Journal article
Development of self-healing hydrogels to support choroidal endothelial cell transplantation for the treatment of early age related macular degeneration
Acta biomaterialia, Vol.194, pp.98-108
03/2025
DOI: 10.1016/j.actbio.2024.12.052
PMCID: PMC11867867
PMID: 39710218
Abstract
In retinal diseases such as age-related macular degeneration (AMD) and choroideremia, a key pathophysiologic step is loss of endothelial cells of the choriocapillaris. Repopulation of choroidal vasculature early in the disease process may halt disease progression. Prior studies have shown that injection of donor cells in suspension results in significant cellular efflux and poor cell survival. As such, the goal of this study was to develop a hydrogel system designed to support choroidal endothelial cell transplantation. A library of hydrogels was synthesized using laminin (i.e., LN111, LN121, and LN421), carboxy methyl chitosan, and oxidized dextran via reversible Schiff base chemistry. Each of the developed self-healing hydrogels was readily injectable into the suprachoroidal space, with ideal gelation, mechanical, and degradation properties. While all hydrogels were found to be compatible with choroidal endothelial cell survival in vitro, only LN111 and LN121 gels were well-tolerated in vivo. To determine if hydrogel mediated cell delivery enhances donor cell retention and survival in vivo, iPSC-derived choroidal endothelial cell laden hydrogels were injected into the suprachoroidal space of an immunocompromised choroidal cell injury rat model. Significantly more donor cells were retained and survived in eyes that received cell laden hydrogels versus contralateral hydrogel free controls. Furthermore, donor cells positive for human nuclear antigen were identified in the choroid of hydrogel eyes only. These findings pave the way for future cell replacement studies in large animal models of choroidal cell dropout focused on evaluating functional integration of donor cells within decellularized vascular tubes.
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Details
- Title: Subtitle
- Development of self-healing hydrogels to support choroidal endothelial cell transplantation for the treatment of early age related macular degeneration
- Creators
- Narendra Pandala - University of Iowa, The University of Iowa Institute for Vision ResearchIan Han - University of IowaLauryn Renze - University of IowaHailey SteffenEmily Meyering - University of IowaEdwin M. Stone - University of IowaKelly Mulfaul - University of IowaRobert Mullins - University of IowaBudd Tucker - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Acta biomaterialia, Vol.194, pp.98-108
- DOI
- 10.1016/j.actbio.2024.12.052
- PMID
- 39710218
- PMCID
- PMC11867867
- NLM abbreviation
- Acta Biomater
- ISSN
- 1742-7061
- eISSN
- 1878-7568
- Publisher
- Elsevier Ltd
- Grant note
- National Eye Institute: R01EY024605, R01EY033331 Sramek Charitable Trust
We would like to thank the National Eye Institute (R01EY024605, R01EY033331) and the Sramek Charitable Trust for providing funding for this work.
- Language
- English
- Electronic publication date
- 12/20/2024
- Date published
- 03/2025
- Academic Unit
- The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; John and Marcia Carver Nonprofit Genetic Testing Laboratory; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
- Record Identifier
- 9984769631402771
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