Modulation of Macrophage Phenotype, Maturation, and Graft Integration through Chondroitin Sulfate Cross-Linking to Decellularized Cornea
Abstract
Decellularized corneas obtained from other species have gained intense popularity in the field of tissue engineering due to its role to serve as an alternative to the limited availability of high-quality donor tissues. However, the decellularized cornea is found to evoke an immune response inspite of the removal of the cellular contents and antigens due to the distortion of the collagen fibrils that exposes certain antigenic sites, which often lead to graft rejection. Therefore, in this study we tested the hypothesis that cross-linking the decellularized corneas with chondroitin sulfate may help in restoring the distorted conformationation changes of fibrous matrix and thus help in reducing the occurrence of graft rejection. Cross-linking of the decellularized cornea with oxidized chondroitin sulfate was validated by ATR-FTIR analysis. An in vitro immune response study involving healthy monocytes and differentiated macrophages with their surface marker analysis by pHrodo red, Lysotracker red, ER tracker, and CD63, LAMP-2 antibodies confirmed that the cross-linked decellularized matrices elicited the least immune response compared to the decellularized ones. We implanted three sets of corneal scaffolds obtained from goat, i.e., native, decellularized, and decellularized corneas conjugated with chondroitin sulfate into the rabbit stroma. Histology analysis, three months after implantation into the rabbit corneal stromal region, confirmed the restoration of the collagen fibril conformation and the migration of cells to the implanted constructs, affirming proper graft integration. Hence we conclude that the chondroitin sulfate cross-linked decellularized corneal matrix may serve as an efficient alternative to the allograft and human cadaveric corneas.
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Distortions in collagen α-helix 3D structure during decellularization may expose hidden antigenic sites and provoke immune reactions, leading to graft rejection.
“These distortions in collagen α-helix 3D structure may expose hidden antigenic sites and provoke immune reactions, leading to graft rejection [162].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [162]
Crosslinking reduces decellularized tissues' immunogenicity by restoring structural distortions that occurred during decellularization.
“Crosslinking reduces decellularized tissues’ immunogenicity by restoring the structural distortions that occurred during decellularization.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [162]
Chondroitin sulfate crosslinking simultaneously ameliorates mechanical properties of dECM scaffolds and decreases inflammatory response by impeding the NF-κB transcriptional pathway in the immune system.
“Crosslinking with chondroitin sulfate simultaneously ameliorates the mechanical properties of dECM scaffolds and decreases inflammatory response by impeding the NF-κB transcriptional pathway in the immune system.”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [162]
In a preclinical study, chondroitin sulfate crosslinking of acellular goat corneas significantly reduced their immunogenicity following implantation into rabbits and promoted host regenerative processes.
“In a preclinical study, the application of chondroitin sulfate for crosslinking acellular goat corneas significantly reduced their immunogenicity following implantation into rabbits and promoted host regenerative processes [162].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [162]
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- Authors
- Chakraborty, J., Roy, S., Murab, S., Ravani, R., Kaur, K., Devi, S., Singh, D., Sharma, S., Mohanty, S., Dinda, A. K., Tandon, R., & Ghosh, S.
- Affiliations
- Indian Institute of Technology Delhi (IN)
- All India Institute of Medical Sciences (IN)
- Corresponding author
- Ghosh, Sourabh
- ORCID
- Venue
- ACS Biomaterials Science & Engineering
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-05-01
- Volume
- 5
- Issue
- 1
- Pages
- 165-179
- ISSN
- 2373-9878 (ISSN-L)
- OpenAlex
- W2799703809
- Cited by
- 42
- References
- 60
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 6 · 2023: 8 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 2 · 2018: 1
- FWCI
- 3.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Biomaterials Science & Engineering (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Biotechnology , Ministry of Science and Technology (BT/MB/INDO-US/VR/09/2013)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Corneal Surgery and Treatments
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- graft rejection, macrophage phenotype, macrophage maturation, graft integration, immune response, corneal scaffolds, rabbit model, allograft alternatives
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