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Valved allografts and xenografts for reconstruction of the right ventricular outflow tract (RVOT) lack durability and do not grow. We report the first clinical use of a completely bioabsorbable valved conduit (Xeltis pulmonary valve - XPV) in children. Twelve children (six male), median age five (two to twelve) years and median weight 17 (10 to 43) kg, underwent RVOT reconstruction with the XPV. Diagnoses were: pulmonary atresia with ventricular septal defect (VSD) (n = 4), tetralogy of Fallot (n = 4), common arterial trunk (n = 3), and transposition of the great arteries with VSD and pulmonary stenosis (n = 1). All had had previous surgery, including prior RVOT conduit implantation in six. Two diameters of conduit 16mm (n = 5) and 18mm (n = 7) were used. At 24 months none of the patients has required surgical re-intervention, 9 of the 12 are in NYHA functional class I and three patients in NYHA class II. None of the conduits has shown evidence of progressive stenosis, dilation or aneurysm formation. Residual peak gradient of >40 mm Hg was observed in three patients, caused by kinking of the conduit at implantation in 1 and distal stenosis in the peripheral pulmonary arteries in 2 patients. Five patients developed severe pulmonary valve insufficiency (PI); the most common mechanism was prolapse of at least one of the valve leaflets. The XPV conduit is a promising innovation for RVOT reconstruction. Progressive PI requires however an improved design (geometry, thickness) of the valve leaflets.

Background To present a 2-year follow-up regarding safety and hemodynamic performance of a new restorative vascular graft used as extracardiac cavo-pulmonary connection in patients with univentricular congenital heart malformations. Methods The graft was implanted in five patients (aged 4-12 years) as extracardiac connection between the inferior vena cava and the pulmonary artery. The conduit consists of a bioabsorbable polymer-based implant able to generate endogenous tissue restoration leading to a fully functional neo-vessel while the polymer progressively absorbs. All patients have reached more than 24 months following surgery and underwent echocardiography and magnetic resonance imaging. Results All patients are doing well at 24 months follow-up, with no graft-related serious adverse events. Transthoracic echocardiography demonstrated adequate function of the conduit in all patients while magnetic resonance imaging showed anatomical and functional stability of the restorative grafts. Conclusions The new restorative conduit has been successfully used for the second step of the Fontan procedure as extracardiac total cavopulmonary connection. The results are promising because they suggest that complete transformation of a bioabsorbable polymer and replacement through endogenous tissue may represent a major advantage in the treatment of congenital heart disease patients. Further monitoring will allow to evaluate the long-term behavior of this new graft, in terms of clinical and hemodynamic performance, thrombogenicity and ability to grow.

Synthetic polymers are widely used to fabricate porous scaffolds for the regeneration of cardiovascular tissues. To ensure mechanical integrity, a balance between the rate of scaffold absorption and tissue formation is of high importance. A higher rate of tissue formation is expected in fast-degrading materials than in slow-degrading materials. This could be a result of synthetic cells, which aim to compensate for the fast loss of mechanical integrity of the scaffold by deposition of collagen fibers. Here, we studied the effect of fast-degrading polyglycolic acid scaffolds coated with poly-4-hydroxybutyrate (PGA-P4HB) and slow-degrading poly-caprolactone (PCL) scaffolds on amount of tissue, composition, and mechanical characteristics in time, and compared these engineered values with values for native human heart valves. Electrospun PGA-P4HB and PCL scaffolds were either kept unseeded in culture or were seeded with human vascular-derived cells. Tissue formation, extracellular matrix (ECM) composition, remaining scaffold weight, tissue-to-scaffold weight ratio, and mechanical properties were analyzed every week up to 6 weeks. Mass of unseeded PCL scaffolds remained stable during culture, whereas PGA-P4HB scaffolds degraded rapidly. When seeded with cells, both scaffold types demonstrated increasing amounts of tissue with time, which was more pronounced for PGA-P4HB-based tissues during the first 2 weeks; however, PCL-based tissues resulted in the highest amount of tissue after 6 weeks. This study is the first to provide insight into the tissue-to-scaffold weight ratio, therewith allowing for a fair comparison between engineered tissues cultured on scaffolds as well as between native heart valve tissues. Although the absolute amount of ECM components differed between the engineered tissues, the ratio between ECM components was similar after 6 weeks. PCL-based tissues maintained their shape, whereas the PGA-P4HB-based tissues deformed during culture. After 6 weeks, PCL-based engineered tissues showed amounts of cells and ECM that were comparable to the number of human native heart valve leaflets, whereas values were lower in the PGA-P4HB-based tissues. Although increasing in time, the number of collagen crosslinks were below native values in all engineered tissues. In conclusion, this study indicates that slow-degrading scaffold materials are favored over fast-degrading materials to create organized ECM-rich tissues in vitro, which keep their three-dimensional structure before implantation.

Objective To evaluate the safety and the short-term function of a novel pulmonary valved conduit (Xeltis Pulmonary Valved Conduit; XPV) up to 12 months in a sheep model. Methods XPV and Hancock bioprosthetic valved conduits (H, used as control) were implanted in adult sheep in the pulmonary artery position. Animals were killed at 2 months (n = 6 XPV), 6 months (n = 6 XPV and n = 3 H), and 12 months (n = 6 XPV) and examined histologically. During follow-up, function of the device as well as diameter of both XPV and H were assessed by transthoracic echocardiography. Results Of 18 animals that received an XPV, 15 survived until they were killed; 3 animals that received H survived the planned observational interval. XPV showed mild neointimal thickening and degradation beginning at 2 months with an ongoing process until 12 months. Only 1 of the 18 animals with XPV had significant calcification at 6 months. Pathologic specimen did not show any significant narrowing of the conduit whereas neointimal thickness showed a peak at 6 months. Inflammatory process reached a maximum at 6 months and the degradation process at 12 months. Gel permeation chromatography analysis showed molecular weight loss beginning at 2 months with a peak at 12 months for the conduit with slower absorption for the leaflets. The wall of the H conduits showed more neointimal thickening, narrowing, and calcification compared with XPV, but the leaflets demonstrated minimal changes. Conclusions Both conduits demonstrated an acceptable safety and functionality. Significant calcification was rarely observed in the XPV, whereas the H developed more neointimal thickness with calcification of the porcine aortic root portion of the wall.

The emerging field of in situ tissue engineering (TE) of load bearing tissues places high demands on the implanted scaffolds, as these scaffolds should provide mechanical stability immediately upon implantation. The new class of synthetic supramolecular biomaterial polymers, which contain non-covalent interactions between the polymer chains, thereby forming complex 3D structures by self assembly. Here, we have aimed to map the degradation characteristics of promising (supramolecular) materials, by using a combination of in vitro tests. The selected biomaterials were all polycaprolactones (PCLs), either conventional and unmodified PCL, or PCL with supramolecular hydrogen bonding moieties (either 2-ureido-[1H]-pyrimidin-4-one or bis-urea units) incorporated into the backbone. As these materials are elastomeric, they are suitable candidates for cardiovascular TE applications. Electrospun scaffold strips of these materials were incubated with solutions containing enzymes that catalyze hydrolysis, or solutions containing oxidative species. At several time points, chemical, morphological, and mechanical properties were investigated. It was demonstrated that conventional and supramolecular PCL-based polymers respond differently to enzyme-accelerated hydrolytic or oxidative degradation, depending on the morphological and chemical composition of the material. Conventional PCL is more prone to hydrolytic enzymatic degradation as compared to the investigated supramolecular materials, while, in contrast, the latter materials are more susceptible to oxidative degradation. Given the observed degradation pathways of the examined materials, we are able to tailor degradation characteristics by combining selected PCL backbones with additional supramolecular moieties. The presented combination of in vitro test methods can be employed to screen, limit, and select biomaterials for pre-clinical in vivo studies targeted to different clinical applications.

Aims: The Xeltis bioabsorbable pulmonary valved conduit (XPV), designed to guide functional restoration of patients' own tissue, is potentially more durable than current pulmonary bioprosthetic valves/valved conduits. The aim of this study was to assess the haemodynamic performance of the novel XPV implanted in an ovine model. Methods and results: The XPV was surgically implanted in adult sheep under general anaesthesia and cardiopulmonary bypass (XPV group, n= 20). Sheep that received a Hancock bioprosthetic pulmonary valved conduit served as a control group (HPV group, n = 3). Transthoracic echocardiograms from VARC-2 recommended time points at 3, 6, 9, 12, 18 and 24 months (XPV group) and at 3 and 6 months (HPV group) after the procedure were analysed in an independent core laboratory. The primary endpoint was favourable valved conduit performance, defined as peak systolic pressure gradient

Creating autologous tissues with on-demand and native-like biomechanical properties is the ultimate challenge in functional heart valve tissue engineering. A promising approach toward this goal is to induce development of native-like tissue structure in vitro by mimicking the diastolic loading phase in a bioreactor. Heart valves cultured with this approach showed in vitro sufficient strength to withstand systemic pressures. This study aims to link global functioning of these valves to the development of a native-like fiber architecture induced by in vitro diastolic loading. It is hypothesized that increased loading magnitude during culture will lead to increased collagen fiber alignment. To test this hypothesis, 10 tissue-engineered heart valves were subjected to different loading protocols in vitro. Local fiber distribution and mechanics were determined in an inverse numerical-experimental approach, combining indentation tests with confocal imaging. Indentation tests on native ovine heart valves were used as a comparison. Although the effect of loading magnitude was small within the tested range, results indicated that the local fiber architecture indeed developed toward native structural properties for all loading protocols. However, apparent fiber mechanics were much stiffer compared with native. This confirms that in vitro mechanical conditioning induces development of a native-like tissue architecture, which underlines its importance for functional heart valve tissue engineering.

The mechanical properties of soft biological tissues in general and early stage engineered tissues in particular limit the feasibility of conventional tensile tests for their mechanical characterisation. Furthermore, the most important mode in development of deep tissue injury (DTI) is compression. Therefore, an inverse numerical-experimental approach using a finite spherical indentation test is proposed. To demonstrate the feasibility of the approach indentation tests are applied to bio-artificial muscle (BAM) tissue. BAMs are cultured in vitro with (n = 20) or without (n = 12) myoblast cells to quantify the effect of the cells on the passive transverse mechanical properties. Indentation tests are applied up to 80% of the tissue thickness. A non-linear Neo-Hookean constitutive model is fitted to the experimental results for parameter estimation. BAMs with cells demonstrated both stiffer and more non-linear material behaviour than BAMs without cells.