Hydrophilic-hydrophobic microphase-separated block copolymers: synthesis, characerization and blood compatibility.

Two types of amphiphilic block copolymers--one containing repeating blocks of poly(ethylene oxide) (PEO) and polystyrene (PS) and another containing poly(dimethylsiloxane) (PDMS), PEO, and heparin (Hep)--were synthesized to examine the effects of hydrophilic-hydrophobic balance on blood compatibility. Unlike analogous random copolymer systems, these amphiphilic block copolymers demonstrated various degrees of phase separation, providing a macromolecular hydrophilic-hydrophobic chain segment distribution and microscale ordered surface heterogeneity. In the PEO-PS multiblock copolymer synthesis, functionalized telechelic prepolymers were coupled in solution. Synthesis of the triblock of PDMS-PEO-Hep involved solution coupling of PDMS to derivatized diamino PEO with various diisocyanates. Subsequent coupling of the primary amine group on the derivatized PEO chain to solubilized heparin was achieved via carbodiimide activation of heparins carboxylic groups as well as by reductive amination using sodium cyanoborohydride. Bulk characterization involved GPC, DSC, FTIR, and NMR methods. Surface analysis utilized contact angle, ATR/FTIR, ADESCA, and transmission electron microscopy. Varying degrees of phase mixing and phase-separation were observed. Differences between bulk and surface compositions were significant and generally involved surface enrichment by the low-energy (hydrophobic) blocks. Hydration effects, as monitored by contact angle, showed changes in surface composition and mobility. In vitro evaluation by coagulation assays and platelet adhesion and activation assessments demonstrated interesting differences between block copolymers and their homopolymer controls. Those results were correlated with whole blood ex vivo results from implantation in low flow-rate shunts in rabbits. Copolymer coatings on the interior lumens of these shunts showed increased times to occlusion for block copolymers over their homopolymer controls. Improved blood compatibility was attributed to the unique heterogeneous hydrophilic-hydrophobic character demonstrated in these block copolymer systems.