Physical adsorption of human thrombomodulin (ART-123) onto polymeric biomaterials for developing an antithrombogenic blood-contacting material.
Human thrombomodulin (hTM) is an endothelial cell-associated protein with potent natural anticoagulant activity by converting thrombin from a procoagulant protease to an anticoagulant. ART-123 is a recombinant soluble hTM (amino acid residues 1-498), and we focused on the physical adsorption of ART-123 onto a polymeric biomaterial surface to develop an antithrombogenic blood-contacting material with preventing the denaturation of hTM and the remaining chemical reagents. The adsorption of hTM onto polysulfone (PSF) films was analyzed quantitatively by quartz crystal microbalance analysis. The adsorption constant and the maximum adsorption amount, calculated by the assumption of a Langmuir-type adsorption, showed that hTM adsorbed with a relatively weak interaction onto the PSF film. The hydrophilic protein lysozyme also showed a Langmuir-type monolayer adsorption, although hydrophobic catalase and fibrinogen showed multilayer adsorption accompanying the denaturation. The physically adsorbed hTM showed high coenzymatic activity for the activation of protein C, as well as anticoagulant activity. Furthermore, the surface wettability of the PSF film was easily controllable by the physical adsorption of hydrophobic and hydrophilic bioactive proteins. The physical adsorption of hTM or bioactive proteins onto polymeric biomaterials will be instrumental for developing an antithrombogenic blood-contacting biomaterial, and for controlling the surface properties of biomaterials.
Matsusaki
Michiya
M
Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-Oka, Suita 565-0871, Japan.
Omichi
Masaaki
M
Maruyama
Ikuro
I
Akashi
Mitsuru
M
D000327:Adsorption; D000991:Antithrombins / Q000737:chemistry* / Q000494:pharmacology / Q000648:ultrastructure; D001672:Biocompatible Materials / Q000737:chemistry*; D001704:Biopolymers / Q000737:chemistry; D001777:Blood Coagulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018625:Microscopy, Atomic Force; D011108:Polymers; D011486:Protein C / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000648:ultrastructure; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013450:Sulfones; D013499:Surface Properties; D018180:Thrombomodulin / Q000737:chemistry* / Q000648:ultrastructure; D014867:Water / Q000737:chemistry
C472045:ART123; D000991:Antithrombins; D001672:Biocompatible Materials; D001704:Biopolymers; D011108:Polymers; D011486:Protein C; D011994:Recombinant Proteins; D012996:Solutions; D013450:Sulfones; D018180:Thrombomodulin; D014867:Water; C017662:polysulfone P 1700