Fabrication of Biomatrix/Polymer Hybrid Scaffold for Heart Valve Tissue Engineering in Vitro
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Decellularized extracellular matrix has been suggested as a scaffold for heart valve tissue engineering or direct implantation. However, cell removal impairs the physical properties of the valve leaflet structure and the biomechanical properties of the valve leaflet. Matrix/polymer hybrid scaffold with improved biomechanical characteristics may be advantageous. Mesenchymal stem cells were obtained from rats. Porcine aortic valve leaflets were decellularized enzymatically and coated with biodegradable poly-4-hydroxybutyrate using an electrospinning technique, reseeded and cultured over a time period of 14 days. The morphologic, biochemical, and biomechanical characteristics of hybrid scaffolds were tested. Morphologic and biochemical assays indicated that mesenchymal stem cells survive and proliferate on hybrid scaffolds, and control decellularized scaffolds revealed comparable amounts of cell mass, 4-hydroxyproline and collagen after cultured in vitro for 14 days. Mechanical testing indicated hybrid scaffolds had superior tensile strength and elastic modulus. Altogether this study demonstrates the feasibility and improved biomechanical characteristics of a novel hybrid heart valve leaflet scaffold for an application in tissue engineering.Keywords:
Decellularization
Hydroxyproline
Purpose To investigate the biological properties of decellularized porcine heart valve leaflets. Methods Specimens of porcine aortic valve leaflets were treated with Triton-X100,0.25% sodium deoxycholate and RNase and DNase.Then scanning electron microscopy and hematoxylin-eosin staining were examined.Its biomechanical characteristics were tested and soluble protein content was measured.The decellularized porcine heart valve leaflets were transplanted subcutaneously in rabbit for 12 weeks,the histology was examined. Results The heart valve leaflets were completely removed of the cell components and the construction of the valve was maintained.The biomechanical characteristics of decellularized valve leaflets and the fresh ones were almost similar.Soluble protein content was 365 μg/mL and 1632 μg/mL in decellularized and fresh groups.The immunogenicity of the decellularized valve leaflets were alleviated significantly compared with the fresh ones. Conclusions Decellularized porcine heart valve leaflets can be applied to develop tissue engineering heart valve as scaffold.
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Extracellular matrix (ECM) scaffolds are extensively used in tissue engineering studies and numerous clinical applications for tissue and organ reconstructions. Due to the global severe shortage of human tissues and organs, xenogeneic biomaterials are a common source for human tissue engineering and regenerative medicine applications. Traditional methods for decellularization often disrupt the 3D architecture and damage the structural integrity of the ECM scaffold. To efficiently obtain natural ECM scaffolds from animal tissues and organs with intact architecture, we have developed a platform decellularization process using supercritical CO2 and tested its potential application in tissue engineering. A combination of human mesenchymal stem cells with a decellularized dermal matrix scaffold allowed complete regeneration of skin structure in a porcine full-thickness wound model.
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Despite significant advances in the fabrication of bioengineered scaffolds for tissue engineering, delivery of nutrients in complex engineered human tissues remains a challenge. By taking advantage of the similarities in the vascular structure of plant and animal tissues, we developed decellularized plant tissue as a prevascularized scaffold for tissue engineering applications. Perfusion-based decellularization was modified for different plant species, providing different geometries of scaffolding. After decellularization, plant scaffolds remained patent and able to transport microparticles. Plant scaffolds were recellularized with human endothelial cells that colonized the inner surfaces of plant vasculature. Human mesenchymal stem cells and human pluripotent stem cell derived cardiomyocytes adhered to the outer surfaces of plant scaffolds. Cardiomyocytes demonstrated contractile function and calcium handling capabilities over the course of 21 days. These data demonstrate the potential of decellularized plants as scaffolds for tissue engineering, which could ultimately provide a cost-efficient, "green" technology for regenerating large volume vascularized tissue mass.
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Biomaterials have been used for a long time in the field of medicine. Since the success of "tissue engineering" pioneered by Langer and Vacanti in 1993, tissue engineering studies have advanced from simple tissue generation to whole organ generation with three-dimensional reconstruction. Decellularized scaffolds have been widely used in the field of reconstructive surgery because the tissues used to generate decellularized scaffolds can be easily harvested from animals or humans. When a patient's own cells can be seeded onto decellularized biomaterials, theoretically this will create immunocompatible organs generated from allo- or xeno-organs. The most important aspect of lung tissue engineering is that the delicate three-dimensional structure of the organ is maintained during the tissue engineering process. Therefore, organ decellularization has special advantages for lung tissue engineering where it is essential to maintain the extremely thin basement membrane in the alveoli. Since 2010, there have been many methodological developments in the decellularization and recellularization of lung scaffolds, which includes improvements in the decellularization protocols and the selection and preparation of seeding cells. However, early transplanted engineered lungs terminated in organ failure in a short period. Immature vasculature reconstruction is considered to be the main cause of engineered organ failure. Immature vasculature causes thrombus formation in the engineered lung. Successful reconstruction of a mature vasculature network would be a major breakthrough in achieving success in lung engineering. In order to regenerate the mature vasculature network, we need to remodel the vascular niche, especially the microvasculature, in the organ scaffold. This review highlights the reconstruction of the vascular niche in a decellularized lung scaffold. Because the vascular niche consists of endothelial cells, pericytes, extracellular matrix (ECM), and the epithelial-endothelial interface, all of which might affect the vascular tight junction, we discuss ECM composition and reconstruction, the contribution of endothelial cells and perivascular cells, the air-blood barrier function, and the effects of physiological factors during the lung microvasculature repair and engineering process. The goal of the present review is to confirm the possibility of success in lung microvascular engineering in whole organ engineering and explore the future direction of the current methodology.
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Tissue-engineered or decellularized heart valves have already been implanted in humans or are currently approaching the clinical setting. The aim of this study was to examine the migratory response of human monocytic cells toward decellularized porcine and human heart valves, a pivotal step in the early immunologic reaction.Porcine and human pulmonary valve conduits were decellularized, and migration of U-937 monocytic cells toward extracted heart valve proteins was examined in a transmigration chamber in vitro. Homogenized tissue specimens were size fractionated by SDS-PAGE. The decellularization procedure effectively reduced the migration of human monocytes toward all heart valve tissue. However, only the antigen reduction of human pulmonary valves abolished the monocytic response (wall, 0.88+/-0.19% versus 30.20+/-3.93% migrated cells [mean+/-SEM]; cusps, 0.10+/-0.06% versus 10.24+/-1.83%) and was significantly lower (P<0.05) than that of the decellularized porcine equivalent (wall, 5.03+/-0.14% versus 24.31+/-2.38%; cusps, 3.18+/-0.38% versus 10.24+/-1.83%). SDS-PAGE of the pulmonary heart valve tissue revealed that considerable amounts of proteins with different molecular weights that were not detected in the human equivalent remain in the decellularized porcine heart valve.We describe for the first time that the remaining potential of decellularized pulmonary heart valves to attract monocytic cells depends strongly on whether porcine or human scaffolds were used. These findings will have an important impact on further investigations in the field of heart valve tissue engineering.
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Abstract Decellularized extracellular matrix (ECM) scaffolds have been broadly used in tissue engineering because of their versatile bioactive nature and biomimetic properties. The ECM can be derived from various tissues, organs and cultured cells. A variety of decellularization methods have been developed to maximize the decellularization effect while minimizing the effect on ECM structures and compositions. The methods can be categorized into chemical, biological, and physical methods and their combinations. The properties and applications of ECM scaffolds are dependent on decellularization methods. This article summarizes the decellularization methods for preparation of decellularized ECM scaffolds for tissue engineering applications.
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