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Fibrin hydrogels are safe, degradable scaffolds for sub-retinal implantation


Autoři: Jarel K. Gandhi aff001;  Fukutaro Mano aff001;  Raymond Iezzi, Jr. aff001;  Stephen A. LoBue aff001;  Brad H. Holman aff001;  Michael P. Fautsch aff001;  Timothy W. Olsen aff001;  Jose S. Pulido aff001;  Alan D. Marmorstein aff001
Působiště autorů: Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, United States of America aff001
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0227641

Souhrn

Retinal pigment epithelium (RPE) transplantation for the treatment of macular degeneration has been studied for over 30 years. Human clinical trials have demonstrated that RPE monolayers exhibit improved cellular engraftment and survival compared to single cell suspensions. The use of a scaffold facilitates implantation of a flat, wrinkle-free, precisely placed monolayer. Scaffolds currently being investigated in human clinical trials are non-degradable which results in the introduction of a chronic foreign body. To improve RPE transplant technology, a degradable scaffold would be desirable. Using human fibrin, we have generated scaffolds that support the growth of an RPE monolayer in vitro. To determine whether these scaffolds are degraded in vivo, we developed a surgical approach that delivers a fibrin hydrogel implant to the sub-retinal space of the pig eye and determined whether and how fast they degraded. Using standard ophthalmic imaging techniques, the fibrin scaffolds were completely degraded by postoperative week 8 in 5 of 6 animals. Postmortem histologic analysis confirmed the absence of the scaffold from the subretinal space at 8 weeks, and demonstrated the reattachment of the neurosensory retina and a normal RPE–photoreceptor interface. When mechanical debridement of a region of native RPE was performed during implantation surgery degradation was accelerated and scaffolds were undetectable by 4 weeks. These data represent the first in situ demonstration of a fully biodegradable scaffold for use in the implantation of RPE and other cell types for treatment of macular degeneration and other retinal degenerative diseases.

Klíčová slova:

Eyes – Fibrin – Gels – Macular degeneration – Medical devices and equipment – Medical implants – Retina – Swine


Zdroje

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