Immobilization of NaIO₄‐treated heparin on PEG‐modified 316L SS surface for high anti‐thrombin‐III binding

Abstract

Poor compatibility between blood and metallic coronary artery stents is one reason for arterial restenosis; however, the immobilization of anticoagulant agents on the surface of the stent is a feasible method of improving stent compatibility. Heparin, a well-known anticoagulant, has been frequently used to coat the surfaces of certain biomaterials to attain blood compatibility. The compound 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide has often been utilized for the immobilization of heparin, but the critical carboxyl groups of heparin (with regards to heparin's anticoagulant activity) will be reduced by this method. This study examined possible methods of heparin immobilization without consuming these carboxyl groups. The 316L stainless steel surface was first activated with hexamethylene diisocyanate and then coupled with bis-amine-terminated poly (ethylene glycol) (BA-PEG) so as to create active amine groups. Sodium periodate (NaIO(4); SP) was then used to oxidize heparin to form aldehyde groups. The treated heparin could then be grafted onto the activated surface of the test material without losing its carboxyl groups. Effective surface modification of the hexamethylene diisocyanate-activated and BA-PEG-grafted 316L SS surface was confirmed using Fourier Transform Infrared Spectroscopy, electron spectroscopy for chemical analysis and a water contact angle test. After the heparin was immobilized on the BA-PEG-grafted 316L SS surface by SP, the surface showed an improvement in antithrombrin III (AT III) binding ability, its anticoagulant property, and hemocompatibility in comparison with heparin grafted by 1-ethyl-3-(3-dimethyl-aminopropyl) carbodiimide.

Blood compatible materials: state of the art

“…Surfaces modied with bis-amino-terminated poly(ethylene glycol) (BA-PEG) as spacer and graed with heparin were shown to have improved antithrombin (AT) binding and anticoagulant properties compared to the same surfaces without the PEG spacer. 140 The PEG spacer provides a more hydrophilic environment and a reduction in non-specic protein adsorption as well as a greater level of conformational freedom for the heparin. Similarly, three-dimensional porous PLGA scaffolds modied with heparin via PEG as spacer suppressed non-specic protein adsorption, and growth factors could be tethered and presented to cells in a bioactive conguration.…”

A novel antithrombotic coronary stent: lysine-poly(HEMA)-modified cobalt–chromium stent with fibrinolytic activity

“…Surface modification is a widely used approach for improving the anticoagulant activity of blood contacting devices. For example, Chuang et al immobilized NaIO 4 -treated heparin on 316L stainless steel surface using bis-amine PEG as a spacer [8]. In other work, heparin was attached to the stent via layer-by-layer (LbL) deposition; in vitro coagulation times for plasma in contact with these stents were prolonged by about 60 min compared with unmodified stents [9].…”

Covalent Attachment of Multilayers on Poly(tetrafluoroethylene) Surfaces

“…Other approaches, including UV surface grafting or end-capping of anticoagulants molecules to polymers were also employed, but achieving controllable biochemical and morphological features is not obvious. While covalent attachments ,,− of molecules or macromolecules to polymers that exhibit anticoagulant characteristics offer significant advantages, inertness of polymeric substrates and the low surface energies impose other limitations. Ideally, one would like to covalently attach multilayered structures that are stable, exhibit suitable effectiveness against formation of blood clots inside blood vessels obstructing the flow (thrombosis), and are antifouling, thus facilitating dual and longer protection.…”