The DOI matches its Crossref record.
In vivo performance of freeze-dried decellularized pulmonary heart valve allo- and xenografts orthotopically implanted into juvenile sheep
Abstract
The decellularization of biological tissues decreases immunogenicity, allows repopulation with cells, and may lead to improved long-term performance after implantation. Freeze drying these tissues would ensure off-the-shelf availability, save storage costs, and facilitates easy transport. This study evaluates the in vivo performance of freeze-dried decellularized heart valves in juvenile sheep. TritonX-100 and sodium dodecylsulfate decellularized ovine and porcine pulmonary valves (PV) were freeze-dried in a lyoprotectant sucrose solution. After rehydration for 24 h, valves were implanted into the PV position in sheep as allografts (fdOPV) and xenografts (fdPPV), while fresh dezellularized ovine grafts (frOPV) were implanted as controls. Functional assessment was performed by transesophageal echocardiography at implantation and at explantation six months later. Explanted grafts were analysed histologically to assess the matrix, and immunofluorescence stains were used to identify the repopulating cells. Although the graft diameters and orifice areas increased, good function was maintained, except for one insufficient, strongly deteriorated frOPV. Cells which were positive for either endothelial or interstitial markers were found in all grafts. In fdPPV, immune-reactive cells were also found. Our findings suggest that freeze-drying does not alter the early hemodynamic performance and repopulation potential of decellularized grafts in vivo, even in the challenging xenogeneic situation. Despite evidence of an immunological reaction for the xenogenic valves, good early functionalities were achieved. Statement of significance Decellularized allogeneic heart valves show excellent results as evident from large animal experiments and clinical trials. However, a long-term storing method is needed for an optimal use of this limited resource in the clinical setting, where an optimized matching of graft and recipient is requested. As demonstrated in this study, freeze-dried and freshly decellularized grafts reveal equally good results after implantation in the juvenile sheep concerning function and repopulation with recipients' cells. Thus, freeze-drying arises as a promising method to extend the shelf-life of valvular grafts compared to those stored in antibiotic-solution as currently practised.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
γ sterilization affects the scaffold's elasticity, subsequently affecting cell attachment, behavior, and viability.
“It has been reported that γ sterilization affects the scaffold's elasticity, subsequently affecting cell attachment, behavior, and viability [[180], [181], [182]].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [180]
Citations
Cites
No references could be resolved yet.
Research works printed but not linked: 28
- Brockbank, 2011, Guidance for removal of fetal bovine serum from cryopreserved heart valve processing, Cells Tissues Organs., 193, 264, 10.1159/000321166 · DOI
- Huber, 2013, Characterization of a simplified ice-free cryopreservation method for heart valves, Cell Tissue Bank., 14, 195, 10.1007/s10561-012-9319-z · DOI
- Ross, 1962, Homograft replacement of the aortic valve, Lancet, 280, 487, 10.1016/S0140-6736(62)90345-8 · DOI
- Kirklin, 1993, Kirklin long-term function of cryopreserved aortic homografts : a ten-year study, J. Thorac. Cardiovasc. Surg., 154, 10.1016/S0022-5223(19)33752-3 · DOI
- Sarikouch, 2016, Decellularized fresh homografts for pulmonary valve replacement: a decade of clinical experience, Eur. J. Cardiothorac. Surg., ezw050
- da Costa, 2017, Decellularized allografts for right ventricular outflow tract reconstruction in children, World J. Pediatr. Congenit. Heart Surg., 8, 605, 10.1177/2150135117723916 · DOI
- Tudorache, 2016, Decellularized aortic homografts for aortic valve and aorta ascendens replacement, Eur. J. Cardiothorac. Surg., ezw013
- Drury, 1982, Morphological assessment of sucrose preservation for porcine heart valves, Thorax, 37, 466, 10.1136/thx.37.6.466 · DOI
- Aidulis, 2002, Processing of ovine cardiac valve allografts: 1 Effects of preservation method on structure and mechanical properties, Cell Tissue Bank., 3, 79, 10.1023/A:1022873513040 · DOI
- Schenke-Layland, 2006, Impact of cryopreservation on extracellular matrix structures of heart valve leaflets, Ann. Thorac. Surg., 81, 918, 10.1016/j.athoracsur.2005.09.016 · DOI
- Brockbank, 2012, Ice-free cryopreservation of heart valve allografts: better extracellular matrix preservation in vivo and preclinical results, Cell Tissue Bank., 13, 663, 10.1007/s10561-011-9288-7 · DOI
- Davies, 1968, Homograft replacement of the aortic valve, Am. J. Cardiol., 22, 195, 10.1016/0002-9149(68)90226-9 · DOI
- Moore, 1975, Analysis of homograft valve failure in 311 patients followed up to 10 years, Ann. Thorac. Surg., 20, 274, 10.1016/S0003-4975(10)64219-1 · DOI
- Curtil, 1997, Freeze drying of cardiac valves in preparation for cellular repopulation, Cryobiology, 34, 13, 10.1006/cryo.1996.1982 · DOI
- Wang, 2012, Freeze-dried heart valve scaffolds, Tissue Eng. Part C Methods, 18, 517, 10.1089/ten.tec.2011.0398 · DOI
- Wang, 1844, Protein stability in stored decellularized heart valve scaffolds and diffusion kinetics of protective molecules, Biochim. Biophys. Acta, 2014, 430
- Wang, 2015, Sucrose diffusion in decellularized heart valves for freeze-drying, Tissue Eng. Part C Methods, 21, 922, 10.1089/ten.tec.2014.0681 · DOI
- Crowe, 2005, Stabilization of dry mammalian cells: lessons from nature, Integr. Comp. Biol., 45, 810, 10.1093/icb/45.5.810 · DOI
- Crowe, 1992, Anhydrobiosis, Annu. Rev. Physiol., 54, 579, 10.1146/annurev.ph.54.030192.003051 · DOI
- Theodoridis, 2015, Successful matrix guided tissue regeneration of decellularized pulmonary heart valve allografts in elderly sheep, Biomaterials, 52, 221, 10.1016/j.biomaterials.2015.02.023 · DOI
- Baraki, 2009, Orthotopic replacement of the aortic valve with decellularized allograft in a sheep model, Biomaterials, 30, 6240, 10.1016/j.biomaterials.2009.07.068 · DOI
- Cebotari, 2011, Use of fresh decellularized allografts for pulmonary valve replacement may reduce the reoperation rate in children and young adults early report, Circulation, 124, S115, 10.1161/CIRCULATIONAHA.110.012161 · DOI
- Yacoub, 1970, Sterilization of valve homografts by antibiotic solutions, Circulation, 41, II-29, 10.1161/01.CIR.41.5S2.II-29 · DOI
- Talman, 1995, Glutaraldehyde fixation alters the internal shear properties of porcine aortic heart valve tissue, Ann. Thorac. Surg., 60, S369, 10.1016/0003-4975(95)00250-O · DOI
- Jayakrishnan, 1996, Glutaraldehyde as a fixative in bioprostheses and drug delivery matrices, Biomaterials, 17, 471, 10.1016/0142-9612(96)82721-9 · DOI
- Siddiqui, 2009, Bioprosthetic heart valves: modes of failure, Histopathology, 55, 135, 10.1111/j.1365-2559.2008.03190.x · DOI
- Curtil, 1997, Repopulation of freeze-dried porcine valves with human fibroblasts and endothelial cells, J. Heart Valve Dis., 6, 296
- Tudorache, 2016, Decellularized aortic allografts versus pulmonary autografts for aortic valve replacement in the growing sheep model: haemodynamic and morphological results at 20 months after implantation, Eur. J. Cardiothorac. Surg., 49, 1228, 10.1093/ejcts/ezv362 · DOI
Cited by
Sorted by citations
Tao, M., Ao, T., Mao, X., Yan, X., Javed, R., Hou, W., Wang, Y., Sun, C., Lin, S., Yu, T., et al. (2021) · Bioactive Materials · doi:10.1016/j.bioactmat.2021.02.010 · Cited by 119
Hussein, K. H., Ahmadzada, B., Correa, J. C., Sultan, A., Wilken, S., Amiot, B., & Nyberg, S. L. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.06.001 · Cited by 28
“It has been reported that γ sterilization affects the scaffold ’ s elasticity, subsequently affecting cell attachment, behavior, and viability [180 – 182].”
Background
Metadata
- Authors
- Goecke, T., Theodoridis, K., Tudorache, I., Ciubotaru, A., Cebotari, S., Ramm, R., Höffler, K., Sarikouch, S., Vásquez Rivera, A., Haverich, A., Wolkers, W. F., & Hilfiker, A.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Leibniz University Hannover (DE)
- Corresponding author
- Hilfiker, Andres
- ORCID
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 68
- Pages
- 41-52
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W2772554686
- Cited by
- 60
- References
- 0
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 15 · 2020: 8 · 2019: 3 · 2018: 4
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Congenital Heart Disease Studies
- Keywords
- decellularized heart valves, pulmonary valve replacement, freeze-drying, xenografts, allograft, porcine valves, graft immunogenicity, graft storage, shelf life extension, hemodynamic performance
- MeSH terms
- Animals, Calorimetry, Differential Scanning, Extracellular Matrix, Female, Fluorescent Antibody Technique, Freeze Drying, Heart Valve Prosthesis, Protein Denaturation, Pulmonary Valve, Sheep, Temperature, Transplantation, Heterologous, Transplantation, Homologous
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
