Genipin crosslinking reduced the immunogenicity of xenogeneic decellularized porcine whole-liver matrices through regulation of immune cell proliferation and polarization
Open accessAbstract
Decellularized xenogeneic whole-liver matrices are plausible biomedical materials for the bioengineering of liver transplantation. A common method to reduce the inflammatory potential of xenogeneic matrices is crosslinking. Nevertheless, a comprehensive analysis of the immunogenic features of cross-linked decellularized tissue is still lacking. We aimed to reduce the immunogenicity of decellularized porcine whole-liver matrix through crosslinking with glutaraldehyde or genipin, a new natural agent and investigated the mechanism of the immune-mediated responses. The histologic assessment of the host’s immune reaction activated in response to these scaffolds, as well as the M1/M2 phenotypic polarization profile of macrophages, was studied in vivo. The genipin-fixed scaffold elicited a predominantly M2 phenotype response, while the glutaraldehyde-fixed scaffold resulted in disrupted host tissue remodeling and a mixed macrophage polarization profile. The specific subsets of immune cells involved in the responses to the scaffolds were identified in vitro. Crosslinking alleviated the host response by reducing the proliferation of lymphocytes and their subsets, accompanied by a decreased release of both Th1 and Th2 cytokines. Therefore, we conclude that the natural genipin crosslinking could lower the immunogenic potential of xenogeneic decellularized whole-liver scaffolds.
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?
Genipin and carbodiimide have been utilized as biocompatible crosslinking agents, but achieving high effectiveness comparable to GA remains unresolved.
“genipin19 and carbodiimide20 have also been utilized as biocompatible crosslinking agents, but achieving high effectiveness comparable to the effectiveness of GA remains unresolved.”
From Bioengineered liver crosslinked with nano-graphene oxide enables efficient liver regeneration via MMP suppression and immunomodulation (2023) · cites this paper as [19]
The paper’s introductory passage (page unavailable) describes genipin as a crosslinking substitute for glutaraldehyde and reports better in vivo biocompatibility for genipin-treated grafts. It does not say that achieving crosslinking effectiveness comparable to glutaraldehyde remains unresolved. Carbodiimide is attached to a separate citation in the citing sentence, so it is not assessed here. (LLM, conf=0.86)
Experimental — accuracy not yet measuredComparative preclinical studies on porcine decellularized esophagus and liver demonstrated that genipin-treated scaffolds induced a shift in infiltrating macrophages toward the M2 subtype and decreased the number of infiltrating pan-macrophages upon implantation into rats, unlike GA-processed dECM.
“Comparative preclinical studies on porcine decellularized esophagus and liver demonstrated that despite GA-processed dECM, genipin-treated scaffolds induced a shift in infiltrating macrophages toward the M2 subtype and decreased the number of infiltrating pan-macrophages upon their implantation into rats [207, 208].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [208]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredDecellularization has demonstrated efficient capability in removing or reducing the alpha-gal content from porcine liver.
“Decellularization has demonstrated efficient capability in removing or reducing the alpha-gal content from porcine liver [[67], [68], [69]].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [69]
Genipin cross-linking showed non-significant suppressive effects on the viability of primary hepatocytes and endothelial cells, unlike glutaraldehyde cross-linking, which displayed significant cytotoxicity.
“Genipin cross-linking showed non-significant suppressive effects on the viability of primary hepatocytes and endothelial cells, unlike glutaraldehyde cross-linking, which displayed significant cytotoxicity.”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [69]
Wang et al. used genipin for porcine liver cross-linking following perfusion decellularization with 1% Triton X-100 and 1% SDS.
“Wang et al. used genipin, a naturally occurring cross-linking agent, for porcine liver cross-linking following perfusion decellularization with 1 % Triton X-100 and 1 % SDS [69].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [69]
Genipin alleviates immunogenicity by impeding CD4+ T cell proliferation and pro-inflammatory cytokine secretion and has beneficial effects on angiogenesis of implanted dECM scaffolds.
“Genipin also alleviates immunogenicity by impeding CD4+ T cell proliferation and pro-inflammatory cytokine secretion [191] and has beneficial effects on the angiogenesis of implanted dECM scaffolds [203, 208].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [208]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Foreign body reaction to biomaterials
Anderson, J. M., Rodriguez, A., & Chang, D. T. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2007.11.004 · Cited by 5,138 · see citing works
An overview of tissue and whole organ decellularization processes
Crapo, P. M., Gilbert, T. W., & Badylak, S. F. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.01.057 · Cited by 3,591 · see citing works
M-1/M-2 Macrophages and the Th1/Th2 Paradigm
Mills, C. D., Kincaid, K., Alt, J. M., Heilman, M. J., & Hill, A. M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.12.6166 · Cited by 3,287 · see citing works
Decellularization of tissues and organs
Gilbert, T. W., Sellaro, T. L., & Badylak, S. F. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.02.014 · Cited by 2,222 · see citing works
Formation and function of the myofibroblast during tissue repair
Hinz, B. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5700613 · Cited by 1,658 · see citing works
Immune response to biologic scaffold materials
Badylak, S. F., & Gilbert, T. W. (2008) · Seminars in Immunology · doi:10.1016/j.smim.2007.11.003 · Cited by 857 · see citing works
Acellular vascular tissues: natural biomaterials for tissue repair and tissue engineering
Schmidt, C. E., & Baier, J. M. (2000) · Biomaterials · doi:10.1016/s0142-9612(00)00148-4 · Cited by 762 · see citing works
Brown, B. N., Londono, R., Tottey, S., Zhang, L., Kukla, K. A., Wolf, M. T., Daly, K. A., Reing, J. E., & Badylak, S. F. (2012) · Acta Biomaterialia · doi:10.1016/j.actbio.2011.11.031 · Cited by 745 · see citing works
Calcification of Tissue Heart Valve Substitutes: Progress Toward Understanding and Prevention
Schoen, F. J., & Levy, R. J. (2005) · The Annals of Thoracic Surgery · doi:10.1016/j.athoracsur.2004.06.033 · Cited by 731 · see citing works
Macrophage Phenotype as a Determinant of Biologic Scaffold Remodeling
Badylak, S. F., Valentin, J. E., Ravindra, A. K., McCabe, G. P., & Stewart-Akers, A. M. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2007.0264 · Cited by 729 · see citing works
Early failure of the tissue engineered porcine heart valve SYNERGRAFT™ in pediatric patients
Simon, P. (2003) · European Journal of Cardio-Thoracic Surgery · doi:10.1016/s1010-7940(03)00094-0 · Cited by 623 · see citing works
Consequences of ineffective decellularization of biologic scaffolds on the host response
Keane, T. J., Londono, R., Turner, N. J., & Badylak, S. F. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2011.10.054 · Cited by 613 · see citing works
Glutaraldehyde as a protein cross-linking reagent
Richards, F. M., & Knowles, J. R. (1968) · Journal of Molecular Biology · doi:10.1016/0022-2836(68)90086-7 · Cited by 541 · see citing works
Sung, H., Huang, R., Huang, L. L. H., & Tsai, C.-C. (1999) · Journal of Biomaterials Science Polymer Edition · doi:10.1163/156856299x00289 · Cited by 507 · see citing works
Biological effects of residual glutaraldehyde in glutaraldehyde‐tanned collagen biomaterials
Speer, D. P., Chvapil, M. S., Eskelson, C. D., & Ulreich, J. B. (1980) · Journal of Biomedical Materials Research · doi:10.1002/jbm.820140607 · Cited by 473 · see citing works
EXTRACELLULAR MATRIX BIOSCAFFOLDS FOR ORTHOPAEDIC APPLICATIONS
Valentin, J. E., Badylak, J. S., McCabe, G. P., & Badylak, S. F. (2006) · Journal of Bone and Joint Surgery · doi:10.2106/jbjs.e.01008 · Cited by 410 · see citing works
XENOGENEIC EXTRACELLULAR MATRIX GRAFTS ELICIT A TH2-RESTRICTED IMMUNE RESPONSE1
Allman, A. J., McPherson, T. B., Badylak, S. F., Merrill, L. C., Kallakury, B., Sheehan, C., Raeder, R. H., & Metzger, D. W. (2001) · Transplantation · doi:10.1097/00007890-200106150-00024 · Cited by 388 · see citing works
Extracellular matrix: A gatekeeper in the transition from dormancy to metastatic growth
Barkan, D., Green, J. E., & Chambers, A. F. (2010) · European Journal of Cancer · doi:10.1016/j.ejca.2010.02.027 · Cited by 378 · see citing works
Feasibility study of a natural crosslinking reagent for biological tissue fixation
Sung, H., Huang, R., Huang, L. L. H., Tsai, C.-C., & Chiu, C.-T. (1998) · Journal of Biomedical Materials Research · doi:10.1002/(sici)1097-4636(19981215)42:4 · Cited by 307 · see citing works
Matsuyama, T., Yamada, A., Kay, J., Yamada, K. M., Akiyama, S. K., Schlossman, S. F., & Morimoto, C. (1989) · The Journal of Experimental Medicine · doi:10.1084/jem.170.4.1133 · Cited by 288 · see citing works
Crosslinking of biological tissues using genipin and/or carbodiimide
Sung, H., Chang, W., Ma, C., & Lee, M. (2003) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.10346 · Cited by 285 · see citing works
Glutaraldehyde-Fixed Bioprosthetic Heart Valve Conduits Calcify and Fail From Xenograft Rejection
Manji, R. A., Zhu, L. F., Nijjar, N. K., Rayner, D. C., Korbutt, G. S., Churchill, T. A., Rajotte, R. V., Koshal, A., & Ross, D. B. (2006) · Circulation · doi:10.1161/circulationaha.105.549311 · Cited by 242 · see citing works
Estimation of hydroxyproline by the AutoAnalyser
Grant, R. A. (1964) · Journal of Clinical Pathology · doi:10.1136/jcp.17.6.685 · Cited by 200 · see citing works
Chang, Y., Tsai, C.-C., Liang, H., & Sung, H. (2002) · Biomaterials · doi:10.1016/s0142-9612(01)00379-9 · Cited by 175 · see citing works
Tissue Engineering of Heart Valves
Rieder, E., Seebacher, G., Kasimir, M., Eichmair, E., Winter, B., Dekan, B., Wolner, E., Simon, P., & Weigel, G. (2005) · Circulation · doi:10.1161/circulationaha.104.473629 · Cited by 171 · see citing works
Dardik, H., Miller, N., Dardik, A., Ibrahim, I. M., Sussman, B., Berry, S. M., Wolodiger, F., Kahn, M., & Dardik, I. I. (1988) · Journal of Vascular Surgery · doi:10.1016/0741-5214(88)90153-x · Cited by 128 · see citing works
Wang, Y., Bao, J., Wu, Q., Zhou, Y., Li, Y., Wu, X., Shi, Y., Li, L., & Bu, H. (2015) · Xenotransplantation · doi:10.1111/xen.12141 · Cited by 125 · see citing works
Self-citationAllman, A. J., McPherson, T. B., Merrill, L. C., Badylak, S. F., & Metzger, D. W. (2002) · Tissue Engineering · doi:10.1089/107632702753503054 · Cited by 119 · see citing works
Immunogenicity of Decellularized Porcine Liver for Bioengineered Hepatic Tissue
Mirmalek-Sani, S.-H., Sullivan, D. C., Zimmerman, C., Shupe, T. D., & Petersen, B. E. (2013) · The American Journal of Pathology · doi:10.1016/j.ajpath.2013.05.002 · Cited by 115 · see citing works
Phenotypic dichotomies in the foreign body reaction
Anderson, J. M., & Jones, J. A. (2007) · Biomaterials · doi:10.1016/j.biomaterials.2007.07.010 · Cited by 110 · see citing works
Yao, C., Liu, B., Hsu, S., Chen, Y.-S., & Tsai, C. (2004) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.30045 · Cited by 97 · see citing works
Bayrak, A., Tyralla, M., Ladhoff, J., Schleicher, M., Stock, U. A., Volk, H.-D., & Seifert, M. (2010) · Biomaterials · doi:10.1016/j.biomaterials.2010.01.120 · Cited by 96 · see citing works
McDade, J. K., Brennan-Pierce, E. P., Ariganello, M. B., Labow, R. S., & Michael Lee, J. (2013) · Acta Biomaterialia · doi:10.1016/j.actbio.2013.02.021 · Cited by 80 · see citing works
Haag, J. C., Baiguera, S., Jungebluth, P., Barale, D., Gaudio, C. D., Castiglione, F., Bianco, A., Comin, C., Ribatti, D., & Macchiarini, P. (2011) · Biomaterials · doi:10.1016/j.biomaterials.2011.10.008 · Cited by 77 · see citing works
Estimation of hydroxyproline by the AutoAnalyzer.
Grant, R. A. (1965) · Journal of Clinical Pathology · doi:10.1136/jcp.18.5.686 · Cited by 72 · see citing works
Ferretti, M., Marra, K. G., Kobayashi, K., Defail, A. J., & Chu, C. R. (2006) · Tissue Engineering · doi:10.1089/ten.2006.12.2657 · Cited by 69 · see citing works
Modulation of the immune response by extracellular matrix proteins
Morwood, S. R., & Nicholson, L. (2006) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-006-0043-x · Cited by 53 · see citing works
Preparation and characterization of genipin-crosslinked rat acellular spinal cord scaffolds
Jiang, T., Ren, X., Tang, J., Yin, H. Z., Wang, K., & Zhou, C.-L. (2013) · Materials Science and Engineering C · doi:10.1016/j.msec.2013.04.046 · Cited by 51 · see citing works
Kneib, C., von Glehn, C. Q. C., da Costa, F. D. A., Costa, M. T., & Susin, M. F. (2012) · Tissue Antigens · doi:10.1111/j.1399-0039.2012.01885.x · Cited by 48 · see citing works
Scaffolds for liver tissue engineering
Hammond, J. S., Beckingham, I. J., & Shakesheff, K. M. (2005) · Expert Review of Medical Devices · doi:10.1586/17434440.3.1.21 · Cited by 48 · see citing works
Rieder, E., Nigisch, A., Dekan, B., Kasimir, M., Mühlbacher, F., Wolner, E., Simon, P., & Weigel, G. (2006) · Biomaterials · doi:10.1016/j.biomaterials.2006.06.020 · Cited by 46 · see citing works
Zachman, A. L., Crowder, S. W., Ortiz, O., Zienkiewicz, K. J., Bronikowski, C., Yu, S. S., Giorgio, T. D., Guelcher, S. A., Kohn, J., & Sung, H. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2012.0158 · Cited by 38 · see citing works
Preparation of immunogen-reduced and biocompatible extracellular matrices from porcine liver
Park, K.-M., Park, S.-M., Yang, S.-R., Hong, S.-H., & Woo, H.-M. (2013) · Journal of Bioscience and Bioengineering · doi:10.1016/j.jbiosc.2012.08.023 · Cited by 38 · see citing works
New Insights Into Mechanisms of Allograft Rejection
Pattison, J. M., & Krensky, A. M. (1997) · The American Journal of the Medical Sciences · doi:10.1016/s0002-9629(15)40113-2 · Cited by 36 · see citing works
Bao, J., Fisher, J. E., Lillegard, J. B., Wang, W., Amiot, B. P., Yu, Y., Dietz, A. B., Nahmias, Y., & Nyberg, S. L. (2012) · Cell Transplantation · doi:10.3727/096368912x656054 · Cited by 35 · see citing works
Self-citationReducing Gal expression on the pig organ – a retrospective review
Ezzelarab, M. B., & Cooper, D. K. C. (2005) · Xenotransplantation · doi:10.1111/j.1399-3089.2005.00236.x · Cited by 26 · see citing works
Interactions of Migrating T Lymphocytes, Inflammatory Mediators, and the Extracellular Matrix
Lider, O., Hershkoviz, R., & Kachalsky, S. G. (1995) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v15.i3-4.50 · Cited by 19 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Huang L. L., Sung H. W., Tsai C. C. & Huang D. M. Biocompatibility study of a biological tissue fixed with a naturally occurring crosslinking reagent. J. Biomed. Mater. Res. 42, 568– 576 (1998). 9827681
Cited by
Sorted by citations
Oryan, A., Kamali, A., Moshiri, A., Baharvand, H., & Daemi, H. (2018) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2017.08.184 · Cited by 500 · see citing works
Kim, B. S., Das, S., Jang, J., & Cho, D.-W. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00808 · Cited by 465 · see citing works
Joyce, K., Fabra, G. T., Bozkurt, Y., & Pandit, A. S. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00512-8 · Cited by 333 · see citing works
Collagen- and hyaluronic acid-based hydrogels and their biomedical applications
Xu, Q., Torres, J. E., Hakim, M. H., Babiak, P. M., Pal, P., Battistoni, C. M., Nguyen, M. B., Panitch, A., Solorio, L., & Liu, J. C. (2021) · Materials Science and Engineering R Reports · doi:10.1016/j.mser.2021.100641 · Cited by 326 · see citing works
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
Novel Biomedical Applications of Crosslinked Collagen
Gu, L., Shan, T., Ma, Y.-X., Tay, F. R., & Niu, L. (2019) · Trends in Biotechnology · doi:10.1016/j.tibtech.2018.10.007 · Cited by 305 · see citing works
Macroscale biomaterials strategies for local immunomodulation
Dellacherie, M. O., Seo, B. R., & Mooney, D. J. (2019) · Nature Reviews Materials · doi:10.1038/s41578-019-0106-3 · Cited by 259 · see citing works
Extracellular Matrix-Based Biomaterials and Their Influence Upon Cell Behavior
Cramer, M. C., & Badylak, S. F. (2020) · Annals of Biomedical Engineering · doi:10.1007/s10439-019-02408-9 · Cited by 196 · see citing works
Výborný, K., Vallová, J., Kočí, Z., Kekulová, K., Jiráková, K., Jendelová, P., Hodan, J., & Kubinová, Š. (2019) · Scientific Reports · doi:10.1038/s41598-019-47059-x · Cited by 140 · see citing works
Massaro, M. S., Pálek, R., Rosendorf, J., Červenková, L., Liška, V., & Moulisová, V. (2021) · Materials Science and Engineering: C · doi:10.1016/j.msec.2021.112203 · Cited by 82 · see citing works
Pervez, M. N., & Stylios, G. K. (2018) · Nanomaterials · doi:10.3390/nano8060395 · Cited by 78 · see citing works
Sridharan, R., Ryan, E. J., Kearney, C. J., Kelly, D. J., & O’Brien, F. J. (2018) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.8b00910 · Cited by 72 · see citing works
Extracellular matrix scaffold-immune microenvironment modulates tissue regeneration
Yu, Y., Zhang, W., Liu, X., Wang, H., Shen, J., Xiao, H., Mei, J., Chai, Y., & Wen, G. (2021) · Composites Part B Engineering · doi:10.1016/j.compositesb.2021.109524 · Cited by 63 · see citing works
Crosslinking Biopolymers for Advanced Drug Delivery and Tissue Engineering Applications
Thakur, G., Rodrigues, F. C., & Singh, K. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-0950-2_11 · Cited by 62 · see citing works
Zheng, C., Sui, B., Hu, C., Qiu, X., Zhao, P., & Jin, Y. J. (2018) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2676 · Cited by 59 · see citing works
Membranous Extracellular Matrix-Based Scaffolds for Skin Wound Healing
Da, L., Huang, Y., Xie, H., Zheng, B., Huang, Y., & Du, S. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13111796 · Cited by 59 · see citing works
Recent advances in liver engineering with decellularized scaffold
Dai, Q., Jiang, W., Huang, F., Song, F., Zhang, J., & Zhao, H. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.831477 · Cited by 57 · see citing works
Decellularized xenografts in regenerative medicine: From processing to clinical application
Capella‐Monsonís, H., & Zeugolis, D. I. (2021) · Xenotransplantation · doi:10.1111/xen.12683 · Cited by 57 · see citing works
Tan, J., Zhang, Q.-Y., Huang, L.-P., Huang, K., & Xie, H.-Q. (2021) · Biomaterials Science · doi:10.1039/d1bm00470k · Cited by 57 · see citing works
Exploiting crosslinked decellularized matrix to achieve uterus regeneration and construction
Yao, Q., Zheng, Y.-W., Lin, H.-L., Lan, Q.-H., Huang, Z.-W., Wang, L.-F., Chen, R., Xiao, J., Kou, L., Xu, H.-L., et al. (2020) · Artificial Cells, Nanomedicine, and Biotechnology · doi:10.1080/21691401.2019.1699828 · Cited by 56 · see citing works
Younes, H. M., Kadavil, H., Ismail, H. M., Adib, S. S. A., Zamani, S., Alany, R. G., & Al-Kinani, A. A. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics16010032 · Cited by 55 · see citing works
Types of Crosslinkers and Their Applications in Biomaterials and Biomembranes
Yammine, P., Safadi, A. E., Kassab, R., El‐Nakat, H., Obeid, P. J., Nasr, Z., Tannous, T., Sari‐Chmayssem, N., Mansour, A., & Chmayssem, A. (2025) · Chemistry · doi:10.3390/chemistry7020061 · Cited by 54 · see citing works
Kim, D.-H., Kim, M.-J., Kwak, S.-Y., Jeong, J., Choi, D., Choi, S. W., Ryu, J., & Kang, K.-S. (2023) · Nature Communications · doi:10.1038/s41467-023-35941-2 · Cited by 53 · see citing works
Chen, D., Zhu, T., Fu, W. E., & Zhang, H. (2019) · International Journal of Nanomedicine · doi:10.2147/ijn.s192699 · Cited by 51 · see citing works
Datta, S., Rameshbabu, A. P., Bankoti, K., Roy, M., Gupta, C., Jana, S., Das, A. K., Sen, R., & Dhara, S. (2020) · Materials Science and Engineering C · doi:10.1016/j.msec.2020.111604 · Cited by 49 · see citing works
Salvatore, L., Calò, E., Bonfrate, V., Pedone, D., Gallo, N., Natali, M. L., Sannino, A., & Madaghiele, M. (2020) · Polymer Testing · doi:10.1016/j.polymertesting.2020.106966 · Cited by 48 · see citing works
Mazloomnejad, R., Babajani, A., Kasravi, M., Ahmadi, A., Shariatzadeh, S., Bahrami, S., & Niknejad, H. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1103727 · Cited by 46 · see citing works
Furdella, K. J., Higuchi, S., Behrangzade, A., Kim, K., Wagner, W. R., & Geest, J. P. V. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.12.058 · Cited by 45 · see citing works
Saleh, T., Ahmed, E., Yu, L., Hussein, K., Park, K.-M., Lee, Y.-S., Kang, B.-J., Choi, K.-Y., Choi, S., Kang, K.-S., et al. (2018) · Artificial Cells, Nanomedicine, and Biotechnology · doi:10.1080/21691401.2018.1457037 · Cited by 41 · see citing works
Gao, M., Wang, Y., He, Y., Li, Y., Wu, Q., Yang, G., Zhou, Y., Wu, D., Bao, J., & Bu, H. (2019) · Xenotransplantation · doi:10.1111/xen.12470 · Cited by 41 · see citing works
Self-citationLiu, C., Jin, Z., Ge, X., Zhang, Y., & Xu, H. (2019) · Tissue Engineering Part A · doi:10.1089/ten.tea.2018.0297 · Cited by 41 · see citing works
Tethering peptides onto biomimetic and injectable nanofiber microspheres to direct cellular response
John, J. V., Choksi, M., Chen, S., Boda, S. K., Su, Y., McCarthy, A. D., Teusink, M. J., Reinhardt, R. A., & Xie, J. (2019) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2019.102081 · Cited by 40 · see citing works
Crosslinking strategies of decellularized extracellular matrix in tissue regeneration
Qiao, S., Peijie, T., & Jiang, N. (2023) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.37650 · Cited by 39 · see citing works
Barkestani, M. N., Naserian, S., Uzan, G., & Shamdani, S. (2021) · Journal of Tissue Engineering · doi:10.1177/2041731420983562 · Cited by 38 · see citing works
From waste to wealth: Repurposing slaughterhouse waste for xenotransplantation
Khan, R. L., Khraibi, A. A., Dumée, L. F., & Corridon, P. R. (2023) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2023.1091554 · Cited by 38 · see citing works
Recent Advances in Decellularization and Recellularization for Tissue-Engineered Liver Grafts
Wang, Y., Nicolas, C. T., Chen, H. S., Ross, J. J., Lorenzo, S. B. D., & Nyberg, S. L. (2016) · Cells Tissues Organs · doi:10.1159/000452761 · Cited by 36 · see citing works
Self-citationArslan, Y. E., Galata, Y. F., Arslan, T. S., & Derkuş, B. (2018) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-018-6135-4 · Cited by 34 · see citing works
Kumar, M., Nandi, S. K., Kaplan, D. L., & Mandal, B. B. (2017) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.7b00218 · Cited by 33 · see citing works
Recent Advances in Decellularization and Recellularization for Tissue-Engineered Liver Grafts
Wang, Y., Nicolas, C. T., Chen, H. S., Ross, J. J., Lorenzo, S. B. D., & Nyberg, S. L. (2017) · Cells Tissues Organs · doi:10.1159/000479597 · Cited by 33 · see citing works
Self-citationIsali, I., McClellan, P. E., Shankar, E., Gupta, S., Jain, M. K., Anderson, J. M., Hijaz, A., & Akkuş, O. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.06.043 · Cited by 33 · see citing works
Ardila, D. C., Tamimi, E. A., Doetschman, T. C., Wagner, W. R., & Geest, J. P. V. (2019) · Journal of Controlled Release · doi:10.1016/j.jconrel.2019.02.024 · Cited by 30 · see citing works
Gobinathan, S., Zainol, S. S., Azizi, S. F., Iman, N. M., Muniandy, R., Hasmad, H. N., Yusof, M. R., Husain, S. B., Aziz, H. A., & Lokanathan, Y. (2018) · Journal of Biomaterials Science Polymer Edition · doi:10.1080/09205063.2018.1485814 · Cited by 30 · see citing works
Hussein, K. H., Ahmadzada, B., Correa, J. C., Sultan, A., Wilken, S., Amiot, B., & Nyberg, S. L. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.06.001 · Cited by 28 · see citing works
“Decellularization has demonstrated efficient capability in removing or reducing the alpha-gal content from porcine liver [67 – 69].”
BackgroundDelgado, L. M., Fuller, K., & Zeugolis, D. I. (2018) · ACS Biomaterials Science & Engineering · doi:10.1021/acsbiomaterials.8b00052 · Cited by 27 · see citing works
Human, P., Ofoegbu, C., Ilsley, H., Bezuidenhout, D., de Villiers, J., Williams, D. F., & Zilla, P. (2020) · European Journal of Cardio-Thoracic Surgery · doi:10.1093/ejcts/ezaa257 · Cited by 26 · see citing works
New Insights into the Pros and Cons of Cross-Linking Decellularized Bioartificial Organs
Hussein, K. H., Park, K., Lee, Y., Woo, J.-S., Kang, B., Choi, K., Kang, K., & Woo, H. (2017) · The International Journal of Artificial Organs · doi:10.5301/ijao.5000541 · Cited by 26 · see citing works
Erten, E., Arslan, T. S., Derkuş, B., & Arslan, Y. E. (2016) · RSC Advances · doi:10.1039/c6ra16647d · Cited by 25 · see citing works
Cross-linking of a biopolymer-peptide co-assembling system
Inostroza-Brito, K. E., Collin, E. C., Majkowska, A., Elsharkawy, S., Rice, A. J., Hernández, A. E. D. R., Xiao, X. X., Rodríguez‐Cabello, J. C., & Mata, Á. (2017) · Acta Biomaterialia · doi:10.1016/j.actbio.2017.05.043 · Cited by 23 · see citing works
Medicinal Plants As Natural Polarizers of Macrophages: Phytochemicals and Pharmacological Effects
Davoodvandi, A., Sahebnasagh, R., Mardanshah, O., Asemi, Z., Nejati, M., Shahrzad, M. K., Mirzaei, H. R., & Mirzaei, H. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190829154934 · Cited by 24 · see citing works
Arslan, Y. E., Efe, B., & Arslan, T. S. (2019) · Biotechnology Progress · doi:10.1002/btpr.2814 · Cited by 20 · see citing works
Liver Bioengineering: Promise, Pitfalls, and Hurdles to Overcome
Acun, A., Oganesyan, R. V., & Uygun, B. E. (2019) · Current Transplantation Reports · doi:10.1007/s40472-019-00236-3 · Cited by 20 · see citing works
Elagin, V. V., Kuznetsova, D. S., Grebenik, E. A., Zolotov, D. A., Istranov, L. P., Zharikova, T. M., Istranova, E. V., Polozova, A. V., Reunov, D. G., Kurkov, A. V., et al. (2020) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2020.00107 · Cited by 18 · see citing works
Saleh, T., Ahmed, E., Yu, L., Song, S., Park, K., Kwak, H., & Woo, H. (2020) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.36920 · Cited by 19 · see citing works
Uddin, M. S., & Ju, J. (2020) · Journal of Polymer Research · doi:10.1007/s10965-020-02059-8 · Cited by 19 · see citing works
Genipin in an Ex Vivo Corneal Model of Bacterial and Fungal Keratitis
Koudouna, E., Huertas-Bello, M., Rodriguez, C. N., Riveros, S. C. H., Navarrete, M. L., & Avila, M. Y. (2021) · Translational Vision Science & Technology · doi:10.1167/tvst.10.9.31 · Cited by 17 · see citing works
Jin, L., He, H., Yang, F., Xu, L., Guo, G., & Wang, Y. (2020) · Biomedical Materials · doi:10.1088/1748-605x/aba239 · Cited by 17 · see citing works
Self-citationLight-activated decellularized extracellular matrix-based bioinks for enhanced mechanical integrity
Kim, M., Kang, D., Han, H., & Jang, J. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2025.101859 · Cited by 16 · see citing works
Soltanmohammadi, F., Gharehbaba, A. M., Alizadeh, E., & Javadzadeh, Y. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.138893 · Cited by 15 · see citing works
Saleh, T., Ahmed, E., Yu, L., Kwak, H., Hussein, K. H., Park, K., Kang, B., Choi, K., Kang, K., & Woo, H. (2018) · The International Journal of Artificial Organs · doi:10.1177/0391398818775522 · Cited by 15 · see citing works
Liu, P., Tian, B., Yang, L., Zheng, X., Zhang, X., Li, J., Liu, X., Lv, Y., & Xiang, J. (2018) · Biomedical Materials · doi:10.1088/1748-605x/aaf375 · Cited by 15 · see citing works
Recent advances in optimization of liver decellularization procedures used for liver regeneration
Khajavi, M., Hashemi, M., & Kalalinia, F. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119801 · Cited by 14 · see citing works
Farr, N. T. H., Pashneh‐Tala, S., Stehling, N., Claeyssens, F., Green, N. H., & Rodenburg, C. (2019) · Macromolecular Rapid Communications · doi:10.1002/marc.201900484 · Cited by 14 · see citing works
Cheng, C., Xu, P., Qi, H., Wang, X., Yu, X., Wang, Y., & Yu, X. (2021) · Biomedical Materials · doi:10.1088/1748-605x/ac246d · Cited by 13 · see citing works
Self-citationEx vivo organ engineering using decellularized tissue scaffolds
Saleh, T., Caciolli, L., Giobbe, G. G., & Coppi, P. D. (2025) · Nature Reviews Bioengineering · doi:10.1038/s44222-025-00322-5 · Cited by 11 · see citing works
Collagen-Based Biomimetic Systems to Study the Biophysical Tumour Microenvironment
Cambi, A., & Ventre, M. (2022) · Cancers · doi:10.3390/cancers14235939 · Cited by 11 · see citing works
Huertas-Bello, M., Cuéllar-Sáenz, J. A., Rodriguez, C. N., Cortés‐Vecino, J. A., Navarrete, M. L., Avila, M. Y., & Koudouna, E. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24086904 · Cited by 11 · see citing works
The Great Harmony in Translational Medicine: Biomaterials and Stem Cells
Erten, E., & Arslan, Y. E. (2018) · Advances in experimental medicine and biology · doi:10.1007/5584_2018_231 · Cited by 12 · 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
Clickable Biomaterials for Modulating Neuroinflammation
Cornelison, R. C., & Fadel, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158496 · Cited by 10 · see citing works
Liu, C., & Sun, J. (2020) · RSC Advances · doi:10.1039/c9ra03736e · Cited by 10 · see citing works
Wang, D., Sant, S., Lawless, C., & Ferrell, N. J. (2022) · Integrative Biology · doi:10.1093/intbio/zyac016 · Cited by 9 · see citing works
Agarwal, G., Shumard, S., McCrary, M. W., Osborne, O., Mojica-Santiago, J., Ausec, B., & Schmidt, C. E. (2024) · Journal of Neural Engineering · doi:10.1088/1741-2552/ad5939 · Cited by 10 · see citing works
Tendon Tissue-Engineering Scaffolds
Nguyen, P. K., Baek, K., Deng, F., Criscione, J. D., Tuan, R. S., & Kuo, C. K. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-816137-1.00084-2 · Cited by 8 · see citing works
Tissue Engineering for Mimics and Modulations of Immune Functions
Tao, C., & Wang, D. (2021) · Advanced Healthcare Materials · doi:10.1002/adhm.202100146 · Cited by 7 · see citing works
Development of a novel in vitro cell model for evaluation of nanofiber mats immunogenicity
Zidar, A., Zupančič, Š., Kristl, J., & Jeras, M. (2023) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2023.123696 · Cited by 7 · see citing works
The effect of decellularization processes on the immune response and compatibility of tissues
Nochalabadi, A., Khazaei, M., Zamani, S., & Rezakhani, L. (2025) · Tissue and Cell · doi:10.1016/j.tice.2025.103135 · Cited by 6 · see citing works
Redox-Activation of Neutrophils Induced by Pericardium Scaffolds
Vlasova, I. I., Suleimanov, S. K., Mikhalchik, E., Urmantaeva, N., Salimov, E., Ragimov, A., Khlebnikova, T. M., & Timashev, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232415468 · Cited by 5 · see citing works
Liu, Y., Cheng, C., Xing, J., Deng, Z., & Xu, P. (2025) · Collagen and Leather · doi:10.1186/s42825-025-00192-y · Cited by 5 · see citing works
Scaffolds Mimicking the Tumor Microenvironment for In Vitro Malignancy Models
Rosellini, E., & Cascone, M. G. (2025) · Biomimetics · doi:10.3390/biomimetics10100695 · Cited by 5 · see citing works
Morawski, M., Krasnodębski, M., Rochoń, J., Kubiszewski, H., Marzęcki, M., Topyła, D., Murat, K., Staszewski, M., Szczytko, J., Maleszewski, M., et al. (2025) · Biomolecules · doi:10.3390/biom15010098 · Cited by 5 · see citing works
Overview of Decellularized Materials for Tissue Repair and Organ Replacement
Liao, J., Guo, Q., Xu, B., & Li, X. (2021) · Springer eBooks · doi:10.1007/978-981-33-6962-7_1 · Cited by 4 · see citing works
Porcine Hepatocytes: Isolation and Liver Tissue Engineering for Xenotransplantation
Li, Y., Wu, Q., Wang, Y., Bu, H., & Bao, J. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0255-3_18 · Cited by 4 · see citing works
Self-citationNanotechnology-based regenerative approaches
Roy, S., Das, A., Chakraborty, T., & Bhattacharya, B. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-95134-0.00005-5 · Cited by 4 · see citing works
Soft and rigid scaffolds for spinal cord injury regeneration
Kubinová, Š. (2019) · Elsevier eBooks · doi:10.1016/b978-0-08-102807-0.00007-7 · Cited by 4 · see citing works
Strategies for decellularization, re-cellularization and crosslinking in liver bioengineering
Wang, J., & Jin, X. (2024) · The International Journal of Artificial Organs · doi:10.1177/03913988231218566 · Cited by 3 · see citing works
Novel genipin-crosslinked acellular biogenic conduits for tissue engineering applications
García‐García, Ó. D., Escalante-Quirós, S., Llinares-Monllor, C., Ávila‐Fernández, P., Sánchez‐Porras, D., Etayo‐Escanilla, M., Campos, F., Chato‐Astrain, J., & Carriel, V. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118064 · Cited by 3 · see citing works
The Decellularization of Whole Organs
Huang, Y. H., Yue, H., Lian, Z., & Li, X. (2021) · Springer eBooks · doi:10.1007/978-981-33-6962-7_5 · Cited by 3 · see citing works
Yakimov, B. P., Vlasova, I. I., Efremov, Y. M., Maksimov, E. G., Shirshin, E. A., Kagan, V. E., & Timashev, P. S. (2022) · Scientific Reports · doi:10.1038/s41598-022-14138-5 · Cited by 3 · see citing works
Liver Assist Systems for Bridging to Transplantation: Devices and Concepts
Raschzok, N., Hillebrandt, K. H., & Sauer, I. M. (2019) · Springer eBooks · doi:10.1007/978-3-319-92934-7_13 · Cited by 2 · see citing works
Amato, G., Saleh, T., Carpino, G., Gaudio, E., Alvaro, D., & Cardinale, V. (2021) · Current Transplantation Reports · doi:10.1007/s40472-021-00325-2 · Cited by 2 · see citing works
Chronic graft-specific cell-mediated immune response toward candidate xenogeneic biomaterial
Gates, K. V., & Griffiths, L. G. (2018) · Immunologic Research · doi:10.1007/s12026-018-8985-8 · Cited by 2 · see citing works
Genipin Attachment of Conjugated Gold Nanoparticles to a Decellularized Tissue Scaffold
Bellrichard, M., Snider, C., Dittmar, C., Brockman, J. D., Grant, D., & Grant, S. A. (2019) · Applied Sciences · doi:10.3390/app9235231 · Cited by 2 · see citing works
Nguyen, N. T., Vu, B. D., Huynh, T. D., Bui, T. Q., & Tran, H. L. B. (2025) · Artificial Organs · doi:10.1111/aor.15037 · Cited by 1 · see citing works
Improving ligament tissue scaffold with the use of genipin and gold nanoparticles
Bellrichard, M. (2020) · doi:10.32469/10355/83759 · Cited by 1 · see citing works
The Islet Confidential: Recent Trends and Perspectives in Pancreatic Islet Transplantation
Radha, B., Muniraj, G., Rengasamy, N., Arumugam, D., Paramasivam, R., Krishnan, P., & Rasu, R. (2016) · International Journal of Pharmacology Phytochemistry and Ethnomedicine · doi:10.18052/www.scipress.com/ijppe.3.54
Porcine Acellular Lung Matrix in Wound Healing and Hernia Repair
Chegireddy, V., Caplan, K. D., & Fernandez-Moure, J. S. (2018) · Recent clinical techniques, results, and research in wounds · doi:10.1007/15695_2017_102
Decellularized liver extracellular matrix for iPSC-based liver engineering
Acun, A., & Uygun, B. E. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-85766-6.00006-1
Functionalized nanofibers toward food packaging
El‐Naggar, M. E., & Rashdan, H. R. M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99461-3.00005-4
Coşkun, B., Say, R., & Ersöz, A. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.147249
- Authors
- Wang, Y., Bao, J., Wu, X., Wu, Q., Li, Y., Zhou, Y., Li, L., & Bu, H.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- Bu, Hong
- Venue
- Scientific Reports
- Published
- 2016-04-21
- Volume
- 6
- Issue
- 1
- Pages
- 24779-24779
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4838870
- OpenAlex
- W2341478524
- Cited by
- 101
- References
- 48
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 4 · 2023: 11 · 2022: 6 · 2021: 18 · 2020: 13 · 2019: 15 · 2018: 15 · 2017: 5 · 2016: 3
- FWCI
- 14.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Novartis
- Novartis Pharma
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- genipin crosslinking, glutaraldehyde crosslinking, immunogenicity, macrophage polarization, M2 macrophages, lymphocyte proliferation, Th1/Th2 cytokines, host immune response, tissue remodeling
- MeSH terms
- Animals, Biocompatible Materials, Extracellular Matrix, T-Lymphocytes, Helper-Inducer, Humans, Immune System, Leukocytes, Mononuclear, Liver, Macrophages, Swine, Liver Transplantation, Cytokines, Coculture Techniques, Tissue Engineering, Iridoids, Cell Proliferation, Tissue Scaffolds, Allografts, Heterografts
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
