Title: 3D cell printed corneal stromal equivalent for corneal tissue engineering

Biography:

Hyeonji Kim received B.S degree in mechanical engineering from POSTECH, South Korea, in 2013. She is currently pursuing the Ph.D. degree in department of mechanical engineering from POSTECH. Her research interest lies on the building the functional human tissues from stem cells via the 3D bioprinting technology and printable biomaterials.

Abstract

The microenvironments of tissues or organs are complex architectures comprised of fibrous proteins including collagen. The spatial organization of collagen fibrils contribute tissue-specific mechanical properties to the fibrillar matrix and mediates cell attachment, proliferation, differentiation, and migration. In particular, the cornea is organized in a lattice pattern of collagen fibrils which play a significant role in its transparency. Recent studies suggested various engineering methods to control the collagen fibril architectures and replicate the transparent corneal structure using synthetic and natural biomaterials [1-2]. However, the application of fabricated corneal scaffolds was reported to result in insufficient corneal features including low transparency. In this paper, we introduce a transparent bioengineered corneal structure. The structure is fabricated by inducing shear stress to a corneal stroma-derived decellularized extracellular matrix bioink [3] based on 3D cell-printing technique. The printed structure recapitulates the native macrostructure of the cornea with aligned collagen fibrils which results in the construction of a highly matured and transparent cornea stroma analogue. The level of shear stress, controlled by the various size of the printing nozzle, manipulates the arrangement of the fibrillar structure. With proper parameter selection, the printed cornea exhibits high cellular alignment capability, indicating tissuespecific structural organization of collagen fibrils. In addition, this structural regulation enhances critical cellular events in the assembly of collagen over time. Interestingly, the collagen fibrils that remodelled along with the printing path create a lattice pattern similar to the structure of native human cornea after 4 weeks in vivo. Taken together, these results establish the possibilities and versatility of fabricating aligned collagen fibrils; this represents significant advances in corneal tissue engineering. In vivo (a-c) and in vitro (d-f) evaluation results of 3D cell-printed and non-printed corneal implants. Optical images from slit lamp examination, 2D cross-sectional OCT images (a, d), and second harmonic generation (SHG) microscopic images of non-specific collagen (b, e) with Distribution analysis of collagen fibrillar orientation (c, f). In 3D cell-printed group, higher  transparency was exhibited compared to non-printed group and corneal stromal pattern by shear-induced collagen alignment was reconstructed similar to that in human cornea.