Multi-compartment Organ-on-a-Chip Based on Electrospun Nanofiber Membrane as In Vitro Jaundice Disease Model

Organ-on-a-chip (OOC) is now becoming a potential alternative to the classical preclinical animal models, which reconstitutes in vitro the basic function of specific human tissues/organs and dynamically simulates physiological or pathological activities in tissue and organ level. Despite of the much progress achieved so far, there is still an urgent need to explore new biomaterials to construct a reliable and efficient tissue–tissue interface and a general fabrication strategy to expand from single-organ OOC to multi-organ OOC in an easy manner. In this paper, we propose a novel strategy to prepare double-compartment organ-on-a-chip (DC-OOC) using electrospun poly(l-lactic acid)/collagen I (PLLA/Col I) nanofiber membrane as tissue–tissue interface. The unique features of PLLA/Col I nanofiber membrane like excellent biocompatibility, strong affinity to multiple cells, adjustable orientation, controllable thickness and porosity endow the tissue–tissue interface with excellent semi-permeability, appropriate mechanical support, inducible cell orientation, good cell adhesion and proliferation. The integration of 3D printing technology during the fabrication process enables precise size control of the tissue–tissue interface and stable bonding with microfluidic channels. More importantly, our fabrication strategy and OOC configuration makes it easy to extend from DC-OOC to multi-compartment organ-on-a-chip (MC-OOC). To show its possible application, in vitro jaundice disease model is established by constructing blood vessel/skin/liver/lung organ-on-a-chip via MC-OOC. The downward trends of the cell viability after perfusion of bilirubin, the variation in cell sensitivity to bilirubin for different type of cells and recovery of cell viability after blue light therapy prove the feasibility of this jaundice disease model. We believe this general strategy of constructing tissue–tissue interface and multi-organ OOC can be used for many other in vitro physiological and pathological models.