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Ex Vivo Organotypic Corneal Model of Acute Epithelial Herpes Simplex Virus Type I Infection
Published on: November 3, 2012
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Collagen Analogs Promote Tissue Regeneration in HSV-1-Infected Corneas in Animal Models
Oleksiy Buznyk1,2,3, Hamid Goodarzi4,5, Jaime Gómez Laguna6
1Department of Biomedical and Clinical Sciences, Linköping University, SE-581 83 Linköping, Sweden.
Journal of Functional Biomaterials
|October 28, 2025
Summary
Synthetic corneal implants show promise for tissue regeneration in herpes simplex keratitis (HSK) models. While promoting cell repopulation, these cell-free implants did not prevent HSV-1 reactivation or re-infection, indicating further research is needed.
Area of Science:
- Ophthalmology
- Biomaterials Science
- Infectious Diseases
Background:
- Herpes simplex keratitis (HSK), caused by HSV-1, is a major cause of infectious corneal blindness.
- Current treatment involves human donor corneal transplantation, which carries risks of re-infection and immune rejection.
- Alternative strategies are needed to address the limitations of current HSK treatments.
Purpose of the Study:
- To develop and evaluate cell-free, regeneration-stimulating corneal implants as an alternative to donor grafts for HSK.
- To assess the efficacy of synthetic collagen-like peptide-polyethylene glycol (CLP-PEG) implants in promoting corneal tissue regeneration under inflammatory conditions.
- To investigate the performance of these implants in animal models of HSK caused by different HSV-1 strains.
Main Methods:
- Development of cell-free corneal implants using synthetic CLP-PEG crosslinked with carbodiimide chemistry.
- Experimental induction of HSK in rabbit and guinea pig models using three different HSV-1 strains.
- Evaluation of implant performance through histopathological examination and assessment of tissue regeneration, haze, and neovascularization at three months post-operation.
Main Results:
- All treated corneas demonstrated tissue regeneration with neocorneal tissue repopulation by ingrowing cells, despite the inflammatory environment.
- The CLP-PEG implants did not prevent HSV-1 reactivation or re-infection, evidenced by neovascularization and disorganization within the regenerated tissue.
- Histopathological analysis indicated viral strain-specific differences in neovascularization, with KOS infection showing interspecies variations.
Conclusions:
- Cell-free CLP-PEG implants show potential for stimulating corneal tissue regeneration in HSK models.
- These synthetic implants can integrate and promote neocorneal formation in an inflammatory setting.
- Further research is warranted to optimize implant design and evaluate their long-term efficacy in preventing viral reactivation and improving outcomes in HSK treatment.
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Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
Herpes
Herpes simplex type 1 (HSV‑1) is a widespread pathogen responsible for orolabial lesions. It is an enveloped, double-stranded DNA (dsDNA) virus belonging to the family Herpesviridae. Once the virus infects a host cell, its double‑stranded DNA genome is delivered into the nucleus, where a coordinated cascade of immediate‑early, early, and late gene expression directs viral DNA replication, structural protein synthesis, and virion assembly. After primary infection of epithelial cells, HSV-1...

