Regulation of thromboinflammation in therapeutic medicine : Special focus on surface coating strategies

Biomaterials are an integral part of modern health care and offer potential treatment modalities to diseases and conditions otherwise intractable. However, the critical issue herein is incompatibility reactions. Our innate immune system is fundamental in protection against pathogens and foreign intruders and controls the discrimination between self and non-self. Biomaterials come in contact with blood upon implantation where they are sensed by innate immune mediators which through a cascade of complex, multifaceted reactions induce inflammation as well as thrombosis which may induce biomaterial dysfunction and rejection. This explains why patients undergoing haemodialysis therapy exhibit an increased incidence of whole-body inflammation and other thrombotic events. Similarly, therapeutic cells such as hepatocytes upon implantation initiate an instant blood mediated inflammatory reaction, responsible for cell damage and death via apoptosis. In order to achieve safer and more efficient therapeutic interventions, engineering of materials and cells that can avoid these adverse reactions is essential. Fabrication of biomaterials consisting of coating of bioinert polymers to avoid immune recognition and activation is a promising approach to modulate immune reactions. In this thesis, we have employed a PEG-lipid polymer coating, which intercalates in to biomembranes via hydrophobic interactions and thus shields from immune rejection. Treatment with PEG-lipid not only makes the surface “invisible” to immune cells but it also acts as a filter which prevents entry of immune cells without inducing cytotoxicity. Results from this thesis illustrate that fabrication of bio-surfaces by bio-inert PEG-lipid polymer is a harmless procedure which not only attenuates thrombo-inflammation but also assist in design of self-tailored materials for a wide range of biomedical applications