REFERENCES
1. Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of liver disease: 2023 update. J Hepatol. 2023;79:516-37.
2. Mak LY, Liu K, Chirapongsathorn S, et al. Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions. Nat Rev Gastroenterol Hepatol. 2024;21:834-51.
3. Terrault NA, Francoz C, Berenguer M, Charlton M, Heimbach J. Liver transplantation 2023: status report, current and future challenges. Clin Gastroenterol Hepatol. 2023;21:2150-66.
4. Dai Q, Jiang W, Huang F, Song F, Zhang J, Zhao H. Recent advances in liver engineering with decellularized scaffold. Front Bioeng Biotechnol. 2022;10:831477.
5. Shaheen MF, Joo DJ, Ross JJ, et al. Sustained perfusion of revascularized bioengineered livers heterotopically transplanted into immunosuppressed pigs. Nat Biomed Eng. 2020;4:437-45.
6. Li K, Tharwat M, Larson EL, et al. Re-endothelialization of decellularized liver scaffolds: a step for bioengineered liver transplantation. Front Bioeng Biotechnol. 2022;10:833163.
7. Hussein KH, Ahmadzada B, Correa JC, et al. Liver tissue engineering using decellularized scaffolds: current progress, challenges, and opportunities. Bioact Mater. 2024;40:280-305.
8. Goldaracena N, Cullen JM, Kim D, Ekser B, Halazun KJ. Expanding the donor pool for liver transplantation with marginal donors. Int J Surg. 2020;82:30-5.
9. Plunkett J, Thinzar, King J, et al. Addressing global variation and systemic inequities in access to liver transplantation. npj Gut Liver. 2025;2:30.
10. Manzia TM, Angelico R, Gazia C, et al. De novo malignancies after liver transplantation: the effect of immunosuppression-personal data and review of literature. World J Gastroenterol. 2019;25:5356-75.
11. Magro B, Tacelli M, Mazzola A, Conti F, Celsa C. Biliary complications after liver transplantation: current perspectives and future strategies. Hepatobiliary Surg Nutr. 2021;10:76-92.
12. Mehtani R, Saigal S. Long term complications of immunosuppression post liver transplant. J Clin Hepatol. 2023;13:1103-15.
13. Yu Z, Keskinocak P, Magliocca JF, Romero R, Sokol J. Split or whole liver transplantation? Utilization and posttransplant survival. Hepatol Commun. 2023;7:e0225.
14. Lau NS, Jacques A, McCaughan G, Crawford M, Liu K, Pulitano C. Addressing the challenges of split liver transplantation through technical advances. A systematic review. Transplant Rev. 2021;35:100627.
15. Bowring MG, Massie AB, Schwarz KB, et al. Survival benefit of split‐liver transplantation for pediatric and adult candidates. Liver Transpl. 2022;28:969-82.
16. Ge J, Perito ER, Bucuvalas J, et al. Split liver transplantation is utilized infrequently and concentrated at few transplant centers in the United States. Am J Transplant. 2020;20:1116-24.
17. Groen PC, van Leeuwen OB, de Jonge J, Porte RJ. Viability assessment of the liver during ex-situ machine perfusion prior to transplantation. Curr Opin Organ Transplant. 2024;29:239-47.
18. Liew B, Nasralla D, Iype S, Pollok JM, Davidson B, Raptis DA. Liver transplant outcomes after ex vivo machine perfusion: a meta-analysis. Br J Surg. 2021;108:1409-16.
19. Op den Dries S, Karimian N, Westerkamp AC, et al. Normothermic machine perfusion reduces bile duct injury and improves biliary epithelial function in rat donor livers. Liver Transpl. 2016;22:994-1005.
20. Boehnert MU, Yeung JC, Bazerbachi F, et al. Normothermic acellular ex vivo liver perfusion reduces liver and bile duct injury of pig livers retrieved after cardiac death. Am J Transplant. 2013;13:1441-9.
21. Schliephake F, Lurje I, Uluk D, et al. Effects of hypothermic oxygenated machine perfusion on bile composition after liver transplantation - Findings from a randomized controlled trial. JHEP Rep. 2026;8:101647.
22. Ekser B, Li P, Cooper DKC. Xenotransplantation: past, present, and future. Curr Opin Organ Transplant. 2017;22:513-21.
23. Samy KP, Butler JR, Li P, Cooper DKC, Ekser B. The role of costimulation blockade in solid organ and islet xenotransplantation. J Immunol Res. 2017;2017:8415205.
24. Cross-Najafi AA, Lopez K, Isidan A, et al. Current barriers to clinical liver xenotransplantation. Front Immunol. 2022;13:827535.
25. Tao KS, Yang ZX, Zhang X, et al. Gene-modified pig-to-human liver xenotransplantation. Nature. 2025;641:1029-36.
27. Zhang W, Xu Q, Xu K, et al. Genetically engineered pig-to-human liver xenotransplantation. J Hepatol. 2026;84:587-98.
28. Mazza G, Rombouts K, Rennie Hall A, et al. Decellularized human liver as a natural 3D-scaffold for liver bioengineering and transplantation. Sci Rep. 2015;5:13079.
29. Toprakhisar B, Verfaillie CM, Kumar M. Advances in recellularization of decellularized liver grafts with different liver (stem) cells: towards clinical applications. Cells. 2023;12:301.
30. Verstegen MMA, Willemse J, van den Hoek S, et al. Decellularization of Whole Human Liver Grafts Using Controlled Perfusion for Transplantable Organ Bioscaffolds. Stem Cells Dev. 2017;26:1304-15.
31. Gao Y, Gadd VL, Heim M, et al. Combining human liver ECM with topographically featured electrospun scaffolds for engineering hepatic microenvironment. Sci Rep. 2024;14:23192.
32. Acun A, Oganesyan R, Uygun K, Yeh H, Yarmush ML, Uygun BE. Liver donor age affects hepatocyte function through age-dependent changes in decellularized liver matrix. Biomaterials. 2021;270:120689.
33. Golebiowska AA, Intravaia JT, Sathe VM, Kumbar SG, Nukavarapu SP. Decellularized extracellular matrix biomaterials for regenerative therapies: advances, challenges and clinical prospects. Bioact Mater. 2024;32:98-123.
34. Willemse J, Verstegen MMA, Vermeulen A, et al. Fast, robust and effective decellularization of whole human livers using mild detergents and pressure controlled perfusion. Mater Sci Eng C Mater Biol Appl. 2020;108:110200.
35. Jiang Y, Li R, Han C, Huang L. Extracellular matrix grafts: from preparation to application (Review). Int J Mol Med. 2021;47:463-74.
36. Kasravi M, Ahmadi A, Babajani A, et al. Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine. Biomater Res. 2023;27:10.
37. Moffat D, Ye K, Jin S. Decellularization for the retention of tissue niches. J Tissue Eng. 2022;13:20417314221101151.
38. Kim S, Park SH, Mun J, et al. Enhancing peripheral nerve regeneration throughNaOH‐based decellularization of human nerve tissue. Bioeng Transl Med. 2025;10:e70072.
39. Neishabouri A, Soltani Khaboushan A, Daghigh F, Kajbafzadeh AM, Majidi Zolbin M. Decellularization in tissue engineering and regenerative medicine: evaluation, modification, and application methods. Front Bioeng Biotechnol. 2022;10:805299.
40. Koo MA, Jeong H, Hong SH, Seon GM, Lee MH, Park JC. Preconditioning process for dermal tissue decellularization using electroporation with sonication. Regen Biomater. 2021;9:rbab071.
41. Ansari T, Southgate A, Obiri-Yeboa I, et al. Development and characterization of a porcine liver scaffold. Stem Cells Dev. 2020;29:314-26.
42. Kasturi M, Vasanthan KS. Harvesting decellularized liver extracellular matrix from rodents for 3D scaffold fabrication. Artif Cells Nanomed Biotechnol. 2024;52:175-85.
43. Weigl EJ, Demir S, Schmid T, Hotes A, Muensterer O, Kappler R. Establishing a three-dimensional scaffold model of hepatoblastoma. Front Bioeng Biotechnol. 2023;11:1229490.
44. Rabbani M, Zakian N, Alimoradi N. Contribution of physical methods in decellularization of animal tissues. J Med Signals Sens. 2021;11:1-11.
45. Zhang Y, Lv Y, Wang Y, Chang TT, Rubinsky B. Pancreatic islets implanted in an irreversible electroporation generated extracellular matrix in the liver. Radiol Oncol. 2023;57:51-8.
46. Stefan L, Uehara MK, Ikegami Y, et al. Early-stage transplant responses in miniature-liver implants based on decellularization-recellularization technology. J Biosci Bioeng. 2025;140:244-51.
47. Ijima H, Fukuda Y, Uehara MK, et al. Decellularized mouse liver as a small-scale scaffold for the creation of a miniaturized human liver. J Chem Eng Japan. 2023;56:2204899.
48. Alaby Pinheiro Faccioli L, Suhett Dias G, Hoff V, et al. Optimizing the decellularized porcine liver scaffold protocol. Cells Tissues Organs. 2022;211:385-94.
49. Anderson BD, Nelson ED, Joo D, et al. Functional characterization of a bioengineered liver after heterotopic implantation in pigs. Commun Biol. 2021;4:1157.
50. Higashi H, Yagi H, Kuroda K, et al. Transplantation of bioengineered liver capable of extended function in a preclinical liver failure model. Am J Transplant. 2022;22:731-44.
51. Horie H, Oshima Y, Fukumitsu K, et al. Antithrombotic revascularization strategy of bioengineered liver using a biomimetic polymer. Tissue Eng Part A. 2025;31:433-41.
52. Liu J, Hanson A, Yin W, et al. Decellularized liver scaffolds for constructing drug-metabolically functional ex vivo human liver models. Bioact Mater. 2024;43:162-80.
53. Afzal Z, Huguet EL. Bioengineering liver tissue by repopulation of decellularised scaffolds. World J Hepatol. 2023;15:151-79.
54. Afrin S, Yadav U, Yadav CJ, Kamel J, Lee JY, Park KM. Development of an enhanced liver scaffold recellularization using fibronectin. J Biomater Appl. 2025;40:513-28.
55. Panahi F, Baheiraei N, Sistani MN, Salehnia M. Analysis of decellularized mouse liver fragment and its recellularization with human endometrial mesenchymal cells as a candidate for clinical usage. Prog Biomater. 2022;11:409-20.
56. Kang SH, Kim MY, Eom YW, Baik SK. Mesenchymal stem cells for the treatment of liver disease: present and perspectives. Gut Liver. 2020;14:306-15.
57. Takeishi K, Collin de l’Hortet A, Wang Y, et al. Assembly and function of a bioengineered human liver for transplantation generated solely from induced pluripotent stem cells. Cell Rep. 2020;31:107711.
58. Acun A, Oganesyan R, Jaramillo M, Yarmush ML, Uygun BE. Human-origin iPSC-based recellularization of decellularized whole rat livers. Bioengineering. 2022;9:219.
59. Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells. 2009;24:1294-301.
60. Kadota Y, Yagi H, Inomata K, et al. Mesenchymal stem cells support hepatocyte function in engineered liver grafts. Organogenesis. 2014;10:268-77.
61. Chen J, Ma S, Yang H, et al. Generation and metabolomic characterization of functional ductal organoids with biliary tree networks in decellularized liver scaffolds. Bioact Mater. 2023;26:452-64.
62. Sassi L, Ajayi O, Campinoti S, et al. A perfusion bioreactor for longitudinal monitoring of bioengineered liver constructs. Nanomaterials. 2021;11:275.
63. Nelson VL, Stumbras AR, Palumbo RN, et al. Manufacturing and Functional Characterization of Bioengineered Liver Grafts for Extracorporeal Liver Assistance in Acute Liver Failure. Bioengineering. 2023;10:1201.
64. Campinoti S, Almeida B, Goudarzi N, et al. Rat liver extracellular matrix and perfusion bioreactor culture promote human amnion epithelial cell differentiation towards hepatocyte-like cells. J Tissue Eng. 2023;14:20417314231219813.
65. Yadav CJ, Yadav U, Afrin S, Lee JY, Kamel J, Park KM. Heparin immobilization enhances hemocompatibility, re-endothelization, and angiogenesis of decellularized liver scaffolds. Int J Mol Sci. 2024;25:12132.
66. Guo B, Zhou Q, Chen J, et al. Orthotopic transplantation of functional bioengineered livers in rats. ACS Biomater Sci Eng. 2023;9:1940-51.
67. Dias ML, Paranhos BA, Goldenberg RCDS. Liver scaffolds obtained by decellularization: a transplant perspective in liver bioengineering. J Tissue Eng. 2022;13:20417314221105305.
68. Zahmatkesh E, Khoshdel Rad N, Hossein-Khannazer N, et al. Cell and cell-derivative-based therapy for liver diseases: current approaches and future promises. Expert Review of Gastroenterol Hepatol. 2023;17:237-49.
69. Chen W, Lv L, Chen N, Cui E. Immunogenicity of mesenchymal stromal/stem cells. Scand J Immunol. 2023;97:e13267.
70. Zhao T, Zhang ZN, Rong Z, Xu Y. Immunogenicity of induced pluripotent stem cells. Nature. 2011;474:212-5.
71. Otsuka R, Wada H, Murata T, Seino KI. Immune reaction and regulation in transplantation based on pluripotent stem cell technology. Inflamm Regen. 2020;40:12.
72. Yoon J, Lee S, Kim MJ, Kim JH. Brief summary of the regulatory frameworks of regenerative medicine therapies. Front Pharmacol. 2025;15:1486812.
73. van Hengel EVA, van der Laan LJW, de Jonge J, Verstegen MMA. Towards safety and regulation criteria for clinical applications of decellularized organ-derived matrices. Bioengineering. 2025;12:136.
74. Framework for the regulation of regenerative medicine products. Available from: https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/framework-regulation-regenerative-medicine-products. [Last accessed on 9 Jun 2026].
75. Fang WH, Vangsness CT Jr. Governmental regulations and increasing food and drug administration oversight of regenerative medicine products: what’s new in 2020? Arthroscopy. 2020;36:2765-70.
76. Detela G, Lodge A. EU regulatory pathways for ATMPs: standard, accelerated and adaptive pathways to marketing authorisation. Mol Ther Methods Clin Dev. 2019;13:205-32.
77. European Medicines Agency. Advanced therapy medicinal products: overview. Available from: https://www.ema.europa.eu/en/human-regulatory-overview/advanced-therapy-medicinal-products-overview. [Last accessed on 9 Jun 2026].
78. Pharmaceuticals and Medical Devices Agency. Medical devices. Available from: https://www.pmda.go.jp/english/pnavi_e-06.html. [Last accessed on 9 Jun 2026].
79. Maria Cristina Galli. Regulatory aspects of gene therapy and cell therapy products: a global perspective. 2nd ed. Springer Cham; 2023. Available from: https://doi.org/10.1007/978-3-031-34567-8. [Last accessed on 9 Jun 2026].
80. Yokomizo R, Hosoya S, Umezawa A, Okamoto A. Amendment of the Act on the Safety of Regenerative Medicine: a new voyage of regenerative medicine in Japan and the dawn of a new era for young investigators. Regen Ther. 2025;29:237-46.
81. Silva DN, Chrobok M, Ahlén G, Blomberg P, Sällberg M, Pasetto A. ATMP development and pre-GMP environment in academia: a safety net for early cell and gene therapy development and manufacturing. Immunooncol Technol. 2022;16:100099.
82. Kanani T, Isherwood J, Chung WY, et al. A O03 ex vivo perfusion of isolated human liver segments: the development of a novel model for ethical, translational research. Br J Surg. 2022;109:znac404.003.
83. Wu G, Wu D, Lo J, et al. A bioartificial liver support system integrated with a DLM/GelMA-based bioengineered whole liver for prevention of hepatic encephalopathy via enhanced ammonia reduction. Biomater Sci. 2020;8:2814-24.





