Contribution of Physical Methods in Decellularization of Animal Tissues
Open accessAbstract
Biologic scaffolds composed of extracellular matrix (ECM) are frequently used for clinical purposes of tissue regeneration. Different methods have been developed for this purpose. All methods of decellularization including chemical and physical approaches leave some damage on the ECM; however, the effects of these methods are different which make some of these procedures more proper to maintain ECM structure than other methods. This review is aimed to introduce and compare new physical methods for the decellularization of different tissues and organs in tissue engineering. All recent reports and research that have used at least one physical method in the procedure of decellularization, were included and evaluated in this paper. The advantages and drawbacks of each method were examined and compared considering the effectiveness. This review tried to highlight the prospective potentials and benefits of applying physical methods for decellularization protocols in tissue engineering instead of the current chemical methods. These chemical methods are harsh in nature and were shown to be destructive and harmful to essential substances of ECM and scaffold structure. Therefore, using physical methods as a partial or even a whole protocol could save time, costs, and quality of the final acellular tissue in complicated decellularization procedures. Moreover, regarding the control factor that could be achieved easily with physical methods, optimization of different decellularization protocols would be quite satisfactory. Combined methods take advantage of both chemical and physical approaches.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Physical decellularization techniques' less toxicity makes them attractive options for adjuvant treatment for enhancing chemical and biological agent effectiveness.
“Nonetheless, their less toxicity makes them attractive options for adjuvant treatment for enhancing the chemical and biological agent effectiveness [67].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [67]
The Abstract and Combined methods section (pages not provided) describe physical methods as less damaging to tissue structure and say that combining methods improves decellularization efficiency. The Introduction calls chemical agents toxic, but the paper does not establish that physical methods have lower toxicity or that lower toxicity is what makes them useful alongside chemical and enzymatic agents. (LLM, conf=0.82)
Experimental — accuracy not yet measuredVacuum-assisted decellularization, employing negative pressure to expedite the process, can be utilized in conjunction with other techniques to enhance outcomes.
“Vacuum‐assisted decellularization, employing negative pressure to expedite the process, can be utilized in conjunction with other techniques to enhance outcomes.”
From Bioactive scaffolds for tissue engineering: A review of decellularized extracellular matrix applications and innovations (2025) · cites this paper as [83]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 65 · Cited by 87
Research works printed but not linked: 55
- [2]Chan BP Leong KW Scaffolding in tissue engineering: General approaches and tissue-specific considerations Eur Spine J 2008 17 Suppl 4 467 79 19005702 PMC2587658
- [3]Badylak SF Freytes DO Gilbert TW Extracellular matrix as a biological scaffold material: Structure and function Acta Biomater 2009 5 1 3 18938117
- [4]Crapo PM Gilbert TW Badylak SF An overview of tissue and whole organ decellularization processes Biomaterials 2011 32 3233 43 21296410 PMC3084613
- [5]Badylak SF Decellularized allogeneic and xenogeneic tissue as a bioscaffold for regenerative medicine: Factors that influence the host response Ann Biomed Eng 2014 42 1517 27 24402648
- [6]Londono R Badylak SF Biologic scaffolds for regenerative medicine: Mechanisms of in vivo remodeling Ann Biomed Eng 2015 43 577 92 25213186
- [8]Keane TJ Swinehart IT Badylak SF Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance Methods 2015 84 25 34 25791470
- [9]Azuma C Tohyama H Nakamura H Kanaya F Yasuda K Antibody neutralization of TGF-beta enhances the deterioration of collagen fascicles in a tissue-cultured tendon matrix with ex vivo fibroblast infiltration J Biomech 2007 40 2184 90 17462658
- [10]Gilpin A Yang Y Decellularization Strategies for Regenerative Medicine: From Processing Techniques to Applications Biomed Res Int 2017 2017 9831534 28540307 PMC5429943
- [11]Xing Q Yates K Tahtinen M Shearier E Qian Z Zhao F Decellularization of fibroblast cell sheets for natural extracellular matrix scaffold preparation Tissue Eng Part C Methods 2015 21 77 87 24866751 PMC4291209
- [12]Elder BD Kim DH Athanasiou KA Developing an articular cartilage decellularization process toward facet joint cartilage replacement Neurosurgery 2010 66 722 7 20305493 PMC3164496
- [13]Burk J Erbe I Berner D Kacza J Kasper C Pfeiffer B Freeze-thaw cycles enhance decellularization of large tendons Tissue Eng Part C Methods 2014 20 276 84 23879725 PMC3968887
- [14]Roth SP Glauche SM Plenge A Erbe I Heller S Burk J Automated freeze-thaw cycles for decellularization of tendon tissue – A pilot study BMC Biotechnol 2017 17 13 28193263 PMC5307874
- [15]Poornejad N Frost TS Scott DR Elton BB Reynolds PR Roeder BL Freezing/thawing without cryoprotectant damages native but not decellularized porcine renal tissue Organogenesis 2015 11 30 45 25730294 PMC4594613
- [16]Nonaka PN Campillo N Uriarte JJ Garreta E Melo E de Oliveira LV Effects of freezing/thawing on the mechanical properties of decellularized lungs J Biomed Mater Res A 2014 102 413 9 23533110
- [17]Zhao Y Fan J Bai S Biocompatibility of injectable hydrogel from decellularized human adipose tissue in vitro and in vivo J Biomed Mater Res B Appl Biomater 2019 107 1684 94 30352138
- [18]Gilbert TW Strategies for tissue and organ decellularization J Cell Biochem 2012 113 2217 22 22415903
- [19]Hashimoto Y Funamoto S Sasaki S Honda T Hattori S Nam K Preparation and characterization of decellularized cornea using high-hydrostatic pressurization for corneal tissue engineering Biomaterials 2010 31 3941 8 20163852
- [20]Funamoto S Nam K Kimura T Murakoshi A Hashimoto Y Niwaya K The use of high-hydrostatic pressure treatment to decellularize blood vessels Biomaterials 2010 31 3590 5 20149445
- [21]Santoso EG Yoshida K Hirota Y Aizawa M Yoshino O Kishida A Application of detergents or high hydrostatic pressure as decellularization processes in uterine tissues and their subsequent effects on in vivo uterine regeneration in murine models PLoS One 2014 9 e103201 25057942 PMC4109986
- [23]Watanabe N Mizuno M Matsuda J Nakamura N Otabe K Katano H Comparison of high-hydrostatic-pressure decellularized versus Freeze-Thawed porcine menisci J Orthop Res 2019 37 2466 75 31115925
- [24]Phillips M Maor E Rubinsky B Nonthermal irreversible electroporation for tissue decellularization J Biomech Eng 2010 132 091003 20815637
- [26]Zager Y Kain D Landa N Leor J Maor E Optimization of irreversible electroporation protocols for in vivo myocardial decellularization PLoS One 2016 11 e0165475 27893744 PMC5125564
- [27]Azhim A Yamagami K Muramatsu K Morimoto Y Tanaka M The use of sonication treatment to completely decellularize blood arteries: A pilot study Conf Proc IEEE Eng Med Biol Soc 2011 2011 2468 71 22254841
- [28]Oliveira AC Garzón I Ionescu AM Carriel V Cardona Jde L González-Andrades M Evaluation of small intestine grafts decellularization methods for corneal tissue engineering PLoS One 2013 8 e66538 23799114 PMC3682956
- [29]Forouzesh F Rabbani M Bonakdar S A comparison between ultrasonic bath and direct sonicator on osteochondral tissue decellularization J Med Signals Sens 2019 9 227 33 31737551 PMC6839442
- [30]Yusof F Sha'ban M Azhim A Development of decellularized meniscus using closed sonication treatment system: Potential scaffolds for orthopedics tissue engineering applications Int J Nanomedicine 2019 14 5491 502 31410000 PMC6650458
- [32]Sierad LN Shaw EL Bina A Brazile B Rierson N Patnaik SS Functional heart valve scaffolds obtained by complete decellularization of porcine aortic roots in a novel differential pressure gradient perfusion system Tissue Eng Part C Methods 2015 21 1284 96 26467108 PMC4663650
- [33]Montoya CV McFetridge PS Preparation of ex vivo-based biomaterials using convective flow decellularization Tissue Eng Part C Methods 2009 15 191 200 19196128 PMC2819706
- [34]Lange P Greco K Partington L Carvalho C Oliani S Birchall MA Pilot study of a novel vacuum-assisted method for decellularization of tracheae for clinical tissue engineering applications J Tissue Eng Regen Med 2017 11 800 11 25689270
- [36]Vas WJ Shah M Blacker TS Duchen MR Sibbons P Roberts SJ Decellularized cartilage directs chondrogenic differentiation: Creation of a fracture callus mimetic Tissue Eng Part A 2018 24 1364 76 29580181
- [39]Guler S Aslan B Hosseinian P Aydin HM Supercritical carbon dioxide-assisted decellularization of aorta and cornea Tissue Eng Part C Methods 2017 23 540 7 28726559
- [40]Wang JK Luo B Guneta V Li L Foo SEM Dai Y Supercritical carbon dioxide extracted extracellular matrix material from adipose tissue Mater Sci Eng C Mater Biol Appl 2017 75 349 58 28415472
- [42]Syed O Walters NJ Day RM Kim HW Knowles JC Evaluation of decellularization protocols for production of tubular small intestine submucosa scaffolds for use in oesophageal tissue engineering Acta Biomater 2014 10 5043 54 25173840
- [43]Baptista PM Orlando G Mirmalek-Sani SH Siddiqui M Atala A Soker S Whole organ decellularization-a tool for bioscaffold fabrication and organ bioengineering Conf Proc IEEE Eng Med Biol Soc 2009 2009 6526 9 19964173
- [44]He M Callanan A Comparison of methods for whole-organ decellularization in tissue engineering of bioartificial organs Tissue Eng Part B Rev 2013 19 194 208 23083305 PMC3627431
- [45]Ott HC Matthiesen TS Goh SK Black LD Kren SM Netoff TI Perfusion-decellularized matrix: Using nature's platform to engineer a bioartificial heart Nat Med 2008 14 213 21 18193059
- [46]Wainwright JM Czajka CA Patel UB Freytes DO Tobita K Gilbert TW Preparation of cardiac extracellular matrix from an intact porcine heart Tissue Eng Part C Methods 2010 16 525 32 19702513 PMC2945869
- [47]Remlinger NT Wearden PD Gilbert TW Procedure for decellularization of porcine heart by retrograde coronary perfusion J Vis Exp 2012 70 e50059 PMC3567168 23242494
- [48]Momtahan N Sukavaneshvar S Roeder BL Cook AD Strategies and processes to decellularize and recellularize hearts to generate functional organs and reduce the risk of thrombosis Tissue Eng Part B Rev 2015 21 115 32 25084164
- [49]Methe K Bäckdahl H Johansson BR Nayakawde N Dellgren G Sumitran-Holgersson S An alternative approach to decellularize whole porcine heart Biores Open Access 2014 3 327 38 25469317 PMC4245870
- [50]Petersen TH Calle EA Zhao L Lee EJ Gui L Raredon MB Tissue engineered lungs for in vivo implantation Science 2010 329 538 41 20576850 PMC3640463
- [51]Song JJ Guyette JP Gilpin SE Gonzalez G Vacanti JP Ott HC Regeneration and experimental orthotopic transplantation of a bioengineered kidney Nat Med 2013 19 646 51 23584091 PMC3650107
- [52]Caralt M Uzarski JS Iacob S Obergfell KP Berg N Bijonowski BM Optimization and critical evaluation of decellularization strategies to develop renal extracellular matrix scaffolds as biological templates for organ engineering and transplantation Am J Transplant 2015 15 64 75 25403742 PMC4276475
- [53]Pellegata AF Asnaghi MA Zonta S Zerbini G Mantero S A novel device for the automatic decellularization of biological tissues Int J Artif Organs 2012 35 191 8 22461114
- [54]Kajbafzadeh AM Javan-Farazmand N Monajemzadeh M Baghayee A Determining the optimal decellularization and sterilization protocol for preparing a tissue scaffold of a human-sized liver tissue Tissue Eng Part C Methods 2013 19 642 51 23270591
- [55]Verstegen MM Willemse J van den Hoek S Kremers GJ Luider TM van Huizen NA Decellularization of whole human liver grafts using controlled perfusion for transplantable organ bioscaffolds Stem Cells Dev 2017 26 1304 15 28665233
- [56]Gerli MFM Guyette JP Evangelista-Leite D Ghoshhajra BB Ott HC Perfusion decellularization of a human limb: A novel platform for composite tissue engineering and reconstructive surgery PLoS One 2018 13 e0191497 29352303 PMC5774802
- [57]Tajima K Kuroda K Otaka Y Kinoshita R Kita M Oyamada T Decellularization of canine kidney for three-dimensional organ regeneration Vet World 2020 13 452 7 32367949 PMC7183470
- [58]Flynn LE The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells Biomaterials 2010 31 4715 24 20304481
- [59]Luo L Eswaramoorthy R Mulhall KJ Kelly DJ Decellularization of porcine articular cartilage explants and their subsequent repopulation with human chondroprogenitor cells J Mech Behav Biomed Mater 2015 55 21 31 26521085
- [60]Cortiella J Niles J Cantu A Brettler A Pham A Vargas G Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation Tissue Eng Part A 2010 16 2565 80 20408765
- [61]Gardin C Ricci S Ferroni L Guazzo R Sbricoli L De Benedictis G Decellularization and delipidation protocols of bovine bone and pericardium for bone grafting and guided bone regeneration procedures PLoS One 2015 10 e0132344 26191793 PMC4507977
- [62]Hung SH Su CH Lee FP Tseng H Larynx decellularization: Combining freeze-drying and sonication as an effective method J Voice 2013 27 289 94 23490126
- [64]Manalastas TM Dugos N Ramos G Mondragon JM Effect of decellularization parameters on the efficient production of kidney bioscaffolds Appl Biochem Biotechnol 2020 10.1007/s12010- 020-03338-2 doi:10.1007/s12010-020-03338-2 32418019 · DOI
- [65]Batioglu-Karaaltin A Ovali E Karaaltin MV Yener M Yılmaz M Eyüpoğlu F Decellularization of trachea with combined techniques for tissue-engineered trachea transplantation Clin Exp Otorhinolaryngol 2019 12 86 94 30326701 PMC6315211
- Authors
- Rabbani, M., Zakian, N., & Alimoradi, N.
- Affiliations
- University of Isfahan (IR)
- Corresponding author
- Rabbani, Mohsen
- ORCID
- Alimoradi, Nima
- Venue
- Journal of Medical Signals & Sensors
- Published
- 2021-01
- Volume
- 11
- Issue
- 1
- Pages
- 1-11
- ISSN
- 2228-7477 (ISSN-L)
- PMC
- PMC8043117
- OpenAlex
- W3126606565
- Cited by
- 87
- References
- 65
- Citations by year
- 2026: 11 · 2025: 22 · 2024: 25 · 2023: 14 · 2022: 13 · 2021: 2
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- Journal of Medical Signals & Sensors (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- decellularization, extracellular matrix, biological scaffolds, tissue engineering, tissue regeneration
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