Development of a deep vein valve replacement

Abstract

Background Chronic venous disease is a common, distressing and significant cause of health care expense. There have been few developments in the treatment of deep venous disease as the understanding of the clinical and pathophysiological significance of deep vein reflux and valve failure remains poor. Previous attempts to develop a prosthetic vein valve implant have been disappointing. Difficulties with early thrombosis led researchers to abandon their efforts many years ago. Attempts to create a valve implant should be revisited. Aims The aims of this project are to: evaluate variables around normal deep vein valves, to develop validated computational and laboratory flow models for deep venous function, and to develop and investigate a novel material to engineer a prototype bioprosthetic deep vein valve replacement. Methods Functional Anatomy: This is a prospective observational study evaluating subjects with normal deep veins. B and M Mode ultrasound, contrast (microbubble) enhanced ultrasound and dynamic magnetic resonance imaging of normal subjects was carried out. This has given the flow, velocity data and anatomical images required for the project. Modelling: A preliminary computational flow model has been developed using the data obtained from the imaging stage of the project. This is a 2-dimensional model incorprating flexible valve leaflets. A laboratory model of venous function, in the form of a flow rig has been created. Materials: Presently, polymers and polymer coated metal stents, used in the vascular system have several problems: they are very thrombogenic and they lack haemocompatibilty and biocompatibility, in addition they lack the required mechanical properties. A novel material that is biocompatible, a copolymer of methacrylolyoxyethyl phosphorylcholine (MPC), trimethylsilyl-2-propyl methacrylate (TMSPMA) and Hydroxypropyl methacrylate (HPMA), has been synthesised. Its properties have been modified by electrospinning and crosslinking to change its solubility and mechanical properties, without altering its biocompatibility. Impact This project aims to guide the development of a treatment for patients, for whom few options are available. Chronic venous disease and venous ulceration are painful and debilitating, potentially requiring years of treatment. Effective, minimally invasive treatment options could result in accelerated ulcer healing and improvements in symptoms and quality of life as well as reduced costs.