Synthetic biodegradable alternatives to the use of the amniotic membrane for corneal regeneration: assessment of local and systemic toxicity in rabbits

Abstract

AimThe aim of this study was to assess the local and systemic response to poly-lactic co-glycolic acid (PLGA) 50:50 membranes, developed as synthetic biodegradable alternatives to the use of human donor amniotic membrane in the treatment of limbal stem cell deficiency.MethodsPLGA membranes of 2 cm diameter and 50 µm thickness were placed on one eye of rabbits and secured in place using fibrin glue and a bandage contact lens, suturing the eye close with a single stitch. Control animals were treated identically, with the absence of the membranes. Plain and microfabricated electrospun membranes (containing micropockets which roughly emulate the native limbal niche) were examined over 29 days. All animals were subjected to a detailed gross and histopathological observation as well as a detailed examination of the eye.ResultsApplication of the membranes both with and without microfabricated pockets did not adversely affect animal welfare. There was complete degradation of the membranes by day 29. The membranes did not induce any significant local or systemic toxicity. Conjunctival congestion and corneal vascularisation were noted in a few control and PLGA-treated animals. Intraocular pressure was normal and the retinal status was unaltered. The ocular surface was clear and intact in all animals by the end of 29 days.ConclusionMembranes of 50:50 PLGA can be safely applied to rabbit corneas without inducing any local or systemic toxicity and these break down completely within 29 days.

Proof-of-concept study of electrospun PLGA membrane in the treatment of limbal stem cell deficiency

“…This was confirmed in a prior study in rabbits where we looked for any evidence of topical or systemic toxicity. 18 This finding is consistent with the current report in humans.…”

“…15 Toxicology studies in rabbits confirmed the absence of local or systemic toxic effects and showed that the membranes disappeared completely within 28 days. 18 After these satisfactory preclinical studies, our next step was to conduct a proof-of-concept trial in man. The study objectives were to assess the performance of the PLGA membranes in terms of their safety (primary outcome) and efficacy (secondary outcome) in restoring the health of the ocular surface and vision in patients with LSCD.…”

Designing Scaffolds for Corneal Regeneration

“…[51,232,248] These materials have better strength and degradation resistance than many natural polymers, however in most cases the materials lack transparency; therefore, sufficient spacing is required between fibers to allow light to pass through. Rather than generating full thickness corneal scaffolds, synthetic polymers are more suitable for generating thin electrospun sheets for epithelial [248b,d] or endothelial [248a] transplantation, as an alternative to amniotic membranes [249] or as mechanical support for a stromal hydrogel material. [51] Natural polymers including gelatin and collagen have been investigated for use in generating scaffolds for corneal regeneration.…”

Corneal Repair and Regeneration: Current Concepts and Future Directions

“…AM is one of the thickest basement membranes that exists in the human body, with the ability to promote epithelial cell healing, besides inhibiting fibroblast proliferation and myofibroblast differentiation. In addition, it contains several anti-angiogenic, anti-inflammatory, and neurotrophic factors (Ramachandran et al, 2019). At present, AM transplantation has been used for various indications including repairing persistent epithelial defects and treating corneal ulceration, limbal stem cell deficiency, acute Stevens Johnson Syndrome (SJS), chemical and thermal burns, infectious keratitis, and after refractive surgery (St. Denis et al, 2012; Manolova et al, 2017; Prabhasawat, 2017; Westekemper et al, 2017).…”