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RSC Advances · 2016 ·Vol. 6 ·期 48 ·42684-42692 · IF 3.289

APTES assisted surface heparinization of polylactide porous membranes for improved hemocompatibility

Jinglong Li,Fu Liu,Xuemin Yu,Ziyang Wu,Yunze Wang,Zhu Xiong,Jidong He

Surface heparinization is considered an efficient strategy to improve the hemocompatibility of polymeric membranes. We aim to realize the feasible surface heparinization of polylactide (PLA) membranes by means of a colourless 3-aminopropyltriethoxysilane (APTES) functionalized platform. APTES conjugated heparin (Hep–APTES) was first synthesized through the amidation reaction and then anchored onto PLA membrane via surface attachment, condensation, multilayer formation. The surface chemistry was confirmed by Fourier Transform Infrared-Attenuated Total Reflectance (ATR-FTIR) and X-ray Photoelectron Spectroscopy (XPS). The influences of heparinization time and micro-swelling agent (DMAc) on the heparin density, stability and sustained-release were investigated. The hydrophilicity, flux and morphology were also studied by contact angle, pure water flux and Scanning Electron Microscope (SEM). The hemocompatibility was evaluated by the activated partial thromboplastin time (APTT), prothrombin time (PT), the content of fibrinogen (FIB), platelet and Bovine Serum Albumin (BSA) adsorption respectively. All results demonstrated that APTES assisted surface heparinization provided a feasible and efficient strategy to improve the hemocompatibility of PLA membrane.

研究领域: 生物材料 · 医学工程
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2014 · IF 3.552

Route to hemocompatible polyethersulfone membranes via surface aminolysis and heparinization

Linghui Wang,Yu Cai,Yihang Jing,Baoku Zhu,Liping Zhu,Youyi Xu

Polyethersulfone (PES) membranes with improved hemocompatibility were prepared via solid–liquid interface aminolysis and heparinization. Reactive amino groups were generated by immersing solid PES membranes in proper diamine solution. Heparin was covalent immobilized on the surface via amide bond. The feasibility of surface aminolysis for the introduction of amino groups and the effectiveness for further heparin immobilization were confirmed by surface group analysis. The effect of aminolysis time on surface amino group concentration and bulk mechanical properties was investigated. The surface amino group concentration determined the amount and bioactivity of immobilized heparin chains. SEM images suggested that both the aminolysis and heparinization reaction had little effect on the surface morphology of PES membranes. Contact angle measurement, surface charge analysis, protein and platelet adsorption/adhesion experiment were applied to study the surface properties. The results showed that the heparinized PES membranes displayed enhanced hydrophilicity and hemocompatibility, indicating potential application in blood purification and other blood contacting fields.

CAS / MDL: 25952-53-8 92-31-9
研究领域: 生物医学工程 · 材料科学
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APPLIED SURFACE SCIENCE · 2016 · IF 3.15

Facile preparation of heparinized polysulfone membrane assisted by polydopamine/polyethyleneimine co-deposition for simultaneous LDL selectivity and biocompatibility

Liwei Wang,Fei Fang,Yang Liu,Jing Li,Xiaojun Huang

Low-density lipoprotein (LDL) gains worldwide attention for decades as the key risk factor to atherosclerosis that progressively deteriorating into cardiovascular diseases. Until recent years, LDL-apheresis comes to be extensively used as a direct and efficient LDL removal method, with LDL adsorption materials particularly important. In this paper, a new strategy based on the co-deposition of polydopamine (PDA) with polyethylenimine (PEI) onto polysulfone (PSf) membranes, then subsequent heparinization by amino-carbonyl reactions, to achieve LDL selectivity and simultaneous biocompatibility, is proposed. Surface properties of modified PSf membranes are characterized by ATR-FTIR, XPS, FESEM, Zeta potential and WCA measurements. LDL adsorption ability is investigated by ELISA, while blood biocompatibility is evaluated by platelet adhesion experiments. Results suggest that heparin-modified PSf membranes show high selectivity for LDL removal and fine biocompatibility in contact with plasma, as excellent potential materials for LDL-apheresis.

CAS / MDL: 9002-98-6
研究领域: 生物医学工程 · 材料科学
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Polymer Chemistry · 2017 ·Vol. 8 ·期 14 ·2266-2275 · IF 5.375

Mussel-inspired post-heparinization of a stretchable hollow hydrogel tube and its potential application as an artificial blood vessel

Jie Deng,Chong Cheng,Yingying Teng,Chuanxiong Nie,Changsheng Zhao

We report the fabrication of a highly stretchable hydrogel tube and its postfunctionalization for potential application as an artificial blood vessel. Although stretchable hydrogels have been well studied in the last decade, functionalization of the hydrogel remains a grand challenge because of the deterioration of its mechanical strength induced by the newly incorporated functional monomers. Herein, we use a mussel-inspired coating method to bestow the highly stretchable hydrogel with super hemocompatibility; meanwhile, the mechanical properties of the hydrogel matrix were not obviously damaged. Briefly, dopamine grafted heparin was anchored to an alginate/polyacrylamide double-network hydrogel via the mussel-inspired coating. The prolonged activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) demonstrated the enhanced anticoagulant activity of the heparin functionalized hydrogl tube. The clotting time, platelet adhesion, hemolysis ratio, and complement activation results of the hydrogel indicated that the heparinized hydrogel tube has excellent hemocompatibility and can be used as an artificial blood vessel. Compared to the unmodified hydrogel, the heparinized hydrogel also shows an improved cell adhesion affinity towards blood endothelial cells. More importantly, after the mussel-inspired coating, the mechanical strength of the highly stretchable hydrogel tube can be retained. Thus, the obtained highly hemocompatible hollow hydrogel tube can meet the needs of the dynamic functionality of stretchable blood vessels as well as other highly elastic soft tissues.

研究领域: 生物材料 · 组织工程 · 血液动力学
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International Journal of Nanomedicine · 2019 · IF 4.471

Anti-Adhesive And Antiproliferative Synergistic Surface Modification Of Intraocular Lens For Reduced Posterior Capsular Opacification

Yuemei Han,Junmei Tang,Jiayi Xia,Rui Wang,Chen Qin,Sihao Liu,Xia Zhao,Hao Chen,Quankui Lin

Background Posterior capsular opacification (PCO) is the main complication after intraocular lens (IOL) implantation in cataract surgery, which is the result of lens epithelial cell (LEC) adhesion, proliferation and migration on the IOL and at the lens capsule interface. Hydrophilic surface modification, such as surface heparinization, decreases the cell adhesion, which has been commercialized and used clinically. However, clinical long-term observation results show no significant difference between the pristine and heparinized IOLs.Methods To prevent PCO over the long time span, we modified the IOLs with an antiproliferative drug-loaded hydrophilic coating. The antiproliferative drug doxorubicin (DOX)-incorporated chitosan (CHI) nanoparticle was fabricated by sodium tripolyphosphate (TPP) gelation. Such antiproliferative drug-loaded CHI-TPP-DOX nanoparticles (CTDNP) were used as one of the building blocks to prepare polyelectrolyte multilayer with heparin (HEP) via layer-by-layer assembly, obtaining (HEP/CTDNP)n multilayers. The assembly process was characterized by quartz crystal microbalance with dissipation (QCM-D). The drug release behavior of the coating was investigated by ultra-HPLC (UPLC). In vitro cell experiments were carried out to monitor the effects of multifunctional coatings on cellular adhesion, proliferation and migration. And the intraocular implantation was performed on rabbits to evaluate the in vivo PCO inhibitory effect of such surface-functionalized IOLs.Results The positively charged CTDNP was successfully prepared by ionic gelation. The QCM-D results indicate the successful preparation of the (HEP/CTDNP)n multilayer film. Drug release profiles showed that surface-multifunctionalized IOL had drug-sustained release properties. In vitro cell culture results showed significant inhibition of adhesion, proliferation and migration of LECs after surface modification. The in vivo results showed that the IOLs with multifunctionalized surface can effectively reduce the posterior hyperplasia and Soemmering’s ring (SR) formation.Conclusion These findings suggested that such multifunctionalized drug-eluting IOLs can effectively reduce the posterior hyperplasia and SR formation when intraocular implantation has a major impact on reducing PCO incidence. Thus they have a great potential in improving patient vision recovery and maintenance.

CAS / MDL: 9012-76-4 603-35-0
研究领域: 眼科 · 生物材料 · 药物递送系统
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BIOMACROMOLECULES · 2025 · IF 5.4

Simultaneous Removal of Endotoxin and Circulating Histones by Heparin-Grafted Chitosan-Cellulose Composite Microspheres for Multitargeted Hemoperfusion in Septic Blood

Yu Cheng,Yu Chen,Tao Song,Luojia Jiang,Yuhan He,Yupei Li,Weifeng Zhao,Baihai Su

Endotoxin and circulating histones form a pathogenic loop, driving immune dysregulation in sepsis. A multitargeted extracorporeal blood purification combining endotoxin adsorption with histone neutralization may represent a critical therapeutic approach to improve the clinical outcomes of septic patients. However, existing hemoperfusion adsorbents are often heparin-dependent and single-target and exhibit limited hemocompatibility. Herein, we developed self-anticoagulant heparin-grafted chitosan/cellulose composite microspheres (CSCEHEP) for the simultaneous adsorption of endotoxin and circulating histones. The obtained CSCEHEP microspheres significantly prolonged plasma coagulation time while maintaining excellent hemocompatibility, owing to the heparin coating. In vitro, CSCEHEP microspheres exhibited adsorption capacities of 251.0 EU/g (81.8% clearance) for endotoxin and 288.6 μg/g (62.8% clearance) for histones, respectively. Meanwhile, CSCEHEP microspheres effectively adsorbed histones in whole blood and counteracted histone-induced endothelial and kidney epithelial cytotoxicity, erythrocyte fragility, and thrombocytopenia. In conclusion, CSCEHEP microspheres are promising adsorbents for hemoperfusion to simultaneously remove endotoxins and circulating histones in septic blood.

研究领域: 免疫学 · 重症医学 · 生物材料学 · 血液净化 · 分子病理学 · 转化医学 · 药用高分子
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JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS · 2020 · IF 1.624

Preparation and evaluation of heparinized sponge based on collagen and chitosan for wound healing

Kun Wu,Dan Zhao,Huifei Cui

The wound dressing can temporarily replace the skin and play a protective role in the process of wound healing, preventing wound infection and inflammation, and providing a favorable environment for wound healing. In this study, a mixture of collagen and chitosan was lyophilized to be the host material of the sponge. This sponge was soaked into 1-ethyl-(dimethylaminopropyl) carbodiimide/N-hydroxy sulfosuccinimide cross-linking solution containing heparin and experienced secondary lyophilization to prepare the heparinized sponge (CT-CL/Hp). The surface morphology and structural characterization of the sponge was characterized by scanning electron microscope and Fourier transform infrared spectrometer, respectively. Relatively favorable water absorption capability were observed by measuring the physical properties. Satisfactory antibacterial properties against various bacteria and microbial isolation performance were observed by the antibacterial effect analysis in vitro. The sustained-release property of heparin from the sponges was measured using Alcian Blue assay. Experiments in vitro and in vivo showed that the sponges had satisfactory biocompatibility and lower sensitization. Moreover, the effect of sponge on early stages of wound healing was evaluated by guinea pigs wound healing models. Analysis of wound healing rates and histological examination showed satisfactory results. CT-CL/Hp enhanced expression of growth factors, particularly VEGF and EGF at day 7. These results demonstrated that CT-CL/Hp–treated sponges benefit to wound skin healing and regeneration.

研究领域: 生物材料 · 伤口愈合 · 生物医学工程
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JOURNAL OF APPLIED POLYMER SCIENCE · 2024 · IF 2.7

Preparation and performance study of heparinized multi-walled carbon nanotube/cellulose acetate hemodialysis membrane

Xingtong Gao,Kai Liu,Wenjin Hu,Aixiang Li,Zijian Lyu,Haiqiang Chen,Hu Zhu

Currently, the incidence of kidney failure is increasing worldwide. Hemodialysis is the main method for the treatment of kidney diseases, and the continuous development of new hemodialysis membranes is the key to improve the treatment effect and the quality of life of patients. In this study, heparinized multi-walled carbon nanotube/cellulose acetate (Hep/MWCNTs@CA) membranes were prepared by non-solvent induced phase separation (NIPS). The morphology and pore structure of Hep/MWCNTs@CA membranes were characterized by scanning electron microscopy (SEM). The elongation at break and tensile strength of the membranes were characterized by a mechanical property universal tester. The results showed that mechanical properties of 0.1 wt% MWCNTs enhanced the membrane is best. The water contact angle test confirmed that MWCNTs can improve the membrane hydrophilicity, and combined with the adsorption test results for proteins, it was found that the hydrophilicity can reduce the adsorption of proteins to the composite membrane and improve the blood compatibility of the material. The dialysis performance of urea and lysozyme was tested by a self-made simulated hemodialysis device, and the clearance rates of urea and lysozyme were 84% and 47.2%, respectively, which showed that the interfacial gap between MWCNTs and CA matrix can make the composite membrane retain a high retention rate of macromolecular proteins (92.3%) and further improved the clearance rate of small and medium molecular toxins. In addition, the good blood compatibility and biocompatible properties of the materials were confirmed by hemolysis, recalcification and cytotoxicity tests on Hep/MWCNTs@CA membranes. In conclusion, the prepared Hep/MWCNTs@CA holds great potential for application in the field of hemodialysis.

CAS / MDL: 308068-56-6 57-13-6
研究领域: 材料科学 · 医学 · 生物工程
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2014 · IF 4.287

Hemocompatibility and selective cell fate of polydopamine-assisted heparinized PEO/PLLA composite coating on biodegradable AZ31 alloy

Zhongling Wei,Peng Tian,Xuanyong Liu,Bangxin Zhou

Biodegradable magnesium and its alloys have attracted much attention, as they have been used as cardiovascular stents recently because of their biodegradation after implantation. However, their corrosion resistance, hemocompatibility and surface biocompatibility are needed for practical applications. In this work, heparinization of the plasma electrolytic oxidation/poly( l -lactic acid) (PEO/PLLA) composite coating on biodegradable AZ31 alloy was achieved by the strong adhesion of mussel-inspired polydopamine (PDAM). The corrosion resistance of the coated substrates was evaluated in simulated body fluid. In particular, the hemolysis ratio and platelet adhesion tests were conducted to evaluate the hemocompatibility of the composite coatings. The in vitro cytotoxicity of the composite coatings was evaluated with human umbilical vein endothelial cells (HUVECs). The adhesion and proliferation of HUVECs and human umbilical artery smooth muscle cells (HUASMCs) directly incubated on the composite coatings were also investigated. The results showed that although PDAM modification and further heparinization reduced the corrosion resistance of the PEO/PLLA composite coating, the protection of the coating for the substrate was mainly maintained. Moreover, PDAM modification and further heparinization significantly suppressed the adhesion of platelets and had little influence on sustaining a low hemolysis ratio thus resulting in good surface hemocompatibility of the composite coating. The in vitro cell test demonstrated that none of the composite coatings presented obvious cytotoxicity. Significantly, after surface heparinization, the composite coating became more suitable for HUVEC growth and simultaneously inhibited HUASMC growth. The results show that further modification of the PEO/PLLA composite coating on biodegradable magnesium alloy is a promising method to obtain good surface hemocompatibility for anticoagulation and to regulate the cell fate for fast re-endothelialization while sustaining the corrosion resistance of biodegradable magnesium-based cardiovascular stents.

CAS / MDL: 62-31-7
研究领域: 生物医学工程 · 材料科学 · 心血管医学
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JOURNAL OF COLLOID AND INTERFACE SCIENCE · 2015 · IF 3.368

The correlation between fibronectin adsorption and attachment of vascular cells on heparinized polycaprolactone membrane

Mingcong Sun,Jun Deng,Changyou Gao

The heparin-immobilized polycaprolactone (PCL) membrane was developed to investigate the effect of heparin on the adsorption behaviors of serum proteins, in particular fibronectin (Fn), and the attachment of different types of vascular cells. The heparin was covalently immobilized onto aminolyzed PCL membrane by amidation reaction. The grafting amount of heparin increased from 0.35   μg/cm 2 to 1.31   μg/cm 2 when the aminolysis time was prolonged from 10   min to 60   min. The adhesion of endothelial cells (ECs) and smooth muscle cells (SMCs) on the heparinized PCL surface was significantly enhanced and reduced, respectively. The adsorption of Fn was strongly improved on the heparinized PCL surface than on the pristine PCL, and showed a positive correlation with the heparin density. Therefore, the adsorbed Fn takes a decisive role on the selective adhesion of ECs and the suppression of SMCs attachment.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 生物材料 · 细胞生物学 · 组织工程
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JOURNAL OF POLYMER RESEARCH · 2015 ·Vol. 22 ·期 5 ·1-12 · IF 1.92

Surface biocompatible construction of polyurethane by heparinization

Zhang Qin,Liao Jian-Fang,Shi Xu-Hua,Qiu Yong-Ge,Chen Han-Jia

A macromolecular biocompatible surface modifier for polyurethane (PU), namely, polyurethane-block-poly (chloromethyl styrene) (PU- b -PCMS) copolymer, was synthesized by coupling hydroxyl-terminated PCMS with diisocyanate-terminated PU and further quaternizing. The synthesized surface modifier was blended with PU and heparin was absorbed on PU surface by ion exchange. The modification effectively increased the hydrophilicity and water absorption of PU. To evaluate the hemocompatibility of the modified blend films, the extent of platelet adsorption, plasma recalcification time and hemolysis were measured. To determine if the blend films were toxic to mammalian cells, viability of the cells cultured on the blend films was assayed. All results indicated that the blood and cell compatibilities of the PU films were improved significantly after entrapment of a few quaternized PU- b -PCMS copolymers into PU and further heparinizing.

CAS / MDL: 94-36-0 75-09-2 301-10-0
研究领域: 材料科学 · 生物医学工程 · 生物材料
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION · 2021 · IF 3.517

Gelatin coating promotes in situ endothelialization of electrospun polycaprolactone vascular grafts

Yuehao Xing,Yongquan Gu,Lianrui Guo,Jianming Guo,Zeqin Xu,Yonghao Xiao,Zhiping Fang,Cong Wang,Zeng-Guo Feng,Zhonggao Wang

Rapid endothelialization is crucial for in situ tissue engineering vascular grafts to prevent graft failure in the long-term. Gelatin is a promising nature material that can promote endothelial cells (ECs) adhesion, proliferation, and migration. In this study, the internal surface of electrospun polycaprolactone (PCL) vascular grafts was coated with gelatin. Endothelialization and vascular wall remolding were investigated by imaging and histological studies in the rat abdominal aorta replacement model. The endothelialization of heparinized gelatin-coated PCL (GP-H) vascular grafts was more rapid and complete than heparinized PCL (P-H) grafts. Intimal hyperplasia was milder in the GP-H vascular grafts than the P-H vascular grafts in the long-term. Meanwhile, smooth muscle cells (SMCs) and extracellular matrix (ECM) regeneration were better in the GP-H vascular grafts. By comparison, an aneurysm was observed in the P-H group in 6 months. Calcification was observed in both groups. All vascular grafts were patient after implantation in both groups. Our results showed that gelatin coating on the internal surface of PCL grafts is a simple and effective way to promote endothelialization. A more rapid endothelialization and complete endothelium can inhibit intimal hyperplasia in the long-term.

CAS / MDL: 75-09-2 67-56-1
研究领域: 生物医学工程 · 组织工程 · 血管生物学
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