Three Dimensional Liver Project

Description of projects available to graduate students:
The research focus of the Badylak laboratory involves the use of extracellular matrix (ECM) as a biologic scaffold for tissue engineering and regenerative medicine applications. As such, all projects in the laboratory are highly interdisciplinary in nature and draw upon the concepts of developmental biology, stem cell biology, matrix biology, tissue engineering, and biochemistry to identify potential therapies for regeneration of complex tissues and organs. All work in the laboratory is directed at clinical translation and in fact, at any one time, there are typically two or three clinical trials occurring.

The project of this rotation will focus upon the development and approach for whole organ engineering. The concept of the project revolves around the ideal structure and composition of the native organ extracellular matrix as a template for seeding with site appropriate organ parenchymal cells. The present rotation will focus upon the liver.

The tasks that will be included in this rotation include investigation of various methods to decellularize intact whole livers (usually rat or pig livers). Characterization of the remaining extracellular matrix will be conducted that will include ultrastructural imaging, positive contrast imaging, light microscopy, immunolabeling, and standard histology.

The project will also involve investigation of methods to seed the (decellularized) scaffold with hepatocytes, ductular epithelial cells, and endothelial cells. The seeded construct will then be allowed time (typically 1-3 days) for the cells to attach prior to in vivo implantation in an animal model.

The objective of the project is to replace organ function in the animal. The intended clinical application addresses the shortage of donor organs for patients with end stage liver disease. The same concept is being approached for heart, lung, and kidney replacement.

Techniques graduate student will learn:
1. Biomaterial (matrix scaffold) preparation

2. Characterization of the composition and structure of ECM templates
a. Cell culture
b. Electrophoresis
c. Microscopy
d. Chemotaxis assays
e. Mitogenic assays
f. Quantitative RT-PCR

3. Animal model techniques
a. Preparation of IACUC protocols
b. Surgical techniques in small animals
c. Monitoring of small animals following surgery
d. Sacrifice of animals
e. Harvesting of tissues for analysis