Immunogenicity in xenogeneic scaffold generation: Antigen removal vs. decellularization
Open accessAbstract
Decades of research have been undertaken towards the goal of tissue engineering using xenogeneic scaffolds. The primary advantages associated with use of xenogeneic tissue-derived scaffolds for in vitro development of replacement tissues and organs stem from the inherent extracellular matrix (ECM) composition and architecture. Native ECM possesses appropriate mechanical properties for physiological function of the biomaterial and signals for cell binding, growth and differentiation. Additionally, xenogeneic tissue is readily available. However, translation of xenogeneic scaffold-derived engineered tissues or organs into clinical therapies requires xenoantigenicity of the material to be adequately addressed prior to implantation. Failure to achieve this goal will result in a graft-specific host immune rejection response, jeopardizing in vivo survival of the resultant scaffold, tissue or organ. This review explores (i) the appropriateness of scaffold acellularity as an outcome measure for assessing reduction of the immunological barriers to the use of xenogeneic scaffolds for tissue engineering applications and (ii) the need for tissue engineers to strive for antigen removal during xenogeneic scaffold generation.
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α-galactosidase utilization is cost-effective in removing α-gal epitopes without ECM damage.
“α-galactosidase utilization is cost-effective in removing α-gal epitopes without ECM damage [130, 185].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [130]
Section 4.1 (page unavailable) reports that α-galactosidase removes α-gal epitopes and that a bacterial-derived enzyme avoids potentially damaging acidic conditions. It does not establish that the treatment is cost-effective or that it causes no ECM damage; Section 5 describes preservation of ECM structure as a goal for antigen-removal strategies, not a demonstrated result here. (LLM, conf=0.87)
Experimental — accuracy not yet measuredSalts such as KCl and reducing agents such as dithiothreitol are exploited to enhance the extraction of hydrophilic antigens.
“Therefore, salts such as KCl and reducing agents such as dithiothreitol are exploited to enhance the extraction of hydrophilic antigens [130].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [130]
Section 4.2 reports that a reducing agent enhanced removal of hydrophilic antigens from bovine pericardium and that adding salt further promoted their solubilization and removal. Our copy does not identify the agents as dithiothreitol and KCl, so it supports the approach but not those specific examples. (LLM, conf=0.85)
Experimental — accuracy not yet measuredSubsequent studies suggested retention of α-gal epitopes as an etiology for Synergraft failure.
“Subsequent studies also suggested the retention of α-gal epitopes as an etiology for Synergraft ™ failure [130].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [130]
Known antigens such as α-gal can be exclusively eliminated via enzymatic treatment.
“Known antigens, such as α-gal, could be exclusively eliminated via enzymatic treatment.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [130]
Maintenance of salts within an elaborated range has been shown to decrease protein aggregation.
“Maintenance of salts within an elaborated range has been shown to decrease protein aggregation.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [130]
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References 111 · Cited by 254
Research works printed but not linked: 1
- [106]Koolman J Roehm K-H Isolation and analysis of proteins Color Atlas of Biochemistry 2005 2nd ed. Stuttgart and New York Thieme 78 79
- Authors
- Wong, M. L., & Griffiths, L. G.
- Affiliations
- University of California, Davis (US)
- Corresponding author
- Griffiths, Leigh G.
- Venue
- Acta Biomaterialia
- Publisher
- Elsevier BV
- Published
- 2014-05
- Volume
- 10
- Issue
- 5
- Pages
- 1806-1816
- ISSN
- 1742-7061 (ISSN-L)
- PMC
- PMC3976714
- OpenAlex
- W2158722130
- Cited by
- 254
- References
- 111
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 15 · 2023: 19 · 2022: 19 · 2021: 38 · 2020: 31 · 2019: 26 · 2018: 22 · 2017: 26 · 2016: 9 · 2015: 9 · 2014: 8
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Biomaterialia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL115205)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Keywords
- immunogenicity, antigen removal, decellularization, extracellular matrix, graft rejection, tissue engineering, xenotransplantation
- MeSH terms
- Animals, Antigens, Humans, Transplantation Immunology, Transplantation, Heterologous, Tissue Engineering, Tissue Scaffolds
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