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David C Mundy, Fang Chen, Peter Le, David Myung; In vitro characterization of a novel in situ-forming semi-interpenetrating polymer network of crosslinked collagen and glycosaminoglycans for corneal defect repair. Invest. Ophthalmol. Vis. Sci. 2021;62(8):859.
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© ARVO (1962-2015); The Authors (2016-present)
In situ-forming hydrogels are promising new candidates to treat corneal injury and disease, as global corneal donor shortages leave millions at risk for or affected by corneal blindness without effective treatment. The extracellular matrix of the corneal stroma consists of collagen type I and glycosaminoglycans (GAGs) which together provide biomechanical and biochemical cues that modulate cellular behavior. We have developed and characterized a novel semi-interpenetrating polymer network (SIPN) of crosslinked collagen and GAGs that can potentially treat corneal stromal defects and promote wound healing.
The SIPN was formed by crosslinking collagen type I with succinimidyl glutamic acid ester difunctionalized polyethylene glycol (PEG) using N-hydroxysuccinimide (NHS) ester chemistry, which was then mixed with hyaluronic acid (HA), chondroitin sulfate (CS), or both. To determine gel stiffness, storage (G') and loss (G'') moduli were measured. Transparency was evaluated by UV/Vis spectroscopy as transmittance after gelation. Gel cytocompatibility was assessed by live/dead assay using human corneal epithelial cells seeded on the gels.
The collagen-PEG NHS gel and its SIPNs with HA and/or CS started to form within 1 minute, reaching 50% gelation within 10 minutes under ambient conditions. Mechanical properties were tunable by changing the concentration of PEG and the ratio of collagen:GAGs. 4% PEG (v/v PEG to collagen) gels had higher storage moduli than 8% PEG gels, whereas addition of GAGs decreased gel stiffness. The collagen-PEG and SIPN gels all showed over 95% transparency from 380 to 700 nm. Transmittance remained over 95% at 48 hours, whereas transmittance of non-crosslinked collagen decreased significantly over time. All gels were cytocompatible, with the SIPN with HA and/or CS demonstrating improved cell viability over collagen-PEG NHS alone.
We have developed a novel, collagen-PEG SIPN with GAGs that forms quickly in situ under ambient conditions. The hydrogel displays tunable mechanical properties, maintains excellent transparency, and promotes corneal epithelial cell viability, demonstrating the potential to promote wound healing and advance the treatment of corneal injury and disease.
This is a 2021 ARVO Annual Meeting abstract.
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