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Simon Philipp Hoerstrup - One of the best experts on this subject based on the ideXlab platform.
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Transcatheter tissue engineered Heart Valves.
Expert Review of Medical Devices, 2013Co-Authors: Maximilian Y. Emmert, Benedikt Weber, Volkmar Falk, Simon Philipp HoerstrupAbstract:Valvular Heart disease represents a leading cause of mortality worldwide. Transcatheter Heart valve replacement techniques have been recently introduced into the clinical routine expanding the treatment options for affected patients. However, despite this technical progress toward minimally invasive, transcatheter strategies, the available Heart valve prostheses for these techniques are bioprosthetic and associated with progressive degeneration. To overcome such limitations, the concept of Heart valve tissue engineering has been repeatedly suggested for future therapy concepts. Ideally, a clinically relevant Heart valve tissue engineering concept would combine minimally invasive strategies for both, living autologous valve generation as well as valve implantation. Therefore, merging transcatheter techniques with living tissue engineered Heart Valves into a trascatheter tissue engineered Heart valve concept could significantly improve current treatment options for patients suffering from valvular Heart disease. This report provides an overview on transcatheter tissue engineered Heart Valves and summarizes available pre-clinical data.
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Tissue engineering of Heart Valves
Comprehensive Biomaterials, 2011Co-Authors: Petra E. Dijkman, Simon Philipp Hoerstrup, Anita Anita Driessen-mol, Cvc Carlijn Bouten, Fpt Frank BaaijensAbstract:Heart valve disease is a significant cause of morbidity and mortality worldwide. Its spectrum ranges from congenital disorders, where Heart Valves are either absent or malformed, to dysfunctional Heart Valves due to infection or age-related structural changes. Current options of surgical Heart valve replacement are associated with several disadvantages. Mechanical Valves require lifelong anticoagulation therapy as they are associated with a significant risk of thromboembolism. Fixed biological xeno- or homografts suffer from structural dysfunction due to progressive tissue deterioration, causing limited durability. Contemporary clinically available valve prostheses basically represent nonviable structures and lack the potential to grow, repair, and remodel. Heart valve tissue engineering represents a promising scientific concept to overcome these limitations aiming at the fabrication of living autologous Heart Valves with a thromboresistant surface and a viable interstitium, revealing repair and remodeling capabilities. According to the in vitro tissue engineering concept, autologous cells are harvested and seeded onto three-dimensional matrices followed by biomimetic conditioning, enabling the development of the neo-Heart valve tissue. This chapter provides a detailed overview on the principles of in vitro as well as in vivo Heart valve tissue engineering, focusing in particular on different synthetic scaffold materials and available cell sources.
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autologous human tissue engineered Heart Valves prospects for systemic application
Circulation, 2006Co-Authors: Anita Mol, Cvc Carlijn Bouten, Fpt Frank Baaijens, Marcel C M Rutten, Niels J B Driessen, Gregor Zund, Simon Philipp HoerstrupAbstract:Background— Tissue engineering represents a promising approach for the development of living Heart valve replacements. In vivo animal studies of tissue-engineered autologous Heart Valves have focused on pulmonary valve replacements, leaving the challenge to tissue engineer Heart Valves suitable for systemic application using human cells. Methods and Results— Tissue-engineered human Heart Valves were analyzed up to 4 weeks and conditioning using bioreactors was compared with static culturing. Tissue formation and mechanical properties increased with time and when using conditioning. Organization of the tissue, in terms of anisotropic properties, increased when conditioning was dynamic in nature. Exposure of the Valves to physiological aortic valve flow demonstrated proper opening motion. Closure dynamics were suboptimal, most likely caused by the lower degree of anisotropy when compared with native aortic valve leaflets. Conclusions— This study presents autologous tissue-engineered Heart Valves based on human saphenous vein cells and a rapid degrading synthetic scaffold. Tissue properties and mechanical behavior might allow for use as living aortic valve replacements.
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Application of stereolithography for scaffold fabrication for tissue engineered Heart Valves
ASAIO Journal, 2002Co-Authors: Ralf Sodian, Tim Lueth, Harald Hausmann, Evich Vasil Prokopij Potapov, Matthias Loebe, Andreas Hein, Simon Philipp Hoerstrup, David P Martin, Roland HetzerAbstract:A crucial factor in tissue engineering of Heart Valves is the functional and physiologic scaffold design. In our current experiment, we describe a new fabrication technique for Heart valve scaffolds, derived from x-ray computed tomography data linked to the rapid prototyping technique of stereolithography. To recreate the complex anatomic structure of a human pulmonary and aortic homograft, we have used stereolithographic models derived from x-ray computed tomography and specific software (CP, Aachen, Germany). These stereolithographic models were used to generate biocompatible and biodegradable Heart valve scaffolds by a thermal processing technique. The scaffold forming polymer was a thermoplastic elastomer, a poly-4-hydroxybutyrate (P4HB) and a polyhydroxyoctanoate (PHOH) (Tepha, Inc., Cambridge, MA). We fabricated one human aortic root scaffold and one pulmonary Heart valve scaffold. Analysis of the Heart valve included functional testing in a pulsatile bioreactor under subphysiological and supraphysiological flow and pressure conditions. Using stereolithography, we were able to fabricate plastic models with accurate anatomy of a human valvular homograft. Moreover, we fabricated Heart valve scaffolds with a physiologic valve design, which included the sinus of Valsalva, and that resembled our reconstructed aortic root and pulmonary valve. One advantage of P4HB and PHOH was the ability to mold a complete trileaflet Heart valve scaffold from a stereolithographic model without the need for suturing. The Heart Valves were tested in a pulsatile bioreactor, and it was noted that the leaflets opened and closed synchronously under subphysiological and supraphysiological flow conditions. Our preliminary results suggest that the reproduction of complex anatomic structures by rapid prototyping techniques may be useful to fabricate custom made polymeric scaffolds for the tissue engineering of Heart Valves.
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functional living trileaflet Heart Valves grown in vitro
Circulation, 2000Co-Authors: Simon Philipp Hoerstrup, David P Martin, Ralf Sodian, Sabine Daebritz, Jun Wang, Emile A Bacha, Adrian M Moran, Kristine J Guleserian, Jason S SperlingAbstract:Background—Previous tissue engineering approaches to create Heart Valves have been limited by the structural immaturity and mechanical properties of the valve constructs. This study used an in vitro pulse duplicator system to provide a biomimetic environment during tissue formation to yield more mature implantable Heart Valves derived from autologous tissue. Methods and Results—Trileaflet Heart Valves were fabricated from novel bioabsorbable polymers and sequentially seeded with autologous ovine myofibroblasts and endothelial cells. The constructs were grown for 14 days in a pulse duplicator in vitro system under gradually increasing flow and pressure conditions. By use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and the valve constructs were implanted into 6 lambs (weight 19±2.8 kg). All animals had uneventful postoperative courses, and the Valves were explanted at 1 day and at 4, 6, 8, 16, and 20 weeks. Echocardiography demonstrated mobile functioning leaflets without stenosi...
Maximilian Y. Emmert - One of the best experts on this subject based on the ideXlab platform.
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next generation tissue engineered Heart Valves with repair remodelling and regeneration capacity
Nature Reviews Cardiology, 2020Co-Authors: Emanuela S Fioretta, Fpt Frank Baaijens, S.p. Hoerstrup, Volkmar Falk, Sarah E Motta, Valentina Lintas, Sandra S Loerakker, Kevin Kit Parker, Maximilian Y. EmmertAbstract:Valvular Heart disease is a major cause of morbidity and mortality worldwide. Surgical valve repair or replacement has been the standard of care for patients with valvular Heart disease for many decades, but transcatheter Heart valve therapy has revolutionized the field in the past 15 years. However, despite the tremendous technical evolution of transcatheter Heart Valves, to date, the clinically available Heart valve prostheses for surgical and transcatheter replacement have considerable limitations. The design of next-generation tissue-engineered Heart Valves (TEHVs) with repair, remodelling and regenerative capacity can address these limitations, and TEHVs could become a promising therapeutic alternative for patients with valvular disease. In this Review, we present a comprehensive overview of current clinically adopted Heart valve replacement options, with a focus on transcatheter prostheses. We discuss the various concepts of Heart valve tissue engineering underlying the design of next-generation TEHVs, focusing on off-the-shelf technologies. We also summarize the latest preclinical and clinical evidence for the use of these TEHVs and describe the current scientific, regulatory and clinical challenges associated with the safe and broad clinical translation of this technology. Next-generation tissue-engineered Heart Valves (TEHVs) are a promising therapeutic option for patients with valvular Heart disease. In this Review, Emmert and colleagues discuss the current Heart valve replacement options, describe the design of TEHVs and summarize the data from preclinical and clinical studies on the use of TEHVs.
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transcatheter implantation of homologous off the shelf tissue engineered Heart Valves with self repair capacity long term functionality and rapid in vivo remodeling in sheep
Journal of the American College of Cardiology, 2014Co-Authors: Anita Anita Driessenmol, Petra E. Dijkman, Maximilian Y. Emmert, Benedikt Weber, Laura Frese, Bart Sanders, Nikola Cesarovic, Michele Sidler, Jori Leenders, Rolf JenniAbstract:Objectives This study sought to evaluate long-term in vivo functionality, host cell repopulation, and remodeling of “off-the-shelf” tissue engineered transcatheter homologous Heart Valves. Background Transcatheter valve implantation has emerged as a valid alternative to conventional surgery, in particular for elderly high-risk patients. However, currently used bioprosthetic transcatheter Valves are prone to progressive dysfunctional degeneration, limiting their use in younger patients. To overcome these limitations, the concept of tissue engineered Heart Valves with self-repair capacity has been introduced as next-generation technology. Methods In vivo functionality, host cell repopulation, and matrix remodeling of homologous transcatheter tissue-engineered Heart Valves (TEHVs) was evaluated up to 24 weeks as pulmonary valve replacements (transapical access) in sheep (n = 12). As a control, tissue composition and structure were analyzed in identical not implanted TEHVs (n = 5). Results Transcatheter implantation was successful in all animals. Valve functionality was excellent displaying sufficient leaflet motion and coaptation with only minor paravalvular leakage in some animals. Mild central regurgitation was detected after 8 weeks, increasing to moderate after 24 weeks, correlating to a compromised leaflet coaptation. Mean and peak transvalvular pressure gradients were 4.4 ± 1.6 mm Hg and 9.7 ± 3.0 mm Hg, respectively. Significant matrix remodeling was observed in the entire valve and corresponded with the rate of host cell repopulation. Conclusions For the first time, the feasibility and long-term functionality of transcatheter-based homologous off-the-shelf tissue engineered Heart Valves are demonstrated in a relevant pre-clinical model. Such engineered Heart Valves may represent an interesting alternative to current prostheses because of their rapid cellular repopulation, tissue remodeling, and therewith self-repair capacity. The concept of homologous off-the-shelf tissue engineered Heart Valves may therefore substantially simplify previous tissue engineering concepts toward clinical translation.
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Transcatheter tissue engineered Heart Valves.
Expert Review of Medical Devices, 2013Co-Authors: Maximilian Y. Emmert, Benedikt Weber, Volkmar Falk, Simon Philipp HoerstrupAbstract:Valvular Heart disease represents a leading cause of mortality worldwide. Transcatheter Heart valve replacement techniques have been recently introduced into the clinical routine expanding the treatment options for affected patients. However, despite this technical progress toward minimally invasive, transcatheter strategies, the available Heart valve prostheses for these techniques are bioprosthetic and associated with progressive degeneration. To overcome such limitations, the concept of Heart valve tissue engineering has been repeatedly suggested for future therapy concepts. Ideally, a clinically relevant Heart valve tissue engineering concept would combine minimally invasive strategies for both, living autologous valve generation as well as valve implantation. Therefore, merging transcatheter techniques with living tissue engineered Heart Valves into a trascatheter tissue engineered Heart valve concept could significantly improve current treatment options for patients suffering from valvular Heart disease. This report provides an overview on transcatheter tissue engineered Heart Valves and summarizes available pre-clinical data.
S.p. Hoerstrup - One of the best experts on this subject based on the ideXlab platform.
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next generation tissue engineered Heart Valves with repair remodelling and regeneration capacity
Nature Reviews Cardiology, 2020Co-Authors: Emanuela S Fioretta, Fpt Frank Baaijens, S.p. Hoerstrup, Volkmar Falk, Sarah E Motta, Valentina Lintas, Sandra S Loerakker, Kevin Kit Parker, Maximilian Y. EmmertAbstract:Valvular Heart disease is a major cause of morbidity and mortality worldwide. Surgical valve repair or replacement has been the standard of care for patients with valvular Heart disease for many decades, but transcatheter Heart valve therapy has revolutionized the field in the past 15 years. However, despite the tremendous technical evolution of transcatheter Heart Valves, to date, the clinically available Heart valve prostheses for surgical and transcatheter replacement have considerable limitations. The design of next-generation tissue-engineered Heart Valves (TEHVs) with repair, remodelling and regenerative capacity can address these limitations, and TEHVs could become a promising therapeutic alternative for patients with valvular disease. In this Review, we present a comprehensive overview of current clinically adopted Heart valve replacement options, with a focus on transcatheter prostheses. We discuss the various concepts of Heart valve tissue engineering underlying the design of next-generation TEHVs, focusing on off-the-shelf technologies. We also summarize the latest preclinical and clinical evidence for the use of these TEHVs and describe the current scientific, regulatory and clinical challenges associated with the safe and broad clinical translation of this technology. Next-generation tissue-engineered Heart Valves (TEHVs) are a promising therapeutic option for patients with valvular Heart disease. In this Review, Emmert and colleagues discuss the current Heart valve replacement options, describe the design of TEHVs and summarize the data from preclinical and clinical studies on the use of TEHVs.
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6.15 Tissue Engineering of Heart Valves
Comprehensive Biomaterials II, 2017Co-Authors: B. Weber, S.p. HoerstrupAbstract:Heart valve disease is a significant cause of morbidity and mortality worldwide. Its spectrum ranges from congenital disorders, where Heart Valves are either absent or malformed, to dysfunctional Heart Valves due to infection or age-related structural changes. Current options of surgical Heart valve replacement are associated with several disadvantages. Mechanical Valves require lifelong anticoagulation therapy as they are associated with a significant risk of thromboembolism. Fixed biological xeno- or homografts suffer from structural dysfunction due to progressive tissue deterioration, causing limited durability. Contemporary clinically available valve prostheses basically represent nonviable structures and lack the potential to grow, repair, and remodel. Heart valve tissue engineering represents a promising scientific concept to overcome these limitations aiming at the fabrication of living autologous Heart Valves with a thromboresistant surface and a viable interstitium, revealing repair and remodeling capabilities. According to the in vitro tissue engineering concept, autologous cells are harvested and seeded onto three-dimensional matrices followed by biomimetic conditioning, enabling the development of the neo-Heart valve tissue. This chapter provides a detailed overview on the principles of in vitro as well as in vivo Heart valve tissue engineering, focusing in particular on different synthetic scaffold materials and available cell sources.
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Regenerating Heart Valves
Regenerating the Heart, 2011Co-Authors: Benedikt Weber, S.p. HoerstrupAbstract:Valvular Heart disease is a significant cause of morbidity and mortality worldwide. Current options for surgical Heart valve replacement are associated with several major disadvantages as clinically available valve prostheses represent nonviable structures and lack the potential to grow, repair, and remodel. Heart valve tissue engineering represents a promising scientific concept to overcome these limitations, aiming at the fabrication of living autologous Heart Valves with a thromboresistant surface and a viable interstitium with repair and remodeling capabilities. Following the in vitro tissue engineering concept, autologous cells are harvested and seeded onto three-dimensional matrices followed by biomimetic conditioning enabling the development of neo-Heart valve tissue. Here, we review the concept of both in vitro and in vivo Heart valve tissue engineering, focusing in particular on different synthetic scaffold materials and available cell sources for the fabrication of living autologous Heart valve substitutes.
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tissue engineering of functional trileaflet Heart Valves from human marrow stromal cells
Circulation, 2002Co-Authors: S.p. Hoerstrup, Ralf Sodian, Alexander Kadner, Serguei Melnitchouk, Andreas Trojan, Karim Eid, Jay Tracy, Jeroen Visjager, Stefan A Kolb, Jurg GrunenfelderAbstract:Background We previously demonstrated the successful tissue engineering and implantation of functioning autologous Heart Valves based on vascular-derived cells. Human marrow stromal cells (MSC) exhibit the potential to differentiate into multiple cell-lineages and can be easily obtained clinically. The feasibility of creating tissue engineered Heart Valves (TEHV) from MSC as an alternative cell source, and the impact of a biomimetic in vitro environment on tissue differentiation was investigated. Methods and Results Human MSC were isolated, expanded in culture, and characterized by flow-cytometry and immunohistochemistry. Trileaflet Heart Valves fabricated from rapidly bioabsorbable polymers were seeded with MSC and grown in vitro in a pulsatile-flow-bioreactor. Morphological characterization included histology and electron microscopy (EM). Extracellular matrix (ECM)-formation was analyzed by immunohistochemistry, ECM protein content (collagen, glycosaminoglycan) and cell proliferation (DNA) were biochemically quantified. Biomechanical evaluation was performed using Instron™. In all Valves synchronous opening and closing was observed in the bioreactor. Flow-cytometry of MSC pre-seeding was positive for ASMA, vimentin, negative for CD 31, LDL, CD 14. Histology of the TEHV-leaflets demonstrated viable tissue and ECM formation. EM demonstrated cell elements typical of viable, secretionally active myofibroblasts (actin/myosin filaments, collagen fibrils, elastin) and confluent, homogenous tissue surfaces. Collagen types I, III, ASMA, and vimentin were detected in the TEHV-leaflets. Mechanical properties of the TEHV-leaflets were comparable to native tissue. Conclusion Generation of functional TEHV from human MSC was feasible utilizing a biomimetic in vitro environment. The neo-tissue showed morphological features and mechanical properties of human native-Heart-valve tissue. The human MSC demonstrated characteristics of myofibroblast differentiation.
Ralf Sodian - One of the best experts on this subject based on the ideXlab platform.
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tissue engineering of functional trileaflet Heart Valves from human marrow stromal cells
Circulation, 2002Co-Authors: S.p. Hoerstrup, Ralf Sodian, Alexander Kadner, Serguei Melnitchouk, Andreas Trojan, Karim Eid, Jay Tracy, Jeroen Visjager, Stefan A Kolb, Jurg GrunenfelderAbstract:Background We previously demonstrated the successful tissue engineering and implantation of functioning autologous Heart Valves based on vascular-derived cells. Human marrow stromal cells (MSC) exhibit the potential to differentiate into multiple cell-lineages and can be easily obtained clinically. The feasibility of creating tissue engineered Heart Valves (TEHV) from MSC as an alternative cell source, and the impact of a biomimetic in vitro environment on tissue differentiation was investigated. Methods and Results Human MSC were isolated, expanded in culture, and characterized by flow-cytometry and immunohistochemistry. Trileaflet Heart Valves fabricated from rapidly bioabsorbable polymers were seeded with MSC and grown in vitro in a pulsatile-flow-bioreactor. Morphological characterization included histology and electron microscopy (EM). Extracellular matrix (ECM)-formation was analyzed by immunohistochemistry, ECM protein content (collagen, glycosaminoglycan) and cell proliferation (DNA) were biochemically quantified. Biomechanical evaluation was performed using Instron™. In all Valves synchronous opening and closing was observed in the bioreactor. Flow-cytometry of MSC pre-seeding was positive for ASMA, vimentin, negative for CD 31, LDL, CD 14. Histology of the TEHV-leaflets demonstrated viable tissue and ECM formation. EM demonstrated cell elements typical of viable, secretionally active myofibroblasts (actin/myosin filaments, collagen fibrils, elastin) and confluent, homogenous tissue surfaces. Collagen types I, III, ASMA, and vimentin were detected in the TEHV-leaflets. Mechanical properties of the TEHV-leaflets were comparable to native tissue. Conclusion Generation of functional TEHV from human MSC was feasible utilizing a biomimetic in vitro environment. The neo-tissue showed morphological features and mechanical properties of human native-Heart-valve tissue. The human MSC demonstrated characteristics of myofibroblast differentiation.
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Application of stereolithography for scaffold fabrication for tissue engineered Heart Valves
ASAIO Journal, 2002Co-Authors: Ralf Sodian, Tim Lueth, Harald Hausmann, Evich Vasil Prokopij Potapov, Matthias Loebe, Andreas Hein, Simon Philipp Hoerstrup, David P Martin, Roland HetzerAbstract:A crucial factor in tissue engineering of Heart Valves is the functional and physiologic scaffold design. In our current experiment, we describe a new fabrication technique for Heart valve scaffolds, derived from x-ray computed tomography data linked to the rapid prototyping technique of stereolithography. To recreate the complex anatomic structure of a human pulmonary and aortic homograft, we have used stereolithographic models derived from x-ray computed tomography and specific software (CP, Aachen, Germany). These stereolithographic models were used to generate biocompatible and biodegradable Heart valve scaffolds by a thermal processing technique. The scaffold forming polymer was a thermoplastic elastomer, a poly-4-hydroxybutyrate (P4HB) and a polyhydroxyoctanoate (PHOH) (Tepha, Inc., Cambridge, MA). We fabricated one human aortic root scaffold and one pulmonary Heart valve scaffold. Analysis of the Heart valve included functional testing in a pulsatile bioreactor under subphysiological and supraphysiological flow and pressure conditions. Using stereolithography, we were able to fabricate plastic models with accurate anatomy of a human valvular homograft. Moreover, we fabricated Heart valve scaffolds with a physiologic valve design, which included the sinus of Valsalva, and that resembled our reconstructed aortic root and pulmonary valve. One advantage of P4HB and PHOH was the ability to mold a complete trileaflet Heart valve scaffold from a stereolithographic model without the need for suturing. The Heart Valves were tested in a pulsatile bioreactor, and it was noted that the leaflets opened and closed synchronously under subphysiological and supraphysiological flow conditions. Our preliminary results suggest that the reproduction of complex anatomic structures by rapid prototyping techniques may be useful to fabricate custom made polymeric scaffolds for the tissue engineering of Heart Valves.
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functional living trileaflet Heart Valves grown in vitro
Circulation, 2000Co-Authors: Simon Philipp Hoerstrup, David P Martin, Ralf Sodian, Sabine Daebritz, Jun Wang, Emile A Bacha, Adrian M Moran, Kristine J Guleserian, Jason S SperlingAbstract:Background—Previous tissue engineering approaches to create Heart Valves have been limited by the structural immaturity and mechanical properties of the valve constructs. This study used an in vitro pulse duplicator system to provide a biomimetic environment during tissue formation to yield more mature implantable Heart Valves derived from autologous tissue. Methods and Results—Trileaflet Heart Valves were fabricated from novel bioabsorbable polymers and sequentially seeded with autologous ovine myofibroblasts and endothelial cells. The constructs were grown for 14 days in a pulse duplicator in vitro system under gradually increasing flow and pressure conditions. By use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and the valve constructs were implanted into 6 lambs (weight 19±2.8 kg). All animals had uneventful postoperative courses, and the Valves were explanted at 1 day and at 4, 6, 8, 16, and 20 weeks. Echocardiography demonstrated mobile functioning leaflets without stenosi...
Fpt Frank Baaijens - One of the best experts on this subject based on the ideXlab platform.
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next generation tissue engineered Heart Valves with repair remodelling and regeneration capacity
Nature Reviews Cardiology, 2020Co-Authors: Emanuela S Fioretta, Fpt Frank Baaijens, S.p. Hoerstrup, Volkmar Falk, Sarah E Motta, Valentina Lintas, Sandra S Loerakker, Kevin Kit Parker, Maximilian Y. EmmertAbstract:Valvular Heart disease is a major cause of morbidity and mortality worldwide. Surgical valve repair or replacement has been the standard of care for patients with valvular Heart disease for many decades, but transcatheter Heart valve therapy has revolutionized the field in the past 15 years. However, despite the tremendous technical evolution of transcatheter Heart Valves, to date, the clinically available Heart valve prostheses for surgical and transcatheter replacement have considerable limitations. The design of next-generation tissue-engineered Heart Valves (TEHVs) with repair, remodelling and regenerative capacity can address these limitations, and TEHVs could become a promising therapeutic alternative for patients with valvular disease. In this Review, we present a comprehensive overview of current clinically adopted Heart valve replacement options, with a focus on transcatheter prostheses. We discuss the various concepts of Heart valve tissue engineering underlying the design of next-generation TEHVs, focusing on off-the-shelf technologies. We also summarize the latest preclinical and clinical evidence for the use of these TEHVs and describe the current scientific, regulatory and clinical challenges associated with the safe and broad clinical translation of this technology. Next-generation tissue-engineered Heart Valves (TEHVs) are a promising therapeutic option for patients with valvular Heart disease. In this Review, Emmert and colleagues discuss the current Heart valve replacement options, describe the design of TEHVs and summarize the data from preclinical and clinical studies on the use of TEHVs.
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Tissue engineering of Heart Valves
Comprehensive Biomaterials, 2011Co-Authors: Petra E. Dijkman, Simon Philipp Hoerstrup, Anita Anita Driessen-mol, Cvc Carlijn Bouten, Fpt Frank BaaijensAbstract:Heart valve disease is a significant cause of morbidity and mortality worldwide. Its spectrum ranges from congenital disorders, where Heart Valves are either absent or malformed, to dysfunctional Heart Valves due to infection or age-related structural changes. Current options of surgical Heart valve replacement are associated with several disadvantages. Mechanical Valves require lifelong anticoagulation therapy as they are associated with a significant risk of thromboembolism. Fixed biological xeno- or homografts suffer from structural dysfunction due to progressive tissue deterioration, causing limited durability. Contemporary clinically available valve prostheses basically represent nonviable structures and lack the potential to grow, repair, and remodel. Heart valve tissue engineering represents a promising scientific concept to overcome these limitations aiming at the fabrication of living autologous Heart Valves with a thromboresistant surface and a viable interstitium, revealing repair and remodeling capabilities. According to the in vitro tissue engineering concept, autologous cells are harvested and seeded onto three-dimensional matrices followed by biomimetic conditioning, enabling the development of the neo-Heart valve tissue. This chapter provides a detailed overview on the principles of in vitro as well as in vivo Heart valve tissue engineering, focusing in particular on different synthetic scaffold materials and available cell sources.
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autologous human tissue engineered Heart Valves prospects for systemic application
Circulation, 2006Co-Authors: Anita Mol, Cvc Carlijn Bouten, Fpt Frank Baaijens, Marcel C M Rutten, Niels J B Driessen, Gregor Zund, Simon Philipp HoerstrupAbstract:Background— Tissue engineering represents a promising approach for the development of living Heart valve replacements. In vivo animal studies of tissue-engineered autologous Heart Valves have focused on pulmonary valve replacements, leaving the challenge to tissue engineer Heart Valves suitable for systemic application using human cells. Methods and Results— Tissue-engineered human Heart Valves were analyzed up to 4 weeks and conditioning using bioreactors was compared with static culturing. Tissue formation and mechanical properties increased with time and when using conditioning. Organization of the tissue, in terms of anisotropic properties, increased when conditioning was dynamic in nature. Exposure of the Valves to physiological aortic valve flow demonstrated proper opening motion. Closure dynamics were suboptimal, most likely caused by the lower degree of anisotropy when compared with native aortic valve leaflets. Conclusions— This study presents autologous tissue-engineered Heart Valves based on human saphenous vein cells and a rapid degrading synthetic scaffold. Tissue properties and mechanical behavior might allow for use as living aortic valve replacements.
