Decellularized Matrix Scaffolds for Vascular Transplantation: Addressing Immunogenicity, Sterilization, and Current Strategies for Long-Term Storage
Abstract
Cardiovascular diseases are the leading cause of death globally, with their incidence rising rapidly. For obstructive cardiovascular diseases, definitive treatment options include surgical interventions such as vascular stenting, replacement surgery, or vascular bypass. Decellularized extracellular matrix scaffolds, designed through tissue engineering, hold great potential in addressing the donor shortage issue.
The aim. To conduct a comparative analysis of sterilization methods for decellularized matrix scaffolds used in vascular transplantation, based on information from open sources.
Materials and methods. Publications were selected from the databases PubMed, Clinical Key Elsevier, Cochrane Library, eBook Business Collection, and Google Scholar, focusing on sterilization methods for decellularized matrix scaffolds. The literature search used keywords such as tissue engineering, decellularization, extracellular matrix, sterilization, gamma sterilization, and acellular transplant.
Results. The transplantation of synthetic scaffolds into the human body triggers an immune response to foreign materials. Ideal sterilization or disinfection for decellularized extracellular matrix should effectively eliminate microorganisms while ensuring the sterilized material is non-toxic and preserves physical and chemical properties, as well as biological activity of the biomaterial. Radiation sterilization primarily involves gamma irradiation from Cobalt-60 isotopes and electron beams generated by electron accelerators. In addition to sterilization, decellularized tissue constructs require long-term preservation methods, including cryopreservation, lyophilization, and the use of antibiotics and antifungals stored at –20 °C to –80 °C.
Conclusions. Decellularized tissue is receiving significant attention as a potential biological scaffold, as it retains the structure and functions of the extracellular matrix. The application of sterilization methods, such as gamma irradiation from Cobalt-60, ensures deep penetration and preservation of physical properties of the materials.
References
- Cai Z, Tan Z, Tian R, Chen X, Miao P, Yao C, et al. Acellular Vascular Scaffolds Preloaded With Heparin and Hepatocyte Growth Factor for Small-Diameter Vascular Grafts Might Inhibit Intimal Hyperplasia. Cell Transplant. 2022;31:9636897221134541. https://doi.org/10.1177/09636897221134541
- Chen J, Zhang D, Wu LP, Zhao M. Current Strategies for Engineered Vascular Grafts and Vascularized Tissue Engineering. Polymers (Basel). 2023;15(9):2015. https://doi.org/10.3390/polym15092015
- Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, et al.; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021;143(8):e254-e743. https://doi.org/10.1161/CIR.0000000000000950
- Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al.; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141(9):e139-e596. https://doi.org/10.1161/CIR.0000000000000757
- Kim HC. Epidemiology of cardiovascular disease and its risk factors in Korea. Glob Health Med. 2021;3(3):134-141. https://doi.org/10.35772/ghm.2021.01008
- Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al.; GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study. J Am Coll Cardiol. 2020;76(25):2982-3021. https://doi.org/10.1016/j.jacc.2020.11.010
- Di Francesco D, Pigliafreddo A, Casarella S, Di Nunno L, Mantovani D, Boccafoschi F. Biological Materials for Tissue-Engineered Vascular Grafts: Overview of Recent Advancements. Biomolecules. 2023;13(9):1389. https://doi.org/10.3390/biom13091389
- Komorovsky R, Desideri A, Coscarelli S, Cortigiani L, Celegon L. Impact of Carotid Arterial Narrowing on Outcomes of Patients With Acute Coronary Syndromes. Am J Cardiol. 2004;93(12):1552-1555. https://doi.org/10.1016/j.amjcard.2004.03.012
- Caproni S, Riva A, Barresi G, Costanti D, Costantini F, Galletti F, et al. Predictors of Carotid Atherosclerosis Progression: Evidence from an Ultrasonography Laboratory. Brain Sci. 2022;12(12):1600. https://doi.org/10.3390/brainsci12121600
- Guo Y, Canton G, Baylam Geleri D, Balu N, Sun J, Kharaji M, et al. Plaque Evolution and Vessel Wall Remodeling of intracranial Arteries: A Prospective, Longitudinal Vessel Wall MRI Study. J Magn Reson Imaging. 2024;60(3):889-899. https://doi.org/10.1002/jmri.29185
- Dimeling G, Bakaeen L, Khatri J, Bakaeen FG. CABG: when, why, and how? Cleve Clin J Med. 2021;88(5):295-303. https://doi.org/10.3949/ccjm.88a.20115
- Taggart DP. The Role of Multiple Arterial Grafts in CABG: All Roads Lead to ROMA.J Am Coll Cardiol. 2019;74(18):2249-2253. https://doi.org/10.1016/j.jacc.2019.09.016
- Moore MJ, Tan RP, Yang N, Rnjak-Kovacina J, Wise SG. Bioengineering artificial blood vessels from natural materials. Trends Biotechnol. 2022;40(6):693-707. https://doi.org/10.1016/j.tibtech.2021.11.003
- Hall AB, Brilakis ES. Saphenous vein graft failure: seeing the bigger picture.J Thorac Dis. 2019;11Suppl9:S1441-S1444. https://doi.org/10.21037/jtd.2019.03.09
- Leal BBJ, Wakabayashi N, Oyama K, Kamiya H, Braghirolli DI, Pranke P. Vascular Tissue Engineering: Polymers and Methodologies for Small Caliber Vascular Grafts. Front Cardiovasc Med. 2021;7:592361. https://doi.org/10.3389/fcvm.2020.592361
- Best CA, Szafron JM, Rocco KA, Zbinden J, Dean EW, Maxfield MW, et al. Differential outcomes of venous and arterial tissue engineered vascular grafts highlight the importance of coupling long-term implantation studies with computational modeling. Acta Biomater. 2019;94:183-194. https://doi.org/10.1016/j.actbio.2019.05.063
- Dai Z, Ronholm J, Tian Y, Sethi B, Cao X. Sterilization techniques for biodegradable scaffolds in tissue engineering applications. J Tissue Eng. 2016;7:2041731416648810. https://doi.org/10.1177/2041731416648810
- Golebiowska AA, Intravaia JT, Sathe VM, Kumbar SG, Nukavarapu SP. Decellularized extracellular matrix biomaterials for regenerative therapies: Advances, challenges and clinical prospects. Bioact Mater. 2023;32: 98-123. https://doi.org/10.1016/j.bioactmat.2023.09.017
- Shevchenko YeV, Hladkykh FV, Matvieienko MS. Cryomedical technologies as a key to effective decellularization in the creation of scaffolds for vascular transplantation. The Journal of V. N. Karazin Kharkiv National University. Series Medicine. 2024;32(3):366– 386. Ukrainian. English. https://doi.org/10.26565/2313-6693-2024-50-08
- Kasravi M, Ahmadi A, Babajani A, Mazloomnejad R, Hatamnejad MR, Shariatzadeh S, et al. Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine. Biomater Res. 2023;27(1):10. https://doi.org/10.1186/s40824-023-00348-z
- Sykes M, Sachs DH. Transplanting organs from pigs to humans. Sci Immunol. 2019;4(41):eaau6298. https://doi.org/10.1126/sciimmunol.aau6298
- Massaro MS, Pálek R, Rosendorf J, Červenková L, Liška V, Moulisová V. Decellularized xenogeneic scaffolds in transplantation and tissue engineering: Immunogenicity versus positive cell stimulation. Mater Sci Eng C Mater Biol Appl. 2021;127:112203. https://doi.org/10.1016/j.msec.2021.112203
- Sánchez-Fueyo A, Dazzi F. On minor histocompatibility antigens, mixed chimerism, and transplantation tolerance. Am J Transplant. 2021;21(3):919-920. https://doi.org/10.1111/ajt.16276
- Veiseh O, Vegas AJ. Domesticating the foreign body response: Recent advances and applications. Adv Drug Deliv Rev. 2019;144:148-161. https://doi.org/10.1016/j.addr.2019.08.010
- Callemeyn J, Lamarthée B, Koenig A, Koshy P, Thaunat O, Naesens M. Allorecognition and the spectrum of kidney transplant rejection. Kidney Int. 2022;101(4):692-710. https://doi.org/10.1016/j.kint.2021.11.029
- Gong T, Liu L, Jiang W, Zhou R. DAMP-sensing receptors in sterile inflammation and inflammatory diseases. Nat Rev Immunol. 2020;20(2):95-112. https://doi.org/10.1038/s41577-019-0215-7
- Chen H, Agrawal DK, Thankam FG. Biomaterials-Driven SterileInflammation.TissueEngPartBRev.2022;28(1):22-34. https://doi.org/10.1089/ten.TEB.2020.0253
- Shrivastava R, Shukla N. Attributes of alternatively activated (M2) macrophages. Life Sci. 2019;224:222-231. https://doi.org/10.1016/j.lfs.2019.03.062
- Zhao Y, Zhu B, Wang Y, Liu C, Shen C. Effect of different sterilization methods on the properties of commercial biodegradable polyesters for single-use, disposable medical devices. Mater Sci Eng C Mater Biol Appl. 2019;105:110041. https://doi.org/10.1016/j.msec.2019.110041
- 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;6(9):2927-2945. https://doi.org/10.1016/j.bioactmat.2021.02.010
- Montgomery A, Bolle-Reddat R, Formica S, Lundahl B, McDonnell G. Regulatory Approach for Transitioning from Gamma Ray to X-ray Radiation Sterilization. Biomed Instrum Technol. 2021;55(s3):58-66. https://doi.org/10.2345/0899-8205-55.s3.58
- Feng L, Hu YL, Ma P, Feng Y, Guo YB, Huang H, et al. Decellularized gastric matrix as a mesh for gastric perforation repair. J Biomed Mater Res B Appl Biomater. 2021;109(3):451-462. https://doi.org/10.1002/jbm.b.34713
- Chai Y, Xu J, Zhang Y, Zhang J, Hu Z, Zhou H. Evaluation of decellularization protocols for production of porcine small intestine submucosa for use in abdominal wall reconstruction. Hernia. 2020;24(6):1221-1231. https://doi.org/10.1007/s10029-019-01954-4
- Li Q, Zhang F, Wang H, Pan T. Preparation and characterization of a novel acellular swim bladder as dura mater substitute. Neurol Res. 2019;41(3):242-249. https://doi.org/10.1080/01616412.2018.1550139
- Sun Y, Lovric V, Wang T, Oliver RA, Walsh WR. Effects of SCCO₂, Gamma Irradiation, and Sodium Dodecyl Sulfate Treatments on the Initial Properties of Tendon Allografts. Int J Mol Sci. 2020;21(5):1565. https://doi.org/10.3390/ijms21051565
- Qiu S, Rao Z, He F, Wang T, Xu Y, Du Z, et al. Decellularized nerve matrix hydrogel and glial-derived neurotrophic factor modifications assisted nerve repair with decellularized nerve matrix scaffolds. J Tissue Eng Regen Med. 2020;14(7):931-943. https://doi.org/10.1002/term.3050
- Hunt CJ. Technical Considerations in the Freezing, Low-Temperature Storage and Thawing of Stem Cells for Cellular Therapies. Transfus Med Hemother. 2019;46(3):134-150. https://doi.org/10.1159/000497289
- Zouhair S, Aguiari P, Iop L, Vásquez-Rivera A, Filippi A, RomanatoF,etal.Preservationstrategiesfordecellularizedpericardial scaffolds for off-the-shelf availability. Acta Biomater. 2019;84:208-221. https://doi.org/10.1016/j.actbio.2018.10.026
- Alshaikh AB, Padma AM, Dehlin M, Akouri R, Song MJ, Brännström M, et al. Decellularization of the mouse ovary: comparison of different scaffold generation protocols for future ovarian bioengineering. J Ovarian Res. 2019;12(1):58. https://doi.org/10.1186/s13048-019-0531-3