Treatment of microbial keratitis and corneal wound healing - The goal of this Phase I SBIR proposal is to test the feasibility of an antimicrobial tissue scaffolding
hydrogel matrix in eliminating infections of the eye and promoting corneal epithelial wound
regeneration. There are approximately 2.4 million eye injuries each year in the United States alone and a failure
to promote re-epithelialization in corneal wounds within normal two-week time frame causes persistent corneal
epithelial defects (PCED’s). Such defects lead to compromised vision or loss, ocular discomfort, infection,
scarring, corneal neovascularization, opacification and perforations. Current treatment strategies for PCED’s
involve aggressive lubrication with artificial tears/ointments, bandage contact lens, tarsorrhaphy, topical
antibiotics, steroids and amniotic membrane grafting or autologous serum and scleral contact lenses. However,
neither antibiotics nor amniotic membrane are sufficient to promote corneal re-epithelialization and wound
healing in wounds associated with infections. Hence, there is an unmet clinical need to develop a product to
promote corneal wound healing while preventing and eliminating infections.
Therefore, we propose here a novel self-assembling tissue scaffolding matrix – G4I to (i) prevent
infectious pathogens through a unique mechanism of action that is broad spectrum antibacterial, and (2)
promoting tissue regeneration by providing cell attachment sites within the scaffolding matrix. Additionally, G4I
can gel in situ and conforms to unique wound shapes and depths easily thereby enabling easy administration.
Phase I hypothesis. The Phase I SBIR hypothesis is that G4I antimicrobial regenerative matrix can treat
microbial keratitis while promoting corneal epithelial wound healing in vitro and in vivo.
Phase I Specific Aims.
SA1. Demonstrate safety and biocompatibility of G4I to confirm its safety by performing the Draize rabbit eye
test and quantifying gel dwell time in the rabbit cornea. Criterion for acceptance: Demonstrate G4I is safe and
biocompatible throughout the in-life period, as measured by a Draize score with swelling, edema, and discharge
with a score less than 3.
SA2. Demonstrate in vivo antimicrobial efficacy of G4I to eliminate Pseudomonas aeruginosa from
infected corneal wounds. Criterion for acceptance: Demonstrate effective clearing of P. aeruginosa from
wounds by at least 3 log reductions in G4I treated groups on Day 1, 3 and 7.
SA3. Demonstrate in vivo efficacy of G4I to promote healing of corneal epithelial wounds. Criterion for
acceptance: Improved rate of wound closure in G4I treated groups compared to controls by visual examination,
photographs and a histopathological assessment on Day 14.
