02577nas a2200301   4500000000100000000000100001008003900002260001700041653001600058653002200074653002500096653001100121653002100132653001500153653001600168653001800184100001500202700001700217700002100234700002200255700002100277245009200298856008300390300001300473490000700486520176800493022001402261       0                             d  cDec 26, 202510aBasal cells10aBasement membrane10aCell Differentiation10aCornea10aEpithelial Cells10aEpithelium10aHomeostasis10awound healing1 aJoel Vanin1 aMichael Getz1 aCatherine Mahony1 aThomas B. Knudsen1 aJames A. Glazier00aV-Cornea: A computational model of corneal epithelium homeostasis, injury, and recovery  uhttps://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1013410  ae10134100 v213 aPurpose To develop a computational model that addresses limitations in current ocular irritation assessment methods, particularly regarding long-term effects, and recovery patterns following chemical exposure or trauma to the cornea. Methods V-Cornea is an agent-based computer simulation implemented in CompuCell3D that models corneal epithelial homeostasis and injury response. The model incorporates biologically-inspired rules governing cell behaviors (proliferation, differentiation, death) and key signaling pathways including Epidermal Growth Factor (EGF), translating cell-level behaviors to tissue-level outcomes (in vitro to in vivo extrapolation, IVIVE). Results V-Cornea successfully reproduces corneal epithelial architecture and maintains tissue homeostasis over extended simulated periods. Following simulated trauma or toxicant exposure, the model accurately predicts healing timeframes of 3–5 days for slight and mild injuries. For moderate injuries with basement membrane disruption, the model demonstrates longer recovery times and emergent dynamic structural disorganization that mimics recurrent corneal erosions, providing mechanistic insights into these pathological conditions. Conclusions V-Cornea’s modular CompuCell3D implementation is easily extensible to incorporate additional recovery and injury mechanisms. Future versions will include more realistic basement membrane dynamics and explicit representation of stromal tissue and immune response to improve predictivity for moderate injuries. This virtual-tissue approach shows potential not only for toxicological assessments but also for drug discovery and therapy optimization by providing a platform to test interventions and predict outcomes across various injury scenarios.  a1553-7358