Immobilization of heparin onto the surfaces of biomaterials is an effective approach for improving their anticoagulant properties and biocompatibility. In this article are reviewed the relevant principle, experimental researches and applications. Finally, a prospect for heparin immobilization is made as well.
Animals ; Anticoagulants ; chemistry ; Coated Materials, Biocompatible ; chemistry ; Heparin ; chemistry ; Humans ; Surface Properties ; Tissue Engineering

In order to enhance the anticoagulant properties of decellularized biological materials as scaffolds for tissue engineering research via heparinized process, the decellularized porcine liver scaffolds were respectively immobilized with heparin through layer-by-layer self-assembly technique (LBL), multi-point attachment (MPA) or end-point attachment (EPA). The effects of heparinization and anticoagulant ability were tested. The results showed that the three different scaffolds had different contents of heparin. All the three kinds of heparinized scaffolds gained better performance of anticoagulant than that of the control scaffold. The thrombin time (TT), prothrombin time (PT) and activated partial thromboplastin time (APTT) of EPA scaffold group were longest in all the groups, and all the three times exceeded the measurement limit of the instrument. In addition, EPA scaffolds group showed the shortest prepared time, the slowest speed for heparin release and the longest recalcification time among all the groups. The decellularized biological materials for tissue engineering acquire the best effect of anticoagulant ability in vitro via EPA heparinized technique.
Animals ; Anticoagulants ; chemistry ; Biocompatible Materials ; chemistry ; Heparin ; chemistry ; Liver ; Swine ; Tissue Engineering ; Tissue Scaffolds

BACKGROUNDPeople recently realized that it is important for artificial vascular biodegradable graft to bionically mimic the functions of the native vessel. In order to overcome the high risk of thrombosis and keep the patency in the clinical small-diameter vascular graft (SDVG) transplantation, a double-layer bionic scaffold, which can offer anticoagulation and mechanical strength simultaneously, was designed and fabricated via electrospinning technique.

METHODSHeparin-conjugated polycaprolactone (hPCL) and polyurethane (PU)-collagen type I composite was used as the inner and outer layers, respectively. The porosity and the burst pressure of SDVG were evaluated. Its biocompatibility was demonstrated by the 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H tetrazolium bromide (MTT) test in vitro and subcutaneous implants in vivo respectively. The grafts of diameter 2.5 mm and length 4.0 cm were implanted to replace the femoral artery in Beagle dog model. Then, angiography was performed in the Beagle dogs to investigate the patency and aneurysm of grafts at 2, 4, and 8 weeks post-transplantation. After angiography, the patent grafts were explanted for histological analysis.

RESULTSThe double-layer bionic SDVG meet the clinical mechanical demand. Its good biocompatibility was proven by cytotoxicity experiment (the cell's relative growth rates (RGR) of PU-collagen outer layer were 102.8%, 109.2% and 103.5%, while the RGR of hPCL inner layer were 99.0%, 100.0% and 98.0%, on days 1, 3, and 5, respectively) and the subdermal implants experiment in the Beagle dog. Arteriography showed that all the implanted SDVGs were patent without any aneurismal dilatation or obvious anastomotic stenosis at the 2nd, 4th, and 8th week after the operation, except one SDVG that failed at the 2nd week. Histological analysis and SEM showed that the inner layer was covered by new endothelial-like cells.

CONCLUSIONThe double-layer bionic SDVG is a promising candidate as a replacement of native small-diameter vascular graft.

Animals ; Bionics ; Blood Vessel Prosthesis ; Cell Line ; Collagen ; Dogs ; Heparin ; chemistry ; Mice ; Polyesters ; chemistry ; Polyurethanes ; chemistry

Blood compatibility is the main restriction of blood-contacting medical devices in clinical application, especially long-term blood-contacting medical devices will stimulate the immune defense mechanism of the host, resulting in thrombosis. Heparin anticoagulant coating links heparin molecules to the surface of medical device product materials, improves the compatibility between the material surface interface and the body, and reduces the host immune defense reactions. This study reviews the structure and biological properties of heparin, the market application status of heparin-coated medical products, the insufficiency and improvement of heparin coating, which can provide a reference for the application research of blood contact medical devices.
Humans ; Heparin/chemistry* ; Anticoagulants/chemistry* ; Thrombosis ; Coated Materials, Biocompatible/chemistry* ; Surface Properties

OBJECTIVETo evaluate the anticoagulant and antineoplastic activities of chemically modified low-molecular-weight heparin (LMWH).

METHODSLMWH obtained by splitting unfractionated heparin (UFH) with sodium periodate oxidation and sodium borohydride reduction was subjected to acetylation catalyzed by DCC and DMAP to produce acetylated LMWH (ALMWH). The anticoagulant activity of ALMWH was determined in mice, and its antiproliferative and anti-invasion activities was assessed in human breast cancer cells MDA-MB-231 and MFC-7.

RESULTSThe anticoagulant activity of LMWH was decreased significantly after acetylation. The concentrations of commercial LMWH* and ALMWH for doubling the coagulation time (CT) were 33.04 µmol/L and 223.56 µmol/L, respectively, and the IC(50) of ALMWH for doubling CT was 6 times of that of LMWH*. ALMWH and LMWH at 0.1, 0.3, 0.9, 2.7 and 8.1 mmol/L both significantly inhibited the proliferation of MDA-MB-231 and MCF-7 cells in a concentration-dependent manner, but ALMWH produced stronger inhibitory effects. The IC(50) of LMWH and ALMWH for inhibiting cell proliferation was 3168.4 µmol/L and 152.6 µmol/L in MCF-7 cells, and 12299.6 µmol/L and 22.2 µmol/L in MDA-MB-231 cells, respectively. ALMWH and LMWH all markedly suppressed the invasion of MDA-MB-231 cells with comparable effects.

CONCLUSIONChemical modification of structure can endow LMWH with a low anticoagulant and high antiproliferative activities.

Animals ; Anticoagulants ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Blood Coagulation ; Blood Coagulation Tests ; Cell Line, Tumor ; Heparin ; chemistry ; Heparin, Low-Molecular-Weight ; chemistry ; pharmacology ; Humans ; Mice

OBJECTIVEThis paper aimed to review the current literature on the surface modification of intraocular lenses (IOLs).

DATA SOURCESAll articles about surface modification of IOLs published up to 2015 were identified through a literature search on both PubMed and ScienceDirect.

STUDY SELECTIONThe articles on the surface modification of IOLs were included, but those on design modification and surface coating were excluded.

RESULTSTechnology of surface modification included plasma, ion beam, layer-by-layer self-assembly, ultraviolet radiation, and ozone. The main molecules introduced into IOLs surface were poly (ethylene glycol), polyhedral oligomeric silsesquioxane, 2-methacryloyloxyethyl phosphorylcholine, TiO 2 , heparin, F-heparin, titanium, titanium nitride, vinyl pyrrolidone, and inhibitors of cytokines. The surface modification either resulted in a more hydrophobic lens, a more hydrophilic lens, or a lens with a hydrophilic anterior and hydrophobic posterior surface. Advances in research regarding surface modification of IOLs had led to a better biocompatibility in both in vitro and animal experiments.

CONCLUSIONThe surface modification is an efficient, convenient, economic and promising method to improve the biocompatibility of IOLs.

Animals ; Heparin ; chemistry ; Humans ; Hydrophobic and Hydrophilic Interactions ; Lenses, Intraocular ; Methacrylates ; chemistry ; Ozone ; chemistry ; Phosphorylcholine ; analogs & derivatives ; chemistry ; Ultraviolet Rays

Heparin is a very important anticoagulant drug. Currently, heparin is mainly extracted from porcine mucosa. However, animal-derived heparin shows low anticoagulant activity due to the low proportion of the anticoagulant active unit, the GlcNS6S-GlcA-GlcNS6S3S-Ido2S-GlcNS6S pentasaccharide. In this study we proposed an enzymatic strategy to sulfate the animal-sourced heparin to increase the proportion of anticoagulant pentasaccharide and the anticoagulant activity. First, three sulfotransferases HS2ST, HS6ST, and HS3ST were expressed tentatively in Escherichia coli and Pichia pastoris. After measuring the sulfotransferase activity, we confirmed P. pastoris GS115 is the better host for sulfotransferases production. Then, the maltose binding protein (MBP) and thioredoxin (TrxA) were fused separately to the N-terminal of sulfotransferases to increase enzyme solubility. As a result, the yields of HS2ST and HS6ST were increased to (839±14) U/L and (792±23) U/L, respectively. Subsequent sulfation of the animal-sourced heparin with the recombinant HS2ST, HS6ST and HS3ST increased the anticoagulant activity from (76±2) IU/mg to (189±17) IU/mg.
Animals ; Escherichia coli ; Heparin ; chemistry ; Oligosaccharides ; chemistry ; Pichia ; Sulfotransferases ; biosynthesis ; Swine

Photoreactive heparin was synthesized by reaction of 4-azidoaniline and heparin. An organic layer was introduced on the surface of Ti-O by 3-aminopropylphosphonic acid assembling, and then the modified heparin was immobilized on the surface by UV irradiation. Water contact angle was used to characterize the hydrophilicity, quantitive assay was done by azure staining methods, and blood compatibility was evaluated by platelet adhesion experiment. Water contact angle of heparinized surface was smaller than that of Ti-O film, which indicated more hydrophilic property of heparinized surface. The surface density of heparin increased with the prolonging of irradiation time and the density was 2.1 microg/cm2 when irradiated for 300s. It showed the heparinized surface was effective in resisting platelets from adhesion and aggregation.
Aniline Compounds ; chemistry ; Azo Compounds ; chemistry ; Blood Proteins ; pharmacology ; Fibrinolytic Agents ; pharmacology ; Heparin ; chemistry ; Humans ; Membranes, Artificial ; Propylamines ; chemistry ; Surface Properties ; Titanium ; chemistry

BACKGROUND: Plasma specimens are recently used instead of serum in clinical chemistry to improve (test result turnaround time, TAT). We evaluated the performance of lithium heparin gel plasma separating tube in comparison to existing vacutainer gel serum tube in common clinical chemistry assays. METHODS: Total 52 subjects who had visited the health promotion center were included in the study. Lithium heparin plasma tubes and serum tubes were tested for 30 clinical chemistry items and 3 cardiac markers. Test results were analyzed by calculation of mean bias and percent difference. RESULTS: The performance of the lithium heparin plasma tube was considered to be clinically equivalent to the serum tube for all assays except for potassium. The difference of potassium levels between lithium heparin plasma tube and the serum tube was -7.32%. Test results of some analytes including glucose, lactate dehydrogenase, total CO2 and potassium using the lithium heparin tube were significantly changed after 24 hours of storage. CONCLUSIONS: The lithium heparin plasma tube provided acceptable results comparison to the existing serum separating tube in common clinical chemistries and can be used for reducing, TAT. However, the stability of plasma gel tubes on 24 hours of storage was unstable in some analytes, it requires attention.
Bias (Epidemiology) ; Chemistry, Clinical ; Glucose ; Health Promotion ; Heparin ; L-Lactate Dehydrogenase ; Lithium ; Plasma ; Potassium

The functional hemocompatibility between fibrinogen (FIG) and a novel vascular stent material (Ti-O film fixed with albumin and heparin) was investigated as follows: (1) Preparing the new biologic material (Ti-O) film; (2) Coating albumin and heparin on the Ti-O film; (3) Testing platelets (PL) adsorption; (4) Determining FIG adhesion number by use of enzyme linked immunoassay (ELISA); (5) Implanting the films from the test group of Ti-O film and from the comparison group of stainless steel (SS) film into the left and right femoral arteries respectively in 4 dogs. It was proved that albumin and heparin were fixed on Ti-O film. After 6 months, the femoral arteries of the dogs were resected. In the test group of Ti-O film coated with albumin and heparin, few PL adhered to the coat, their form did not change, and no thrombus was found by scanning electron microscopy; the result was better than that of plain Ti-O film, and was much better than that of SS film. Ti-O maintained normal transformation condition of FIG, and no C terminal of gamma chain in FIG was revealed. As it is known whether the hemocompatibility of a biomaterial is good depends upon its adsorption of FIG, and Ti-O has excellent reaction on albumin and heparin by chemical processes. In this study, the Ti-O film coated with albumin and heparin further reduced the absorption of FIG and PL when compared against the plain Ti-O film. So the Ti-O film coated with albumin and heparin has the insistent and permanent anticoagulant character.
Albumins ; chemistry ; Animals ; Coated Materials, Biocompatible ; pharmacology ; Dogs ; Fibrinogen ; chemistry ; Heparin ; chemistry ; Materials Testing ; methods ; Prosthesis Design ; Stents ; Surface Properties ; Titanium ; chemistry