Fibrin gel combines a number of important properties of an ideal scaffold. It can be produced as a complete autologous scaffold. It is moldable and degradation is controllable by the use of aprotinin.
Autologous fibrin-based tissue-engineered heart valves have demonstrated excellent potential as patient-derived valve replacements. The present pilot study aims to evaluate the structure and mechanical durability of fibrin-based heart valves after implantation in a large-animal model (sheep). Tissue-engineered heart valves were molded using a fibrin scaffold and autologous arterial-derived cells before 28 days of mechanical conditioning. Conditioned valves were subsequently implanted in the pulmonary trunk of the same animals from which the cells were harvested. After 3 months in vivo, explanted valve conduits (n = 4) had remained intact and exhibited native tissue consistency, although leaflets demonstrated insufficiency because of tissue contraction. Routine histology showed remarkable tissue development and cell distribution, along with functional blood vessel ingrowth. A confluent monolayer of endothelial cells was present on the valve surface, as evidenced by scanning electron microscopy and positive von Willebrand factor staining. Immunohistochemistry and extracellular matrix (ECM) assay demonstrated complete resorption of the fibrin scaffold and replacement with ECM proteins. Transmission electron microscopy revealed mature collagen formation and viable, active resident tissue cells. The preliminary findings of implanted fibrin-based tissue-engineered heart valves are encouraging, with excellent tissue remodeling and structural durability after 3 months in vivo. The results from this pilot study highlight the potential for construction of completely "autologous" customized tissue-engineered heart valves based on a patient-derived fibrin scaffold.
The autograft principle results in postoperative long-term survival comparable with that of the age- and gender-matched general population and reoperation rates within the 1%/patient-year boundaries and should be considered in young, active patients who want to avoid the shortcomings of conventional prostheses.
Transvenous pacing in the pediatric population is associated with a lower acute stimulation threshold and a lower rate of lead-related complications. If epicardial pacing is necessary (e. g. small body weight, special intracardiac anatomy (e.g. Fontan), impossible access to superior caval vein), steroid-eluting leads may be considered.
Background-Current heart valve prostheses are constructed mimicking the native aortic valve. Special hemodynamic characteristics of the mitral valve such as a nonaxial central inflow with creation of a left ventricular vortex have so far not been taken into account. A new polycarbonaturethane (PCU) bileaflet heart valve prosthesis with special design for the mitral position is introduced, and results of animal testing are presented. Methods and Results-After in vitro testing, 7 PCU-prostheses and 7 commercial bioprostheses (Perimount, nϭ4; Mosaic, nϭ3) were implanted in mitral position into growing Jersey calves (age 3-5 months, weight 60 -97 kg) for 20 weeks. 2-Dimensional echocardiography was performed after implantation and before sacrification. Autopsy included histologic, radiographic, and electron microscopic examination of the valves. In vitro durability was proven for Ͼ15 years. After implantation 2-dimensional-echocardiography showed no relevant gradient or regurgitation of any prosthesis. Clinical course of the animals with PCU valves was excellent. In contrast, 5 of 7 calves with bioprostheses were sacrificed after 1-9 weeks because of congestive heart failure. 2-Dimensional echocardiography of the PCU valves after 20 weeks showed mild leaflet thickening with trivial regurgitation; mean gradient was 8.1Ϯ5.0 mm Hg (weight: 160 -170 kg). The explanted PCU prostheses revealed mild calcification and no structural degeneration. All of the Perimount bioprostheses were severely calcified and degenerated after 11Ϯ7 weeks. One Mosaic bioprosthesis was thrombosed after 1 week, and 2 showed severe and mild-to-moderate degeneration after 4 and 22 weeks, respectively.
Conclusions-Polycarbonaturethane
Small-caliber vascular grafts (< or =5 mm) constructed from synthetic materials for coronary bypass or peripheral vascular repair below the knee have poor patency rates, while autologous vessels may not be available for harvesting. The present study aimed to create a completely autologous small-caliber vascular graft by utilizing a bioabsorbable, macroporous poly(L/D)lactide 96/4 [P(L/D)LA 96/4] mesh as a support scaffold system combined with an autologous fibrin cell carrier material. A novel molding device was used to integrate a P(L/D)LA 96/4 mesh in the wall of a fibrin-based vascular graft, which was seeded with arterial smooth muscle cells (SMCs)/fibroblasts and subsequently lined with endothelial cells. The mold was connected to a bioreactor circuit for dynamic mechanical conditioning of the graft over a 21-day period. Graft cell phenotype, proliferation, extracellular matrix (ECM) content, and mechanical strength were analyzed. alpha-SMA-positive SMCs and fibroblasts deposited ECM proteins into the graft wall, with a significant increase in both cell number and collagen content over 21 days. A luminal endothelial cell lining was evidenced by vWf staining, while the grafts exhibited supraphysiological burst pressure (>460 mmHg) after dynamic cultivation. The results of our study demonstrated the successful production of an autologous, biodegradable small-caliber vascular graft in vitro, with remodeling capabilities and supraphysiological mechanical properties after 21 days in culture. The approach may be suitable for a variety of clinical applications, including coronary artery and peripheral artery bypass procedures.
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