3D printing collagen type IV for corneal endothelium transplantation

Abstract

Collagen type IV (Col-IV) is a critical matrix protein component in the basement membrane. In the cornea, it is the key contributor to the formation of Descemet’s membrane — the layer for corneal endothelial cells to reside on. Currently, endothelial keratopathy, which uses the healthy donor corneal endothelium layer as a transplanted tissue, is the gold standard surgery to cure corneal blindness caused by endothelial dysfunction. However, its use is being limited by the shortage of donor corneas. Bioengineering Descemet’s membrane is an alternative to overcome the tissue shortage. In this study, we developed a printable Col-IV ink to construct a Col-IV membrane. We demonstrated that the printed Col-IV membrane has a seven times higher corneal endothelial cell attachment over other matrix proteins (e.g., Col-I, laminin, and chondroitin) and a significantly faster healing rate compared to Col-I. The human endothelial cells cultured on the Col-IV membrane retained their hexagonal shapes, expressed typical endothelial markers ZO-1 and Na+/K+-ATPase, and retained the ability to deposit laminin. As this collagen subtype is prevalent in the basement membranes of all body tissues, our work suggests an important role for Col-IV as a printable biomaterial in tissue engineering in general.