tuned surface biodegradation via high and low molecular weight PLCL blends. This strategy seeks to physically prevent prolonged retention of adhesion-generating molecules at the site of injury, as well as biologically counteract underlying inflammatory processes through controlled release of a therapeutic, apolipoprotein mimetic peptide from composite PLCL fiber mat. Adhesion prevention efficacy was qualified in high impact pre-clinical mouse models of cecal ligation and cecal anastomosis, and compared to pre-fabricated, dried hydrogel barrier and aqueous therapeutic suspension controls. Both adhesion severity and resultant wound healing response were significantly improved versus no treatment and clinically adopted controls.