# Bioengineered 3D Human Trabecular Meshwork Models for Outflow Physiology and Glaucoma Research

## TL;DR

This paper reviews bioengineered 3D models of the human trabecular meshwork to study eye pressure regulation and glaucoma, aiming to improve drug discovery.

## Contribution

The paper provides a comprehensive review of bioengineering strategies for creating 3D HTM models that capture outflow physiology and IOP regulation.

## Key findings

- 3D HTM models using hydrogels and microfluidic devices can mimic key features of the conventional outflow pathway.
- These models allow measurement of outflow facility, reflecting pressure-dependent resistance in HTM physiology.
- Integration with stem cell technologies offers a framework for next-generation human-relevant TM models.

## Abstract

Primary open angle glaucoma (POAG) is one of the leading causes of irreversible blindness and is associated with dysfunction of the trabecular meshwork (TM), a three-dimensional (3D) structure that regulates aqueous humor outflow and, consequently, intraocular pressure (IOP). IOP is the only modifiable factor for glaucoma. Outflow facility is the inverse of aqueous humor outflow resistance caused by the presence of the TM and adjacent tissues, and reflects the TM’s central role in IOP control, representing the most physiologically relevant measure of human trabecular meshwork (HTM) function. Therefore, development of ex vivo systems to study outflow facility and IOP regulation is critical for advancing glaucoma research. We present a comprehensive review of bioengineering approaches to generation of 3D HTM models using synthetic, natural, and hybrid hydrogels, micro- and nanofabricated synthetic substrates or porous scaffolds, and microfluidic devices. These 3D HTM systems have been designed to capture key features such as topography, stiffness, and fluid flow in the conventional outflow pathway. In particular, we highlight HTM models that recapitulate IOP regulation and allow measurement of outflow facility, which directly reflect pressure-dependent outflow resistance in dynamic HTM physiology and glaucoma pathophysiology. By integrating these bioengineering approaches with emerging stem cell technologies, this review offers an evidence-based landscape overview and framework for designing next-generation 3D human-relevant TM models for outflow physiological studies and IOP-modulating drug discovery.