Research Projects

Corneal and conjunctival injuries, particularly chemical eye injuries (CEIs) or chemical ocular injuries, represent a significant global cause of vision impairment and ocular morbidity [1] [2]. These injuries often result in severe disruption of the ocular surface architecture, leading to inflammation, scarring, neovascularization, and vision loss. Current treatments, including allogeneic tissue grafts, synthetic bandage substitutes, and conventional amniotic membrane grafting, offer only partial and often temporary relief [3] [4]. Previous clinical observations by our team [5] [6] and several other groups [7] indicate that amniotic membrane transplantation (AMT) significantly contributes to maintaining best-corrected visual acuity (BCVA) and promoting a stable ocular surface. We hypothesize that amniotic membrane-hydrogels (AM-hydrogels) can effectively recapitulate the native ocular surface microenvironment and provide a biomimetic platform for enhancing endogenous wound healing mechanisms. The development of an ocular drug delivery system is necessary to enhance corneal permeability and prolong drug retention, thereby improving patient compliance and dual role (ocular repair/regeneration and antifungal or antibacterial drug delivery). A model drug (natamycin or moxifloxacin hydrochloride) will be incorporated into the AM-hydrogel to assess controlled-release properties for enhancement of ocular bioavailability. By leveraging the natural bioactivity of the amniotic extracellular matrix (ECM), rich in anti-inflammatory cytokines, growth factors, and matrix components, we hypothesize that the AM-hydrogel will facilitate localized, sustained, and bioavailable delivery of therapeutic cues. The proposed work will be done in three integrated phases: Phase 1: Hydrogel Fabrication and Characterization We will fabricate AM-hydrogels through an acellular human amniotic membrane. The physicochemical properties of the hydrogels will be evaluated. Additionally, ex vivo permeability studies using goat corneal tissue will assess the adherence, penetration, and retention behavior of hydrogel. Phase 2: In Vitro Bioactivity and Drug Delivery Evaluation The in vitro assessment will evaluate the cytocompatibility, cellular adhesion, and proliferation of the hydrogel using primary corneal epithelial cells and stromal fibroblasts. A model drug (natamycin or moxifloxacin hydrochloride) will be incorporated into the AM-hydrogel to assess controlled-release properties and enhancement of ocular bioavailability and related antimicrobial properties. Drug release kinetics, degradation profiles, and tissue interaction will be investigated in simulated ocular environments. Phase 3: In Vivo Efficacy in Rabbit CEI Model We will use a bilateral rabbit chemical eye injury model with standardized grade IV epithelial defects. In each animal, one eye will receive standard care with topical carboxymethyl cellulose (CMC), while the contralateral eye will receive CMC + AM-hydrogel or CMC + amniotic membrane patch as adjunct therapy. Parameters to be evaluated include photophobia, conjunctival injection, eyelid edema, and tear production. Corneal wound healing will be tracked using fluorescein staining, slit-lamp microscopy, and serial photography to assess epithelial closure and corneal clarity. Tear samples will be collected for biomarker analysis. At the endpoint, eyes will be harvested for histopathological, immunohistochemical, and molecular evaluation to assess inflammation, fibrosis, angiogenesis, and stem cell recruitment. This project aims to establish a therapeutic strategy for chemical eye injuries by developing a regenerative, ECM-based hydrogel system specifically tailored to the ocular surface and suitable for controlled drug release applications. This modality offers several key advantages, including accelerated improvement in corneal clarity, enhanced pain control, and the potential avoidance of surgical intervention in inflamed eyes.