Decellularization and engineered crosslinking: a promising dual approach towards bioprosthetic heart valve longevity
Open accessAbstract
OBJECTIVES: While decellularization has previously significantly improved the durability of bioprosthetic tissue, remnant immunogenicity may yet necessitate masking through crosslinking. To alleviate the fears of reintroducing the risk of calcific degeneration, we investigated the application of rationally designed crosslinking chemistry, capable of abrogating mineralization in isolation, in decellularized tissue. METHODS: Bovine and porcine pericardium were decellularized using the standard Triton X/sodium deoxycholate/DNAse/RNAse methodology and thereafter combined incrementally with components of a four-stage high-density dialdehyde-based fixation regimen. Mechanical properties prior to, and calcium levels following, subcutaneous implantation for 6 and 10 weeks in rats were assessed. RESULTS: Enhanced four-stage crosslinking, independent of decellularization, or decellularization followed by any of the crosslinking regimens, achieved sustained, near-elimination of tissue calcification. Decellularization additionally resulted in significantly lower tissue stiffness and higher fatigue resistance in all groups compared to their non-decellularized counterparts. CONCLUSIONS: The dual approach of combining decellularization with enhanced crosslinking chemistry in xenogeneic pericardial tissue offers much promise in extending bioprosthetic heart valve longevity.
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An optimized crosslinking strategy could retain dECM properties similar to native tissue and decrease immunogenicity via masking remaining antigens.
“An optimized crosslinking strategy could add the advantages of retaining dECM properties similar to native tissue and decreasing its immunogenicity via masking the remaining antigens [188, 189].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [188]
The Discussion (page unavailable) describes effective crosslinking as masking remnant extracellular-matrix immunogenicity, supporting the proposed reduction in immune response. Transmission electron microscopy found preserved collagen and elastin, and the Discussion says strength and stiffness remained acceptable for bioprostheses; neither passage establishes that the treated dECM retained properties similar to native tissue. (LLM, conf=0.84)
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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
- Authors
- Human, P., Ofoegbu, C., Ilsley, H., Bezuidenhout, D., de Villiers, J., Williams, D. F., & Zilla, P.
- Affiliations
- University of Cape Town (ZA)
- Strait Access Technologies (SAT), University of Cape Town, Cape Town, South Africa
- Corresponding author
- Zilla, Peter
- Venue
- European Journal of Cardio-Thoracic Surgery
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-09-07
- Volume
- 58
- Issue
- 6
- Pages
- 1192-1200
- ISSN
- 1010-7940 (ISSN-L)
- 1873-734X
- OpenAlex
- W3084048358
- Cited by
- 26
- References
- 30
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 1
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- European Journal of Cardio-Thoracic Surgery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Physical Sciences › Materials Science › Biomaterials › Collagen: Extraction and Characterization
- Keywords
- bioprosthetic heart valves, decellularization, pericardium, calcification, immunogenicity, valve durability, tissue stiffness, fatigue resistance, subcutaneous implantation
- MeSH terms
- Animals, Bioprosthesis, Cattle, Heart Valve Prosthesis, Heart Valves, Longevity, Pericardium, Swine, Rats
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