Biofabrication of Sodium Alginate Hydrogel Scaffolds for Heart Valve Tissue Engineering (original) (raw)
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Design and Fabrication of Three-Dimensional Scaffolds for Tissue Engineering of Human Heart Valves
European Surgical Research, 2009
We developed a new fabrication technique for 3-dimensional scaffolds for tissue engineering of human heart valve tissue. A human aortic homograft was scanned with an X-ray computer tomograph. The data derived from the X-ray computed tomogram were processed by a computer-aided design program to reconstruct a human heart valve 3-dimensionally. Based on this stereolithographic model, a silicone valve model resembling a human aortic valve was generated. By taking advantage of the thermoplastic properties of polyglycolic acid as scaffold material, we molded a 3-dimensional scaffold for tissue engineering of human heart valves. The valve scaffold showed a deviation of only 8 3-4% in height, length and inner diameter compared with the homograft. The newly developed technique allows fabricating custom-made, patient-specific polymeric cardiovascular scaffolds for tissue engineering without requiring any suture materials.
Rapid manufacturing techniques for the tissue engineering of human heart valves
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 2014
Three-dimensional (3D) printing technologies have reached a level of quality that justifies considering rapid manufacturing for medical applications. Herein, we introduce a new approach using 3D printing to simplify and improve the fabrication of human heart valve scaffolds by tissue engineering (TE). Custom-made human heart valve scaffolds are to be fabricated on a selective laser-sintering 3D printer for subsequent seeding with vascular cells from human umbilical cords. The scaffolds will be produced from resorbable polymers that must feature a number of specific properties: the structure, i.e. particle granularity and shape, and thermic properties must be feasible for the printing process. They must be suitable for the cell-seeding process and at the same time should be resorbable. They must be applicable for implementation in the human body and flexible enough to support the full functionality of the valve. The research focuses mainly on the search for a suitable scaffold materi...
Fiber-reinforced hydrogel scaffolds for heart valve tissue engineering
Journal of Biomaterials Applications, 2014
Heart valve-related disorders are among the major causes of death worldwide. Although prosthetic valves are widely used to treat this pathology, current prosthetic grafts cannot grow with the patient while maintaining normal valve mechanical and hemodynamic properties. Tissue engineering may provide a possible solution to this issue through using biodegradable scaffolds and patients' own cells. Despite their similarity to heart valve tissue, most hydrogel scaffolds are not mechanically suitable for the dynamic stresses of the heart valve microenvironment. In this study, we integrated electrospun poly(glycerol sebacate) (PGS)-poly(ε-caprolactone) (PCL) microfiber scaffolds, which possess enhanced mechanical properties for heart valve engineering, within a hybrid hydrogel made from methacrylated hyaluronic acid and methacrylated gelatin. Sheep mitral valvular interstitial cells were encapsulated in the hydrogel and evaluated in hydrogel-only, PGS-PCL scaffold-only, and composite scaffold conditions. Although the cellular viability and metabolic activity were similar among all scaffold types, the presence of the hydrogel improved the three-dimensional distribution of mitral valvular interstitial cells. As seen by similar values in both the Young's modulus and the ultimate tensile strength between the PGS-PCL scaffolds and the composites, microfibrous scaffolds preserved their mechanical properties in the presence of the hydrogels. Compared to electrospun or hydrogel scaffolds alone, this combined system may provide a more suitable three-dimensional structure for generating scaffolds for heart valve tissue engineering.
Tissue engineering a functional aortic heart valve: an appraisal
Future Cardiology, 2005
Valvular heart disease is an important cause of morbidity and mortality, and currently available substitutes for failing hearts have serious limitations. A new promising alternative that may overcome these shortcomings is provided by the relatively new field of tissue engineering (TE). TE techniques involve the growth of autologous cells on a 3D matrix that can be a biodegradable polymer scaffold, or an acellular tissue matrix. These approaches provide the potential to create living matrix valve structures with an ability to grow, repair and remodel within the recipient. This article provides an appraisal of artificial heart valves and an overview of developments in TE that includes the current limitations and challenges for creating a fully functional valve. Biomaterials and stem cell technologies are now providing the potential for new avenues of research and if combined with advances in the rapid prototyping of biomaterials, the engineering of personalized, fully functional, and ...
Acta Biomaterialia, 2015
The development of advanced scaffolds that recapitulate the anisotropic mechanical behavior and biological functions of the extracellular matrix in leaflets would be transformative for heart valve tissue engineering. In this study, anisotropic mechanical properties were established in poly(ethylene glycol) (PEG) hydrogels by crosslinking stripes of 3.4 kDa PEG diacrylate (PEGDA) within 20 kDa PEGDA base hydrogels using a photolithographic patterning method. Varying the stripe width and spacing resulted in a tensile elastic modulus parallel to the stripes that was 4.1 to 6.8 times greater than that in the perpendicular direction, comparable to the degree of anisotropy between the circumferential and radial orientations in native valve leaflets. Biomimetic PEG-peptide hydrogels were prepared by tethering the cell-adhesive peptide RGDS and incorporating the collagenase-degradable peptide PQ (GGGPQG↓IWGQGK) into the polymer network. The specific amounts of RGDS and PEG-PQ within the resulting hydrogels influenced the elongation, de novo extracellular matrix deposition and hydrogel degradation behavior of encapsulated valvular interstitial cells (VICs). In addition, the morphology and activation of VICs grown atop PEG hydrogels could be modulated by controlling the concentration or micropatterning profile of PEG-RGDS. These results are promising for the fabrication of PEG-based hydrogels using anatomically and biologically inspired scaffold design features for heart valve tissue engineering.
Tissue engineering of heart valves – challenges and opportunities
2019
Background: Heart valve disease is a clinically serious condition. The replacement of damaged valves practiced since the 1950’s is the ultimate treatment for end-stage heart failure caused by severe valve dysfunction. The choice of adequate prosthesis is challenging. Unfortunately, the treatment options available today do not satisfy completely physicians and scientists’ needs. Mechanical valves require long-term anticoagulation therapy because of poor hemocompatibility. Biological substitutes have better hemodynamics, but need replacement in ~ 10 years due to calcification and degeneration. In order to overcome the shortcomings of current treatment options many researches are motivated to fabricate a functional, living heart valve replacement by tissue engineering. Conclusions: Tissue engineering is a promising approach that may lead novel constructs that will satisfy the need and overcome the limitations of current valve prosthetics. Scaffolds, fabricated from synthetic or biologi...
In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding
Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2014
In-body tissue architecture-a novel and practical regeneration medicine technology-can be used to prepare a completely autologous heart valve, based on the shape of a mold. In this study, a three-dimensional (3D) printer was used to produce the molds. A 3D printer can easily reproduce the 3D-shape and size of native heart valves within several processing hours. For a tri-leaflet, valved conduit with a sinus of Valsalva (Biovalve type VII), the mold was assembled using two conduit parts and three sinus parts produced by the 3D printer. Biovalves were generated from completely autologous connective tissue, containing collagen and fibroblasts, within 2 months following the subcutaneous embedding of the molds (success rate, 27/30). In vitro evaluation, using a pulsatile circulation circuit, showed excellent valvular function with a durability of at least 10 days. Interposed between two expanded polytetrafluoroethylene grafts, the Biovalves (N 5 3) were implanted in goats through an apicoaortic bypass procedure. Postoperative echocardiography showed smooth movement of the leaflets with minimal regurgitation under systemic circulation. After 1 month of implantation, smooth white leaflets were observed with minimal thrombus formation. Functional, autologous, 3D-shaped heart valves with clinical application potential were formed following in-body embedding of specially designed molds that were created within several hours by 3D printer. V C 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 1-11, 2015. . 2015. In-body tissue-engineered aortic valve (Biovalve type VII) architecture based on 3D printer molding. J Biomed Mater Res Part B 2015:103B:1-11. V C 2014 WILEY PERIODICALS, INC.
Heart Valve Tissue Engineering: Concepts, Approaches, Progress, and Challenges
Annals of Biomedical Engineering, 2006
Potential applications of tissue engineering in regenerative medicine range from structural tissues to organs with complex function. This review focuses on the engineering of heart valve tissue, a goal which involves a unique combination of biological, engineering, and technological hurdles. We emphasize basic concepts, approaches and methods, progress made, and remaining challenges. To provide a framework for understanding the enabling scientific principles, we first examine the elements and features of normal heart valve functional structure, biomechanics, development, maturation, remodeling, and response to injury. Following a discussion of the fundamental principles of tissue engineering applicable to heart valves, we examine three approaches to achieving the goal of an engineered tissue heart valve: (1) cell seeding of biodegradable synthetic scaffolds, (2) cell seeding of processed tissue scaffolds, and (3) in-vivo repopulation by circulating endogenous cells of implanted substrates without prior in-vitro cell seeding. Lastly, we analyze challenges to the field and suggest future directions for both preclinical and translational (clinical) studies that will be needed to address key regulatory issues for safety and efficacy of the application of tissue engineering and regenerative approaches to heart valves. Although modest progress has been made toward the goal of a clinically useful tissue engineered heart valve, further success and ultimate human benefit will be dependent upon advances in biodegradable polymers and other scaffolds, cellular manipulation, strategies for rebuilding the extracellular matrix, and techniques to characterize and potentially non-invasively assess the speed and quality of tissue healing and remodeling.
Strategies for development of decellularized heart valve scaffolds for tissue engineering
Biomaterials, 2022
Valvular heart diseases (VHDs) are currently treated using either mechanical or bioprosthetic heart valves. Unfortunately, mechanical valves require lifelong anticoagulation therapy, and bioprosthetic valves calcify and degrade over time, requiring subsequent valve replacement surgeries. Besides, both valves cannot grow with patients. Heart valve tissue engineering uses scaffolds as valve replacements with the potential to grow with patents, function indefinitely, and not require anticoagulation medication. These scaffolds provide threedimensional supports for cellular adhesion and growth, leading to tissue formation and, finally, a new functional heart valve development. Heart valve scaffolds are made of either polymeric materials or decellularized tissue obtained from allogeneic or xenogeneic sources. This review discusses processes for preparing decellularized heart valve scaffolds, including decellularization, crosslinking, surface-coating, and sterilization. We also examine the predominant issues in scaffold development. Further, decellularized heart valve scaffold function in vitro and in vivo is evaluated.
Romanian Journal of Cardiology, 2021
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 ...