Development and characterization of acellular porcine pulmonary valve scaffolds for tissue engineering.

Currently available replacement heart valves all have limitations. This study aimed to produce and characterize an acellular, biocompatible porcine pulmonary root conduit for reconstruction of the right ventricular outflow tract e.g. during Ross procedure. A process for the decellularization of porcine pulmonary roots was developed incorporating trypsin treatment of the adventitial surface of the scraped pulmonary artery and sequential treatment with: hypotonic Tris buffer (HTB; 10mM Tris pH 8.0, 0.1% (w/v) EDTA, 10KIU aprotinin), 0.1% (w/v) SDS in HTB, two cycles of DNase and RNase, and sterilisation with 0.1% (v/v) peracetic acid. Histology confirmed an absence of cells and retention of the gross histoarchitecture. Immunohistochemistry further confirmed cell removal and partial retention of the extra cellular matrix, but a loss of collagen type IV. DNA levels were reduced by more than 96 % throughout all regions of the acellular tissue and no functional genes were detected using PCR. Total collagen levels were retained but there was a significant loss of glycosaminoglycans following decellularization. The biomechanical, hydrodynamic and leaflet kinematics properties were minimally affected by the process. Both immunohistochemical labelling and antibody absorption assay confirmed a lack of α-gal epitopes in the acellular porcine pulmonary roots and in vitro biocompatibility studies indicated that acellular leaflets and pulmonary arteries were not cytotoxic. Overall the acellular porcine pulmonary roots have excellent potential for development of a tissue substitute for right ventricular out flow tract reconstruction e.g. during the Ross procedure

Poly(ethylmethacrylate-co-diethylaminoethyl acrylate) coating improves endothelial re-population, bio-mechanical and anti-thrombogenic properties of decellularized carotid arteries for blood vessel replacement

Decellularized vascular scaffolds are promising materials for vessel replacements. However, despite the natural origin of decellularized vessels, issues such as biomechanical incompatibility, immunogenicity risks and the hazards of thrombus formation, still need to be addressed. In this study, we coated decellularized vessels obtained from porcine carotid arteries with poly (ethylmethacrylate-co-diethylaminoethylacrylate) (8g7) with the purpose of improving endothelial coverage and minimizing platelet attachment while enhancing the mechanical properties of the decellularized vascular scaffolds. The polymer facilitated binding of endothelial cells (ECs) with high affinity and also induced endothelial cell capillary tube formation. In addition, platelets showed reduced adhesion on the polymer under flow conditions. Moreover, the coating of the decellularized arteries improved biomechanical properties by increasing its tensile strength and load. In addition, after 5 days in culture, ECs seeded on the luminal surface of 8g7-coated decellularized arteries showed good regeneration of the endothelium. Overall, this study shows that polymer coating of decellularized vessels provides a new strategy to improve re-endothelialization of vascular grafts, maintaining or enhancing mechanical properties while reducing the risk of thrombogenesis. These results could have potential applications in improving tissue-engineered vascular grafts for cardiovascular therapies with small caliber vessels

Heart Valve Tissue Engineering: Concepts, Approaches, Progress, and Challenges

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

Übersicht über gegenwärtige Strategien zur Reduktion der intraoperativen bakteriellen Kontamination von Op-Wunden

Surgical site infections are a mean topic in cardiac surgery, leading to a prolonged hospitalization, and substantially increased morbidity and mortality. One source of pathogens is the endogenous flora of the patient's skin, which can contaminate the surgical site. A number of preoperative skin care strategies are performed to reduce bacterial contamination like preoperative antiseptic showering, hair removal, antisepsis of the skin, adhesive barrier drapes, and antimicrobial prophylaxis. Furthermore we can also support the natural host defense by optimal intra-operative management of oxygen supply, normoglycemia, and temperature. Nevertheless we still have a number of patients, who develop a surgical site infection. Therefore new skin care strategies are introduced to reduce the contamination by the endogenous skin flora. We present the use of a new microbial sealant, InteguSeal®, which was evaluated in patients undergoing cardiac surgery. The preliminary results of this investigation showed a trend in surgical site infection reduction by the use of this new microbial sealant.Die Prävention postoperativer Wundinfektionen ist ein wichtiges Anliegen in der Herzchirurgie, weil diese mit erhöhter Morbidität, Mortalität und verlängerter Krankenhausverweildauer verbunden sind. Eine gesicherte Infektionsquelle ist die residente Hautflora des Patienten, die die Op-Wunde kontaminieren kann. Deshalb wird eine Reihe präoperativer Maßnahmen zur Reduktion der Hautflora durchgeführt wie antiseptisches Ganzkörperduschen, Haarentfernung, Hautantiseptik, Inzisionsfolien und Antibiotikaprophylaxe. Weiterhin kann die natürliche Wirtsabwehr durch optimale intraoperative Sauerstoffversorgung, adäquate Einstellung des Blutglukosespiegels und Gewährleistung der Normothermie für die Op-Dauer unterstützt werden. Weil trotzdem postoperative Wundinfektionen auftreten können, werden neue Strategien zur Vermeidung der intraoperativen Kontamination durch die Hautflora benötigt. Hierfür wurde als neue aussichtsreiche Möglichkeit InteguSeal® entwickelt und die Effektivität dieser Versiegelungsmethode im Bereich der Hautdurchtrennung bei Patienten mit herzchirurgischen Operationen untersucht. Die vorläufigen Ergebnisse zeigen den Trend einer Reduktion der Rate postoperativer Wundinfektionen