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Zusammenfassung Hintergrund Perikard wird vielfältig als Biomaterial eingesetzt, insbesondere in der Herzchirurgie. Im Falle von xenogenem Gewebe sind Methoden zur Prozessierung für die klinische Anwendung unabdingbar. In dieser Arbeit wurden verschiedene Methoden zur Aufbereitung entwickelt, angewandt und systematisch verglichen. Material und Methoden Natives Rinderperikard wurde durch Glutaraldehyd (GA) fixiert oder dezellularisiert. Nach der Dezellularisierung erfolgte entweder eine Sterilisation (DEZ), oder es wurde eine Fixierung mit GA durchgeführt (DEZ-GA). Die Proben wurden hinsichtlich ihrer Struktur, Biomechanik und ihres DNA-Gehalts analysiert. Ebenso erfolgten die Evaluation des entwickelten Sterilisationsprotokolls sowie die Testung der Biokompatibilität durch statische und dynamische Besiedelung mit humanen Endothelzellen. Als Vergleichsgruppe standen industriell dezellularisierte und sterilisierte Rinder- (RPi) und Pferde-Perikard-Patchs (PPi) zur Verfügung. Ergebnisse Durch die Fixierung mit Glutaraldehyd konnten strukturelle Gewebeschäden und Zytotoxizität festgestellt werden. Die Proben zeigten keine zuverlässige Sterilität. Dahingegen waren DEZ-Proben nach der Dezellularisierung steril und wiesen eine signifikante Reduzierung des DNA-Gehalts auf. Proben der Gruppen RPi und PPi wiesen ebenfalls Sterilität auf; der DNA-Gehalt der RPi-Proben war im Vergleich aber höher. Die Biokompatibilität aller dezellularisierter Proben konnte durch Zelladhäsion von Endothelzellen bestätigt werden und wurde durch dynamische Konditionierung weiter optimiert. Schlussfolgerung Dezellularisierung zeigte sich als zu bevorzugendes Verfahren zur Prozessierung von Biomaterialien. Die Flusskonditionierung von Endothelzellen stellt eine gute Möglichkeit der Reendothelialisierung für Patchs dar. Im Allgemeinen ergab sich die Notwendigkeit eines standardisierten Protokolls zur Vorauswahl des tierischen Gewebes, das vor Prozessierungsmethoden angewandt wird.

Background: This project aims to develop a new concept in training pediatric cardiologists to meet the requirements of interventional cardiac catheterizations today in terms of complexity and importance. This newly developed hands-on training program is supposed to enable the acquisition of certain skills which are necessary when investigating and treating patients in a catheter laboratory. Methods: Based on anonymous CT-scans of pediatric patients’ digital 3D heart models with or without cardiac defects were developed and printed three-dimensionally in a flexible material visible under X-ray. Hands-on training courses were offered using models of a healthy heart and the most common congenital heart defects (CHD). An evaluation was performed by quantifying fluoroscopy times (FL-time) and a questionnaire. Results: The acceptance of theoretical and practical contents within the hands-on training was very positive. It was demonstrated that it is possible to master various steps of a diagnostic procedure and an intervention as well as to practice and repeat them independently which significantly reduced FL-time. The participants stated that the hands-on training led to more confidence in interventions on real patients. Conclusion: With the development of a training module using 3D-printed heart models, basic and advanced training in the field of diagnostic cardiac examinations as well as interventional therapies of CHD is possible. The learning effect for both, practical skills and theoretical understanding, was significant which underlines the importance of integrating such hands-on trainings on 3D heart models in education and practical training., Zielsetzung: Ziel dieses Projektes ist die Entwicklung eines neuen Aus- und Weiterbildungskonzepts in der Kinderkardiologie, um der zunehmenden Komplexität und dem Stellenwert interventioneller Eingriffe mittels Herzkatheter (HK) gerecht zu werden. Das neu entwickelte Hands-on Training soll den Erwerb entsprechender Fertigkeiten für die Durchführung der HK-Untersuchung an Patient*innen ermöglichen. Methodik: Basierend auf anonymisierten CT-Bildern von pädiatrischen Patient*innen wurden digitale 3D-Herzmodelle entwickelt und in einem flexiblen, unter Röntgenstrahlung sichtbaren Material dreidimensional ausgedruckt. Es fanden Hands-on Trainingskurse statt, bei denen Modelle eines gesunden Herzens sowie der häufigsten angeborenen Herzfehler (AHF) zum Einsatz kamen. Eine Evaluation erfolgte anhand der Quantifizierung von Durchleuchtungszeiten (DL-Zeit) und eines Fragebogens. Ergebnisse: Die Akzeptanz der theoretischen und praktischen Inhalte des Hands-on Trainings war sehr gut. Es hat sich gezeigt, dass sowohl das Erlernen diverser Schritte als auch selbstständiges Üben und Wiederholen und eine damit verbundene signifikante Verkürzung der benötigten DL-Zeit möglich sind. Die Teilnehmenden gaben an, dass das Hands-on Training zu mehr Sicherheit bei der Intervention an Patient*innen führen würde. Schlussfolgerung: Mit der Entwicklung eines Trainingsmoduls unter dem Einsatz 3D-gedruckter Herzmodelle sind Aus- und Weiterbildung im Bereich diagnostischer HK-Untersuchungen sowie interventioneller Therapien von AHF möglich. Der signifikante Lerneffekt sowohl für die praktischen Fähigkeiten als auch für das theoretische Verständnis spricht für die Integration des Simulationstrainings an 3D-Herzmodellen in Aus- und Weiterbildung.

Electrospinning has become a widely used technique in cardiovascular tissue engineering as it offers the possibility to create (micro-)fibrous scaffolds with adjustable properties. The aim of this study was to create multilayered scaffolds mimicking the architectural fiber characteristics of human heart valve leaflets using conductive 3D-printed collectors. Models of aortic valve cusps were created using commercial computer-aided design (CAD) software. Conductive polylactic acid was used to fabricate 3D-printed leaflet templates. These cusp negatives were integrated into a specifically designed, rotating electrospinning mandrel. Three layers of polyurethane were spun onto the collector, mimicking the fiber orientation of human heart valves. Surface and fiber structure was assessed with a scanning electron microscope (SEM). The application of fluorescent dye additionally permitted the microscopic visualization of the multilayered fiber structure. Tensile testing was performed to assess the biomechanical properties of the scaffolds. 3D-printing of essential parts for the electrospinning rig was possible in a short time for a low budget. The aortic valve cusps created following this protocol were three-layered, with a fiber diameter of 4.1 ± 1.6 µm. SEM imaging revealed an even distribution of fibers. Fluorescence microscopy revealed individual layers with differently aligned fibers, with each layer precisely reaching the desired fiber configuration. The produced scaffolds showed high tensile strength, especially along the direction of alignment. The printing files for the different collectors are available as Supplemental File 1, Supplemental File 2, Supplemental File 3, Supplemental File 4, and Supplemental File 5. With a highly specialized setup and workflow protocol, it is possible to mimic tissues with complex fiber structures over multiple layers. Spinning directly on 3D-printed collectors creates considerable flexibility in manufacturing 3D shapes at low production costs.

OBJECTIVES We evaluated the outcome of patients in cardiogenic shock receiving a paracorporeal pulsatile biventricular assist device as a bridge to transplantation. METHODS We performed a retrospective single-centre analysis of all patients who received a Berlin Heart Excor® at our institution between 2004 and 2019. RESULTS A total of 97 patients (90 adults, 7 paediatric) were analysed. Eighty-four patients were in Interagency Registry for Mechanically Assisted Circulatory Support level 1 (80 adults, 4 paediatric). Diagnoses were dilated cardiomyopathy (n = 41), ischaemic cardiomyopathy (n = 17) or myocardial infarction (n = 4), myocarditis (n = 15), restrictive cardiomyopathy (n = 2), graft failure after heart transplant (n = 7), postcardiotomy heart failure (n = 5), postpartum cardiomyopathy (n = 3), congenital heart disease (n = 1), valvular cardiomyopathy (n = 1) and toxic cardiomyopathy (n = 1). All patients were in biventricular heart failure and had secondary organ dysfunction. The mean duration of support was 63 days (0–487 days). There was a significant decrease in creatinine values after assist device implantation (from 1.83 ± 0.79 to 1.12 ± 0.67 mg/dl, P = 0.001) as well as a decrease in bilirubin values (from 3.94 ± 4.58 to 2.65 ± 3.61 mg/dl, P = 0.084). Cerebral stroke occurred in 16 patients, bleeding in 15 and infection in 13 patients. Forty-eight patients died on support, while 49 patients could be successfully bridged to transplantation. Thirty-day survival and 1-year survival were 70.1% and 41.2%, respectively. CONCLUSIONS A pulsatile biventricular assist device is a reasonable therapeutic option in cardiogenic shock, when immediate high cardiac output is necessary to rescue the already impaired kidney and liver function of the patient.

Transcatheter aortic valve implantation (TAVI) is a fast-growing, exciting field of invasive therapy. During the last years many innovations significantly improved this technique. However, the prostheses are still associated with drawbacks. The aim of this study was to create cell-seeded biohybrid aortic valves (BAVs) as an ideal implant by combination of assets of biological and artificial materials. Furthermore, the influence of TAVI procedure on tissue-engineered BAV was investigated. BAV (n=6) were designed with decellularized homograft cusps and polyurethane walls. They were seeded with fibroblasts and endothelial cells isolated from saphenous veins. Consecutively, BAV were conditioned under low pulsatile flow (500 mL/min) for 5 days in a specialized bioreactor. After conditioning, TAVI-simulation was performed. The procedure was concluded with re-perfusion of the BAV for 2 days at an increased pulsatile flow (1100 mL/min). Functionality was assessed by video-documentation. Samples were taken after each processing step and evaluated by scanning electron microscopy (SEM), immunohistochemical staining (IHC), and Live/Dead-assays. The designed BAV were fully functioning and displayed physiologic behavior. After cell seeding, static cultivation and first conditioning, confluent cell layers were observed in SEM. Additionally, IHC indicated the presence of endothelial cells and fibroblasts. A significant construction of extracellular matrix was detected after the conditioning phase. However, a large number of lethal cells were observed after crimping by Live/Dead staining. Analysis revealed that the cells while still being present directly after crimping were removed in subsequent perfusion. Extensive regions of damaged cell-layers were detected by SEM-analysis substantiating these findings. Furthermore, increased ICAM expression was detected after re-perfusion as manifestation of inflammatory reaction. The approach to generate biohybrid valves is promising. However, damages inflicted during the crimping process seem not to be immediately detectable. Due to severe impacts on seeded cells, the strategy of living TE valves for TAVI should be reconsidered.