Abstract: Synthetic materials mimicking biomolecular structure and function provide an attractive alternative to the use of materials of biological origin for a range of biomaterials and diagnostic applications. The aim of this study is to make molecular imprints of heparin on polymer surfaces in order to attenuate surface-induced complement activation. Molecularly imprinted polymers (MIPs) were prepared by polymerizing various mixtures of monomers in the presence of heparin. The resulting polymers were ground to particles and the bound heparin extracted, leaving cavities complementary to the structure of heparin in the polymers. We compared the MIPs and non-imprinted reference polymer particles regarding complement activation (C3a, sC5b-9) and leukocyte activation (CD11b expression, cytokine release) in lepirudin blood with polystyrene (PS) particles as a control. In addition, adsorption of complement proteins (C1q, properdin, C3, C4, C5, and C4 binding protein; C4BP) to the polymer surfaces was measured by an enzyme immunoassay. The MIPs induced significantly lower complement and cellular activation compared to the reference polymers. This was associated with lower binding of C3, C4 and C5, and a higher ratio between C4BP and C4 for the MIP, while both polymers bound similar amounts of the recognition molecules C1q and properdin. Preincubation of MIP and reference polymers with soluble heparin did not affect any of the measured parameters, indicating that the imprint in the polymer surface was directly responsible for the biological activity. Our study demonstrates that heparin molecularly imprinted polymer particles could significantly attenuate complement and leukocyte activation, offering potential for developing auto-regulating surfaces.
Template and target information: heparin