RESOURCES

Abstract
Age-related macular degeneration (AMD), a leading cause of blindness, initiates in the outer-blood-retina-barrier (oBRB) formed by the retinal pigment epithelium (RPE), Bruch’s membrane, and choriocapillaris. The mechanisms of AMD initiation and progression remain poorly understood owing to the lack of physiologically relevant human oBRB models. To this end, we engineered a native-like three-dimensional (3D) oBRB tissue (3D-oBRB) by bioprinting endothelial cells, pericytes, and fibroblasts on the basal side of a biodegradable scaffold and establishing an RPE monolayer on top. In this 3D-oBRB model, a fully-polarized RPE monolayer provides barrier resistance, induces choriocapillaris fenestration, and supports the formation of Bruch’s-membrane-like structure by inducing changes in gene expression in cells of the choroid. Complement activation in the 3D-oBRB triggers dry AMD phenotypes (including subRPE lipid-rich deposits called drusen and choriocapillaris degeneration), and HIF-α stabilization or STAT3 overactivation induce choriocapillaris neovascularization and type-I wet AMD phenotype. The 3D-oBRB provides a physiologically relevant model to studying RPE-choriocapillaris interactions under healthy and diseased conditions.

Abstract
The permeability of the human trabecular meshwork (HTM) regulates eye pressure via a porosity gradient across its thickness modulated by stacked layers of matrix fibrils and cells. Changes in HTM porosity are associated with increases in intraocular pressure and the progress of diseases such as glaucoma. Engineered HTMs could help to understand the structure–function relation in natural tissues and lead to new regenerative solutions. Here, melt electrowriting (MEW) is explored as a biofabrication technique to produce fibrillar, porous scaffolds that mimic the multilayer, gradient structure of native HTM. Poly(caprolactone) constructs with a height of 125–500 μm and fiber diameters of 10–12 μm are printed. Scaffolds with a tensile modulus between 5.6 and 13 MPa and a static compression modulus in the range of 6–360 kPa are obtained by varying the scaffold design, that is, the density and orientation of the fibers and number of stacked layers. Primary HTM cells attach to the scaffolds, proliferate, and form a confluent layer within 8–14 days, depending on the scaffold design. High cell viability and cell morphology close to that in the native tissue are observed. The present work demonstrates the utility of MEW for reconstructing complex morphological features of natural tissues.

Abstract
Engineering scaffolds with a structure mimicking that of native cornea allows for addressing the severe donor shortage for the corneal blindness treatment, which, however, remains challenging. In the light that corneal stromal (CS) cells can play a key role in corneal stroma formation, in this study we incorporated CS cells into three-dimensional (3D) scaffolds printed from hyaluronic acid-modified gelatin-methacrylate (GelMA-HA) scaffolds and characterized the scaffolds in terms of remodeled extracellular matrix (ECM) in vitro. Our results illustrated that the modification of GelMA by HA allowed for 3D printing of corneal scaffolds and further improved the characteristics of primary rabbit-derived corneal stromal cells for remodelling scaffolds. After 60 days, we decellularized the remodeled corneal scaffolds and examined their optical properties; and our results demonstrated that the 3D printed corneal scaffolds provided CS cells with cues that guided them toward the directional and spatial organization and facilitated the ECM remodelling.

Abstract
Abstract Given its potential for high-resolution, customizable, and waste-free fabrication of medical devices and in vitro biological models, 3-dimensional (3D) bioprinting has broad utility within the biomaterials field. Indeed, 3D bioprinting has to date been successfully used for the development of drug delivery systems, the recapitulation of hard biological tissues, and the fabrication of cellularized organ and tissue-mimics, among other applications. In this study, we highlight convergent efforts within engineering, cell biology, soft matter, and chemistry in an overview of the 3D bioprinting field, and we then conclude our work with outlooks toward the application of 3D bioprinting for ocular research in vitro and in vivo.