The DOI matches its Crossref record; 40 of the 41 references it cites were found in a registry or an index.
Perfusion decellularization of human and porcine lungs: Bringing the matrix to clinical scale
Abstract
Background Organ engineering is a theoretical alternative to allotransplantation for end-stage organ failure. Whole-organ scaffolds can be created by detergent perfusion via the native vasculature, generating an acellular matrix suitable for recellularization with selected cell types. We aimed to up-scale this process, generating biocompatible scaffolds of a clinically relevant scale.Methods Rat, porcine, and human lungs were decellularized by detergent perfusion at constant pressures. Collagen, elastin, and glycosaminoglycan content of scaffolds were quantified by colorimetric assays. Proteomic analysis was performed by microcapillary liquid chromatography tandem mass spectrometry. Extracellular matrix (ECM) slices were cultured with human umbilical vein endothelial cells (HUVEC), small airway epithelial cells (SAEC), or pulmonary alveolar epithelial cells (PAECs) and evaluated by time-lapse live cell microscopy and MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Whole-organ culture was maintained under constant-pressure media perfusion after seeding with PAECs.Results Rat lungs were decellularized using: (1) sodium dodecyl sulfate (SDS), (2) sodium deoxycholate (SDC), or (3) 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Resulting scaffolds showed comparable loss of DNA but greatest preservation of ECM components in SDS-decellularized lungs. Porcine (n = 10) and human (n = 7) lungs required increased SDS concentration, perfusion pressures, and time to achieve decellularization as determined by loss of DNA, with preservation of intact matrix composition and lung architecture. Proteomic analysis of human decellularized lungs further confirmed ECM preservation. Recellularization experiments confirmed scaffold biocompatibility when cultured with mature cell phenotypes and scaffold integrity for the duration of biomimetic culture.Conclusions SDS-based perfusion decellularization can be applied to whole porcine and human lungs to generate biocompatible organ scaffolds with preserved ECM composition and architecture.
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?
In the citing paper
“In order to accurately recapitulate the composition, structure, and vascularization of native ECM in organ development, some organoids have been grown in decellularized ECM from human or animal donors.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [71]
In the citing paper
“Decellularization approaches have been demonstrated for human kidney67, murine kidney67,68, murine heart69,70, human and porcine lung71, and porcine testicular72 tissues, with each type posing unique challenges.”
From Towards organoid culture without Matrigel (2021) · cites this paper as [71]
Citations
Cites
2 retracted
RETRACTED: Clinical transplantation of a tissue-engineered airway
Macchiarini, P., Jungebluth, P., Go, T., Asnaghi, M. A., Rees, L., Cogan, T. A., Dodson, A., Martorell, J., Bellini, S., Parnigotto, P. P., et al. (2008) · The Lancet · doi:10.1016/s0140-6736(08)61598-6 · Cited by 1,431
RetractedRETRACTED: Engineered whole organs and complex tissues
Badylak, S. F., Weiss, D. J., Caplan, A., & Macchiarini, P. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60073-7 · Cited by 417
RetractedAn overview of tissue and whole organ decellularization processes
Crapo, P. M., Gilbert, T. W., & Badylak, S. F. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.01.057 · Cited by 3,591
Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart
Ott, H. C., Matthiesen, T. S., Goh, S.-K., Black, L. D., Kren, S. M., Netoff, T. I., & Taylor, D. A. (2008) · Nature Medicine · doi:10.1038/nm1684 · Cited by 2,650
Self-citationTissue-Engineered Lungs for in Vivo Implantation
Petersen, T. H., Calle, E. A., Zhao, L., Lee, E. J., Gui, L., Raredon, M. S. B., Gavrilov, K., Yi, T., Zhuang, Z. W., Breuer, C. K., et al. (2010) · Science · doi:10.1126/science.1189345 · Cited by 1,189
Regeneration and orthotopic transplantation of a bioartificial lung
Ott, H. C., Clippinger, B., Conrad, C., Schuetz, C., Pomerantseva, I., Ikonomou, L., Kotton, D., & Vacanti, J. P. (2010) · Nature Medicine · doi:10.1038/nm.2193 · Cited by 1,090
Self-citationAcellular Normal and Fibrotic Human Lung Matrices as a Culture System for In Vitro Investigation
Booth, A. J., Hadley, R., Cornett, A. M., Dreffs, A. A., Matthes, S. A., Tsui, J. L., Weiss, K., Horowitz, J. C., Fiore, V. F., Barker, T. H., et al. (2012) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201204-0754oc · Cited by 665
Bousquet, J., & Khaltaev, N. (2007) · Cited by 531
Milavetz, G. (2008) · Journal of Pharmacy Technology · doi:10.1177/875512250802400215 · Cited by 493
Polymicrobial respiratory disease in pigs
Opriessnig, T., Gimenez-Lirola, L. G., & Halbur, P. G. (2011) · Animal Health Research Reviews · doi:10.1017/s1466252311000120 · Cited by 460
Cited by
Sorted by citations
Items 201–262 of 262
Extracellular Matrix Isolation: Sources and Methods
Mendibil, U., Ruiz-Hernández, R., Arnáiz, B., Khatami, N., & Abarrategi, A. (2023) · Springer eBooks · doi:10.1007/978-3-030-92090-6_7-1 · Cited by 4
Complete proteomic profiling of regenerative bio‐scaffolds with a two‐step trypsinization method
Wang, H., Sun, W. Q., & Wang, J. (2022) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.35132 · Cited by 4
Dhandapani, V., Boabekoa, P., Borduas, M., & Vermette, P. (2024) · Journal of Biomedical Materials Research Part B Applied Biomaterials · doi:10.1002/jbm.b.35498 · Cited by 3
Insight into the pathogenesis of interstitial lung diseases and near-to-native lung fibrosis models
Štefániková, M., Sedláková, V., Portakal, T., Hampl, A., Vaňhara, P., & Doubková, M. (2025) · European journal of medical research · doi:10.1186/s40001-025-03504-4 · Cited by 3
Can, S. S., Tuncer, S., Bilgiç, H. A., İmrak, G., Günal, G., Damadoğlu, E., Aydın, H. M., & Karaaslan, Ç. (2024) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2024.2392356 · Cited by 3
Relevance of Protein Content within the Renal Scaffold for Kidney Bioengineering and Regeneration
Guerrero, F., Carmona, A., Ortega, R., Cañadillas, S., Crespo, R., Herrera, C., & Aljama, P. (2017) · Journal of Biomedical Science and Engineering · doi:10.4236/jbise.2017.1011039 · Cited by 3
Decellularized Human-Sized Pulmonary Scaffolds for Lung Tissue Engineering: A Comprehensive Review
Mahfouzi, S. H., Tali, S. H. S., & Amoabediny, G. (2021) · Regenerative Medicine · doi:10.2217/rme-2020-0152 · Cited by 4
Cryopreservation of human lung tissue for 3D ex vivo analysis
Diodati, N. G., Qu, G., Mehrad, B., & Schaller, M. A. (2025) · Respiratory Research · doi:10.1186/s12931-025-03265-y · Cited by 3
Engineering Bioartificial Lungs for Transplantation
Wu, T., Economopoulos, K. P., & Ott, H. C. (2017) · Current Stem Cell Reports · doi:10.1007/s40778-017-0082-8 · Cited by 4
Self-citationZolbin, M. M., Daghigh, F., Shojaie, L., Ekhtiari, M., & Kajbafzadeh, A. M. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-82735-9_3 · Cited by 3
A novel method for providing scaffold: Decellularization of parathyroid capsule
Büyük, N. İ., Tüfekçi, K., Cumbul, A., Ayşan, E., & Köse, G. T. (2021) · Journal of Biomaterials Applications · doi:10.1177/08853282211054321 · Cited by 3
Biofabrication of Vascularized Tissues
Schimelman, J. B., Sun, Y., Lyu, C., Lu, T.-Y., Yao, E. J., Huang, L., Altera, A. K., Xiang, Y., & Chen, S. (2026) · Chemical Reviews · doi:10.1021/acs.chemrev.5c00914 · Cited by 2
Regenerative Medicine of the Respiratory Tract
Gilpin, S. E., Moser, P. T., & Ott, H. C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809880-6.00060-6 · Cited by 2
Self-citationOff-the-Shelf Tissue-Engineered Vascular Conduits: Clinical Translation
Fioretta, E. S., von Boehmer, L., Generali, M., Hoerstrup, S. P., & Emmert, M. Y. (2019) · Springer eBooks · doi:10.1007/978-3-319-71530-8_21-1 · Cited by 3
Optimized Biomanufacturing for Treatment of Volumetric Muscle Loss Enables Physiomimetic Recovery
Bour, R. K., Garner, G. T., Peirce, S. M., & Christ, G. J. (2024) · Tissue Engineering Part A · doi:10.1089/ten.tea.2023.0315 · Cited by 2
Wagner, D. E., Uhl, F. E., Königshoff, M., & Weiss, D. J. (2015) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-319-16232-4_8 · Cited by 2
Characterization of an elastase-induced emphysema model in immune-deficient rats
Becerra, D. C., Jeffs, S. E., Wojtkiewicz, G. R., & Ott, H. C. (2020) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezaa320 · Cited by 2
Self-citationLiquid Ventilation Reconditions Isolated Rat Lungs Following Ischemia–Reperfusion Injury
Becerra, D. C., Linge, H., Jeffs, S. E., Roberts, S., Jane, O., & Ott, H. C. (2022) · Tissue Engineering Part A · doi:10.1089/ten.tea.2022.0084 · Cited by 2
Self-citationCesur, N. P., & Laçin, N. T. (2023) · Springer eBooks · doi:10.1007/978-3-030-92090-6_46-1 · Cited by 3
Matrix Biology of the Salivary Gland: A Guide for Tissue Engineering
Martinez, M., Wu, D., Farach‐Carson, M. C., & Harrington, D. A. (2017) · Springer eBooks · doi:10.1007/978-3-319-43513-8_8 · Cited by 2
Off-the-Shelf Tissue-Engineered Vascular Conduits: Clinical Translation
Fioretta, E. S., von Boehmer, L., Generali, M., Hoerstrup, S. P., & Emmert, M. Y. (2020) · Springer eBooks · doi:10.1007/978-3-030-05336-9_21 · Cited by 2
Three dimensional lung models - Three dimensional extracellular matrix models
Nizamoglu, M., Joglekar, M. M., de Hilster, R. H. J., Ngassie, M. L. K., Teitsma, G. J., Migulina, N., Blokland, K. E. C., & Burgess, J. K. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90871-9.00012-7 · Cited by 3
Decellularization Techniques for Tissue Engineering
Chen, G., Kawazoe, N., & Lu, H. (2015) · Encyclopedia of Analytical Chemistry · doi:10.1002/9780470027318.a9472 · Cited by 2
Naturally Derived Biomaterials: An Overview
Naveen Kumar, C. P., Kumar, V., Shrivastava, S., Gangwar, A. K., Gopinathan, A., Maiti, S. K., Saxena, S., Palakkara, S., Raja, R., & Raghuvanshi, P. D. S. (2022) · Springer protocols handbooks/Springer protocols · doi:10.1007/978-1-0716-2425-8_1 · Cited by 1
Bonciog, D.-D., Berdich, A., Lascu, M.-R., Roman, N. M., & Ordodi, V. L. (2025) · Biomedical Signal Processing and Control · doi:10.1016/j.bspc.2025.108546 · Cited by 1
Living Devices for Organ Replacement: The Rise of Bioartificial Organ Engineering
Pezzino, S., Tumino, D., Crescimanno, C., Luca, T., Puleo, S., & Castorina, S. (2026) · Applied Sciences · doi:10.3390/app16136330 · Cited by 1
Acellular Lung Scaffolds in Lung Bioengineering
Wagner, D. E., Uhl, F. E., & Weiss, D. J. (2015) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-319-21082-7_18 · Cited by 1
Modeling The Spatiotemporal Dynamics Of Cells In The Lung
Pothen, J. J. (2016) · ScholarWorks -A service of University of Vermont Libraries (University of Vermont) · Cited by 1
Kanczler, J. M., Moreno, I. O., Hulsart‐Billström, G., Inglis, S., & Oreffo, R. O. C. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-803581-8.09303-6 · Cited by 1
Development and Bioengineering of Lung Regeneration
Wilson, A. A., & Ikonomou, L. (2017) · Springer eBooks · doi:10.1007/978-981-10-3768-9_13 · Cited by 1
Leung, S. T., Overschmidt, B., Allickson, J. G., Atala, A., Taghizadeh, R. R., Cetrulo, K. J., Verter, F., Couto, P. S., & Murphy, S. V. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-812015-6.00025-x · Cited by 1
Decellularized Tissue Matrix-based 3D Tissue Modeling
Das, S., Gao, G., Lee, J. Y., Jang, J., & Cho, D. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788012683-00148 · Cited by 1
Raredon, M. S. B., Yuan, Y., & Niklason, L. E. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-818422-6.00070-8 · Cited by 1
Delaere, P. (2019) · Leuven University Press eBooks · doi:10.11116/9789461662965 · Cited by 1
Extracellular Matrix Specification of Regenerative Cells in the Adult Lung
Burgess, J. K., & Tjin, G. (2015) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-319-21082-7_11 · Cited by 1
Kuevda, E. V., Gubareva, E. A., Gumenuyk, I. S., & Карал-оглы, Д. Д. (2017) · Современные технологии в медицине · doi:10.17691/stm2017.9.4.10 · Cited by 1
Chen, G., & Kawazoe, N. (2019) · Encyclopedia of Analytical Chemistry · doi:10.1002/9780470027318.a9472.pub2 · Cited by 1
“Bioengineered lungs” Best science paper in JHLT 2014-2015
Schrepfer, S., Cantu, E., Gandy, K. L., Baan, C. C., & West, L. J. (2016) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2016.03.009
Regenerating the Respiratory Tract
Lim, M. L., Firsova, A. B., Feliu, N., Kuevda, E. V., Jungebluth, P., & Macchiarini, P. (2015) · Stem cell biology and regenerative medicine · doi:10.1007/978-3-319-21082-7_17
Porcine Acellular Lung Matrix in Wound Healing and Hernia Repair
Chegireddy, V., Caplan, K. D., & Fernandez-Moure, J. S. (2018) · Recent clinical techniques, results, and research in wounds · doi:10.1007/15695_2017_102
Kuna, V. K. (2018) · Gothenburg University Publications Electronic Archive (Gothenburg University)
Decellularised veins as a scaffold for in situ vascular tissue engineering
Sulaiman, N. S. (2019) · Bristol Research (University of Bristol)
Uses of Ex-Vivo Lung Perfusion in Pulmonary Translational Medicine
Chan, P. G. (2019) · Biomedical Journal of Scientific & Technical Research · doi:10.26717/bjstr.2019.22.003781
Recellularization of Decellularized Whole Organ Scaffolds: Elements, Progresses, and Challenges
Hu, J.-G., Huang, Y., Tan, J., Da, L., & Xie, H. (2021) · Springer eBooks · doi:10.1007/978-981-33-6962-7_6
Stem cell-driven tissue engineering in lung engineering, regeneration, and diseases
El-Hashash, A. H. K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821206-6.00008-4
Metabolic and inflammatory aspects of cardiothoracic surgical interventions
Schipper, D. A. (2021) · EUR Research Repository (Erasmus University Rotterdam)
Microarchitectonic of Decellularized Bovine Pericardium Matrix
Shchotkina, N. V., Sokol, A. A., Yemets, G. I., Galkin, O. Y., Dolinchuk, L. V., Skorokhod, I. M., Shepeleva, O. V., Rudenko, N. M., & Yemets, I. M. (2021) · Proceedings of the World Congress on New Technologies · doi:10.11159/icbb21.167
Bioengineering Approaches for the Distal Lung
Wagner, D. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-08-102723-3.00264-x
Cell-Derived Matrices for Scaffolds Improvement
Maia, F. R., Reis, R. L., & Oliveira, J. M. (2023) · Springer eBooks · doi:10.1007/978-3-030-92090-6_38-1 · Cited by 1
Cell-Derived Matrices for Scaffolds Improvement
Maia, F. R., Reis, R. L., & Oliveira, J. M. (2024) · Springer eBooks · doi:10.1007/978-3-031-56363-8_38
Cesur, N. P., & Laçin, N. T. (2024) · Springer eBooks · doi:10.1007/978-3-031-56363-8_46
Extracellular Matrix Isolation: Sources and Methods
Mendibil, U., Ruiz-Hernández, R., Arnáiz, B., Khatami, N., & Abarrategi, A. (2024) · Springer eBooks · doi:10.1007/978-3-031-56363-8_7
Matrix Biology of the Salivary Gland: A Guide for Tissue Engineering
Martinez, M., Wu, D., Farach‐Carson, M. C., & Harrington, D. A. (2026) · Springer eBooks · doi:10.1007/978-3-032-07458-4_8
Preuß, E. B., Schröder, L., Hähner, C., von Bandemer, J. A., Werlein, C., Plucinski, E. K., Schubert, S., Schlüter, H., Thomas, M. J., Jonigk, D. D., et al. (2026) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2026.1772891
Pan, J., Li, Q., Li, B., Ning, X., Ye, C., Chen, S., Dejun, G. O. N. G., Yu, Q., Liu, L., Han, L., et al. (2026) · Biomedical Materials · doi:10.1088/1748-605x/ae529a
da Silva-Júnior, L. N., Miglino, M. A., Horvath-Pereira, B. D. O., Fireman, J. V. B. T., da Siqueira, G. M., Pereira, M. L. D. R. F., Bezerra, L. D. S., de Oliveira, L. V. F., Morais, S. D. S., Bellini, M. Z., et al. (2026) · Bioengineering · doi:10.3390/bioengineering13050484
Reactors for tissue and organ engineering
Schüler, K., Marcelino, P., Ferreira, F. C., & Silva, J. C. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-36330-6.00009-6
Ghosh, S., & Pati, F. (2026) · Biomaterials · doi:10.1016/j.biomaterials.2026.124508 · Cited by 1
Lost cells, retained structure: proteomic mapping of decellularized lung matrisome across species
Čimborová, K., Pelková, V., Bernatík, O., Potěšil, D., Pustka, V., Vaškovicová, N., Kotasová, H., Mitáš, L., Vaňhara, P., Sedláková, V., et al. (2026) · Materials & Design · doi:10.1016/j.matdes.2026.116823
Zhang, T., Xu, H., Hao, H., & An, M. (2026) · Applied Materials Today · doi:10.1016/j.apmt.2026.103444
Metadata
- Authors
- Gilpin, S. E., Guyette, J. P., Gonzalez, G., Ren, X., Asara, J. M., Mathisen, D. J., Vacanti, J. P., & Ott, H. C.
- Affiliations
- Harvard University (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Ott, Harald C.
- Venue
- The Journal of Heart and Lung Transplantation
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 33
- Issue
- 3
- Pages
- 298-308
- ISSN
- 1053-2498 (ISSN-L)
- OpenAlex
- W2047611832
- Semantic Scholar
- 253777fdc37ab99c976b2319df807c9150ac0b39
- Cited by
- 263
- References
- 41
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 12 · 2023: 18 · 2022: 17 · 2021: 33 · 2020: 25 · 2019: 24 · 2018: 29 · 2017: 26 · 2016: 21 · 2015: 27 · 2014: 14
- FWCI
- 20.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Heart and Lung Transplantation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (1dp2od008749-01)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- perfusion decellularization, lung scaffolds, extracellular matrix preservation, sodium dodecyl sulfate, sodium deoxycholate, CHAPS, human lung, porcine lung, recellularization, alveolar epithelial cells, endothelial cells, small airway epithelial cells, whole organ culture, organ engineering, scaffold biocompatibility
- MeSH terms
- Animals, Biocompatible Materials, Cells, Cultured, Cholic Acids, Deoxycholic Acid, Detergents, Dose-Response Relationship, Drug, Endothelium, Vascular, Epithelial Cells, Extracellular Matrix, Humans, Lung, Perfusion, Sodium Dodecyl Sulfate, Swine, Rats, Sprague-Dawley, Models, Animal, Rats, Tissue Scaffolds, Bioengineering
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
