Models of immunogenicity in preclinical assessment of tissue engineered heart valves
Open accessAbstract
Tissue engineered heart valves may one day offer an exciting alternative to traditional valve prostheses. Methods of construction vary, from decellularised animal tissue to synthetic hydrogels, but the goal is the same: the creation of a 'living valve' populated with autologous cells that may persist indefinitely upon implantation. Previous failed attempts in humans have highlighted the difficulty in predicting how a novel heart valve will perform in vivo. A significant hurdle in bringing these prostheses to market is understanding the immune reaction in the short and long term. With respect to innate immunity, the chronic remodelling of a tissue engineered implant by macrophages remains poorly understood. Also unclear are the mechanisms behind unknown antigens and their effect on the adaptive immune system. No silver bullet exists, rather researchers must draw upon a number of in vitro and in vivo models to fully elucidate the effect a host will exert on the graft. This review details the methods by which the immunogenicity of tissue engineered heart valves may be investigated and reveals areas that would benefit from more research. STATEMENT OF SIGNIFICANCE: Both academic and private institutions around the world are committed to the creation of a valve prosthesis that will perform safely upon implantation. To date, however, no truly non-immunogenic valves have emerged. This review highlights the importance of preclinical immunogenicity assessment, and summarizes the available techniques used in vitro and in vivo to elucidate the immune response. To the authors knowledge, this is the first review that details the immune testing regimen specific to a TEHV candidate.
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Desirable biocompatibility of natural scaffolds is primarily ascribed to inter- and intra-species conservation of ECM.
“Desirable biocompatibility of natural scaffolds is primarily ascribed to the inter- and intra-species conservation of ECM [27] and its MHC-free nature that makes the host immune system recognize them as self-components [28].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [27]
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Flagged first, then by citations
1 of the 136 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
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“Desirable biocompatibility of natural scaffolds is primarily ascribed to the inter- and intra-species conservation of ECM [27] and its MHC-free nature that makes the host immune system recognize them as self-components [28].”
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A Novel Aldehyde Scavenging Modification Boosted Pericardium Valve Materials against Calcification
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Immunogenicity assessment of swim bladder-derived biomaterials
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Self-citationSpecial Issue: Immunomodulatory Biomaterials
Qazi, T. H., & Duda, G. N. (2021) · Acta Biomaterialia · doi:10.1016/j.actbio.2021.09.019 · Cited by 1 · see citing works
Fan, K., Chen, Z., Yang, J.-X., Xu, P.-Y., Zhang, H., & Chen, A. (2026) · Chinese Journal of Chemical Engineering · doi:10.1016/j.cjche.2026.06.008 · Cited by 1 · see citing works
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Self-citationSalthouse, D., Novakovic, K., Hilkens, C. M. U., & Ferreira, A. M. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4193460
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A study on comprehensive anti-calcification treatment technology for bioprosthetic valves
Zhang, Y., Wang, Y., Hao, J., Wei, H., Meng, Y., Yang, X., Hu, S., & Zhou, J. (2025) · Journal of Materials Science Materials in Engineering · doi:10.1186/s40712-025-00263-2
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Human corneal decellularization for regenerative therapy from methods to clinical applications
Attari, S. S., Zamani, S., Doudi, S., Sadeghi, J., & Salehi, M. (2026) · Tissue and Cell · doi:10.1016/j.tice.2026.103746
- Authors
- Ground, M., Waqanivavalagi, S., Walker, R., Milsom, P., & Cornish, J.
- Affiliations
- University of Otago (NZ)
- University of Auckland (NZ)
- Auckland City Hospital (NZ)
- Corresponding author
- Ground, Marcus
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 133
- Pages
- 102-113
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W3164683864
- Cited by
- 31
- References
- 136
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 3
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Acta Biomaterialia (publishedVersion, cc-by-nc-nd)
- SSRN Electronic Journal (publishedVersion)
- PubMed (publishedVersion)
- ResearchSpace (University of Auckland) (submittedVersion, cc-by-nc-nd)
- Funders
- Green Lane Research and Educational Fund
- University of Auckland
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- tissue-engineered heart valves, immunogenicity, preclinical assessment, prosthetic heart valves, innate immunity, adaptive immune response, antigenicity, hydrogels
- MeSH terms
- Animals, Heart Valve Prosthesis, Heart Valves, Humans, Tissue Engineering
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.
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