An overview of animal tissue decellularization techniques and clinical applications



Palabras clave:

Proceso de descellularización, matriz extracelular, tejido, detergente, aplicaciones clínicas


There is a persistent an urgent need to solve tissue and organ donor shortage issues. Decellularized tissues represent a promising alternative to other biologic and synthetic treatments that have been developed, since they aim to retain native tissue characteristics that would help in the regenerative processes such as prolifera-tion, cellular adhesion, and the presence of growth factors, while minimizing the chances of an unwanted host immune response. In the present review, we describe the most common methodologies for decellularization pro-cesses, as well as the clinical applications of these biomaterials.

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Ringo Y, Chilonga K. Burns at KCMC: epidemiology, presentation, management and treatment outcome. Burns J Int Soc Burn Inj. 2014 Aug;40(5):1024–9.

Gilpin A, Yang Y. Decellularization Strategies for Regenerative Medicine: From Processing Techniques to Applications. BioMed Res Int. 2017 Apr 30;2017:e9831534.

Giwa S, Lewis JK, Alvarez L, Langer R, Roth AE, Church GM, et al. The promise of organ and tissue preser-vation to transform medicine. Nat Biotechnol. 2017 Jun 7;35(6):530–42.

Shafiee A, Atala A. Tissue Engineering: Toward a New Era of Medicine. Annu Rev Med. 2017;68(1):29–40.

Lee SJ, Yoo JJ, Atala A. Biomaterials and Tissue Engineering. In: Kim BW, editor. Clinical Regenerative Med-icine in Urology [Internet]. Singapore: Springer; 2018 [cited 2021 May 9]. p. 17–51. Available from:

Darnell M, Mooney DJ. Leveraging advances in biology to design biomaterials. Nat Mater. 2017 Dec;16(12):1178–85.

Naturally Derived Biomaterials: Preparation and Application | IntechOpen [Internet]. [cited 2022 Aug 25]. Available from:

Sarkar K, Xue Y, Sant S. Host Response to Synthetic Versus Natural Biomaterials. In: Corradetti B, editor. The Immune Response to Implanted Materials and Devices: The Impact of the Immune System on the Success of an Implant [Internet]. Cham: Springer International Publishing; 2017 [cited 2021 May 9]. p. 81–105. Available from:

Nakamura N, Kimura T, Kishida A. Overview of the Development, Applications, and Future Perspectives of Decellularized Tissues and Organs. ACS Biomater Sci Eng. 2017 Jul 10;3(7):1236–44.

Choudhury D, Yee M, Sheng ZLJ, Amirul A, Naing MW. Decellularization systems and devices: State-of-the-art. Acta Biomater. 2020 Oct 1;115:51–9.

Damodaran RG, Vermette P. Tissue and organ decellularization in regenerative medicine. Biotechnol Prog. 2018;34(6):1494–505.

Pan MX, Hu PY, Cheng Y, Cai LQ, Rao XH, Wang Y, et al. An efficient method for decellularization of the rat liver. J Formos Med Assoc. 2014 Oct 1;113(10):680–7.

Gilbert TW, Sellaro TL, Badylak SF. Decellularization of tissues and organs. Biomaterials. 2006 Jul 1;27(19):3675–83.

Naranjo TÁ, Noguera-Salvá R, Guerrero FF. La matriz extracelular: morfología, función y biotensegridad (parte I). Rev Esp Patol. 2009 Oct;42(4):249–61.

Theocharis AD, Skandalis SS, Gialeli C, Karamanos NK. Extracellular matrix structure. Adv Drug Deliv Rev. 2016 Feb;97:4–27.

Schultz GS, Ladwig G, Wysocki A. Extracellular matrix: review of its roles in acute and chronic wounds. World Wide Wounds [Internet]. 2005 Aug [cited 2021 Sep 16]; Available from:

Light DB, Cooley DA. Cells, Tissues, and Skin (The Human Body, How It Works). Chelsea House Pub; 2009. 157 p.

McKee TJ, Perlman G, Morris M, Komarova SV. Extracellular matrix composition of connective tissues: a systematic review and meta-analysis. Sci Rep. 2019 Jul 22;9(1):10542.

Karamanos NK, Theocharis AD, Piperigkou Z, Manou D, Passi A, Skandalis SS, et al. A guide to the com-position and functions of the extracellular matrix. FEBS J. 2021;288(24):6850–912.

Theocharis AD, Manou D, Karamanos NikosK. The extracellular matrix as a multitasking player in disease. 2019 Mar 25;286(15):2830–69.

Dussoyer M, Michopoulou A, Rousselle P. Decellularized Scaffolds for Skin Repair and Regeneration. Appl Sci. 2020 May 15;10(10):3435.

Álvaro T, Noguera-Salvá R, Fariñas-Guerrero F. La matriz extracelular: de la mecánica molecular al microam-biente tumoral (parte II). Rev Esp Patol. 2010 Jan;43(1):24–32.

Wong VW, Longaker MT, Gurtner GC. Soft tissue mechanotransduction in wound healing and fibrosis. Semin Cell Dev Biol. 2012 Dec;23(9):981–6.

Chiquet M, Gelman L, Lutz R, Maier S. From mechanotransduction to extracellular matrix gene expression in fibroblasts. Biochim Biophys Acta BBA - Mol Cell Res. 2009 May;1793(5):911–20.

Chantre CO, Hoerstrup SP, Parker KK. Engineering biomimetic and instructive materials for wound healing and regeneration. Curr Opin Biomed Eng. 2019 Jun;10:97–106.

Giebel J. Mecanotransducción y transducción de señales a través del tejido conjuntivo. Rev Int Acupunt. 2008 Jan;2(1):9–14.

Agha R, Ogawa R, Pietramaggiori G, Orgill DP. A Review of the Role of Mechanical Forces in Cutaneous Wound Healing. J Surg Res. 2011 Dec;171(2):700–8.

Parmaksiz M, Elçin AE, Elçin YM. Decellularized bSIS-ECM as a Regenerative Biomaterial for Skin Wound Repair. In: Turksen K, editor. Skin Stem Cells [Internet]. New York, NY: Springer New York; 2018 [cited 2021 Aug 18]. p. 175–85. (Methods in Molecular Biology; vol. 1879). Available from:

Whitaker MJ, Quirk RA, Howdle SM, Shakesheff KM. Growth factor release from tissue engineering scaf-folds. J Pharm Pharmacol. 2010 Feb 18;53(11):1427–37.

Benton G, Arnaoutova I, George J, Kleinman HK, Koblinski J. Matrigel: from discovery and ECM mimicry to assays and models for cancer research. Adv Drug Deliv Rev. 2014 Dec 15;79–80:3–18.

Markeson D, Pleat JM, Sharpe JR, Harris AL, Seifalian AM, Watt SM. Scarring, stem cells, scaffolds and skin repair. J Tissue Eng Regen Med. 2015;9(6):649–68.

Kabirian F, Mozafari M. Decellularized ECM-derived bioinks: Prospects for the future. Methods. 2020 Jan 15;171:108–18.

Solarte David VA, Güiza-Argüello VR, Arango-Rodríguez ML, Sossa CL, Becerra-Bayona SM. Decellularized Tissues for Wound Healing: Towards Closing the Gap Between Scaffold Design and Effective Extracellular Ma-trix Remodeling. Front Bioeng Biotechnol. 2022 Feb 16;10:821852.

Zhang X, Chen X, Hong H, Hu R, Liu J, Liu C. Decellularized extracellular matrix scaffolds: Recent trends and emerging strategies in tissue engineering. Bioact Mater. 2022 Apr;10:15–31.

Das S, Kim SW, Choi YJ, Lee S, Lee SH, Kong JS, et al. Decellularized extracellular matrix bioinks and the external stimuli to enhance cardiac tissue development in vitro. Acta Biomater. 2019 Sep 1;95:188–200.

Bejleri D, Davis ME. Decellularized Extracellular Matrix Materials for Cardiac Repair and Regeneration. Adv Healthc Mater. 2019;8(5):1801217.

Bordbar S, Bakhshaiesh NL, Khanmohammadi M, Sayahpour FA, Alini M, Eslaminejad MB. Production and evaluation of decellularized extracellular matrix hydrogel for cartilage regeneration derived from knee cartilage. J Biomed Mater Res A. 2020;108(4):938–46.

Chen W, Xu Y, Li Y, Jia L, Mo X, Jiang G, et al. 3D printing electrospinning fiber-reinforced decellularized extracellular matrix for cartilage regeneration. Chem Eng J. 2020 Feb 15;382:122986.

Ferreira LP, Gaspar VM, Mano JF. Decellularized Extracellular Matrix for Bioengineering Physiomimetic 3D in Vitro Tumor Models. Trends Biotechnol. 2020 Dec 1;38(12):1397–414.

Hrebikova H, Diaz D, Mokry J. Chemical decellularization: a promising approach for preparation of extracel-lular matrix. Biomed Pap Med Fac Univ Palacky Olomouc Czechoslov. 2015 Mar;159(1):12–7.

Zahmati AHA, Alipoor R, Shahmirzadi AR, Khori V, Abolhasani MM. Chemical Decellularization Methods and Its Effects on Extracellular Matrix. Intern Med Med Investig J. 2017 Sep 11;2(3):76–83.

Sadaf A, Cho KH, Byrne B, Chae PS. Amphipathic agents for membrane protein study. Methods Enzymol. 2015;557:57–94.

Crapo PM, Gilbert TW, Badylak SF. An overview of tissue and whole organ decellularization processes. Biomaterials. 2011 Apr;32(12):3233–43.

G-Biosciences. Detergents for Protein Extraction & Cell Lysis Guide [Internet]. 1st ed. United States; 2010 [cited 2021 May 9]. (1; vol. Protein Research). Available from:,ionic%20detergents,for%20separation%20during%20gel%20electrophoresis.

Gupta SK, Mishra NC, Dhasmana A. Decellularization Methods for Scaffold Fabrication. In: Turksen K, edi-tor. Decellularized Scaffolds and Organogenesis: Methods and Protocols [Internet]. New York, NY: Springer; 2018 [cited 2021 May 9]. p. 1–10. (Methods in Molecular Biology). Available from:

Mattson JM, Turcotte R, Zhang Y. Glycosaminoglycans contribute to extracellular matrix fiber recruitment and arterial wall mechanics. Biomech Model Mechanobiol. 2017 Feb;16(1):213–25.

Keane TJ, Saldin LT, Badylak SF. 4 - Decellularization of mammalian tissues: Preparing extracellular matrix bioscaffolds. In: Tomlins P, editor. Characterisation and Design of Tissue Scaffolds [Internet]. Woodhead Pub-lishing; 2016 [cited 2021 May 12]. p. 75–103. (Woodhead Publishing Series in Biomaterials). Available from:

Fitzpatrick JC, Clark PM, Capaldi FM. Effect of Decellularization Protocol on the Mechanical Behavior of Porcine Descending Aorta. Int J Biomater [Internet]. 2010 [cited 2021 May 12];2010. Available from:

Sarvazyan N. Scaffolds and Tissue Decellularization. In: Sarvazyan N, editor. Tissue Engineering: Principles, Protocols, and Practical Exercises [Internet]. Cham: Springer International Publishing; 2020 [cited 2021 May 12]. p. 103–14. (Learning Materials in Biosciences). Available from:

Wilson SL, Sidney LE, Dunphy SE, Rose JB, Hopkinson A. Keeping an Eye on Decellularized Corneas: A Review of Methods, Characterization and Applications. J Funct Biomater. 2013 Jul 10;4(3):114–61.

Rana D, Zreiqat H, Benkirane‐Jessel N, Ramakrishna S, Ramalingam M. Development of decellularized scaf-folds for stem cell-driven tissue engineering. J Tissue Eng Regen Med. 2017;11(4):942–65.

Lee PF, Chau E, Cabello R, Yeh AT, Sampaio LC, Gobin AS, et al. Inverted orientation improves decellulari-zation of whole porcine hearts. Acta Biomater. 2017 Feb 1;49:181–91.

Mendibil U, Ruiz-Hernandez R, Retegi-Carrion S, Garcia-Urquia N, Olalde-Graells B, Abarrategi A. Tissue-Specific Decellularization Methods: Rationale and Strategies to Achieve Regenerative Compounds. Int J Mol Sci. 2020 Jul 30;21(15):5447.

Carbonaro D, Putame G, Castaldo C, Meglio FD, Siciliano K, Belviso I, et al. A low-cost scalable 3D-printed sample-holder for agitation-based decellularization of biological tissues. Med Eng Phys. 2020 Nov 1;85:7–15.

Mazza G, Al-Akkad W, Telese A, Longato L, Urbani L, Robinson B, et al. Rapid production of human liver scaffolds for functional tissue engineering by high shear stress oscillation-decellularization. Sci Rep. 2017 Jul 17;7(1):5534.

Cheng J, Wang C, Gu Y. Combination of freeze-thaw with detergents: A promising approach to the decellu-larization of porcine carotid arteries. Biomed Mater Eng. 2019 Jan 1;30(2):191–205.

Negishi J, Funamoto S, Kimura T, Nam K, Higami T, Kishida A. Porcine radial artery decellularization by high hydrostatic pressure. J Tissue Eng Regen Med. 2015;9(11):E144–51.

Guyette JP, Gilpin SE, Charest JM, Tapias LF, Ren X, Ott HC. Perfusion decellularization of whole organs. Nat Protoc. 2014 Jun;9(6):1451–68.

Casali DM, Handleton RM, Shazly T, Matthews MA. A novel supercritical CO2-based decellularization meth-od for maintaining scaffold hydration and mechanical properties. J Supercrit Fluids. 2018 Jan 1;131:72–81.

Bhamidipati M, Scurto AM, Detamore MS. The Future of Carbon Dioxide for Polymer Processing in Tissue Engineering. Tissue Eng Part B Rev. 2013 Jun;19(3):221–32.

Phillips M, Maor E, Rubinsky B. Nonthermal irreversible electroporation for tissue decellularization. J Bio-mech Eng. 2010 Sep;132(9):091003.

Hillebrandt KH, Everwien H, Haep N, Keshi E, Pratschke J, Sauer IM. Strategies based on organ decellulari-zation and recellularization. Transpl Int. 2019;32(6):571–85.

Keane TJ, Swinehart IT, Badylak SF. Methods of tissue decellularization used for preparation of biologic scaffolds and in vivo relevance. Methods. 2015 Aug;84:25–34.

Pirahanchi Y, Sharma S. Biochemistry, Lipase. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Pub-lishing; 2022 [cited 2022 Jul 5]. Available from:

Rose KWJ, Taye N, Karoulias SZ, Hubmacher D. Regulation of ADAMTS Proteases. Front Mol Biosci [Inter-net]. 2021 [cited 2022 Aug 25];8. Available from:

Boccafoschi F, Ramella M, Fusaro L, Catoira MC, Casella F. Biological Grafts: Surgical Use and Vascular Tissue Engineering Options for Peripheral Vascular Implants. In: Narayan R, editor. Encyclopedia of Biomedical Engineering [Internet]. Oxford: Elsevier; 2019 [cited 2022 Aug 25]. p. 310–21. Available from:

Tao M, Ao T, Mao X, Yan X, Javed R, Hou W, et al. Sterilization and disinfection methods for decellularized matrix materials: Review, consideration and proposal. Bioact Mater. 2021 Feb 27;6(9):2927–45.

Safdari M, Bibak B, Soltani H, Hashemi J. Recent advancements in decellularized matrix technology for bone tissue engineering. Differentiation. 2021 Sep 1;121:25–34.

Katagiri T, Watabe T. Bone Morphogenetic Proteins. Cold Spring Harb Perspect Biol. 2016 Jun 1;8(6):a021899.

McCrary MW, Bousalis D, Mobini S, Song YH, Schmidt CE. Decellularized tissues as platforms for in vitro modeling of healthy and diseased tissues. Acta Biomater. 2020 Jul;111:1–19.

Bhosale AM, Richardson JB. Articular cartilage: structure, injuries and review of management. Br Med Bull. 2008 Sep 1;87(1):77–95.

Kim YS, Majid M, Melchiorri AJ, Mikos AG. Applications of decellularized extracellular matrix in bone and cartilage tissue engineering. Bioeng Transl Med. 2019;4(1):83–95.

Wronska A, Kmiec Z. Structural and biochemical characteristics of various white adipose tissue depots. Acta Physiol. 2012;205(2):194–208.

Chun SY, Ha YS, Yoon BH, Lee EH, Kim BM, Gil H, et al. Optimal delipidation solvent to secure extracellular matrix from human perirenal adipose tissue. J Biomed Mater Res A. 2022 Apr;110(4):928–42.

Moffat D, Ye K, Jin S. Decellularization for the retention of tissue niches. J Tissue Eng. 2022 May 21;13:20417314221101150.

Zajac FE. Muscle and tendon: properties, models, scaling, and application to biomechanics and motor con-trol. Crit Rev Biomed Eng. 1989 Jan 1;17(4):359–411.

Schulze-Tanzil G, Al-Sadi O, Ertel W, Lohan A. Decellularized Tendon Extracellular Matrix—A Valuable Ap-proach for Tendon Reconstruction? Cells. 2012 Dec;1(4):1010–28.

Badylak SF. Xenogeneic extracellular matrix as a scaffold for tissue reconstruction. Transpl Immunol. 2004 Apr;12(3–4):367–77.

Burk J, Erbe I, Berner D, Kacza J, Kasper C, Pfeiffer B, et al. Freeze-Thaw Cycles Enhance Decellularization of Large Tendons. Tissue Eng Part C Methods. 2014 Apr 1;20(4):276–84.

Badylak SF, Taylor D, Uygun K. Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds. Annu Rev Biomed Eng. 2011 Aug 15;13(1):27–53.

Schaner PJ, Martin ND, Tulenko TN, Shapiro IM, Tarola NA, Leichter RF, et al. Decellularized vein as a po-tential scaffold for vascular tissue engineering. J Vasc Surg. 2004 Jul 1;40(1):146–53.

Camasão DB, Mantovani D. The mechanical characterization of blood vessels and their substitutes in the continuous quest for physiological-relevant performances. A critical review. Mater Today Bio. 2021 Mar 1;10:100106.


Devillard CD, Marquette CA. Vascular Tissue Engineering: Challenges and Requirements for an Ideal Large Scale Blood Vessel. Front Bioeng Biotechnol [Internet]. 2021 [cited 2022 Jul 12];9. Available from:

Heath DE. A Review of Decellularized Extracellular Matrix Biomaterials for Regenerative Engineering Appli-cations. Regen Eng Transl Med. 2019 Jun 1;5(2):155–66.

Agmon G, Christman KL. Controlling stem cell behavior with decellularized extracellular matrix scaffolds. Curr Opin Solid State Mater Sci. 2016 Aug;20(4):193–201.

Paulo Zambon J, Atala A, Yoo JJ. Methods to generate tissue-derived constructs for regenerative medicine applications. Methods. 2020 Jan;171:3–10.

Navarro M, Ruberte J, Carretero A. 6 - Respiratory apparatus. In: Ruberte J, Carretero A, Navarro M, editors. Morphological Mouse Phenotyping [Internet]. Academic Press; 2017 [cited 2022 Aug 25]. p. 147–78. Available from:

Etienne H, Fabre D, Gomez Caro A, Kolb F, Mussot S, Mercier O, et al. Tracheal replacement. Eur Respir J. 2018 Feb;51(2):1702211.

Sousa AMM, Meyer KA, Santpere G, Gulden FO, Sestan N. Evolution of the Human Nervous System Func-tion, Structure, and Development. Cell. 2017 Jul 13;170(2):226–47.

Ludwig PE, Reddy V, Varacallo M. Neuroanatomy, Central Nervous System (CNS). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 [cited 2022 Jul 12]. Available from:

Struzyna LA, Harris JP, Katiyar KS, Chen HI, Cullen DK. Restoring nervous system structure and function using tissue engineered living scaffolds. Neural Regen Res. 2015 May;10(5):679–85.

Crapo PM, Medberry CJ, Reing JE, Tottey S, van der Merwe Y, Jones KE, et al. Biologic scaffolds com-posed of central nervous system extracellular matrix. Biomaterials. 2012 May 1;33(13):3539–47.

Whitlock EL, Tuffaha SH, Luciano JP, Yan Y, Hunter DA, Magill CK, et al. Processed allografts and type I collagen conduits for repair of peripheral nerve gaps. Muscle Nerve. 2009 Jun;39(6):787–99.

Szynkaruk M, Kemp SWP, Wood MD, Gordon T, Borschel GH. Experimental and clinical evidence for use of decellularized nerve allografts in peripheral nerve gap reconstruction. Tissue Eng Part B Rev. 2013 Feb;19(1):83–96.

Sridhar MS. Anatomy of cornea and ocular surface. Indian J Ophthalmol. 2018 Feb;66(2):190–4.

Fini ME. Keratocyte and fibroblast phenotypes in the repairing cornea. Prog Retin Eye Res. 1999 Jul;18(4):529–51.

Liu J, Li Z, Li J, Liu Z. Application of benzonase in preparation of decellularized lamellar porcine corneal stroma for lamellar keratoplasty. J Biomed Mater Res A. 2019;107(11):2547–55.

Xu YG, Xu YS, Huang C, Feng Y, Li Y, Wang W. Development of a rabbit corneal equivalent using an acel-lular corneal matrix of a porcine substrate. Mol Vis. 2008;14:2180–9.

Heidary Rouchi A, Mahdavi-Mazdeh M. Regenerative Medicine in Organ and Tissue Transplantation: Shortly and Practically Achievable? Int J Organ Transplant Med. 2015;6(3):93–8.

Kurniawan NA. The ins and outs of engineering functional tissues and organs: evaluating the in-vitro and in-situ processes. Curr Opin Organ Transplant. 2019 Oct;24(5):590–7.

Mandrycky C, Phong K, Zheng Y. Tissue engineering toward organ-specific regeneration and disease modeling. MRS Commun. 2017 Sep;7(3):332–47.




Cómo citar

Pineda-Molina, C., Galvis-Escobar, S. M., Molina-Sierra, J. D., Ruíz-Soto, J. P., & Rego-Londoño, M. A. (2024). An overview of animal tissue decellularization techniques and clinical applications. Revista Politécnica, 20(39), 31–47.