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A strategy for mechanically integrating robust hydrogeltissue hybrid to promote the anti-calcification and endothelialization of bioprosthetic heart valve

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Regenerative Biomaterials 2024年第2期3卷 123-136页

作者： Haoshuang Wu Nuoya Chen Tiantian Zheng Li Li Mengyue Hu Yumei Qin Gaoyang Guo Li Yang Yunbing Wang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China Institute of Clinical Pathology West China Hospital of Sichuan UniversityChengdu 610041China College of Polymer Science and Engineering Sichuan UniversityChengdu 610065China

Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over decades.Most clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed endothelializa-tion.Here,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of BHVs.In particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond interactions.Then,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of substrates.In vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification properties.Therefore,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.

关键词： bioprosthetic heart valves recombinant humanized collagen typeⅢ endothelialization anti-calcification anti-coagulation

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3D printed grafts with gradient structures for organized vascular regeneration

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International Journal of Extreme Manufacturing 2024年第3期6卷 505-520页

作者： Yuewei Chen Zhongfei Zou Tao Fu Zhuang Li Zhaojie Zhang Meng Zhu Qing Gao Shaofei Wu Guosheng Fu Yong He Jiayin Fu State Key Laboratory of Fluid Power and Mechatronic Systems School of Mechanical EngineeringZhejiang UniversityHangzhou 310027People’s Republic of China School of Mechanical Engineering Guizhou UniversityGuiyang 550025People’s Republic of China Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province Department of CardiologySir Run Run Shaw HospitalZhejiang UniversityHangzhou 310016People’s Republic of China School of Mechanical Engineering Guizhou Institute of TechnologyGuiyang 550003People’s Republic of China Department of Oral and Maxillofacial Surgery The Second Affiliated Hospital of Zhejiang University School of MedicineSchool of Stomatologyand Key Laboratory of Oral Biomedical Research of Zhejiang ProvinceHangzhouZhejiang 310006People’s Republic of China

Synthetic vascular grafts suitable for small-diameter arteries(<6 mm) are in great need.However,there are still no commercially available small-diameter vascular grafts(SDVGs) in clinical practice due to thrombosis an... 详细信息

Synthetic vascular grafts suitable for small-diameter arteries(endothelialization.The outer layer was designed to induce fibroblast recruitment by low porosity and minor pore size and provide SDVG with sufficient mechanical strength.One month after implantation,the arteries regenerated by 3D-printed grafts exhibited better pulsatility than electrospun grafts,with a compliance(8.9%) approaching that of natural arteries(11.36%) and significantly higher than that of electrospun ones(1.9%).The 3D-printed vascular demonstrated a three-layer structure more closely resembling natural arteries while electrospun grafts showed incomplete endothelium and immature SML.Our study shows the importance of SML reconstruction during vascular graft regeneration and provides an effective strategy to reconstruct blood vessels through 3D-printed structures rapidly.

关键词： small-diameter vascular graft smooth muscle layer 3D printing endothelialization

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Degradation and biocompatibility of one-step electrodeposited magnesium thioctic acid/magnesium hydroxide hybrid coatings on ZE21B alloys for cardiovascular stents

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Journal of Magnesium and Alloys 2024年第1期12卷 120-138页

作者： Zhao-Qi Zhang Bing-Zhi Li Pei-Duo Tong Shao-Kang Guan Li Wang Zheng-Hui Qiu Cun-Guo Lin Rong-Chang Zeng School of Material Science and Engineering&Henan Key Laboratory of Advanced Magnesium Alloy&Key Laboratory of Materials Processing and Mold Technology(Ministry of Education) Zhengzhou University100 Science RoadZhengzhou 450001China State Key Laboratory for Marine Corrosion and Protection Luoyang Ship Material Research InstituteQingdao 266101China Corrosion Laboratory for Light Metals College of Material Science and EngineeringShandong University of Science and TechnologyQingdao 266590China

Constructing a functional hybrid coating appears to be a promising strategy for addressing the poor corrosion resistance and insufficient endothelialization of Mg-based stents.Nevertheless,the steps for preparing composite coatings are usually complicated and time-consuming.Herein,a novel composite coating,composed of bioactive magnesium thioctic acid(MTA)layer formed by deposition and corrosion-resistant magnesium hydroxide(Mg(OH)_(2))layer grown in situ,is simply fabricated on ZE21B alloys via one-step electrodeposition.Scanning electron microscopy(SEM)shows that the electrodeposited coating has a compact and uniform structure.And the high adhesion of the MTA/Mg(OH)_(2)hybrid coating is also confirmed by the micro-scratch test.Electrochemical test,scanning kelvin probe(SKP),and hydrogen evolution measurement indicate that the hybrid coating effectively reduces the degradation rate of Mg substrates.Haemocompatibility experiment and cell culture trial detect that the composite coating is of fine biocompatibility.Finally,the preparation mechanism of MTA/Mg(OH)_(2)hybrid coatings is discussed and proposed.This coating shows a great potential application for cardiovascular stents.

关键词： Magnesium alloy Corrosion resistance Hybrid coating endothelialization Biocompatibility

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Fabrication of Intracranial Vascular Nitinol Alloy Stents with Improved Mechanical Property and endothelialization Function

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Acta Metallurgica Sinica(English Letters) 2022年第12期35卷 2069-2081页

作者： Yangyang Yan Na Li Feng Guo Anhua Wu Wei Jin Rui Yang Yun Bai Xing Zhang Shi-Changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China College of Life Science and Engineering Shenyang UniversityShenyang 110044China Department of Neurosurgery The First Affi liated Hospital of China Medical UniversityShenyang 110001China

Intracranial vascular stenting has been widely used for ischemic stroke.However,there are complication risks with stent implantation,such as poor wall apposition,stent migration,thromboembolism and stent restenosis,due to the mismatched radial force and conformability of the stents."Therefore,a novel intracranial vascular nitinol stent was fabricated in order to improve mechanical property and endothelialization function.The bending moment of the stents was calculated to be 0.346 N mm,which shows improved conformability.The radial force of the stents evaluated by the flat plate test was0.0112 N/mm,within the range of the commercially available stent force(0.0065-0.0116 N/mm).Furthermore,the TyrIle-Gly-Ser-Arg(YIGSR)peptide derived from laminin was grafted onto the stent surfaces to promote endothelialization on vascular stents evaluated by the proliferation,adhesion and migration of human umbilical vein endothelial cells in vitro.The nitinol stents with improved mechanical property and endothelialization function are expected to reduce the recurrence risk of ischemic stroke after implantation.

关键词： Nitinol stents Conformability Radial force endothelialization Intracranial stenosis treatment

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Recent advances in surface endothelialization of the magnesium alloy stent materials

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Journal of Magnesium and Alloys 2023年第1期11卷 48-77页

作者： Changjiang Pan Xuhui Liu Qingxiang Hong Jie Chen Yuxin Cheng Qiuyang Zhang Lingjie Meng Juan Dai Zhongmei Yang Lingren Wang Faculty of Mechanical and Material Engineering Jiangsu Provincial Engineering Research Center for Biomaterials and Advanced Medical DevicesHuaiyin Institute of TechnologyHuai’an 223003China The Affiliated Huai’an Hospital of Xuzhou Medical University Huai’an 223003China

Magnesium and its alloy have good mechanical properties and biodegradability,and have become the hotspot of the next-generation biodegradable vascular stent materials.However,their rapid degradation in vivo and poor biocompatibility are still the bottlenecks of clinical applications for the cardiovascular stents.In particular,how to induce the repair and regeneration of the vascular endothelial with normal physiological functions on the surface of the magnesium alloy stent materials represents the key to its clinical application in the field of cardiovascular stents.It has been believed that it is an ideal way to completely solve the postoperative complications through constructing the multifunctional anti-corrosive bioactive coating on the magnesium alloy surface to induce the formation of vascular endothelium with normal physiological functions.However,how to construct a corrosion-resistant multifunctional bioactive coating with the good endothelial regeneration abilities on the magnesium alloy surface still faces a great challenge.This paper mainly focused on highlighting and summarizing the recent advances in the surface endothelialization of the magnesium alloy materials for the vascular stent,including the bio-inert coating,in-situ immobilization of bioactive molecules on the surface,polymer coating loaded with bioactive factors,novel multifunctional polymer coating,bioactive micropatterns,bioactive layer with glycocalyx-like structure,NO-releasing coating and bioactive sol-gel coating.The advantages and disadvantages of these strategies were discussed and analyzed.Finally,in the senses of future development and clinical application,this paper analyzed and summarized the development direction and prospect of surface endothelialization of the magnesium alloy vascular stents.It is anticipated that this review can give the new cues to the surface endothelialization of the cardiovascular magnesium alloy stents and promote future advancements in this field.

关键词： Magnesium alloy Stent endothelialization Surface coating Surface modification

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Fucoidan and topography modification improved in situ endothelialization on acellular synthetic vascular grafts

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生物活性材料(英文) 2023年第4期22卷 535-550页

作者： Yuan Yao Aung Moe Zaw Deirdre E.J.Anderson YeJin Jeong Joshua Kunihiro Monica T.Hinds Evelyn K.F.Yim Department of Chemical Engineering University of Waterloo200 University Avenue WestWaterlooONN2L 3G1Canada Department of Biomedical Engineering Oregon Health&Science UniversityPortlandOR97239USA Waterloo Institute for Nanotechnology University of Waterloo200 University Avenue WestWaterlooONN2L 3G1Canada Center for Biotechnology and Bioengineering University of Waterloo200 University Avenue WestWaterlooONN2L 3G1Canada

Thrombogenesis remains the primary failure of synthetic vascular grafts.Endothelial coverage is crucial to provide an antithrombogenic surface.However,most synthetic materials do not support cell adhesion,and transanastomotic endothelial migration is limited.Here,a surface modification strategy using fucoidan and topography was developed to enable fast in situ endothelialization of polyvinyl alcohol,which is not endothelial cell-adhesive.Among three different immobilization approaches compared,conjugation of aminated-fucoidan promoted endothelial monolayer formation while minimizing thrombogenicity in both in vitro platelet rich plasma testing and ex vivo non-human primate shunt assay.Screening of six topographical patterns showed that 2μm gratings increased endothelial cell migration without inducing inflammation responses of endothelial cells.Mechanistic studies demonstrated that fucoidan could attract fibronectin,enabling integrin binding and focal adhesion formation and activating focal adhesion kinase(FAK)signaling,and 2μm gratings further enhanced FAK-mediated cell migration.In a clinically relevant rabbit carotid artery end-to-side anastomosis model,60%in situ endothelialization was observed throughout the entire lumen of 1.7 mm inner diameter modified grafts,compared to 0%of unmodified graft,and the four-week graft patency also increased.This work presents a promising strategy to stimulate in situ endothelialization on synthetic materials for improving long-term performance.

关键词： Blood-contacting devices Small diameter vascular graft endothelialization Topography Fucoidan

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A stage-specific cell-manipulation platform for inducing endothelialization on demand

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National Science Review 2020年第3期7卷 629-643页

作者： Qilong Zhao Juan Wang Yunlong Wang Huanqing Cui Xuemin Du Institute of Biomedical& Health Engineering Shenzhen Institutes of Advanced TechnologyChinese Academy of Sciences

endothelialization is of great significance for vascular remodeling, as well as for the success of implanted vascular grafts/stents in cardiovascular disease treatment. However, desirable endothelialization on synthetic biomaterials remains greatly challenging owing to extreme difficulty in offering dynamic guidance on endothelial cell(EC) functions resembling the native extracellular matrix-mediated effects. Here, we demonstrate a bilayer platform with near-infrared-triggered transformable topographies, which can alter the geometries and functions of human ECs by tunable topographical cues in a remote-controlled manner, yet cause no damage to the cell viability. The migration and the adhesion/spreading of human ECs are respectively promoted by the temporary anisotropic and permanent isotropic topographies of the platform in turn, which appropriately meet the requirements of stage-specific EC manipulation for endothelialization. In addition to the potential of promoting the development of a new generation of vascular grafts/stents enabling rapid endothelialization, this stage-specific cell-manipulation platform also holds promise in various biomedical fields, since the needs for stepwise control over different cell functions are common in wound healing and various tissue-regeneration processes.

关键词： biomaterials tissue engineering shape-memory polymer topographical conversion endothelialization

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In vivo degradation and endothelialization of an iron bioresorbable scaffold

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Bioactive Materials 2021年第4期6卷 1028-1039页

作者： Wenjiao Lin Hongjie Zhang Wanqian Zhang Haiping Qi Gui Zhang Jie Qian Xin Li Li Qin Haifeng Li Xiang Wang Hong Qiu Xiaoli Shi Wei Zheng Deyuan Zhang Runlin Gao Jiandong Ding College of Materials Science and Chemical Engineering Harbin Engineering UniversityHarbin 150001China Biotyx Medical(Shenzhen)Co. LtdShenzhen 518109China State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai 200438China Shenzhen Advanced Medical Services Co. LtdShenzhen518000GuangdongChina Department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Key Laboratory of Advanced Technology for Materials of Education Ministry School of Materials Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Detection of in vivo biodegradation is critical for development of next-generation medical devices such as bioresorbable stents or scaffolds(BRSs).In particular,it is urgent to establish a nondestructive approach to examine in vivo degradation of a new-generation coronary stent for interventional treatment based on mammal experiments;otherwise it is not available to semi-quantitatively monitor biodegradation in any clinical trial.Herein,we put forward a semi-quantitative approach to measure degradation of a sirolimus-eluting iron bioresorbable scaffold(IBS)based on optical coherence tomography(OCT)images;this approach was confirmed to be consistent with the present weight-loss measurements,which is,however,a destructive approach.The IBS was fabricated by a metal-polymer composite technique with a polylactide coating on an iron stent.The efficacy as a coronary stent of this new bioresorbable scaffold was compared with that of a permanent metal stent with the name of trade mark Xience,which has been widely used in clinic.The endothelial coverage on IBS was found to be greater than on Xience after implantation in a rabbit model;and our well-designed ultrathin stent exhibited less individual variation.We further examined degradation of the IBSs in both minipig coronary artery and rabbit abdominal aorta models.The present result indicated much faster iron degradation of IBS in the rabbit model than in the porcine model.The semi-quantitative approach to detect biodegradation of IBS and the finding of the species difference might be stimulating for fundamental investigation of biodegradable implants and clinical translation of the next-generation coronary stents.

关键词： Iron bioresorbable scaffold Species difference endothelialization In vivo biodegradation Optical coherence tomography

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Preparation and endothelialization of Multi-level Vessel-like Network in Enzymated Gelatin Scaffolds

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Journal of Bionic Engineering 2018年第4期15卷 673-681页

作者： Guirong Dong Qin Lian Laixia Yang Wei Mao Shiyang Liu Chao Xu School of Mechanical Engineering Xi' an University of Science and Technology Xi' an 710054 China Faculty of Higher Vocational and Technical Education Xi' an University of Technology Xi' an 710082 China State Key Laboratory for Manufacturing Systems Engineering Xi' an Jiao Tong University Xi' an 710049 China

Loss of function of large tissues is an urgent clinical problem. Although the artificial microfluidic network fabricated in large tis- sue-engineered constructs has great promise, it is still difficult to develop an efficient vessel-like design to meet the requirements of the biomimetic vascular network for tissue engineering applications. In this study, we used a facile approach to fabricate a branched and multi-level vessel-like network in a large muscle scaffolds by combining stereolithography （SL） technology and enzymatic crosslinking mechanism. The morphology of microchannel cross-sections was characterized using micro-computed tomography. The square cross-sections were gradually changed to a seamless circular microfluidic network, which is similar to the natural blood vessel. In the different micro-channels, the velocity greatly affected the attachment and spread of Human Umbilical Vein Endothelial Cell （HUVEC）-Green Fluorescent Protein （GFP）. Our study demonstrated that the branched and multi-level microchannel network simulates biomimetic microenvironments to promote endothelialization. The gelatin scaffolds in the circular vessel-like networks will likely support myoblast and surrounding tissue for clinical use.

关键词： large-size scaffolds vascular network enzymaticaUy gelatin hydrogel endothelialization muscle tissue engineering

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A biomimetic basementmembrane consisted of hybrid aligned nanofibers andmicrofibers with immobilized collagen IV and laminin for rapid endothelialization

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Bio-Design and Manufacturing 2021年第2期4卷 171-189页

作者： Chenglong Yu Guoping Guan Stefanie Glas Lu Wang Zhutong Li Lih-Sheng Turng Key Laboratory of Textile Industry for Biomedical Textile Materials and Technology College of TextilesDonghua University2999 North Renmin RoadSongjiang DistrictShanghai 201620China Engineering Research Center of Technical Textiles of Ministry of Education College of TextilesDonghua UniversityShanghai 201620China Wisconsin Institute for Discovery University of Wisconsin-Madison330 North Orchard StreetMadisonWI 53715USA Department of Mechanical Engineering University of Wisconsin-Madison1513 University AveMadisonWI 53706USA

Rapid formation of a continuous endothelial cell(EC)monolayer with healthy endothelium function on the luminal surface of vascular implants is imperative to improve the longtime patency of small-diameter vascular implants.In the present study,we combined the contact guidance effects of aligned nanofibers,which enhance EC adhesion and proliferation because of its similar fiber scale with native vascular basement membranes,and aligned microfibers,which could induce EC elongation effectively and allow ECs infiltration.It was followed by successive immobilization of collagen IV and laminin to fabricate a biomimetic basement membrane(BBM)with structural and compositional biomimicry.The hemolysis assay and platelet adhesion results showed that the BBM exhibited excellent hemocompatibility.Meanwhile,the adhered human umbilical vein endothelial cells(HUVECs)onto theBBMaligned along the orientation of the microfibers with an elongated morphology,and the data demonstrated that the BBM showed favorable effects on EC attachment,proliferation,and viability.The oriented EC monolayer formed on the BBM exhibited improved antithrombotic capability as indicated by higher production of nitric oxide and prostacyclin(PGI2).Furthermore,fluorescence images indicated that HUVECs could infiltrate into the BBM,implying theBBM’s ability to enhance transmural endothelialization.Hence,theBBMpossessed the properties to regulate ECbehaviors and allow transmural ingrowth,demonstrating the potential to be applied as the luminal surface of small-diameter vascular implants for rapid endothelialization.

关键词： Biomimetic basement membranes Aligned electrospun fibers Surface modification endothelialization Anti-thrombogenicity Transmural ingrowth

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