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Recent progress in functional modification and crosslinking of bioprosthetic heart valves

Regenerative Biomaterials 2024年第1期3卷 1-16页

作者： Cheng Zheng Li Yang Yunbing Wang National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610064China

Valvular heart disease(VHD),clinically manifested as stenosis and regurgitation of native heart valve,is one of the most prevalent cardiovascular diseases with high mortality.heart valve replacement surgery has been recognized as golden standard for the treatment of VHD.Owing to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves(BHVs),implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of VHD.However,BHVs might fail within 10-15 years due to structural valvular degeneration(SVD),which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs,including cytotoxicity,calcification,component degradation,mechanical failure,thrombosis and immune response.To prolong the service life of BHVs,much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of SVD.In this review,we summarized and analyzed the research and progress on:(i)modification strategies based on glutaraldehyde crosslinked BHVs and(ii)nonglutaraldehyde crosslinking strategies for BHVs.

关键词： bioprosthetic heart valves modification crosslinking anticalcification antithrombosis

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Functional non-glutaraldehyde treated porcine pericardium for anti-coagulation,anti-calcification,and endothelial proliferation bioprosthetic heart valves

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Journal of Leather Science and Engineering 2022年第1期4卷 320-332页

作者： Xiaotong Chen Tao Yu Qunshou Kong Dajun Kuang Hong Xu Zhiyu Zhao Li Yang Gaocan Li Haojun Fan Yunbing Wang National Engineering Research Center of Clean Technology in Leather Industry Sichuan UniversityChengdu 610065China National Engineering Research Center for Biomaterials Sichuan UniversityChengdu 610065China Venus Medtech(Hangzhou)Inc. HangzhouChina.

In the last decade,the number of transcatheter heart valve replacement for severe heart valve disease has increased exponentially.Although the bioprosthetic artificial heart valve(BHV)has similar fluid dynamics performance to the original heart valve compared with mechanical heart valve so that there is no need to take long-term anticoagulant drugs to prevent thromboembolism,transcatheter BHV replacement are still at risk for thrombosis during the first few months according to the clinical data.However,the use of antithrombotic drugs can also increase the risk of bleeding.Therefore,it is particularly important to improve the anticoagulant properties for the BHV itself.In this work,a kind of non-glutaraldehyde cross-linked BHV material with excellent antithrombotic ability has been prepared from carboxylated oxazolidine treated porcine pericardium(consisting of collagen,elastin and glycoprotein)with the further graft of the anticoagulant heparin sodium via hydrophilic modified chitosan.Along with the similar mechanical properties and collagen stability comparable to the glutaraldehyde cross-linked porcine pericardium(PP),these functional non-glutaraldehyde cross-linked PPs exhibit better biocompatibility,promoted endothelial proliferation and superior anti-calcification ability.More importantly,excellent anticoagulant activity can be observed in the hematological experiments in vivo and in vitro.In summary,these excellent performances make these functional non-glutaraldehyde cross-linked PPs great potentialities in the BHV applications.

关键词： bioprosthetic heart valves Oxazolidine Cytocompatibility Anti-coagulation

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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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