Immunomodulatory topographies regulate myofibroblast differentiation and influence fibrous encapsulation of glaucoma drainage devices.

Abstract

Elevated intraocular pressure (IOP) is the primary driver of glaucoma, and lowering IOP remains essential for preventing vision loss. Glaucoma drainage devices (GDDs) help reduce IOP but often fail due to fibrosis. This study identifies surface micro topographies capable of modulating the fibrotic response to GDDs both <i>in vitro</i> and <i>in vivo</i>. Using the TopoChip high-throughput platform (2176 topographies), we fabricated poly(styrene-block-isobutylene-block-styrene) SIBS based micro topographies and screened them for their effects on human Tenon fibroblast adhesion and transdifferentiation, as well as primary macrophage attachment and cytokine expression. These screens revealed micro topographies that differentially regulate fibroblast and macrophage behaviour, enabling the selection of three candidate designs for <i>in vivo</i> evaluation. When incorporated into glaucoma shunts implanted in rabbits, these micro topographies produced distinct tissue responses compared with smooth controls, including differences in collagen deposition and density at the implant interface. Overall, this work demonstrates that engineered micro topographies can modulate wound healing around GDDs and provides a foundation for design-driven strategies to improve implant performance. Future studies will focus on long-term implantation to optimize therapeutic outcomes.