Phosphorycholine (PC) is zwitterionic i.e. has a positive and negative charge on the same molecule but is overall electrochemically neutral. This confers the PC group with high polarity and consequently a natural affinity for water. As a result, materials that incorporate the PC group are surrounded by molecular layers of water that effectively mask the substrate to which it is applied, providing a biological “non-stick” surface that resists protein and cell adhesion.
PC biomaterials have been used to successfully coat the following substrates:
- Metals, including stainless steel, nitinol, titanium, gold, platinum
- Rubbers, including silicone, latex, butyl
- Plastics, including:
- Polyethylene terephthalate
- Glasses and ceramics
- Tooth enamel and other tissues
Invariably when a foreign material is placed in the body, it immediately begins to "reject" the material through the deposition of lipids and proteins, which denature, adopting active conformations and encouraging the adhesion of cells from the surrounding environment. These cells may then promote further fouling of the surface. For instance, when blood contacts a foreign material, the clotting cascade is initiated. Plasma proteins become irreversibly bound to the surface, and this is followed by platelet adhesion and activation, leading to the release of additional activating factors and eventually the formation of blood clots, or thrombi. By inhibiting the initial adsorption of proteins, PC materials provide an inert, non-thrombogenic surface. When used as a coating on a medical device the improved hemocompatibility can significantly suppress the usual response of the body to a foreign material. An appreciation of this property may be seen in clinical research work reporting a favourable effect on platelets and lower blood losses during cardiopulmonary bypass surgery. [De SF, Van BY, Caes F, et al (2002) Perfusion 17(1):39-44.] In addition, when used as a coating on coronary guide-wires, it was found that PC aids in the prevention of thrombus formation on the guide wire tip during short term clinical use. [Gobeil, F. et al (2002) Canadian J. Cardiology 18(3): 263-269.]
Suppression of protein fouling can also lead to significant reductions in the adhesion of bacterial cells and to reduced giant cell adhesion and activation.
Schematic diagram indicating how a protein interacts with a foreign body. On the left it is shown how, after a 'passive' interaction with the surface, the protein may lose its own shell of hydration, denature and irreversibly bind to the surface. In vivo, these conformational changes, exposing binding sites for interaction with other proteins and cells, lead to a ‘foreign body’ response which can result in the formation of blood clots, a fibrous capsules or an excessive inflammatory response. In the case of a PC coated substrate (right), the protein can still interact with the surface but it is now energetically unfavourable for irreversible binding to occur. Essentially the surface layer of water bound to the PC disguises the surface such that the protein does not recognise the foreign body and therefore does not denature and activate.
In a variety of applications, PC materials have been shown to improve the biocompatibility and performance of medical devices and materials through reduced:
- protein deposition and activation
- blood activation and thrombus formation
- bacterial adhesion and biofilm deposition
- inflammatory response
- capsule formation
The inherent attributes of PC therefore make Vertellus Biomaterials’ innovative range of PC coatings and bulk polymers particularly valuable when used in conjunction with medical devices. In addition, PC polymers have demonstrated an ability to absorb and elute drugs in a controlled manner.