Procyanidins-crosslinked aortic elastin scaffolds with distinctive anti-calcification and biological properties
Abstract
Elastin, a main component of decellularized extracellular matrices and elastin-containing materials, has been used for tissue engineering applications due to their excellent biocompatibility. However, elastin is easily calcified, leading to the decrease of life span for elastin-based substitutes. How to inhibit the calcification of elastin-based scaffolds, but maintain their good biocompatibility, still remains significantly challenging. Procyanidins (PC) are a type of natural polyphenols with crosslinking ability. To investigate whether pure elastin could be crosslinked by PC with anti-calcification effect, PC was first used to crosslink aortic elastin. Results show that PC can crosslink elastin and effectively inhibit elastin-initiated calcification. Further experiments reveal the possible mechanisms for the anti-calcification of PC crosslinking including (1) inhibiting inflammation cell attachment, and secretion of inflammatory factors such as MMPs and TNF-α, (2) preventing elastin degradation by elastase, and (3) direct inhibition of mineral nucleation in elastin. Moreover, the PC-crosslinked aortic elastin maintains natural structure with high pore volume (1111 μL/g), large pore size (10-300 μm) and high porosity (75.1%) which facilitates recellularization of scaffolds in vivo, and displays excellent hemocompatibility, anti-thrombus and anti-inflammatory potential. The advantages of PC-crosslinked porous aortic elastin suggested that it can serve as a promising scaffold for tissue engineering.
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Cross-linking has been suggested to minimize potential immune responses against transplanted decellularized tissues by masking antigenic markers present in collagen.
“Additionally, cross-linking has been suggested to minimize potential immune responses against transplanted decellularized tissues by masking antigenic markers present in collagen [174,175].”
From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [175]
Procyanidin crosslinking of pure aortic elastin blocks calcification nidi, decreases macrophage-ECM interaction, and prohibits pro-inflammatory cytokines and MMPs release.
“Wang et al. crosslinked pure aortic elastin with procyanidin and demonstrated its efficacy in blocking calcification nidi, decreasing macrophage-ECM interaction, and prohibiting their pro-inflammatory cytokines and MMPs release.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [204]
Procyanidin enhances elastin resistance to MMP-mediated degradation, and its application lowers immunogenicity and calcification of treated dECM.
“Procyanidin enhances elastin resistance to MMPs mediated degradation, and its application lowers the immunogenicity and calcification of treated dECM [204].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [204]
Cites
Mechanisms of calcification: role of collagen, polyphosphates, and phosphatase
Fleish, H., & Neuman, W. F. (1961) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1961.200.6.1296 · Cited by 444 · see citing works
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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
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
“Additionally, cross-linking has been suggested to minimize potential immune responses against transplanted decellularized tissues by masking antigenic markers present in collagen [174,175].”
Background
- Authors
- Wang, X., Zhai, W., Wu, C., Ma, B., Zhang, J., Zhang, H., Zhu, Z., & Chang, J.
- Affiliations
- Chinese Academy of Sciences (CN)
- Shanghai Blood Center (CN)
- East China Normal University (CN)
- Corresponding author
- Zhai, Wanyin
- Chang, Jiang
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2015-04
- Volume
- 16
- Pages
- 81-93
- ISSN
- 1742-7061 (ISSN-L)
- OpenAlex
- W2040424562
- Cited by
- 73
- References
- 1
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 8 · 2022: 12 · 2021: 8 · 2020: 10 · 2019: 5 · 2018: 1 · 2017: 6 · 2016: 1 · 2015: 1
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31070870)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Keywords
- procyanidins, aortic elastin, elastin cross-linking, anticalcification, decellularized extracellular matrix, matrix metalloproteinase inhibition, TNF-α, inflammation, hemocompatibility, recellularization, porous scaffolds, tissue engineering
- MeSH terms
- Animals, Aorta, Blood Coagulation, Calcification, Physiologic, Catechin, Cell Adhesion, Cell Line, Cross-Linking Reagents, Elastin, Glutaral, Heart Valves, Hemolysis, Humans, Macrophages, Minerals, Pancreatic Elastase, Platelet Adhesiveness, Staining and Labeling, Porosity, Rats, Sprague-Dawley, Sus scrofa, Proanthocyanidins, Biflavonoids, Matrix Metalloproteinase 12, Tissue Scaffolds, Proteolysis
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