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Nitric oxide-generating self-assembling peptide hydrogel coating for enhancing hemocompatibility of blood-contacting devices

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Journal of Materials Science & Technology 2022年第36期131卷 106-114页

作者： Hao Li Qianru Guo qiufen tu Kaiqin Xiong Wei Wang Lei Lu Wentai Zhang Nan Huang Zhilu Yang Key Laboratory of Advanced Technology for Materials of Education Ministry School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China Affiliated Dongguan People’s Hospital Southern Medical UniversityDongguan 523059China State Key Laboratory of Molecular Engineering of Polymers(Fudan University) Shanghai 200438China Department of Cardiology Zigong First People’s HospitalZigong 643000China School&Hospital of Stomatology Wenzhou Medical UniversityWenzhou 325035China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China Guangdong Provincial Key Laboratory of Shock and Microcirculation Guangzhou 510080China

Thrombosis is the major stumbling block to the clinical application of blood-contacting ***,a quick and easy surface engineering strategy of hydrogel coating with the therapeutic gas nitric oxide(NO)generation was reported to realize up-regulation of cyclic guanosine monophosphate(c GMP)and improve hemocompatibility for diverse metal *** first introduce the active centre selenocysteine of glutathione peroxidase(GPx)to the self-assembling peptide(RADA)4,obtaining a functionalized *** the hydrogel is directly coated on the 316L stainless steel(SS)for catalytically generating NO from endogenous s-nitrosothiols(RSNO).The generated NO endows the coated surface with regulation of platelet behavior and reduction of plasmatic coagulation activation and complement system activation,hence improving antithrombotic ability in vitro and ex ***,our NO-generating hydrogel coating surface engineering strategy provides a novel solution to remove the obstacle about thrombosis of blood-contacting devices in clinic.

关键词： Blood-contacting device NO generation Self-assembling peptide Hydrogel coating Antithrombotic ability

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A“built-up”composite film with synergistic functionalities on Mg-2Zn-1Mn bioresorbable stents improves corrosion control effects and biocompatibility

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Bioactive Materials 2023年第7期25卷 223-238页

作者： Zhenglong Dou Shuiling Chen Jiacheng Wang Li Xia Manfred F.Maitz qiufen tu Wentai Zhang Zhilu Yang Nan Huang Key Lab of Advanced Technology of Materials of Education Ministry School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu610031China Affiliated Dongguan Hospital Southern Medical UniversityDongguanGuangdong523059China Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation GuangzhouGuangdong510080China Department of Cardiology Third People’s Hospital of Chengdu Affiliated to Southwest Jiaotong UniversityChengdu610031China Max Bergmann Center of Biomaterials Dresden Leibniz Institute of Polymer Research DresdenHohe Strasse 601069DresdenGermany

Control of premature corrosion of magnesium(Mg)alloy bioresorbable stents(BRS)is frequently achieved by the addition of rare earth ***,limited long-term experience with these elements causes concerns for clinical application and alternative methods of corrosion control are sought ***,we report a“built-up”composite film consisting of a bottom layer of MgF2 conversion coating,a sandwich layer of a poly(1,3-trimethylene carbonate)(PTMC)and 3-aminopropyl triethoxysilane(APTES)co-spray coating(PA)and on top a layer of poly(lactic-co-glycolic acid)(PLGA)ultrasonic spray coating to decorate the rare earth element-free Mg-2Zn-1Mn(ZM21)BRS for tailoring both corrosion resistance and biological *** developed“built-up”composite film shows synergistic functionalities,allowing the compression and expansion of the coated ZM21 BRS on an angioplasty balloon without cracking or *** special importance is that the synergistic corrosion control effects of the“built-up”composite film allow for maintaining the mechanical integrity of stents for up to 3 months,where complete biodegradation and no foreign matter residue were observed about half a year after implantation in rabbit iliac ***,the functionalized ZM21 BRS accomplished re-endothelialization within one month.

关键词： Magnesium alloys Bioresorbable stents Composite coating Corrosion control Biocompatibility

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From surface to bulk modification: Plasma polymerization of amine-bearing coating by synergic strategy of biomolecule grafting and nitric oxide loading

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Bioactive Materials 2020年第1期5卷 17-25页

作者： Tong Yang Zeyu Du Hua Qiu Peng Gao Xin Zhao Huaiyu Wang qiufen tu Kaiqin Xiong Nan Huang Zhilu Yang Key Laboratory of Advanced Technology for Materials of the Education Ministry School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu610031China Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHung HomHong KongChina Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen518055China

Integration of two or more biomolecules with synergetic and complementary effects on a material surface can help to obtain multi-functions for various biomedical ***,the amounts of biomolecules integrated and their physiological functions are compromised due to the limited surface anchoring ***,we propose a novel concept of film engineering strategy“from surface to bulk synergetic modification”.This new concept is realized by employing the surface amine groups of plasma polymerized allylamine(PPAm)film for grafting a molecule e.g.,thrombin inhibitor,bivalirudin(BVLD),meanwhile its bulk amine groups is used as a universal depot for storing and releasing therapeutic nitric oxide(NO)gas as supplement to the functions of *** is demonstrated that such a“from surface to bulk synergetic modification”film engineering can impart the modified-substrates with anti-platelet and anti-coagulant dual functions,giving rise to a highly endotheliummimetic thromboresistant *** believe that our research provides a very promising strategy to deliver multifunctional surface versatilely that require NO release in combination with other properties,which will find broad biomedical applications in blood-contacting devices,and et ***,it also provides a brand-new film engineering strategy for tailoring surface multi-functionalities of a wide range of materials.

关键词： Surface chemistry Amine-bearing coating Synergic modification Biomolecule grafting Nitric oxide loading

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Poly-dopamine, poly-levodopa, and poly-norepinephrine coatings: Comparison of physico-chemical and biological properties with focus on the application for blood-contacting devices

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Bioactive Materials 2021年第1期6卷 285-296页

作者： Xing Tan Peng Gao Yalong Li Pengkai Qi Jingxia Liu Ru Shen Lianghui Wang Nan Huang Kaiqin Xiong Wenjie Tian qiufen tu Key Lab of Advanced Technology of Materials of Education Ministry Southwest Jiaotong UniversityChengdu610031China Department of Stem Cell Center Henan Key Laboratory of Stem Cell Differentiation and ModificationHenan Provincial People's HospitalPeople's Hospital of Zhengzhou UniversityZhengzhouHenan450003China Physical Education Department Southwest Jiaotong UniversityChengdu610031China Cardiology Department Sichuan Academy of Medical Sciences&Sichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of China.32 West Second SectionFirst Ring RoadChengdu 610072China

Thanks to its simplicity,versatility,and secondary reactivity,dopamine self-polymerized coatings(pDA)have been widely used in surface modification of biomaterials,but the limitation in secondary molecular grafting and the high roughness restrain their application in some special ***,some other catecholamine coatings analog to pDA have attracted more and more attention,including the smoother poly-norepinephrine coating(pNE),and the poly-levodopa coating(pLD)containing additional carboxyl ***,the lack of a systematic comparison of the properties,especially the biological properties of the above three catecholamine coatings,makes it difficult to give a guiding opinion on the application scenarios of different ***,we systematically studied the physical,chemical,and biological properties of the three catecholamine coatings,and explored the feasibility of their application for the modification of biomaterials,especially cardiovascular *** them,the pDA coating was the roughest,with the largest amount of amino and phenolic hydroxyl groups for molecule grafting,and induced the strongest platelet adhesion and *** pLD coating was the thinnest and most hydrophilic but triggered the strongest inflammatory *** pNE coating was the smoothest,with the best hemocompatibility and histocompatibility,and with the strongest cell selectivity of promoting the proliferation of endothelial cells while inhibiting the proliferation of smooth muscle *** sum up,the pNE coating may be a better choice for the surface modification of cardiovascular materials,especially those for vascular stents and grafts,but it is still not widely recognized.

关键词： Catecholamine Self-polymerization Bioactive coating Surface modification Biocompatibility

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基于“酚-胺”化学构建抗污表面的研究

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材料导报 2023年第17期37卷 257-262页

作者：谢鑫吕楠涂秋芬西南交通大学材料科学与工程学院成都610031

生物污染是医用器械植、介入后的常见问题,尤其是血液接触类器械,如体外循环导管等。生物污染除了影响器械功能发挥外,还可能危及患者生命安全。在器械表面构建抗污涂层是解决此类问题行之有效的策略之一。本工作的灵感来源于“酚-胺”... 详细信息

生物污染是医用器械植、介入后的常见问题,尤其是血液接触类器械,如体外循环导管等。生物污染除了影响器械功能发挥外,还可能危及患者生命安全。在器械表面构建抗污涂层是解决此类问题行之有效的策略之一。本工作的灵感来源于“酚-胺”化学,利用ε-聚赖氨酸(ε-PL)、氢化咖啡酸(HCA)、高碘酸钠(NaIO4)一步浸涂法,快速、高效地构建了ε-PL/HCA“酚-胺”涂层,利用涂层表面丰富的氨基官能团接枝透明质酸(HA),得到具有良好生物除污功能的HA@ε-PL/HCA涂层。傅里叶红外光谱(FTIR)、X射线光电子能谱(XPS)、水接触角的结果证明成功制备了HA@ε-PL/HCA涂层;三种细胞的粘附实验证明HA@ε-PL/HCA涂层具有优异的抗细胞粘附能力;体外血小板粘附与半体内血液循环试验表明HA@ε-PL/HCA涂层具有良好的抗凝血能力。综上,基于“酚-胺”化学构建的HA@ε-PL/HCA涂层可赋予材料良好的抗凝血、抑制细胞粘附的功能,在体外循环导管等器械的表面改性方面具有潜在的应用价值。

关键词： “酚-胺”化学 ε-聚赖氨酸氢化咖啡酸透明质酸抗污抗凝

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A Versatile Surface Bioengineering Strategy Based on Mussel-Inspired and Bioclickable Peptide Mimic

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Research 2020年第1期2020卷 1233-1244页

作者： Yu Xiao Wenxuan Wang Xiaohua Tian Xing Tan Tong Yang Peng Gao Kaiqing Xiong qiufen tu Miao Wang Manfred FMaitz Nan Huang Guoqing Pan Zhilu Yang Key Laboratory of Advanced Technologies of Materials Ministry of EducationSchool of Materials Science and EngineeringSouthwest Jiaotong UniversityChengduSichuan 610031China Institute for Advanced Materials School of Materials Science and EngineeringJiangsu UniversityZhenjiangJiangsu 212013China Max Bergmann Center of Biomaterials Leibniz Institute of Polymer Research DresdenHohe Strasse 601069 DresdenGermany

In this work,we present a versatile surface engineering strategy by the combination of mussel adhesive peptide mimicking and bioorthogonal click *** main idea reflected in this work derived from a novel mussel-inspired peptide mimic with a bioclickable azide group(i.e.,DOPA_(4)-azide).Similar to the adhesion mechanism of the mussel foot protein(i.e.,covalent/noncovalent comediated surface adhesion),the bioinspired and bioclickable peptide mimic DOPA_(4)-azide enables stable binding on a broad range of materials,such as metallic,inorganic,and organic polymer *** addition to the material universality,the azide residues of DOPA_(4)-azide are also capable of a specific conjugation of dibenzylcyclooctyne-(DBCO-)modified bioactive ligands through bioorthogonal click reaction in a second *** demonstrate the applicability of this strategy for diversified biofunctionalization,we bioorthogonally conjugated several typical bioactive molecules with DBCO functionalization on different substrates to fabricate functional surfaces which fulfil essential requirements of biomedically used *** instance,antibiofouling,antibacterial,and antithrombogenic properties could be easily applied to the relevant biomaterial surfaces,by grafting antifouling polymer,antibacterial peptide,and NO-generating catalyst,***,the novel surface bioengineering strategy has shown broad applicability for both the types of substrate materials and the expected ***,the“clean”molecular modification of bioorthogonal chemistry and the universality of mussel-inspired surface adhesion may synergically provide a versatile surface bioengineering strategy for a wide range of biomedical materials.

关键词： materials azide versatile

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Nitric oxide-generating compound and bio-clickable peptide mimic for synergistically tailoring surface anti-thrombogenic and anti-microbial dual-functions

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Bioactive Materials 2021年第6期6卷 1618-1627页

作者： Han Yu Shaoxing Yu Hua Qiu Peng Gao Yingzhong Chen Xin Zhao qiufen tu Minggang Zhou Lin Cai Nan Huang Kaiqin Xiong Zhilu Yang Key Laboratory of Advanced Technology for Materials of the Education Ministry School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu610031China Department of Cardiology Third People’s Hospital of Chengdu Affiliated to Southwest Jiaotong UniversityChengdu610031China Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHung HomHong KongChina

Application of extracorporeal circuits and indwelling medical devices has saved many ***,it is accompanied with two major complications:thrombosis and *** address this issue,we apply therapeutic nitric oxide gas(NO)and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual *** functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(DOTA)chelated copper ions(Cu-DOTA)and dibenzylcyclooctyne-(DBCO-)modified antimicrobial peptide based on carbodiimide and click chemistry *** integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth,but also catalytically generate NO from endogenous s-nitrosothiols(RSNO)to reduce adhesion and activation of platelets,preventing the formation of *** envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices,with reduced clinical complications associated with thrombosis and infection.

关键词： Nitric oxide Bio-clickable peptide mimic Synergic modification Anti-thrombosis Anti-infection

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Durable endothelium-mimicking coating for surface bioengineering cardiovascular stents

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Bioactive Materials 2021年第12期6卷 4786-4800页

作者： Qing Ma Xiuying Shi Xing Tan Rui Wang Kaiqin Xiong Manfred F.Maitz Yuanyuan Cui Zhangmei Hu qiufen tu Nan Huang Li Shen Zhilu Yang Key Lab of Advanced Technology of Materials of Education Ministry School of Materials Science and EngineeringYibin Institute of Southwest Jiaotong UniversitySouthwest Jiaotong UniversityChengdu610031China Shanghai Institute of Cardiovascular Diseases Department of CardiologyZhongshan HospitalFudan University180 Fenglin RoadShanghai200032China Max Bergmann Center of Biomaterials Leibniz Institute of Polymer Research DresdenHohe Strasse 601069DresdenGermany Shimazu China Co.LTD. No.180 Yizhou RoadXuhui DistrictShanghai200233China Analysis&Testing Center Southwest Jiaotong UniversityChengdu610031China

Mimicking the nitric oxide(NO)-release and glycocalyx functions of native vascular endothelium on cardiovascular stent surfaces has been demonstrated to reduce in-stent restenosis(ISR)***,the practical performance of such an endothelium-mimicking surfaces is strictly limited by the durability of both NO release and bioactivity of the glycocalyx ***,we present a mussel-inspired amine-bearing adhesive coating able to firmly tether the NO-generating species(e.g.,Cu-DOTA coordination complex)and glycocalyx-like component(e.g.,heparin)to create a durable endothelium-mimicking *** stent surface was firstly coated with polydopamine(pDA),followed by a surface chemical cross-link with polyamine(pAM)to form a durable pAMDA *** a stepwise grafting strategy,Cu-DOTA and heparin were covalently grafted on the pAMDA-coated stent based on carbodiimide *** to both the high chemical stability of the pAMDA coating and covalent immobilization manner of the molecules,this proposed strategy could provide 62.4%bioactivity retention ratio of heparin,meanwhile persistently generate NO at physiological level from 5.9±0.3 to 4.8±0.4×10^(-10) mol cm^(-2) min^(-1) in 1 *** a result,the functionalized vascular stent showed long-term endothelium-mimicking physiological effects on inhibition of thrombosis,inflammation,and intimal hyperplasia,enhanced re-endothelialization,and hence efficiently reduced ISR.

关键词： Cardiovascular stents Nitric oxide Glycocalyx component Endothelium mimicking Surface bioengineering

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Endothelium-Mimicking Multifunctional Coating Modified Cardiovascular Stents via a Stepwise Metal-Catechol-(Amine)Surface Engineering Strategy

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Research 2020年第1期2020卷 1768-1787页

作者： Ying Yang Peng Gao Juan Wang qiufen tu Long Bai Kaiqin Xiong Hua Qiu Xin Zhao Manfred FMaitz Huaiyu Wang Xiangyang Li Qiang Zhao Yin Xiao Nan Huang Zhilu Yang Key Laboratory of Advanced Technologies of Materials Ministry of EducationSchool of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China Institute of Health and Biomedical Innovation Queensland University of TechnologyBrisbane 4059Australia Australia-China Centre for Tissue Engineering and Regenerative Medicine Queensland University of TechnologyBrisbane 4059Australia Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHung HomKowloonHong KongChina Max Bergmann Center of Biomaterials Leibniz Institute of Polymer Research DresdenHohe Strasse 601069 DresdenGermany Institute of Biomedicine and Biotechnology Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive MaterialsMinistry of EducationCollege of Life SciencesNankai UniversityTianjinChina

Stenting is currently the major therapeutic treatment for cardiovascular ***,the nonbiogenic metal stents are inclined to trigger a cascade of cellular and molecular events including inflammatory response,thrombogenic reactions,smooth muscle cell hyperproliferation accompanied by the delayed arterial healing,and poor reendothelialization,thus leading to restenosis along with late stent *** address prevalence critical problems,we present an endothelium-mimicking coating capable of rapid regeneration of a competently functioning new endothelial layer on stents through a stepwise metal(copper)-catechol-(amine)(MCA)surface chemistry strategy,leading to combinatorial endothelium-like functions with glutathione peroxidase-like catalytic activity and surface *** from the stable nitric oxide(NO)generating rate at the physiological level(2:2×10^(-10) mol/cm^(2)/min lasting for 60 days),this proposed strategy could also generate abundant amine groups for allowing a high heparin conjugation efficacy up to∼1μg/cm^(2),which is considerably higher than most of the conventional heparinized *** resultant coating could create an ideal microenvironment for bringing in enhanced antithrombogenicity,anti-inflammation,anti-proliferation of smooth muscle cells,re-endothelialization by regulating relevant gene expressions,hence preventing restenosis in *** envision that the stepwise MCA coating strategy would facilitate the surface endothelium-mimicking engineering of vascular stents and be therefore helpful in the clinic to reduce complications associated with stenosis.

关键词： coating stepwise bringing

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磁介导功能型纳米粒子在铁支架表面定向捕获CD34阳性细胞

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中国科学：技术科学 2017年第5期47卷 540-546页

作者：范仪李萍赵雅娟涂秋芬黄楠西南交通大学材料先进技术教育部重点实验室成都610031 西南交通大学生命科学与工程学院成都610031

构建内皮祖细胞捕获支架是目前心血管疾病治疗的一个研究热点.利用磁性纳米粒子捕获内皮祖细胞也越来越受到关注,但是单纯的磁性纳米粒子和磁场源地作用相对微弱,本研究引入铁支架作为另一磁响应源,共同作用来提高纳米粒子表面捕获率.... 详细信息

构建内皮祖细胞捕获支架是目前心血管疾病治疗的一个研究热点.利用磁性纳米粒子捕获内皮祖细胞也越来越受到关注,但是单纯的磁性纳米粒子和磁场源地作用相对微弱,本研究引入铁支架作为另一磁响应源,共同作用来提高纳米粒子表面捕获率.首先利用CD34抗体构建了一种定向捕获CD34阳性细胞的功能型磁性纳米粒子,再利用外加磁场将其归巢到铁支架表面.FTIR和TEM结果表明CD34抗体已成功接枝到双羧基PEG包裹的Fe_3O_4纳米粒子上,体外细胞评价证实该纳米粒子不具有细胞毒性.体内动物实验结果表明该Fe_3O_4-PEG@CD34纳米粒子能够特异性识别捕获CD34阳性细胞,并且在外加磁场的作用下能够将其快速归巢到铁支架表面,这为实现支架表面快速内皮化提供了可能.

关键词：内皮祖捕获干细胞磁性纳米粒子 CD34抗体

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