Abstract

This research program focuses on the reconstruction of portions of the biliary tree using tissue engineering approaches, in which cells and biomaterials are combined to generate an implantable medical device. Our goal is to reconstruct the choledocus, which is the distal region of the extrahepatic biliary tree connecting the liver to the duodenum. The clinical need is related to a set of cholangiopathies that include biliary atresia, distal cholangiocarcinoma, choledochal cysts, and injuries resulting from liver transplantation or other procedures performed on the biliary tract or other organs of the epigastrium. These conditions mainly cause strictures that progressively lead to an inflammatory response and possibly liver failure. Therapeutic options are limited and often require liver transplantation. However, due to the shortage of organ donors and given substantial mortality, morbidity, and economic costs associated to these diseases, new therapeutic alternatives are urgently needed. Efforts have been directed towards the bioengineering of bile ducts, however, the results of this research have been often inconclusive and poorly translatable. Our research group is currently working on this direction, optimizing both the cellular source and the biomaterials, with the prospect of creating an implantable bioartificial duct.

Impact:

The generation of a bioartificial choledocus would represent a significant breakthrough in the field of advanced therapies for the treatment of cholangiopathies requiring the use of choledocus substitutes. Despite the need for alternatives to standard therapies, to date there is no bioengineered bile duct in the clinic for several reasons. Most of the challenges concern cells, in terms of type and source, and biomaterials, which must demonstrate unique properties in terms of biocompatibility and biodegradability. The scientific approach that we pursue aims to generate a device that can be implanted in patients. Therefore, the choice of tools to be used for its development, especially cells and biomaterials, are designed in perspective of a clinical application. Many of the previous approaches relied primarily on acellular constructs, but while some showed encouraging results, they were often inconclusive with insufficient preclinical characterization. As also highlighted by other authors, for a successful therapeutic outcome, the bioengineered bile duct must couple the biomaterial(s) with a cellular source. Unlike previous studies, our goal is to perform a deep preclinical analysis over the long term, which will pave the way for a future clinical trial.

Pipeline