Hydrogel device for preventing cardiac adhesions postcardiothoracic surgery
Project Abstract:
Reoperations in cardiac surgery have increased surgical risks due to cardiac adhesions which increase the difficulty of sternal reentry hinder visibility of mediastinal tissues and increase potential injury to cardiovascular tissues This leads to an increased risk of surgical bleeding and increased length of the surgical procedure which increase patient morbidity and mortality This is especially relevant for pediatric patients with congenital heart defects who will experience multiple surgeries over their lifetime Cardiac adhesions have also become a common problem in adults who experience multiple surgeries to repair or replace valves or to undergo coronary revascularization procedures Two main approaches exist for reducing or attempting to prevent cardiac adhesions pharmacological therapy and physical barriers Drugs that prevent or reverse adhesion processes disrupt biochemical pathways of inflammation and fibrin deposition Unfortunately these processes are also vital for wound healing Achieving adequate drug concentration at the site of action is also challenging A more viable approach is the use of a physical barrier to prevent fusion of the heart to surrounding tissues The barriers can be either preformed membranes or injectable hydrogels fast gelling liquids Preformed antiadhesive materials need to be cut before application to the tissue and must be sutured into place to prevent slippage While they can help with sternal reentry they do not prevent cardiac adhesions and do not reduce dissection times Injectable hydrogels allow the freedom of applying material where needed applying the precursor components and are capable of quickly forming a protective gel over the surface of the tissue While a variety of different materials have been investigated in animals and humans no materials to date have been capable of preventing adhesion formation postcardiac surgery without risking deterioration of cardiac function Herein we propose a new approach to prevent postsurgical cardiac adhesions using rapidly forming poly ethylene glycol PEG hydrogels that are crosslinked by oxime bonds Oxime bond formation is the reaction between hydroxyl amines and ketonesaldehydes and will be used to both crosslink the material and attach it to tissue Our approach is a two component polymeric system that can be easily applied directly onto the heart forming an antiadhesion layer within seconds With this system we can control the degree of swelling and degradation time to prevent adhesions yet not interfere with cardiac function As part of this proposal we will demonstrate proofofprinciple for using the PEG oxime system to prevent cardiac adhesions in a rat cardiac surgery model Following successful completion of this study GMP manufacturing of the material will be performed along with ISO 10993 biocompatibility tests and a porcine study with the GMP material In combination with the studies proposed herein this is anticipated to fulfill the requirements for an IDE submission PMA pathway All studies will be performed according to GLP guidelines to facilitate FDA submissions This will also provide sufficient data to license the technology
