Albumin binding surfaces for biomaterials.
The surfaces of medical devices may promote both coagulation and infections caused by adherent microorganisms. In the case of polymeric elastomers, these iatrogenic effects are likely intermediated by absorbed host proteins that spontaneously bind to the device surface, promoting both bacterial adherence and thrombotic events. We earlier attempted to produce biomaterial surfaces that would selectively bind host albumin because albumin-coated surfaces were known to diminish both coagulation and bacterial adherence. To this end, an albumin-binding high molecular weight dextran:Cibacron blue adduct was bulk incorporated into polyetherurethane (Keogh et al., J Biomed Mater Res 1992;26:441). The modified material bound albumin selectively and reversibly and showed evidence of enhanced biocompatibility. However, approximately 30% of the surface of this material was evidently unmodified and still capable of exerting the above adverse effects. In the present work, we have covalently surface-modified polyetherurethane with sequential additions of acrylamide, amino-propylmethacrylamide, dextran, and Cibacron blue. This derivatized polyurethane preferentially and reversibly binds albumin, even from complex mixtures of proteins such as plasma. Furthermore, this material inhibits the clotting of nonanticoagulated whole human blood (for > 16 hours at room temperature), perhaps by virtue of binding and activation of antithrombin III by the sulfonic acid residues on the surface-immobilized Cibacron blue. Finally, such surfaces, especially when bearing bound albumin, diminish the adherence of Staphylococcus epidermidis, a pathogen frequently associated with device-centered infections. We conclude that similar albumin-affinity surfaces may hold promise for the development of more biocompatible materials for implantation and blood contact applications.
Keogh
J R
JR
Medtronic, Inc., Minneapolis.
Eaton
J W
JW
D000925:Anticoagulants / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects; D001672:Biocompatible Materials / Q000378:metabolism*; D004396:Coloring Agents; D003911:Dextrans; D006801:Humans; D008024:Ligands; D011140:Polyurethanes / Q000138:chemical synthesis / Q000494:pharmacology; D012709:Serum Albumin / Q000378:metabolism*; D013499:Surface Properties
D000925:Anticoagulants; D001672:Biocompatible Materials; D004396:Coloring Agents; D003911:Dextrans; D008024:Ligands; D011140:Polyurethanes; D012709:Serum Albumin; C115016:polyetherurethane; C017080:blue dextran