Development of an engineered intestine

Description of projects available to graduate students:
In many of these diseases of the intestinal tract, surgical resection of all or part of the colon is a common end-stage treatment. Surgical resection often results in the creation of a colostomy, whereby waste is collected on the outside of the body with a wearable appliance. Wearers of these appliances can feel embarrassed, leading to social isolation, or experience difficulties or failure of the devices. There is a clearly a need for alternative therapies aimed at intestinal replacement. A number of diseases and disorders can afflict the intestines. Our long-term objective is to develop and evaluate a tissue engineered intestine (TEI). This work will leverage our substantial experience in the engineering of other tubular tissues, such as blood vessel and urethra. To rigorously define our target design goals – i.e., the mechanical and functional properties of native intestine that we wish to replicate in our TEI – we will extend work from the Vorp Laboratory that assessed colon biomechanics and function in health and disease. With design objectives defined and an array of appropriate materials to utilize, we will then generate and characterize intestinal tissue constructs made from porous scaffolds bulk-seeded with stem cells. We will then evaluate various in vitro culture regimens to create an optimal intestinal replacement construct that mimics the structural and biomechanical properties of native intestine. These TEI constructs will undergo preclinical evaluation in a small animal model and scale-up for eventual testing in a large animal model.

Techniques graduate student will learn:
Stem cell culture; cell seeding into elastomeric scaffolds; rat surgery; histology; biological imaging; biomechanical testing.