scholarly journals Tissue engineering of heart valves using decellularized xenogeneic or polymeric starter matrices

2007 ◽  
Vol 362 (1484) ◽  
pp. 1505-1512 ◽  
Author(s):  
Dörthe Schmidt ◽  
Ulrich A Stock ◽  
Simon P Hoerstrup
Keyword(s):  
Tissue Engineering ◽  
Heart Valve ◽  
Heart Valves ◽  
Heart Diseases ◽  
Polymeric Materials ◽  
Major Drawback ◽  
Valvular Heart Diseases ◽  
Future Challenges ◽  
End Stage

Heart valve replacement represents the most common surgical therapy for end-stage valvular heart diseases. A major drawback that all contemporary heart valve replacements have in common is the lack of growth, repair and remodelling capability. In order to overcome these limitations, the emerging new field of tissue engineering is focusing on the in vitro generation of functional, living heart valve replacements. The basic approach uses starter matrices either of decellularized xenogeneic or polymeric materials configured in the shape of the heart valve and subsequent cell seeding. This manuscript will give a detailed overview of these two concepts without giving favour to one or the other. The concluding discussion will focus on current limitations and studies as well as future challenges prior to safe clinical application.

Tissue Engineering of Pulmonary Heart Valves on Allogenic Acellular Matrix Conduits

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Gustav Steinhoff ◽  
Ulrich Stock ◽  
Najibulla Karim ◽  
Heike Mertsching ◽  
Adine Timke ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Endothelial Cells ◽  
Heart Valve ◽  
Heart Valves ◽  
Sheep Model ◽  
Control Valves ◽  
Acellular Matrix ◽  
Valve Tissue

Background —Tissue engineering using in vitro–cultivated autologous vascular wall cells is a new approach to biological heart valve replacement. In the present study, we analyzed a new concept to process allogenic acellular matrix scaffolds of pulmonary heart valves after in vitro seeding with the use of autologous cells in a sheep model. Methods and Results —Allogenic heart valve conduits were acellularized by a 48-hour trypsin/EDTA incubation to extract endothelial cells and myofibroblasts. The acellularization procedure resulted in an almost complete removal of cells. After that procedure, a static reseeding of the upper surface of the valve was performed sequentially with autologous myofibroblasts for 6 days and endothelial cells for 2 days, resulting in a patchy cellular restitution on the valve surface. The in vivo function was tested in a sheep model of orthotopic pulmonary valve conduit transplantation. Three of 4 unseeded control valves and 5 of 6 tissue-engineered valves showed normal function up to 3 months. Unseeded allogenic acellular control valves showed partial degeneration (2 of 4 valves) and no interstitial valve tissue reconstitution. Tissue-engineered valves showed complete histological restitution of valve tissue and confluent endothelial surface coverage in all cases. Immunohistological analysis revealed cellular reconstitution of endothelial cells (von Willebrand factor), myofibroblasts (α-actin), and matrix synthesis (procollagen I). There were histological signs of inflammatory reactions to subvalvar muscle leading to calcifications, but these were not found in valve and pulmonary artery tissue. Conclusions —The in vitro tissue-engineering approach using acellular matrix conduits leads to the in vivo reconstitution of viable heart valve tissue.

scholarly journals Tissue Engineering Heart Valves – a Review of More than Two Decades into Preclinical and Clinical Testing for Obtaining the Next Generation of Heart Valve Substitutes

2021 ◽  
Vol 31 (3) ◽  
pp. 501-510
Author(s):  
Dan SIMIONESCU ◽  
◽  
Marius Mihai HARPA ◽  
Codrut OPRITA ◽  
Ionela MOVILEANU ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Heart Valve ◽  
Heart Valves ◽  
Research Work ◽  
Heart Valve Disease ◽  
Next Generation ◽  
Clinical Scenarios ◽  
Mechanical Prostheses

Well documented shortcomings of current heart valve substitutes – biological and mechanical prostheses make them imperfect choices for patients diagnosed with heart valve disease, in need for a cardiac valve replacement. Regenerative Medicine and Tissue Engineering represent the research grounds of the next generation of valvular prostheses – Tissue Engineering Heart Valves (TEHV). Mimicking the structure and function of the native valves, TEHVs are three dimensional structures obtained in laboratories encompassing scaffolds (natural and synthetic), cells (stem cells and differentiated cells) and bioreactors. The literature stipulates two major heart valve regeneration paradigms, differing in the manner of autologous cells repopulation of the scaffolds; in vitro, or in vivo, respectively. During the past two decades, multidisciplinary both in vitro and in vitro research work was performed and published. In vivo experience comprises preclinical tests in experimental animal model and cautious limited clinical translation in patients. Despite initial encouraging results, translation of their usage in large clinical scenarios represents the most important challenge that needs to be overcome. This review purpose is to outline the most remarkable preclinical and clinical results of TEHV evaluation along with the lessons learnt from all this experience.

CORONARY ARTERY LESIONS IN PATIENTS OVER 50 YEAR OLD WITH VALVULAR HEART DISEASES INDICATED FOR VALVE SURGERY

2016 ◽  
pp. 20-24
Author(s):  
Bang Giap Vo ◽  
Anh Binh Ho ◽  
Van Minh Huynh
Keyword(s):  
Coronary Artery ◽  
Mitral Valve ◽  
Heart Valve ◽  
Right Coronary Artery ◽  
Heart Diseases ◽  
Heart Valve Diseases ◽  
Coronary Artery Lesions ◽  
Circumflex Coronary Artery ◽  
Valvular Heart Diseases ◽  
Valve Diseases

Objectives: To investigate the features of coronary artery lesions in patients over 50 with heart valve diseases and to find out the relationship between the levels of coronary artery lesions and heart valve diseases. Results: In patients over 50 year old with heart valve diseases, the rate of significant coronary artery lesions is 55.5%. In which, significant lesions in the group of both mitral and aorta valve diseases is 44.19%, only mitral valve diseases is of 70%, only aortic valve diseases is of 51.85%. There is a relationship between the severity of mitral valve diseases and right coronary artery lesions (OR 3.74: 1.64 to 8.5, p = 0.0017) and circumflex coronary artery lesions (OR 2.59: 1.16 to 5.75, p = 0.0192). The severity of heart valve lesions in significant coronary artery lesions group is higher than insignificant coronary artery lesions group or normal group. Conclusion: Coronary artery lesions is common in patients > 50 years old with heart valve diseases, there is a relationship between the severity of mitral valve diseases and and right coronary artery lesions and circumflex coronary artery lesions. Key words: coronary artery lesions, mitral valvediseases

scholarly journals MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets

2021 ◽  
Vol 22 (22) ◽  
pp. 12132
Author(s):  
Francesco Nappi ◽  
Adelaide Iervolino ◽  
Sanjeet Singh Avtaar Singh ◽  
Massimo Chello
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Heart Diseases ◽  
Osteoblastic Differentiation ◽  
New Drugs ◽  
Expression Vectors ◽  
Chordae Tendineae ◽  
Valvular Heart Diseases

miRNAs have recently attracted investigators’ interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors are comprised of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

scholarly journals Redox Polymers for Tissue Engineering

2021 ◽  
Vol 3 ◽  
Author(s):  
Binbin Z. Molino ◽  
Junji Fukuda ◽  
Paul J. Molino ◽  
Gordon G. Wallace
Keyword(s):  
Tissue Engineering ◽  
Conducting Polymers ◽  
Polymeric Materials ◽  
Redox Polymers ◽  
Design Synthesis ◽  
Materials Development ◽  
Biologically Relevant ◽  
Fundamental Properties

This review will focus on the targeted design, synthesis and application of redox polymers for use in regenerative medicine and tissue engineering. We define redox polymers to encompass a variety of polymeric materials, from the multifunctional conjugated conducting polymers to graphene and its derivatives, and have been adopted for use in the engineering of several types of stimulus responsive tissues. We will review the fundamental properties of organic conducting polymers (OCPs) and graphene, and how their properties are being tailored to enhance material - biological interfacing. We will highlight the recent development of high-resolution 3D fabrication processes suitable for biomaterials, and how the fabrication of intricate scaffolds at biologically relevant scales is providing exciting opportunities for the application of redox polymers for both in-vitro and in-vivo tissue engineering. We will discuss the application of OCPs in the controlled delivery of bioactive compounds, and the electrical and mechanical stimulation of cells to drive behaviour and processes towards the generation of specific functional tissue. We will highlight the relatively recent advances in the use of graphene and the exploitation of its physicochemical and electrical properties in tissue engineering. Finally, we will look forward at the future of organic conductors in tissue engineering applications, and where the combination of materials development and fabrication processes will next unite to provide future breakthroughs.

Tricuspid and pulmonary valve disease

2021 ◽  
pp. 211-221
Author(s):  
Denisa Muraru ◽  
Elif Leyla Sade
Keyword(s):  
Heart Valves ◽  
Pulmonary Valve ◽  
Multimodality Imaging ◽  
Heart Diseases ◽  
Imaging Modality ◽  
Valvular Heart Diseases ◽  
Alternative Modality ◽  
The Right ◽  
Transcatheter Interventions ◽  
Valve Diseases

Right heart valves have gained significant interest in the context of a plethora of new emerging percutaneous transcatheter interventions for treating tricuspid and pulmonary valve diseases. Multimodality imaging is pivotal for patient diagnosis, management, and prognosis, as well as for planning interventional and surgical valve procedures. Echocardiography is the primary imaging modality for initial diagnosis and longitudinal follow-up of patients with right-sided valvular heart disease. Cardiovascular magnetic resonance has emerged as a complementary or alternative modality for providing diagnostic information on the tricuspid and pulmonary valve anatomy, and particularly on the pulmonary artery and the consequences on the right ventricle. This chapter highlights the current use of various imaging modalities for the state-of-the-art assessment of right-sided valvular heart diseases, with emphasis on the main clinical indications, as well as on the strengths and limitations of each modality.

scholarly journals Hydrogels for Liver Tissue Engineering

2019 ◽  
Vol 6 (3) ◽  
pp. 59 ◽  
Author(s):  
Shicheng Ye ◽  
Jochem W.B. Boeter ◽  
Louis C. Penning ◽  
Bart Spee ◽  
Kerstin Schneeberger
Keyword(s):  
Tissue Engineering ◽  
Liver Tissue ◽  
Drug Testing ◽  
In Vitro Models ◽  
Liver Tissue Engineering ◽  
Synthetic Materials ◽  
Toxicological Studies ◽  
End Stage

Bioengineered livers are promising in vitro models for drug testing, toxicological studies, and as disease models, and might in the future be an alternative for donor organs to treat end-stage liver diseases. Liver tissue engineering (LTE) aims to construct liver models that are physiologically relevant. To make bioengineered livers, the two most important ingredients are hepatic cells and supportive materials such as hydrogels. In the past decades, dozens of hydrogels have been developed to act as supportive materials, and some have been used for in vitro models and formed functional liver constructs. However, currently none of the used hydrogels are suitable for in vivo transplantation. Here, the histology of the human liver and its relationship with LTE is introduced. After that, significant characteristics of hydrogels are described focusing on LTE. Then, both natural and synthetic materials utilized in hydrogels for LTE are reviewed individually. Finally, a conclusion is drawn on a comparison of the different hydrogels and their characteristics and ideal hydrogels are proposed to promote LTE.

scholarly journals Decellularized tissue-engineered heart valves calcification: what do animal and clinical studies tell us?

2020 ◽  
Vol 31 (12) ◽  
Author(s):  
Adel F. Badria ◽  
Petros G. Koutsoukos ◽  
Dimosthenis Mavrilas
Keyword(s):  
Heart Valve ◽  
Clinical Studies ◽  
Heart Valves ◽  
Early Stage ◽  
Anticoagulation Therapy ◽  
Complex Nature ◽  
In Silico Studies ◽  
Decellularized Tissue ◽  
Tissue Engineered Heart Valves

AbstractCardiovascular diseases are the first cause of death worldwide. Among different heart malfunctions, heart valve failure due to calcification is still a challenging problem. While drug-dependent treatment for the early stage calcification could slow down its progression, heart valve replacement is inevitable in the late stages. Currently, heart valve replacements involve mainly two types of substitutes: mechanical and biological heart valves. Despite their significant advantages in restoring the cardiac function, both types of valves suffered from serious drawbacks in the long term. On the one hand, the mechanical one showed non-physiological hemodynamics and the need for the chronic anticoagulation therapy. On the other hand, the biological one showed stenosis and/or regurgitation due to calcification. Nowadays, new promising heart valve substitutes have emerged, known as decellularized tissue-engineered heart valves (dTEHV). Decellularized tissues of different types have been widely tested in bioprosthetic and tissue-engineered valves because of their superior biomechanics, biocompatibility, and biomimetic material composition. Such advantages allow successful cell attachment, growth and function leading finally to a living regenerative valvular tissue in vivo. Yet, there are no comprehensive studies that are covering the performance of dTEHV scaffolds in terms of their efficiency for the calcification problem. In this review article, we sought to answer the question of whether decellularized heart valves calcify or not. Also, which factors make them calcify and which ones lower and/or prevent their calcification. In addition, the review discussed the possible mechanisms for dTEHV calcification in comparison to the calcification in the native and bioprosthetic heart valves. For this purpose, we did a retrospective study for all the published work of decellularized heart valves. Only animal and clinical studies were included in this review. Those animal and clinical studies were further subcategorized into 4 categories for each depending on the effect of decellularization on calcification. Due to the complex nature of calcification in heart valves, other in vitro and in silico studies were not included. Finally, we compared the different results and summed up all the solid findings of whether decellularized heart valves calcify or not. Based on our review, the selection of the proper heart valve tissue sources (no immunological provoking residues), decellularization technique (no damaged exposed residues of the decellularized tissues, no remnants of dead cells, no remnants of decellularizing agents) and implantation techniques (avoiding suturing during the surgical implantation) could provide a perfect anticalcification potential even without in vitro cell seeding or additional scaffold treatment.

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