ECM biomaterials for modeling of outflow cell biology in health and disease

•The complex structural and biochemical environment of the TM and SC tissues, critical for outflow regulation and intraocular pressure homeostasis, is governed by a specialized ECM.•Several 3D ECM-based models for investigations of human TM and SC cell biology in health and disease exist: cell-derived ECM, ECM scaffolds, Matrigel, and ECM hydrogels.•These bioengineered models have the potential to reveal the molecular underpinnings of TM and SC cell function, and to aid in the discovery of novel therapeutic targets for treating ocular hypertension in glaucoma. This review highlights the importance of extracellular matrix (ECM) biomaterials in understanding the biology of human trabecular meshwork (TM) and Schlemm's canal (SC) cells under normal and simulated glaucoma-like conditions. We provide an overview of recent progress in the development and application of state-of-the-art 3D ECM biomaterials including cell-derived ECM, ECM scaffolds, Matrigel, and ECM hydrogels for studies of TM and SC cell (patho)biology. Such bioengineered platforms enable accurate and reliable modeling of tissue-like cell-cell and cell-ECM interactions. They bridge the gap between conventional 2D approaches and in vivo/ex vivo models, and have the potential to aid in the identification of the causal mechanism(s) for outflow dysfunction in ocular hypertensive glaucoma. We discuss each model's benefits and limitations, and close with an outlook on future directions.