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...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.展开更多
Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important ...Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important role in the replacement therapy of severe valvular heart disease,while their durability is limited by degeneration due to calcification,thrombus,endothelialization difficulty and prosthetic valve endocarditis.Herein,we develop a novel BHV,namely,TPly-BP,based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium(Glut-BP).Impressively,tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds,and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPIy-BP with good biocompatibility and hemocompatibility.Compared to Glut-BP,TPIy-BP showed significantly reduced cytotoxicity,improved endothelial cell adhesion,a low hemolysis ratio and obviously reduced platelet adhesion.Importantly,TPly-BP exhibited great antibacterial and in vivo anti-calcification ability,which was expected to improve the in vivo durability of BHVs.These results suggested that TPly-BP would be a potential candidate for BHV.展开更多
Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important ...Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important role in the replacement therapy of severe valvular heart disease,while their durability is limited by degeneration due to calcification,thrombus,endothelialization difficulty and prosthetic valve endocarditis.Herein,we develop a novel BHV,namely,TPly-BP,based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium(Glut-BP).Impressively,tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds,and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPly-BP with good biocompatibility and hemocompatibility.Compared to Glut-BP,TPly-BP showed significantly reduced cytotoxicity,improved endothelial cell adhesion,a low hemolysis ratio and obviously reduced platelet adhesion.Importantly,TPly-BP exhibited great antibacterial and in vivo anti-calcification ability,which was expected to improve the in vivo durability of BHVs.These results suggested that TPly-BP would be a potential candidate for BHV.展开更多
In the past decade,balloon-expandable percutaneous pulmonary valves have been developed and applied in clinical practice.However,all the existing products of pulmonary artery interventional valves in the market have a...In the past decade,balloon-expandable percutaneous pulmonary valves have been developed and applied in clinical practice.However,all the existing products of pulmonary artery interventional valves in the market have a straight structure design,and they require a preset support frame and balloon expansion.This shape design of the valve limits the application range.In addition,the age of the population with pulmonary artery disease is generally low,and the existing products cannot meet the needs of anti-calcification properties and valve material durability.In this study,through optimization of the support frame and leaflet design,a self-expanding pulmonary valve product with a double bell-shaped frame was designed to improve the match of the valve and the implantation site.A loading and deployment study showed that the biomaterial of the valve was not damaged after being compressed.Pulsatile flow and fatigue in vitro tests showed that the fabricated pulmonary valve met the hydrodynamic requirements after 2108 accelerated fatigue cycles.The safety and efficacy of the pulmonary valve product were demonstrated in studies of pulmonary valve implantation in 11 pigs.Angiography and echocardiography showed that the pulmonary valves were implanted in a good position,and they had normal closure and acceptable valvular regurgitation.The 180 days’implantation results showed that the calcium content was 0.31-1.39 mg/g in the anti-calcification treatment group,which was significantly lower than that in the control valve without anti-calcification treatment(16.69 mg/g).Our new interventional pulmonary valve product was ready for clinical trials and product registration.展开更多
基金supported by National Key Research and Development Programs(2022YFB3807303 and 2022YFB3807305),National Natural Science Foundation of China(32101107)and CAMS InnovationFundforMedical Sciences(2021-12M-5-013)。
文摘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.
基金supported by the National Natural Science Foundation of China(81970325 and 82170375)Key Research and Development Support Project of Science&Technology Department of Chengdu(2021-YF08-00121-GX)+3 种基金Post-Doctor Research Project,West China Hospital,Sichuan University(Grant No.20HXBH164 and 20HXBH105)Chinese Medical Association Cardiovascular Branch(CSC)Clinical Research Special Fund Project(CSCF2020B04)West China Hospital"1.3.5"Discipline of Excellence Project-"Percutaneous transcatheter aortic valve implantation""Mechanisms of aortic stenosis and the clinical applications"(ZYGD20002).
文摘Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important role in the replacement therapy of severe valvular heart disease,while their durability is limited by degeneration due to calcification,thrombus,endothelialization difficulty and prosthetic valve endocarditis.Herein,we develop a novel BHV,namely,TPly-BP,based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium(Glut-BP).Impressively,tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds,and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPIy-BP with good biocompatibility and hemocompatibility.Compared to Glut-BP,TPIy-BP showed significantly reduced cytotoxicity,improved endothelial cell adhesion,a low hemolysis ratio and obviously reduced platelet adhesion.Importantly,TPly-BP exhibited great antibacterial and in vivo anti-calcification ability,which was expected to improve the in vivo durability of BHVs.These results suggested that TPly-BP would be a potential candidate for BHV.
基金the National Natural Science Foundation of China(81970325 and 82170375)Key Research and Develop-ment Support Project of Science&Technology Department of Chengdu(2021-YF08-00121-GX)+2 种基金Post-Doctor Research Project,West China Hospital,Sichuan University(Grant No.20HXBH164 and 20HXBH105)Chinese Medical Association Cardiovascular Branch(CSC)Clinical Research Special Fund Project(CSCF2020B04)West China Hospital“1·3·5”Discipline of Excellence Project-“Percutaneous transcatheter aortic valve implantation”and“Mechanisms of aortic stenosis and the clinical applications”(ZYGD20002).
文摘Glutaraldehyde(Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves(BHV),which play an important role in the replacement therapy of severe valvular heart disease,while their durability is limited by degeneration due to calcification,thrombus,endothelialization difficulty and prosthetic valve endocarditis.Herein,we develop a novel BHV,namely,TPly-BP,based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium(Glut-BP).Impressively,tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds,and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPly-BP with good biocompatibility and hemocompatibility.Compared to Glut-BP,TPly-BP showed significantly reduced cytotoxicity,improved endothelial cell adhesion,a low hemolysis ratio and obviously reduced platelet adhesion.Importantly,TPly-BP exhibited great antibacterial and in vivo anti-calcification ability,which was expected to improve the in vivo durability of BHVs.These results suggested that TPly-BP would be a potential candidate for BHV.
基金supported by the National Key Research and Development Programs(SQ2019YFC110002).
文摘In the past decade,balloon-expandable percutaneous pulmonary valves have been developed and applied in clinical practice.However,all the existing products of pulmonary artery interventional valves in the market have a straight structure design,and they require a preset support frame and balloon expansion.This shape design of the valve limits the application range.In addition,the age of the population with pulmonary artery disease is generally low,and the existing products cannot meet the needs of anti-calcification properties and valve material durability.In this study,through optimization of the support frame and leaflet design,a self-expanding pulmonary valve product with a double bell-shaped frame was designed to improve the match of the valve and the implantation site.A loading and deployment study showed that the biomaterial of the valve was not damaged after being compressed.Pulsatile flow and fatigue in vitro tests showed that the fabricated pulmonary valve met the hydrodynamic requirements after 2108 accelerated fatigue cycles.The safety and efficacy of the pulmonary valve product were demonstrated in studies of pulmonary valve implantation in 11 pigs.Angiography and echocardiography showed that the pulmonary valves were implanted in a good position,and they had normal closure and acceptable valvular regurgitation.The 180 days’implantation results showed that the calcium content was 0.31-1.39 mg/g in the anti-calcification treatment group,which was significantly lower than that in the control valve without anti-calcification treatment(16.69 mg/g).Our new interventional pulmonary valve product was ready for clinical trials and product registration.