Immune responses can lead to fibrosis of biomaterial implants and cancerous tumors, which can lead to complications such as hypertrophic scarring, excessive inflammation, and a reduction in the efficacy of cancer therapeutics. During the process of fibrosis, macrophages and fibroblasts deposit collagen to isolate foreign materials from the rest of the body. This process is typically studied by implantation of materials or tumors in in vivo rodent models. Although these models provide valuable information, physiological differences between rodents and humans lead to some inaccuracies when translating in vivo rodent studies to human clinical trials. In vitro microfluidic models enable the incorporation of human cells and physiological cues such as fluid flow and 3D structures. We have developed a 3D microfluidic model (“Fibrosis Chip”) of biomaterial-immune and cancer-immune interactions to study the fibrosis formation process and enable evaluation of potential antifibrotic therapeutics. The Fibrosis Chip allows for implantation of biomaterials or cancer spheroids with subsequent monitoring through microscopy and collection of culture medium. We demonstrated successful co-culture of mouse fibroblasts and macrophages within the device and carried out extensive characterization experiments to optimize cell seeding density, culture times, and biomaterial implantation. Data on cell interactions with biomaterials, as well as comparisons with in vivo mouse studies, will be presented. After optimization of experimental protocols and validation in mouse systems, the use of human cells within the device can enable extrapolation of expected human in vivo immune responses and eventual utilization of the chip for personalized and predictive medicine.

Matthew Wolf

Appearances