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.
Background Regular use of sunbed exposure has been reported to increase 25-hydroxyvitamin-D3 25(OH)D serum levels. However, the influence of sunbeds compliant with the recent European Union standard ...EN-60335-2-27 on 25(OH)D serum levels is unknown. Objective We investigated the impact of standard sunbed use compliant with the European Union standard on 25(OH)D serum modulation and well-being. Methods In a randomized controlled study, 25(OH)D serum levels were measured at enrollment, after 1 week, and after completion of the 12-week period of sunbed use with twice weekly exposure and compared with the control group without any sunbed exposure. Results In the sunbed intervention group (N = 31), a 27% increase of mean 25(OH)D levels was noted 1 week after starting sunbed use ( P < .01). However, after 12 weeks, mean 25(OH)D levels had declined and were no longer different from baseline ( P = .06). After 12 weeks, 25(OH)D levels did not differ between the intervention and control group ( P = .36). Also the 5-item World Health Organization Well-Being Index score did not differ between the sunbed and control groups ( P = .19). Limitations For ethical reasons recruitment was limited to persons actively seeking sunbed exposure. Conclusions Standard use of sunbeds compliant with the European Union standard induced a transient increase of 25(OH)D levels, whereas no change in well-being was observed.
Venous valve aplasia (or valvular rarefication) is a rare cause of chronic venous insufficiency. In the present report, we have described the case of a 33-year-old man with severe symmetric lower leg ...edema and heaviness and pain in both lower legs. Duplex ultrasound demonstrated severe venous insufficiency in the superficial and deep venous system of both legs. Further imaging examinations supported the diagnosis of venous valvular aplasia. Treatment consisted of endovenous thermal ablation of the great saphenous vein and small saphenous vein as well as consistent compression therapy, resulting in a marked reduction of his leg edema, heaviness, and pain.
Objective Anesthetic preconditioning may contribute to the cardioprotective effects of sevoflurane in patients having coronary artery bypass surgery. We investigated whether 2 different sevoflurane ...administration protocols can induce preconditioning in patients having coronary artery bypass. Methods Thirty patients were randomly allocated to 1 of 3 groups. All patients received a total intravenous anesthesia with sufentanil (0.3 μg−1 · kg· h−1 ) and propofol as target controlled infusion (2.5 μg/mL). The control group had no further intervention; 10 minutes prior to establishing the extracorporeal circulation, patients of the sevoflurane-I group received 1 minimum alveolar concentration of sevoflurane for 5 minutes. Patients of the sevoflurane-II group received (2 times) 5 minutes of sevoflurane, interspersed by 5-minute washout 10 minutes prior to extracorporeal circulation. Troponin I was measured as marker of cardiac cellular damage. Results Peak levels of troponin I release were observed at 4 hours after cardiopulmonary bypass and were not affected by 1 cycle of sevoflurane administration (controls: 14 ± 3 ng/mL vs sevoflurane-I group, 14 ± 3 ng/mL). Two periods of sevoflurane preconditioning significantly reduced cellular damage compared with controls (peak troponin I level sevoflurane-II group, 7 ± 2 ng/mL). Conclusion These data show that sevoflurane-induced preconditioning is reproducible in patients having coronary artery bypass but depends on the preconditioning protocol used.
Objectives The aim of this study was to demonstrate the feasibility of combining the novel heart valve replacement technologies of: 1) tissue engineering; and 2) minimally-invasive implantation based ...on autologous cells and composite self-expandable biodegradable biomaterials. Background Minimally-invasive valve replacement procedures are rapidly evolving as alternative treatment option for patients with valvular heart disease. However, currently used valve substitutes are bioprosthetic and as such have limited durability. To overcome this limitation, tissue engineering technologies provide living autologous valve replacements with regeneration and growth potential. Methods Trileaflet heart valves fabricated from biodegradable synthetic scaffolds, integrated in self-expanding stents and seeded with autologous vascular or stem cells (bone marrow and peripheral blood), were generated in vitro using dynamic bioreactors. Subsequently, the tissue engineered heart valves (TEHV) were minimally-invasively implanted as pulmonary valve replacements in sheep. In vivo functionality was assessed by echocardiography and angiography up to 8 weeks. The tissue composition of explanted TEHV and corresponding control valves was analyzed. Results The transapical implantations were successful in all animals. The TEHV demonstrated in vivo functionality with mobile but thickened leaflets. Histology revealed layered neotissues with endothelialized surfaces. Quantitative extracellular matrix analysis at 8 weeks showed higher values for deoxyribonucleic acid, collagen, and glycosaminoglycans compared to native valves. Mechanical profiles demonstrated sufficient tissue strength, but less pliability independent of the cell source. Conclusions This study demonstrates the principal feasibility of merging tissue engineering and minimally-invasive valve replacement technologies. Using adult stem cells is successful, enabling minimally-invasive cell harvest. Thus, this new technology may enable a valid alternative to current bioprosthetic devices.
Objectives This study sought to investigate the combination of transcatheter aortic valve implantation and a novel concept of stem cell-based, tissue-engineered heart valves (TEHV) comprising ...minimally invasive techniques for both cell harvest and valve delivery. Background TAVI represents an emerging technology for the treatment of aortic valve disease. The used bioprostheses are inherently prone to calcific degeneration and recent evidence suggests even accelerated degeneration resulting from structural damage due to the crimping procedures. An autologous, living heart valve prosthesis with regeneration and repair capacities would overcome such limitations. Methods Within a 1-step intervention, trileaflet TEHV, generated from biodegradable synthetic scaffolds, were integrated into self-expanding nitinol stents, seeded with autologous bone marrow mononuclear cells, crimped and transapically delivered into adult sheep (n = 12). Planned follow-up was 4 h (Group A, n = 4), 48 h (Group B, n = 5) or 1 and 2 weeks (Group C, n = 3). TEHV functionality was assessed by fluoroscopy, echocardiography, and computed tomography. Post-mortem analysis was performed using histology, extracellular matrix analysis, and electron microscopy. Results Transapical implantation of TEHV was successful in all animals (n = 12). Follow-up was complete in all animals of Group A, three-fifths of Group B, and two-thirds of Group C (1 week, n = 1; 2 weeks, n = 1). Fluoroscopy and echocardiography displayed TEHV functionality demonstrating adequate leaflet mobility and coaptation. TEHV showed intact leaflet structures with well-defined cusps without signs of thrombus formation or structural damage. Histology and extracellular matrix displayed a high cellularity indicative for an early cellular remodeling and in-growth after 2 weeks. Conclusions We demonstrate the principal feasibility of a transcatheter, stem cell–based TEHV implantation into the aortic valve position within a 1-step intervention. Its long-term functionality proven, a stem cell–based TEHV approach may represent a next-generation heart valve concept.
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