nitinol and Hemolysis

This study adopted the latest self-developed bioabsorbable material lactide-glycolide-1,3-trimethylene carbonate (LA-GA-TMC) and applied the three-dimensional (3D) printing technique to manufacture the occluder for cardiac septal defects, so as to realize the individualized treatment of cardiac septal defects. At the same time, its biosafety was evaluated, with an aim to establish foundation for futural large-scale animal experiment and clinical trial. The traditional "one-pot synthesis" was modified, and the "two-step synthesis method" was utilized to synthesize the LA-GA-TMC terpolymer at the lactide: glycolide: trimethylene carbonate ratio of 6:1:1.7. Afterward, the synthesized terpolymer was used as the raw material to fabricate the occluder model via using 3D printing technique. Then, its biocompatibility was comprehensively evaluated through cytocompatibility, blood compatibility, and histocompatibility. The occluder made from LA-GA-TMC 3D printing had favorable ductility and recoverability; besides, it possessed the temperature-control feature, and the relative cell proliferation rates in extract liquids at various concentrations were all >70%, suggesting that it had favorable cytocompatibility. Moreover, hemolytic experiment revealed that its hemolytic rate was <5%, dynamic blood coagulation experiment demonstrated that the sample material moderately activated the blood coagulation, and the above findings suggested that it had good blood compatibility. In addition, implanting experiment in vivo revealed that its histocompatibility was superior to the traditional nitinol and the emerging poly-l-lactic acid. It is completely feasible to manufacture the cardiac septal defects occluder based on the novel absorbable material LA-GA-TMC, which has favorable biocompatibility, through 3D printing technique and it possesses broad prospects in large-scale animal experiment and clinical trial.

Topics: Absorbable Implants; Alloys; Biocompatible Materials; Blood Coagulation; Cell Survival; Dioxanes; Glycolipids; Hemolysis; Humans; Polyesters; Polymerization; Printing, Three-Dimensional; Prosthesis Design; Septal Occluder Device; Tissue Engineering; Tissue Scaffolds

Carotid-artery atherosclerosis is a common cause of ischemic stroke. Carotid-artery stenting (CAS) is one of the most effective treatments. However, In-stent restenosis (ISR) and re-endothelialization delay are two major issues of intravascular stent which affect clinical safety and reduce effects. In this study, atomic layer deposition (ALD) technology was applied to deposit a layer (10nm) of Al2O3 on Nitinol surface as an intermediate functional layer. The alumina covered surface was then modified with a coupling agent 3-aminopropyltriethoxysilane (APS) and heparin sequentially in order to improve the hemocompatibility of Nitinol stents. The successful graft of APS and heparin onto Nitinol was proven by X-ray photoelectron spectroscopy. Furthermore, the predicted improvement in the biocompatibilities of modified Nitinol was confirmed by water contact angle measurement, protein adsorption, platelet adhesion, and plasma recalcification time determination. The results of hemolysis assay, cell proliferation and cytotoxicity tests revealed that the grafting of heparin on NiTi kept the original positive performance of nitinol material. The results indicate that ALD technology is of great potential for the manufacture of medical devices, especially for surface modifications and functionalization. ALD technology can help with modifications of inert metallic surfaces and therefore benefit implantable medical devices, especially intravascular stents.

Topics: Adsorption; Alloys; Aluminum Oxide; Blood Platelets; Cell Proliferation; Cell Survival; Coated Materials, Biocompatible; Erythrocytes; Hemolysis; Heparin; Human Umbilical Vein Endothelial Cells; Humans; Photoelectron Spectroscopy; Platelet Adhesiveness; Primary Cell Culture; Propylamines; Self Expandable Metallic Stents; Serum Albumin, Bovine; Silanes

A novel stabilized hemocompatible multicomponent coating was engineered by consecutive alternating adsorption of two polysaccharides, alginate (Alg) and heparin (Hep), onto a Nitinol surface via electrostatic interaction in combination with photoreaction in situ. For this purpose, a photosensitive cross-linker, p-diazonium diphenyl amine polymer (PA), was used as an interlayer between alginate and heparin. The optical intensity of UV/vis spectra increased linearly with the number of layers, indicating the buildup of a multilayer structure and uniform coating. Photo-cross-linking resulted in higher stability without compromising its catalytic capacity to promote antithrombin III (ATIII)-mediated thrombin inactivation. Chromogenic assays for heparin activity proved definitively that anticoagulation activity really comes from surface-bound heparin in multilayer film, not from solution-phase free heparin that has leaked from multilayer film. The activated partial thromboplastin time (aPTT) assay showed that both (PA/Hep)8- and (PA/Alg/PA/Hep)4-coated Nitinol were less thrombogenic than the uncoated one. Yet, the latter was found to be more stable under a continuous shaken wash. In addition, (PA/Alg/PA/Hep)4 film exhibited lower surface roughness and higher hydrophilicity than (PA/Hep)8. As a result, hemolysis of (PA/Alg/PA/Hep)4 (0.34 +/- 0.064%) was lower than (PA/Hep)8 (0.52 +/- 0.241%). The naked Nitinol and (PA/Hep)8-coated Nitinol showed relatively strong platelet adhesion. On the contrary, no sign of any cellular matter was seen on the (PA/Alg/PA/Hep)4 surface. It is believed that the phenomenon of interlayer diffusion resulted in blended structures, hence, the enhanced wettability and antifouling properties after the incorporation of alginate layers. It is likely that the cooperative effect of alginate and heparin led to the excellent blood compatibility of the (PA/Alg/PA/Hep)4 coating. To simplify, there is greater advantage in utilizing cross-linked alginate/heparin surfaces rather than merely the heparin surface for improving blood- and tissue-compatible devices.

Topics: Alginates; Alloys; Animals; Cross-Linking Reagents; Diphenhydramine; Glucuronic Acid; Hemolysis; Heparin; Hexuronic Acids; Humans; Microscopy, Electron, Scanning; Molecular Structure; Photochemistry; Platelet Adhesiveness; Static Electricity; Swine; Thrombin; Ultraviolet Rays

Anti-thrombogenicity and rapid endothelialisation are prerequisites for the use of closure devices of intra-atrial communications in order to reduce the risk of cerebral embolism. The purpose of this study was therefore to assess the effect of bioactive coatings on biocompatibility of Nitinol coils designed for the closure of intra-atrial communications. Nitinol coils (n = 10, each) and flat Nitinol bands (n = 3, each) were treated by basic coating with poly(amino-p-xylylene-co-p-xylylene) and then coated with either heparin, r-hirudin or fibronectin. Anti-thrombogenicity was studied in vitro in a dynamic model with whole blood by partial thromboplastin time (PTT), platelet binding and thrombin generation, respectively, and cytotoxicity by hemolysis. Endothelialisation was studied on Nitinol bands with human umbilical venous endothelial cells (HUVEC) by 3-(4,5-dimethylthiazole-2yl)-2,5-triphenyl tetrazolium (MTT) assay and immnuofluorescence analysis of Ki67, vinculin, fibronectin and von Willebrand Factor. Uncoated or coated devices did not influence hemolysis and PTT. r-Hirudin (but not heparin) and fibronectin coating showed lower platelet binding than uncoated Nitinol (p < 0.005, respectively). Heparin and r-hirudin coating reduced thrombin formation (p < 0.05 versus Nitinol, respectively). HUVEC adhesion, proliferation, and matrix formation decreased in the order: fibronectin coating > uncoated Nitinol > r-hirudin coating > heparin coating > basic coating. MTT assay corroborated these findings. In conclusion, r-hirudin and fibronectin coating, by causing no acute cytotoxicity, decreasing thrombogenicity and increasing endothelialisation improve in vitro biocompatibility of Nitinol devices designed for the closure of intra-atrial communications.

Topics: Alloys; Animals; Biocompatible Materials; Blood Platelets; Cells, Cultured; Endothelium, Vascular; Fibronectins; Hemolysis; Heparin; Hirudins; Humans; Immunohistochemistry; Microscopy, Confocal; Microscopy, Electron, Scanning; Partial Thromboplastin Time; Sheep; Tetrazolium Salts; Thiazoles; Umbilical Veins