Small intestinal submucosa: superiority, limitations and solutions, and its potential to address bottlenecks in tissue repair
Abstract
Small intestinal submucosa (SIS) has attracted much attention in tissue repair because it can provide plentiful bioactive factors and a biomimetic three-dimensional microenvironment to induce desired cellular functions.
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Excessive crosslinking, particularly with chemical agents, impairs biodegradability and promotes a higher M1/M2 macrophage ratio, leading to increased inflammation and foreign body reaction compared to a non-crosslinked scaffold.
“While it helps reduce immunogenicity by restoring structural integrity after decellularization, excessive crosslinking-particularly with chemical agents-impairs biodegradability [135,136] and promotes a higher M1/M2 macrophage ratio, leading to increased inflammation and FBR compared to a non-crosslinked scaffold [137].”
From Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review (2025) · cites this paper as [136]
Cites
Decellularization of tissues and organs
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Macrophage Phenotype as a Determinant of Biologic Scaffold Remodeling
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Parmaksiz, M., Dogan, A., Odabas, S., Elçin, A. E., & Elçin, Y. M. (2016) · Biomedical Materials · doi:10.1088/1748-6041/11/2/022003 · Cited by 268 · see citing works
The promotion of a constructive macrophage phenotype by solubilized extracellular matrix
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Rana, D., Zreiqat, H., Benkirane-Jessel, N., Ramakrishna, S., & Ramalingam, M. (2017) · Journal of Tissue Engineering and Regenerative Medicine · doi:10.1002/term.2061 · Cited by 243 · see citing works
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Understanding the Extracellular Matrix to Enhance Stem Cell-Based Tissue Regeneration
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Crosslinking decreases the hemocompatibility of decellularized, porcine small intestinal submucosa
Glynn, J. J., Polsin, E. G., & Hinds, M. T. (2015) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.11.038 · Cited by 30 · see citing works
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Immune Response to Extracellular Matrix Bioscaffolds: A Comprehensive Review
Romero, D. J., Hussey, G., & Capella-Monsonís, H. (2025) · Biologics · doi:10.3390/biologics5030028 · Cited by 7 · see citing works
“…immunogenicity by restoring structural integrity after decellularization, excessive crosslinking—particularly with chemical agents—impairs biodegradability [135,136] and promotes a higher M1/M2 macrophage ratio, leading to increased inflammation and FBR compared to a non-crosslinked scaffold [137].”
- Authors
- Cao, G., Huang, Y., Li, K., Fan, Y., Xie, H., & Li, X.
- Affiliations
- Beihang University (CN)
- Central South University (CN)
- Sichuan University (CN)
- Corresponding author
- Xie, Huiqi
- Li, Xiaoming
- Venue
- Journal of Materials Chemistry B
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2019
- Volume
- 7
- Issue
- 33
- Pages
- 5038-5055
- ISSN
- 2050-750X (ISSN-L)
- 2050-7518
- OpenAlex
- W2961897913
- Cited by
- 101
- References
- 8
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 13 · 2023: 22 · 2022: 17 · 2021: 15 · 2020: 9
- FWCI
- 2.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Materials Chemistry B (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (No. 31771042)
- National Basic Research Program of China (2017YFC1104703)
- State Key Laboratory of New Ceramics and Fine Processing
- Ministry of Education of the People's Republic of China
- West China Hospital, Sichuan University (ZYJC18002)
- Ministry of Science and Technology of the People's Republic of China
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Physical Sciences › Materials Science › Biomaterials › Silk-based biomaterials and applications
- Keywords
- small intestinal submucosa, decellularized extracellular matrix, tissue repair, biomimetic microenvironment, bioactivity (biomaterials), immunogenicity, resorbability, recellularization, degradation rate control, mechanical properties, cardiovascular tissue engineering, abdominal wall repair, skin tissue engineering, bone tissue engineering
- MeSH terms
- Animals, Cardiovascular Diseases, Extracellular Matrix, Humans, Intestinal Mucosa, Intestine, Small, Polymers, Stromal Cells, Tissue Engineering
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