scispace - formally typeset
Open accessJournal ArticleDOI: 10.3389/FCVM.2020.583360

A Novel Restorative Pulmonary Valve Conduit: Early Outcomes of Two Clinical Trials.

04 Mar 2021-Frontiers in Cardiovascular Medicine (Frontiers Media SA)-Vol. 7, pp 583360-583360
Abstract: Objectives: We report the first use of a biorestorative valved conduit (Xeltis pulmonary valve-XPV) in children. Based on early follow-up data the valve design was modified; we report on the comparative performance of the two designs at 12 months post-implantation. Methods: Twelve children (six male) median age 5 (2 to 12) years and weight 17 (10 to 43) kg, had implantation of the first XPV valve design (XPV-1, group 1; 16 mm (n = 5), and 18 mm (n = 7). All had had previous surgery. Based on XPV performance at 12 months, the leaflet design was modified and an additional six children (five male) with complex malformations, median age 5 (3 to 9) years, and weight 21 (14 to 29) kg underwent implantation of the new XPV (XPV-2, group 2; 18 mm in all). For both subgroups, the 12 month clinical and echocardiographic outcomes were compared. Results: All patients in both groups have completed 12 months of follow-up. All are in NYHA functional class I. Seventeen of the 18 conduits have shown no evidence of progressive stenosis, dilation or aneurysm formation. Residual gradients of >40 mm Hg were observed in three patients in group 1 due to kinking of the conduit (n = 1), and peripheral stenosis of the branch pulmonary arteries (n = 2). In group 2, one patient developed rapidly progressive stenosis of the proximal conduit anastomosis, requiring conduit replacement. Five patients in group 1 developed severe pulmonary valve regurgitation (PI) due to prolapse of valve leaflet. In contrast, only one patient in group 2 developed more than mild PI at 12 months, which was not related to leaflet prolapse. Conclusions: The XPV, a biorestorative valved conduit, demonstrated promising early clinical outcomes in humans with 17 of 18 patients being free of reintervention at 1 year. Early onset PI seen in the XPV-1 version seems to have been corrected in the XPV-2, which has led to the approval of an FDA clinical trial. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02700100 and NCT03022708.

... read more

Topics: Pulmonary valve (56%)
Citations
  More

8 results found


Open accessPosted ContentDOI: 10.1101/2021.04.06.438611
de Yaw Yvonne Kort1, Marzi2, Brauchle, Lichauco1  +8 moreInstitutions (3)
08 Apr 2021-bioRxiv
Abstract: In situ heart valve tissue engineering is an emerging approach in which resorbable, off-the-shelf available scaffolds are used to induce endogenous heart valve restoration Such scaffolds are designed to recruit endogenous cells in vivo, which subsequently resorb polymer and produce and remodel new valvular tissue in situ Recently, preclinical studies using electrospun supramolecular elastomeric valvular grafts have shown that this approach enables in situ regeneration of pulmonary valves with long-term functionality in vivo However, the evolution and mechanisms of inflammation, polymer absorption and tissue regeneration are largely unknown, and adverse valve remodeling and intra- and inter-valvular variability have been reported Therefore, the goal of the present study was to gain a mechanistic understanding of the in vivo regenerative processes by combining routine histology and immunohistochemistry, using a comprehensive sheep-specific antibody panel, with Raman microspectroscopy for the spatiotemporal analysis of in situ tissue-engineered pulmonary valves with follow-up to 24 months from a previous preclinical study in sheep The analyses revealed a strong spatial heterogeneity in the influx of inflammatory cells, graft resorption, and foreign body giant cells Collagen maturation occurred predominantly between 6 and 12 months after implantation, which was accompanied by a progressive switch to a more quiescent phenotype of infiltrating cells with properties of valvular interstitial cells Variability among specimens in the extent of tissue remodeling was observed for follow-up times after 6 months Taken together, these findings advance the understanding of key events and mechanisms in material-driven in situ heart valve tissue engineering

... read more

Topics: Regeneration (biology) (52%), Heart valve (52%)

2 Citations


Open accessJournal ArticleDOI: 10.1016/J.ADDR.2021.113960
B.J. de Kort1, Suzanne E Koch1, T.B. Wissing2, Merle M. Krebber3  +2 moreInstitutions (3)
Abstract: In situ tissue engineering using bioresorbable material implants - or scaffolds - that harness the patient's immune response while guiding neotissue formation at the site of implantation is emerging as a novel therapy to regenerate human tissues. For the cardiovascular system, the use of such implants, like blood vessels and heart valves, is gradually entering the stage of clinical translation. This opens up the question if and to what extent patient characteristics influence tissue outcomes, necessitating the precision engineering of scaffolds to guide patient-specific neo-tissue formation. Because of the current scarcity of human in vivo data, herein we review and evaluate in vitro and preclinical investigations to predict the potential role of patient-specific parameters like sex, age, ethnicity, hemodynamics, and a multifactorial disease profile, with special emphasis on their contribution to the inflammation-driven processes of in situ tissue engineering. We conclude that patient-specific conditions have a strong impact on key aspects of in situ cardiovascular tissue engineering, including inflammation, hemodynamic conditions, scaffold resorption, and tissue remodeling capacity, suggesting that a tailored approach may be required to engineer immuno-regenerative biomaterials for safe and predictive clinical applicability.

... read more

Topics: Tissue engineering (54%)

1 Citations


Journal ArticleDOI: 10.1002/JBM.A.37280
Abstract: The host immune response to an implanted biomaterial, particularly the phenotype of infiltrating macrophages, is a key determinant of biocompatibility and downstream remodeling outcome. The present study used a subcutaneous rat model to compare the tissue response, including macrophage phenotype, remodeling potential, and calcification propensity of a biologic scaffold composed of glutaraldehyde-fixed bovine pericardium (GF-BP), the standard of care for heart valve replacement, with those of an electrospun polycarbonate-based supramolecular polymer scaffold (ePC-UPy), urinary bladder extracellular matrix (UBM-ECM), and a polypropylene mesh (PP). The ePC-UPy and UBM-ECM materials induced infiltration of mononuclear cells throughout the thickness of the scaffold within 2 days and neovascularization at 14 days. GF-BP and PP elicited a balance of pro-inflammatory (M1-like) and anti-inflammatory (M2-like) macrophages, while UBM-ECM and ePC-UPy supported a dominant M2-like macrophage phenotype at all timepoints. Relative to GF-BP, ePC-UPy was markedly less susceptible to calcification for the 180 day duration of the study. UBM-ECM induced an archetypical constructive remodeling response dominated by M2-like macrophages and the PP caused a typical foreign body reaction dominated by M1-like macrophages. The results of this study highlight the divergent macrophage and host remodeling response to biomaterials with distinct physical and chemical properties and suggest that the rat subcutaneous implantation model can be used to predict in vivo biocompatibility and regenerative potential for clinical application of cardiovascular biomaterials.

... read more

Topics: Calcification (52%), Biocompatibility (51%), Macrophage (50%)

1 Citations


Journal ArticleDOI: 10.1053/J.SEMTCVS.2021.03.036
Abstract: 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.

... read more

Topics: Pulmonary valve (60%), Pulmonary atresia (59%), Pulmonary Valve Insufficiency (58%) ... read more

1 Citations


Journal ArticleDOI: 10.1080/14779072.2021.1924676
Abstract: The use of bioprosthetic valves (BPV) implanted surgically or by transcatheter valve implantation (TAVI) has increased dramatically in recent years. Currently, BPVs comprise an overwhelming majorit...

... read more

Topics: Aortic valve (68%)

References
  More

24 results found


Journal ArticleDOI: 10.1126/SCIENCE.278.5343.1601
28 Nov 1997-Science
Abstract: Units of 2-ureido-4-pyrimidone that dimerize strongly in a self-complementary array of four cooperative hydrogen bonds were used as the associating end group in reversible self-assembling polymer systems. The unidirectional design of the binding sites prevents uncontrolled multidirectional association or gelation. Linear polymers and reversible networks were formed from monomers with two and three binding sites, respectively. The thermal and environmental control over lifetime and bond strength makes many properties, such as viscosity, chain length, and composition, tunable in a way not accessible to traditional polymers. Hence, polymer networks with thermodynamically controlled architectures can be formed, for use in, for example, coatings and hot melts, where a reversible, strongly temperature-dependent rheology is highly advantageous.

... read more

Topics: Supramolecular polymers (60%), Polymer (53%), End-group (53%) ... read more

1,857 Citations


Journal ArticleDOI: 10.1161/01.CIR.102.SUPPL_3.III-44
Simon P. Hoerstrup1, Ralf Sodian2, Sabine Daebritz2, Jun Wang2  +9 moreInstitutions (2)
07 Nov 2000-Circulation
Abstract: Background—Previous tissue engineering approaches to create heart valves have been limited by the structural immaturity and mechanical properties of the valve constructs. This study used an in vitro pulse duplicator system to provide a biomimetic environment during tissue formation to yield more mature implantable heart valves derived from autologous tissue. Methods and Results—Trileaflet heart valves were fabricated from novel bioabsorbable polymers and sequentially seeded with autologous ovine myofibroblasts and endothelial cells. The constructs were grown for 14 days in a pulse duplicator in vitro system under gradually increasing flow and pressure conditions. By use of cardiopulmonary bypass, the native pulmonary leaflets were resected, and the valve constructs were implanted into 6 lambs (weight 19±2.8 kg). All animals had uneventful postoperative courses, and the valves were explanted at 1 day and at 4, 6, 8, 16, and 20 weeks. Echocardiography demonstrated mobile functioning leaflets without stenosi...

... read more

Topics: Heart valve (57%)

624 Citations


Open accessJournal ArticleDOI: 10.1016/S1010-7940(03)00094-0
Paul Simon1, Marie-Theres Kasimir1, Gernot Seebacher1, G. Weigel1  +4 moreInstitutions (1)
Abstract: Objectives: The first tissue engineered decellularized porcine heart valve, Synergrafte (Cryolife Inc., USA) was introduced in Europe as an alternative to conventional biological valves. This is the first report of the rapid failure of these new grafts in a small series. Materials and methods: In 2001, 2 model 500 and 2 model 700 Synergrafte valves were implanted in four male children (age 2.5‐ 11 years) in the right ventricular outflow tract as a root. Two patients had a Ross operation and two had a homograft replacement. Results: The cryopreserved Synergrafte valves appeared macroscopically unremarkable at implantation. Recovery from surgery was uneventful and good valve function was demonstrated postoperatively. Three children died, two suddenly with severely degenerated Synergrafte valves 6 weeks and 1 year after implantation. The third child died on the 7th day due to Synergrafte rupture. Subsequently the fourth graft was explanted prophylactically 2 days after implantation. Macroscopically all four grafts showed severe inflammation starting on the outside (day 2 explant) leading to structural failure (day 7 explant) and severe degeneration of the leaflets and wall (6 weeks and 1 year explant). Histology demonstrated severe foreign body type reaction dominated by neutrophil granulocytes and macrophages in the early explants and a lymphocytic reaction at 1 year. In addition significant calcific deposits were demonstrated at all stages. Surprisingly pre-implant samples of the Synergrafte revealed incomplete decellularization and calcific deposits. No cell repopulation of the porcine matrix occurred. Conclusion: The xenogenic collagen matrix of the Synergrafte valve elicits a strong inflammatory response in humans which is non-specific early on and is followed by a lymphocyte response. Structural failure or rapid degeneration of the graft occurred within 1 year. Calcific deposits before implantation and incomplete decellularization may indicate manufacturing problems. The porcine Synergrafte treated heart valves should not be implanted at this stage and has been stopped. q 2003 Elsevier Science B.V. All rights reserved.

... read more

Topics: Valve replacement (58%), Heart valve (55%)

580 Citations


Journal ArticleDOI: 10.1016/0003-4975(95)00733-4
Abstract: Background Valve replacements using either bioprosthetic or mechanical valves have the disadvantage that these structures are unable to grow, repair, or remodel and are both thrombogenic and susceptible to infection. These characteristics have significantly limited their durability and longevity. In an attempt to begin to overcome these shortcomings, we have tested the feasibility of constructing heart valve leaflets in lambs by seeding a synthetic polyglycolic acid fiber matrix in vitro with fibroblasts and endothelial cells. Methods Mixed cell populations of endothelial cells and fibroblasts were isolated from explanted ovine arteries. Endothelial cells were selectively labeled with an acetylated low-density lipoprotein marker and separated from the fibroblasts using a fluorescent activated cell sorter. A synthetic biodegradable scaffold constructed from polyglycolic acid fibers was seeded with fibroblasts, which grew to form a tissue-like sheet. This tissue was subsequently seeded with endothelial cells, which formed a cellular monolayer coating around the leaflet. Using these constructs, autologous (n = 3) and allogenic (n = 4) tissue engineered leaflets were implanted in 7 animals. In each animal the right posterior leaflet of the pulmonary valve was resected and replaced with an engineered valve leaflet. Results All animals survived the procedure. Postoperative echocardiography demonstrated no evidence of stenosis and trivial pulmonary regurgitation in the autografts and moderate regurgitation in the allogenic valves. Collagen analysis of the constructs showed development of an extracellular matrix. Histologic evaluation of the constructs demonstrated appropriate cellular architecture. Conclusions This preliminary experiment showed that a tissue engineered valve leaflet constructed from its cellular components can function in the pulmonary valve position. Tissue engineering of a heart valve leaflet is feasible, and these preliminary studies suggest that autograft tissue will probably be superior to allogenic tissue.

... read more

Topics: Heart valve (60%), Aortic valve (56%), Pulmonary valve (55%) ... read more

457 Citations