The objective of the project was the development of new, improved haemocompatible polymers biocompatible polymers and surface treatments for implants and medical devices. The improved materials were achieved by mimicking the chemical structure of the outer surface of the red blood cell membrane. The natural membrane exhibits excellent biocompatibility and haemocompatibility.
A series of new polymers and surface treatments, which contain the same phosphorlycholine structure as the blood cell membrane has been successfully synthesized and the new compounds fully characterized. In a series of in vitro simulated in use tests, the new biomimetic polymers and surface treatments showed significantly better haemocompatibility and biocompatibility than even the best of the polymeric biomaterials in use commercially today. The benefits of this improved biocompatibility will be seen in the improved efficiency and performance of:
specialized blood handling devices such as apheresis and haemodialysis filters;
extracorporeal blood circuitry;
intravenous and central venous catheters which will be less thrombogenic, longer indwelling the easier to introduce;
improved contact and intraocular lenses;
cell culture ware with improved cell attachment, growth and spreading.
The cell membrane contains a wide range of molecular species including phospholipids. It is the phospholipid components which give the membrane its structure and essential characteristics. The phospholipids in the membrane are arranged in a bilayer structure with their phosphate head groups exposed at the surface. Whilst all phospholipids carry a charge, the outer membrane surface contains 90 to 95% zwitterionic, neutral phosphorylcholine (PC) lipids. It has been shown that zwitterionic PCs do not initiate blood coagulation, whereas the other charged PCs do. It was reasoned that by attaching zwitterionic PCs to a surface, the surface would mimic that of the red blood cell membrane and th us become more haemocompatible and biocompatible. The project called for the selection and synthesis of PC containing compounds which could be either polymerized into PC polymers or used to modify other surfaces, (eg, as coatings). In the course of the research, surface reactive PC compounds, PC monomers, PC homopolymers, PC graft polymers, and PC copolymers were all successfully synthesized, characterized and attached or coated onto a range of polymeric surfaces.
In extensive in vitro haemocompatibility tests, all of the PC surfaces showed significant improvements in haemocompatibility compared untreated controls. In simulated in use tests, similarly enhanced biocompatibility resulted from the presence of the PC. The improved haemocompatibility was also confirmed in preliminary in vivo studies.
THE EXTRACELLULAR MEMBRANE SURFACES OF RED BLOOD CELLS ARE EXTREMELY HAEMOCOMPATIBLE. OUR OBJECTIVE IS TO DEVELOP POLYMERS AND SURFACE TREATMENTS WHICH MIMIC THE NATURAL SURFACE OF RED BLOOD CELLS. THE SYNTHETIC BIOMIMETIC POLYMERS AND SURFACE TREATMENTS TO BE DEVELOPED WILL BE DESIGNED TO BE NON-THROMBOGENIC AND HIGHLY RESISTANT TO PROTEIN ADSORPTION.
POTENTIAL AREAS OF APPLICATION WILL BE IN BLOOD CONTACTING IMPLANTS AND DEVICES SUCH AS SMALL-BORE VASCULAR GRAFTS, I-V CATHETERS, CONTACT LENSES AND OTHER OCULAR DEVICES.
BIOTECHNOLOGY APPLICATIONS INCLUDE CELL AND TISSUE CULTURE SUBSTRATES.
Funding SchemeCSC - Cost-sharing contracts