Decellularization in Tissue Engineering and Regenerative Medicine: Evaluation, Modification, and Application Methods
Open accessAbstract
Reproduction of different tissues using scaffolds and materials is a major element in regenerative medicine. The regeneration of whole organs with decellularized extracellular matrix (dECM) has remained a goal despite the use of these materials for different purposes. Recently, decellularization techniques have been widely used in producing scaffolds that are appropriate for regenerating damaged organs and may be able to overcome the shortage of donor organs. Decellularized ECM offers several advantages over synthetic compounds, including the preserved natural microenvironment features. Different decellularization methods have been developed, each of which is appropriate for removing cells from specific tissues under certain conditions. A variety of methods have been advanced for evaluating the decellularization process in terms of cell removal efficiency, tissue ultrastructure preservation, toxicity, biocompatibility, biodegradability, and mechanical resistance in order to enhance the efficacy of decellularization methods. Modification techniques improve the characteristics of decellularized scaffolds, making them available for the regeneration of damaged tissues. Moreover, modification of scaffolds makes them appropriate options for drug delivery, disease modeling, and improving stem cells growth and proliferation. However, considering different challenges in the way of decellularization methods and application of decellularized scaffolds, this field is constantly developing and progressively moving forward. This review has outlined recent decellularization and sterilization strategies, evaluation tests for efficient decellularization, materials processing, application, and challenges and future outlooks of decellularization in regenerative medicine and tissue engineering.
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Various sterilization techniques have been applied for dECM scaffolds, and many utilize aggressive mechanisms which may exert detrimental effects on the structure and immunogenicity of ECM.
“Although various sterilization techniques have been applied for this purpose, many of them utilize aggressive mechanisms which may exert detrimental effects on the structure and immunogenicity of ECM [218].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [218]
Section 3 (Sterilization; page unavailable) describes several methods used for dECM and says they may alter matrix structure and biochemical characteristics, including damage from γ-irradiation. It does not say sterilization adversely affects ECM immunogenicity; its discussion of immunogenicity concerns other factors. (LLM, conf=0.86)
Experimental — accuracy not yet measuredEthanol 70% denatures polypeptides and is incapable of bacterial spore elimination, making it an inferior choice for sterilizing dECM scaffolds.
“Ethanol 70% denatures polypeptides and is incapable of bacterial spore elimination, which makes it an inferior choice for sterilizing dECM scaffolds [218].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [218]
Section 3 (Sterilization; page not provided) says alcohols destroy proteins within microorganisms but do not remove spores, supporting the concern about using them for sterilization. It does not specify 70% ethanol or explicitly rank it as an inferior choice; it also says alcohols are widely used to disinfect dECM. (LLM, conf=0.84)
Experimental — accuracy not yet measuredGamma irradiation and Ethylene oxide sterilization alter collagen 3D ultrastructure and deform ECM binding sites for cell alignment, resulting in inferior biocompatibility of ECM-based biomaterials.
“Of note, Gamma irradiation and Ethylene oxide sterilization also alter collagen 3D ultrastructure and deform ECM binding sites for cell alignment, which results in inferior biocompatibility of ECM-based biomaterials [218].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [218]
Section 3 (Sterilization; page not available) says gamma irradiation can affect scaffold ultrastructure and mechanical properties, supporting that part of the claim. It does not say that ethylene oxide deforms collagen or ECM cell-alignment sites, or that either method thereby reduces biocompatibility; instead, it says ethylene oxide can sterilize decellularized scaffolds without causing toxicity. (LLM, conf=0.87)
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Sorted by citations
Kasravi, M., Ahmadi, A., Babajani, A., Mazloomnejad, R., Hatamnejad, M. R., Shariatzadeh, S., Bahrami, S., & Niknejad, H. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00348-z · Cited by 316 · see citing works
Biomedical Application of Decellularized Scaffolds
Zhang, F., Gao, H., Jiang, X., Yang, F., Zhang, J., Song, S., & Shen, J. (2023) · ACS Applied Bio Materials · doi:10.1021/acsabm.3c00778 · Cited by 10 · see citing works
- Authors
- Neishabouri, A., Soltani Khaboushan, A., Daghigh, F., Kajbafzadeh, A.-M., & Majidi Zolbin, M.
- Affiliations
- University of Tehran (IR)
- Corresponding author
- Kajbafzadeh, Abdol-Mohammad
- Venue
- Frontiers in Bioengineering and Biotechnology
- Publisher
- Frontiers Media SA
- Published
- 2022-04-25
- Volume
- 10
- Pages
- 805299-805299
- ISSN
- 2296-4185 (ISSN-L)
- PMC
- PMC9081537
- OpenAlex
- W4224312994
- Cited by
- 281
- References
- 15
- Citations by year
- 2026: 60 · 2025: 98 · 2024: 76 · 2023: 41 · 2022: 6
- FWCI
- 13.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Bioengineering and Biotechnology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- 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, decellularized extracellular matrix, decellularized scaffolds, tissue engineering, regenerative medicine, organ regeneration, scaffold modification, drug delivery, disease modeling, stem cell proliferation, sterilization, biocompatibility, biodegradability, mechanical properties
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