A Bioprinted Bruch's Membrane for Modeling Smoke-Induced Retinal Pigment Epithelium Degeneration via Hybrid Membrane Printing Technology.

Abstract

The retinal pigment epithelium (RPE) not only forms the outer blood-retinal barrier (oBRB) but also plays a multifunctional role in the ocular system. The loss of this epithelium leads to serious diseases resulting in vision impairment. No effective treatment is available for the repair of RPE damage. A functional in vitro RPE model that allows the recapitulation of oBRB-related pathophysiological responses is lacking. Here, a hybrid membrane printing technology is developed to fabricate cellular monolayers on the basement membrane to mimic human Bruch's membrane (BM). Using this technology, in vitro oBRB model containing the RPE monolayer on the printed BM with stable mechanical properties and fibril diameter similar to that of natural BM is developed. Compared to traditional collagen bioink, BM-based bioink significantly promotes RPE functions in vitro. Finally, smoking-like conditions are exposed to the model to recapitulate the absorption of mainstream cigarette smoke which is known as one of the risk factors for the disease progression. RPE function is damaged due to oxidative stress. Furthermore, the versatility of the model as a drug-testing platform is confirmed by the suppression of oxidative stress via antioxidants. This technology shows potential for fabricating a functional oBRB model that reflects patient conditions.