Engineering a motile, controllable intestine with integrated electronics to study host-microbiome interactions
Abstract
The diverse human gut microbiome plays a central role in health and disease of the gut and remote target organs. The human intestine is a complex organ, comprised of an epithelial layer, providing absorptive function, and two innervated muscular layers, creating peristalsis. The interactions between the gut microbiome, motility and absorption are an active field of research, as well as the microbiome-host target organ interactions. However, physiologically relevant gut models that recapitulate the real, complex 3D structure and function of the gut, and enable to sustain microbial communities in contact with the intestinal epithelium are significantly lacking. Here, we aim to develop an engineered, instrumented intestinal segment, that will recapitulate the structure-function of native intestine, and support stable microbiome communities, as an in-vitro platform for studying host-microbiome interactions. This engineered intestine may serve as a discovery tool for the development of microbiome-related therapeutics. The engineered intestine will be constructed by integrating layers of complex engineered tissues with soft, stretchable electronics. We will use decellularized intestine as a scaffold which will be wrapped with two engineered, anisotropic, muscular layers, to enable peristalsis. The lumen will be coated with intestinal epithelial cells to recreate an absorptive layer. The integrated, multi-modal electronics will be used for stimulating the muscular tissue to induce contraction, monitoring motile and barrier function, and for releasing various compounds to either the musculature or the epithelium, to modify their functions. Moreover, the electronics will enable to sense secreted molecules and their transfer across the epithelial barrier. Different bacterial populations can be introduced to the engineered intestinal segment to assess their direct effect on gut function, and on remote organs via signalling interactions. Supernatants from the intestinal segment can be collected for biochemical analysis, and fed into organchips of interest (brain, skeletal muscle, lung, etc.).
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2023
- Source ID
- FA86552117006
Entities
People
- Tal Dvir
Organizations
- Air Force Office of Scientific Research
- Tel Aviv University
- United States Air Force