Preventing Cardiac Adhesions

About

Background An adhesion is a band of scar tissue that binds two parts of tissue that are not normally joined together. Adhesions may appear as thin sheets of tissue similar to plastic wrap or as thick fibrous bands. The tissue develops when the body's repair mechanisms respond to any tissue disturbance, such as surgery, infection, trauma, or radiation. Although adhesions can occur anywhere, the most common locations are within the stomach, the pelvis, and the heart 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, especially for ischemic tissues, is also challenging. A more viable approach is the use of a physical barrier after surgery to prevent fusion of the heart to surrounding tissues. The barriers can be either preformed membranes or injectable hydrogels (fast gelling liquids). Preformed anti-adhesive materials need to be cut before application to the tissue, and must be sutured into place to prevent slippage. While a variety of different materials have been investigated in animals and humans, no materials, to date, have been capable of preventing adhesion formation post-cardiac surgery.   Technology Description Researchers from UC San Diego have developed a new approach to prevent postsurgical cardiac adhesions using rapidly forming poly(ethylene glycol) (PEG) hydrogels cross-linked by oxime bonds that form a protective layer over the epicardium with bio-inspired catechol-PEG materials that contributed for hydrogels to adhere better to the cardiac surface. This novel approach is a three component polymeric system that can be easily sprayed/dripped/painted directly onto the heart forming an anti-adhesion layer within seconds to minutes not only with two components that forms crosslinking, but also one component with bio-inspired catechol-PEG.   Applications The invention is for use during cardiothoracic surgeries to prevent post-surgical adhesions and protein adsorption to a tissue. The hydrogels are suitable for binding to and coating a tissue or cell.   Advantages This invention is a unique rapid gelling hydrogel to prevent surgical adhesions which are superior to the standard of care including pharmacologic therapy and physical barriers. The hydrogel is composed of three multiarmed PEG components (PEG-aminooxy, PEG-aldehyde/ketone and PEG-catechol) that rapidly react to form a hydrogel that can coat tissue surfaces. The material is injectable with tunable gelation rate of seconds to minutes over a broad range of concentrations (20 mg/mL to 100 mg/mL) and pH’s (4-10). Once formed this novel hydrogel system has very minimal swelling ratio (<125%). This is contrast to the PEG-NHS+amine systems that exhibit a very high swelling ratio from 200-600% the initial volume. Since this novel material is crosslinked via oxime bonds we can reverse the crosslinking with addition of free hydroxyl amines or ketones/aldehydes.   State Of Development The current invention has been tested on a rat heart model.   Intellectual Property Info A provisional patent has been submitted and the technology is available for commercial development.   Patent Status Patent Pending