The mechanical properties of tissue-engineered heart valves still need to be improved to enable their implantation in the systemic circulation. The aim of this study is to develop a tissue-engineered valve for the aortic position - the BioTexValve - by exploiting a bio-inspired composite textile scaffold to confer native-like mechanical strength and anisotropy to the leaflets. This is achieved by multifilament fibers arranged similarly to the collagen bundles in the native aortic leaflet, fixed by a thin electrospun layer directly deposited on the pattern. The textile-based leaflets are positioned into a 3D mould where the components to form a fibrin gel containing human vascular smooth muscle cells are introduced. Upon fibrin polymerization, a complete valve is obtained. After 21 d of maturation by static and dynamic stimulation in a custom-made bioreactor, the valve shows excellent functionality under aortic pressure and flow conditions, as demonstrated by hydrodynamic tests performed according to ISO standards in a mock circulation system. The leaflets possess remarkable burst strength (1086 mmHg) while remaining pliable; pronounced extracellular matrix production is revealed by immunohistochemistry and biochemical assay. This study demonstrates the potential of bio-inspired textile-reinforcement for the fabrication of functional tissue-engineered heart valves for the aortic position.

The biodegradable PLGA and PCL electro-spun scaffolds resulted in equal biocompatibility, while PMMA showed cytotoxicity. Only PLGA preserved hCEC morphology and consequently seems to be a promising candidate for TEEG construction.

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Electro-spinning is widely used in tissue-engineered applications mostly in form of non-woven structures. The development of e-spun yarn opens the door for textile fabrics which combine the micro to nanoscale dimension of electro-spun filaments with three-dimensional (3D) drapable textile fabrics. Therefore, the aim of the study was the implementation of a process for electro-spun yarns. Polylactic acid (PLA) and polyethylene glycol (PEG) were spun from chloroform solutions with varying PLA/PEG ratios (100:0, 90:10, 75:25 and 50:50). The yarn samples produced were analyzed regarding their morphology, tensile strength, water uptake and cytocompatibility. It was found that the yarn diameter decreased when the funnel collector rotation was increasd, however, the fiber diameter was not influenced. The tensile strength was also found to be dependent on the PEG content. While samples composed of 100% PLA showed a tensile strength of 2.5±0.7 cN/tex, the tensile strength increased with a decreasing PLA content (PLA 75%/PEG 25%) to 6.2±0.5 cN/tex. The variation of the PEG content also influenced the viscosity of the spinning solutions. The investigation of the cytocompatibility with endothelial cells was conducted for PLA/PEG 90:10 and 75:25 and indicated that the samples are cytocompatible.

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Introduction: Abdominal aortic aneurysms (AAAs) are associated with overall high mortality in case of rupture. Since the pathophysiology is unclear, no adequate pharmacological therapy exists. Smooth muscle cells (SMCs) dysfunction and extracellular matrix (ECM) degradation have been proposed as underlying causes. We investigated SMC spatial organization and SMC-ECM interactions in our novel 3-dimensional (3D) vascular model. We validated our model for future use by comparing it to existing 2-dimensional (2D) cell culture. Our model can be used for translational studies of SMC and their role in AAA pathophysiology. Materials and Methods: SMC isolated from the medial layer of were the aortic wall of controls and AAA patients seeded on electrospun poly-lactide- co-glycolide scaffolds and cultured for 5 weeks, after which endothelial cells (EC) are added. Cell morphology, orientation, mechanical properties and ECM production were quantified for validation and comparison between controls and patients. Results: We show that cultured SMC proliferate into multiple layers after 5 weeks in culture and produce ECM proteins, mimicking their behavior in the medial aortic layer. EC attach to multilayered SMC, mimicking layer interactions. The novel SMC model exhibits viscoelastic properties comparable to biological vessels; cytoskeletal organization increases during the 5 weeks in culture; increased cytoskeletal alignment and decreased ECM production indicate different organization of AAA patients’ cells compared with control. Conclusion: We present a valuable preclinical model of AAA constructed with patient specific cells with applications in both translational research and therapeutic developments. We observed SMC spatial reorganization in a time course of 5 weeks in our robust, patient-specific model of SMC–EC organization and ECM production.

Background Treatment and time goals for STEMI care are clearly defined in national and international guidelines. However, initiation of therapy relies in accurate diagnosis after first medical contact (FMC). Prehospital logistics with fast transfer to the next available 24/7 PCI-center can be challenging, especially in rural areas and for transfers across state-borders in Germany. Objective To analyze quality of STEMI care in a high volume PCI center serving a city and a large rural area with focus on EMS (emergency medical service) logistics. Two groups of patients admitted by EMS: (1) direct PCI-center admission vs. (2) secondary admission after transfer from a non-PCI hospital were compared. Methods Various administrative, procedural, therapeutic and clinical parameters were registered for each patient including timelines of acute treatment (tables). Inaccurate treatment delays were calculated as cumulative time in any prolongation in timely diagnosis or therapy after FMC. Results From 340 consecutive STEMI patients in or registry, 299 patients were transferred by EMS. Reperfusion therapy with PPCI was significantly delayed and required double of the time in patients secondary transferred from a non-PCI hospital (Contact-to-Balloon: 195.6±134.8 min vs. 99.6±45.3 min, p<0.001, table 1). An inaccurate delay in timely treatment (delay in correct diagnosis or deferred therapy) was determined in 45% of the patients transferred from non-PCI hospitals vs 26% of directly admitted patients (p=0.02, table 1). Accordingly, correct STEMI diagnosis was established by EMS physician prehospital only in 7.1% in the transfer group vs. 61.9% in the direct admission group (p<0.001, table 1). Our data suggest different reasons for STEMI patients falsely transferred to non-PCI hospitals: a) lower qualification of EMS personnel with ECG misinterpretation and/or false working diagnosis, b) inadequate prehospital logistics with transfer of patients to the next near-by hospital instead of next PCI-center, c) personal or system “thresholds” of EMS physicians in rural areas preventing a direct transfer to PCI-centers. Further analysis of the transfer group (table 2) showed even longer treatment times for patients transferred across state borders compared to transfers within a state (C2B: 264.8±142.2 vs. 143.7±107.0 min, p<0.05, table 2). Importantly, transfers across state borders were not associated with a longer absolute distance (km) to PCI center. However, a rescue helicopter was used for across-state transfers in one third of the cases. Conclusion Quality of acute STEMI care is significantly worse in rural areas predominantly due to suboptimal prehospital logistics and poor prehospital emergency care. Our data underline the importance to establish local STEMI networks irrespective of state borders with clearly defined prehospital transfer strategies, continuous medial education of EMS personnel and assessement of local quality of care.

Fragestellung 40 % aller klinisch relevanten Knieverletzungen sind Bandverletzungen, wovon 46 % das vordere Kreuzband betreffen. Synthetische Kreuzband-Rekonstruktionen haben sich nicht bewährt, daher werden intraartikuläre Rekonstruktion mit autologem Sehnenmaterial verwendet. Diese Methode birgt verschiedene Risiken. Über das Tissue Engineering könnten mit Hilfe textiler resorbierbarer Scaffolds und aus einer sehr kleinen Biopsie autologe Kreuzbandzellen isoliert, ausreichend vermehrt und autologe Kreuzband-Transplantate hergestellt werden. MethodenIm Rahmen eines komplexen Scaffold-Designs wurden resorbierbare Polymerfäden synthetischen Ursprungs (Poly(ɛ-caprolacton), Polydioxanon, Polylactid) mittels Sticktechnik zu einer mechanisch belastbaren drei-dimensionalen tri-phasigen Struktur verarbeitet, die den Aufbau des vorderen Kreuzbandes imitieren soll. Die biomimetrische Anpassung erfolgte über die Inkorporation einer geschäumten Kollagenmatrix. Durch einen angepassten Einfrierprozess des in das Scaffold eingebrachten Kollagens und anschließende Gefriertrocknung konnte ein Porengradient eingestellt werden. ErgebnisseDie physikalischen Eigenschaften sowie biomechanischen Kennwerte der zunächst unbesiedelten Scaffolds wurden im Vergleich zum Kaninchenmodell mittels mechanischer Prüfung, µ-CT und Rasterelektronenmikroskopie charakterisiert und geprüft, so dass eine für folgende in-vitro und in-vivo Studien geeignete Auswahl an Scaffoldparametern zur Verfügung steht. SchlussfolgerungenDie sticktechnische Herausforderung bestand in der Gewährleis-tung der Formstabilität der porösen 3-D-Struktur und der Imitation der biomechanischen Eigenschaften des natürlichen Kreuzbandes unter Berücksichtigung des hydrolytischen Abbaus des Scaffolds, wodurch die Auswahl der Fadenmaterialien sowie Stickmuster begrenzt war. Der Porengradient konnte für verschiedene Scaffold-Abschnitte so an die Zelltypen angepasst werden, dass dieser für eine anschließende Besiedlung in Cokultur förderlich erscheint. FragestellungDerzeit werden zur operativen Fixierung des rupturierten vorderen Kreuzbandes Interferenzschrauben aus Titan oder bioresorbierbaren Polymeren eingesetzt. Die Nachteile bei Polymeren sind häufig Fremdkörperreaktionen und Entzündungen der Synovialmembran. Magnesiumlegierungen sind eine vielversprechende Alternative, da diese bioresorbierbar sind und als biokompatibel gelten. Ziel dieser Studie war es, die Auswirkungen der Korrosionsprodukte der Magnesiumlegierung (MAGNEZIX ® , Syntellix AG) auf die Synovialmembran des Kniegelenks zu untersuchen. Aufbauend auf den Ergebnissen dieses Versuches wird in einer Folgestudie die Testung mit einer Interferenzschraube erfolgen. MethodenAls Versuchstiere dienten 36 weibliche Kaninchen der Rasse New Zealand White. Die Tiere wurden in 2 Implantatgruppen (Magnesium/Titan) mit jeweils 18 Tieren eingeteilt. Die beiden Gruppen wurden außerdem in 3 Untergruppen (1, 4, 12 Wochen Implantationszeit) unterteilt. Bei jedem Tier wurde in den linken Femur interkondylär ein Pin implantiert. Jeweils ...