Table 3.

Summary of current innervated 3D models to study corneal tissue biology in vitro. Based on references (Canner et al., 2014; Priyadarsini et al., 2017; Wang et al., 2017; Sharif, 2018).

	Collagen-Based Corneal Model	Silk-Based Corneal Model	Self-Assembled Stromal Model
Cell types	Avian embryonic corneal buttons and ophthalmic division of TG explants	Primary human corneal epithelial cells, corneal stromal stem cells, and chick DRGs	Primary human corneal fibroblasts and human neuroblastoma-derived neurons
Scaffold	Type 1 collagen hydrogels	Functionalized silk scaffolds, rat-tail Collagen type 1	none; de novo ECM production by corneal fibroblasts generates stromal layer Stimulated with a stable
Culture conditions	Maintained for 96 hours in DMEM:F-12 supplemented with 10% inactivated FBS	Maintained at an air-liquid interface for 4 weeks in defined media conditions	Vitamin C derivative to promote ECM secretion and assembly over 4 weeks; maintained on polycarbonate transwell membrane
Advantages	Inclusion of relevant cells types (epi, stroma, endo and neuronal); innervation into corneal tissue can be assessed	Inclusion of relevant cells types (epi, stroma, and neuronal); stable conditions permit chronic studies	Native ECM produced by resident stromal cells allows for studies involving ECM assembly in the context of development or repair