Facile immobilization of heparin on bioabsorbable iron via mussel adhesive protein (MAPs)

Abstract

Motivated by adhesive proteins in mussels, strategies using dopamine to modified surface have become particularly attractive. In the present work, we developed a novel and convenient method to modify the biodegradable Fe plates with heparin. Iron was first treated by a facile one-step pH-induced polymerization of dopamine, and then a high density heparin was successfully grafted onto the surface via coupling with polydopamine (PDA) active layer. Heparin immobilization contributed much longer blood clotting coagulation time than the pure Fe sample, and hence reduced the risk of thrombosis. Cell viability tests suggested that the heparin modified Fe plates were more favorable to the proliferation of ECV304 cells. In summary, the heparin modified Fe plates with good anti-thrombus properties and inhibiting the proliferation of VSMC cells provide great prospects for biodegradable iron.

Development and In Vitro Whole Blood Hemocompatibility Screening of Endothelium-Mimetic Multifunctional Coatings

“…Heparin modification via a polydopamine adhesive layer was shown to lead to some nanoaggregate formation on top of a base layer of adsorbed polydopamine, consistent with prior literature. 20,34 Finally, heparin-modified NO-releasing PET surfaces showed enhanced pDA nanoaggregate deposition and heparin aggregate binding, consistent with prior reports demonstrating increased pDA binding to hydrophilic surfaces. 36 Further energy-dispersive X-ray (EDS) analyses of the vial surfaces were performed to qualitatively evaluate elemental distributions after NO and heparin modifications (see Figure S3).…”

“…35 These findings were consistent with previous reports for heparin immobilization via the interaction of heparin with O-benzoquinonyl residues on pDA through its amino/imino groups. 20,34 A cosolvent system of 40% v/v benzyl alcohol in chloroform was used to achieve SNAP impregnation with solvent depletion after drying at ambient temperatures. SNAP impregnation was found to result in only minor surface defects from solvent exposure and SNAP doping (Figure S2).…”

“…Heparin Surface Density, Bioactivity on Fabricated Blood Collection Tubes, and Surface Leaching. In this study, the pDA−heparin coating was implemented due to its nearly universal substrate scope 20 and direct applicability to medical-grade test materials such as the blood incubation vials. As heparin is a potent anticoagulant, it is critical to determine the surface density of immobilized heparin to correlate to bioactivity.…”

“…Afterward, the solution was decanted, and the tubes were dried under vacuum for an additional 12 h. The vials were then briefly rinsed with methanol (5 mL) to remove loosely bound SNAP and dried under vacuum for 4 h. Heparin immobilization followed previous literature methods with minor deviation (see Scheme 1). 20 Dopamine hydrochloride (2 mg/ mL) in TRIS buffer (10 mM, pH 8.5) was added to the SNAPimpregnated tubes (5 mL). The polymerization and deposition processes were carried out for 24 h with gentle rocking and protection from light.…”

“…Heparin density on the modified incubation vials pre-and post-blood exposure as well as heparin leaching were quantified using the colorimetric toluidine blue (TB) method adapted from previous reports with minor deviation (see Supporting Methods). 20,32 Final values for heparin density normalized to the surface area of the substrate (μg heparin/cm 2 ) were reported as the mean ± standard error. Heparin leaching from the vial surfaces was evaluated over a 4 h incubation study under simulated physiological conditions (1× PBS, 37 °C).…”