Decellularized homograft for aortic valve replacement two years after lung transplantation

Cardiac valvular surgery in patients after lung transplantation is a challenging procedure, reports are scarce. We report a 29-year-old patient who underwent concomitant mitral valve reconstruction and implantation of a decellularized aortic homograft two years after bilateral lung transplantation.Cardiac valvular surgery in patients after lung transplantation is a challenging procedure, reports are scarce. We report a 29-year-old patient who underwent concomitant mitral valve reconstruction and implantation of a decellularized aortic homograft two years after bilateral lung transplantation

Removal of xenoantigenic glycosylation patterns from porcine pulmonary heart valve matrices is dependent of the applied decellularization method

Department of Cardiac-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Hannover Germany and Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany, The 6th International Medical Congress for Students and Young Doctors, May 12-14, 2016Introduction: Matrix guided tissue regeneration (GTR) based on allogeneic decellularized matrices has been shown as an overall convincing method for heart valve replacement. Nevertheless, a substantial donor shortage prevents an unlimited clinical application of human GTR-valves. Utilization of porcine decellularized heart valve matrices could offer a possible solution for overcoming this considerable limitation. In the past, implantation of xenogeneic valve tissues considered to be acellularinto human recipients, however, mostly lead to severe immune responses usually ending up into graft rejection. This study addresses the question whether potential xenoantigenic glycosylation of extracellular matrix components, like the major xenoantigen α-Gal, which served as model epitope for this study, can be removed by adjusted decellularization procedures. Materials and methods: Fresh porcine pulmonary heart valve conduits were decellularized by application of different detergent- and enzyme-based decellularization protocols. Subsequent cleavage of remaining matrix-related α-Gal epitopes was performed by enzymatic deglycosylation treatment on matrix samples of each decellularization group. Resulting tissues, mainly composed from insoluble extracellular matrix proteins, were afterwards divided into the relevant sections pulmonary artery wall specimens and pulmonary valve leaflets, frozen in liquid nitrogen, minced and finally solubilized by protease digestion. Evaluation of thus prepared solutions regarding to α-Gal contents was finally performed using a novel designed lectin-based immunoblot technique. Discussion results: Sole decellularization lead to significant removal of α-Gal, substantial varying in strong dependency to applied protocols between 30 to 50% compared to α-Gal contents of porcine native control tissues. An additional decrease of residual α-Gal in a range of another 15 to 30% was achievable by additional α-Galactosidase treatment. Combining decellularization and subsequent enzymatic digestion resulted in reductions of matrix related α-Gal contents down to levels, which could be measured for respective pulmonary valve tissues of α-Gal-KnockOut pigs. Conclusion: Residual xenoantigenic carbohydrates are detectable on insoluble matrix components of porcine pulmonary heart valves, substantially varying dependent on applied decellularization protocols. Combined with glycolytic digestions, remaining glycosylation contents are reducible to background levels. Impacts of these novel insights have to be evaluated in further in vitro as well as in vivo studies

Metabolic assessment of therapies for the development of drug-eluting stents

Metabolic assessment of therapies for the development of drug-eluting stent

Predictors of aneurysmal formation after surgical correction of aortic coarctation

AbstractObjectivesWe sought to identify the predictors of aneurysmal formation after surgical correction of aortic coarctation.BackgroundIn 9% of patients, aneurysms develop late after corrective surgery of coarctation of the aorta, with a 36% mortality rate if left untreated. However, the predictors of postsurgical aneurysmal formation are unknown.MethodsOf 25 aortic aneurysms requiring corrective surgery 152 ± 78 months after the initial coarctation repair, 8 were located in the ascending aorta (type A) and 17 at the site of previous repair (local type). Seventy-four patients without progression of the aortic diameter within 189 ± 71 months after coarctation repair were used for categorical data analysis in an attempt to identify the predictors of postsurgical aneurysmal formation.ResultsAdvanced age at coarctation repair (p = 0.004) and patch graft technique (p < 0.0005) independently predicted local aneurysmal formation. Type A aneurysm was univariately associated with the presence of a bicuspid aortic valve (p = 0.02), advanced age at coarctation repair (p = 0.044) and a high preoperative peak systolic pressure gradient of 74 ± 21 mm Hg (p = 0.041). Conversely, multivariate analysis confirmed only the presence of a bicuspid aortic valve (p = 0.015) as an independent predictor of type A aneurysm. Receiver operating characteristic curve analysis revealed that 72% of patients with a postsurgical aneurysm had an operation at age 13.5 years or more, whereas 69% with no postsurgical aneurysm had an operation at a younger age.ConclusionsUse of the patch graft technique and late correction of coarctation can predict aneurysmal formation at the site of coarctation repair, although patients with a bicuspid aortic valve may be at risk for an aneurysm developing in the ascending aorta, particularly after late repair of aortic coarctation with high preoperative pressure gradients

Decellularized tissue engineered pericardium as replacement for tricuspid valve in cardiac surgery

Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover Germany and Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Hannover, Germany, The 6th International Medical Congress for Students and Young Doctors, May 12-14, 2016Introduction: Tricuspid valve replacement is the last treatment choice in tricuspid valve pathology. The choice to insert mechanical or bioprosthetic valve remains controversial. Both prostheses have some limitations such as infection, risk of thromboembolism, need for life-long anticoagulation or limited durability. The following study aimed to develop a novel tissue-engineered tricuspid valve based on decellularized pericardium allograft. Materials and methods: Fresh ovine pericardium was harvested at the local slaughter house and decellularized using detergents. For disinfection all samples were treated for 24h with Phosphate Buffered Solution supplemented with 1% gentamicin and 1% streptomycin. The effectiveness of decellularization was evaluated by histological staining (hematoxylin-eosin, Movat’s Pentachrom and Van Gieson), Isolectin B4 staining (a-gal xenoantigen) and by DNA-quantification. Two valvular leaflets were manufactured out of decellularized pericardium and sutured ex-vivo into the tricuspid annulus of an ovine heart and suspended on papillary muscles. Hydraulic test were performed to prove valve competency. Discussion results: After detergent treatment pericardial tissue has been converted in a cell-free scaffold as proven by standard histological analysis. Immunofluorescent examinations revealed the absence of a-gal xenoantigens. DNA-quantification showed a substantial reduction in DNA content compared to the normal tissue. The alignment of collagenous fibers in decellularized scaffolds appeared well-preserved and was not affected by detergent decellularization procedure as proven by histological staining. Graft disinfection and storage in antibiotic solution after decellularization did not affect the texture of the scaffold. Furthermore, two leaflet structure created out of decellularized pericardium and surgically sutured in tricuspid position of ovine heart resulted in a competent valve prosthesis. Conclusion: The present results have shown successful decellularization of the ovine pericardium using detergents. Decellularized pericardial allograft can be used in cardiac surgery as a scaffold for valvular tissue engineering or for in-vivo guided tissue regeneration in tricuspid valve replacement

A European study on decellularized homografts for pulmonary valve replacement: initial results from the prospective ESPOIR Trial and ESPOIR Registry data\u2020

OBJECTIVES: Decellularized pulmonary homografts (DPH) have shown excellent results for pulmonary valve replacement. However, controlled multicentre studies are lacking to date.METHODS: Prospective European multicentre trial evaluating DPH for pulmonary valve replacement. Matched comparison of DPH to bovine jugular vein (BJV) conduits and cryopreserved homografts (CH) considering patient age, type of heart defect and previous procedures.RESULTS: In total, 121 patients (59 female) were prospectively enrolled (August 2014-December 2016), age 21.3 +/- 14.4 years, DPH diameter 24.4 +/- 2.8 mm. No adverse events occurred with respect to surgical handling; there were 2 early deaths (30 + 59 years) due to myocardial failure after multi-valve procedures and no late mortality (1.7% mortality). After a mean follow-up of 2.2 +/- 0.6 years, the primary efficacy end points mean peak gradient (16.1 +/- 12.1 mmHg) and regurgitation (mean 0.25 +/- 0.48, grade 0-3) were excellent. One reoperation was required for recurrent subvalvular stenosis caused by a pericardial patch and 1 balloon dilatation was performed on a previously stented LPA. 100% follow-up for DPH patients operated before or outside the trial (n = 114) included in the ESPOIR Registry, age 16.6 +/- 10.4 years, diameter 24.1 +/- 4.2 mm, follow-up 5.1 +/- 3.0 years. The combined DPH cohort, n = 235, comprising both Trial and Registry data showed significantly better freedom from explantation (DPH 96.7 +/- 2.1%, CH 84.4 +/- 3.2%, P = 0.029 and BJV 82.7 +/- 3.2%, P = 0.012) and less structural valve degeneration at 10 years when matched to CH, n = 235 and BJV, n = 235 (DPH 61.4 +/- 6.6%, CH 39.9 +/- 4.4%, n.s., BJV 47.5 +/- 4.5%, P = 0.029).CONCLUSIONS: Initial results of the prospective multicentre ESPOIR Trial showed DPH to be safe and efficient. Current DPH results including Registry data were superior to BJV and CH.Thoracic Surger

Intrapericardial migration of dislodged sternal struts as late complication of open pectus excavatum repairs

<p>Abstract</p> <p>We present a case of sternal steel strut dislodgement and migration in a patient undergoing Ravitch repair for pectus excavatum (PE) 37 years ago. Broken struts perforated the right ventricle and right ventricular outflow tract (RVOT) and additionally migrated into the left upper lobar bronchus.</p> <p>Dislodged sternal struts represent rare complications after surgical repair of patients suffering from pectus excavatum. Reviewing the literature, only five cases of intrapericardial migration of dislodged sternal struts or wires have been reported so far.</p> <p>In our case, the first strut was removed from the airways through a left antero-lateral thoracotomy. Using cardiopulmonary bypass, a second strut was removed via ventriculotomy. These life-threatening sequelae underscore the importance of postoperative follow-up and early removal of osteosynthetic materials used in open PE repair. Accurate preoperative localization of migrated materials and availability of CPB support are crucial for successful surgical removal.</p> <p>Introduction</p> <p>The migration of dislodged sternal steel struts or wires into the pericardium and cardiac cavities is a rare but life-threatening complication of open pectus excavatum (PE) repair <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. Removal of these materials poses a challenge for cardiothoracic surgeons. Herein, the authors report a case of migration of dislodged steel struts through the right ventricle and right ventricular outflow tract (RVOT) into the left upper lobar bronchus in a patient who underwent Ravitch repair 37 years ago.</p

Three-dimensional laser micro- and nano-structuring of acrylated poly(ethylene glycol) materials and evaluation of their cytoxicity for tissue engineering applications

The natural cell environment is characterised by complex three-dimensional structures, which contain features at multiple length scales. Many in vitro studies of cell behaviour in three dimensions rely on the availability of artificial scaffolds with controlled three-dimensional topologies. In this paper, we demonstrate fabrication of three-dimensional scaffolds for tissue engineering out of poly(ethylene glycol) diacrylate (PEGda) materials by means of two-photon polymerization (2PP). This laser nanostructuring approach offers unique possibilities for rapid manufacturing of three-dimensional structures with arbitrary geometries. The spatial resolution dependence on the applied irradiation parameters is investigated for two PEGda formulations, which are characterized by molecular weights of 302 and 742. We demonstrate that minimum feature sizes of 200 nm are obtained in both materials. In addition, an extensive study of the cytotoxicity of the material formulations with respect to photoinitiator type and photoinitiator concentration is undertaken. Aqueous extracts from photopolymerized PEGda samples indicate the presence of water-soluble molecules, which are toxic to fibroblasts. It is shown that sample aging in aqueous medium reduces the cytotoxicity of these extracts; this mechanism provides a route for biomedical applications of structures generated by 2PP microfabrication and photopolymerization technologies in general. Finally, a fully biocompatible combination of PEGda and a photoinitiator is identified. Fabrication of reproducible scaffold structures is very important for systematic investigation of cellular processes in three dimensions and for better understanding of in vitro tissue formation. The results of this work suggest that 2PP may be used to polymerize poly(ethylene glycol)-based materials into three-dimensional structures with well-defined geometries that mimic the physical and biological properties of native cell environments