We are investigating the interplay between cells, matrix support materials, growth factor signals, and metabolism to develop new tissue equivalents and recondition damaged or dying organs. We currently focus on: (1) development of bio-artificial livers and reconditioning of donor livers to address the shortage of donors for patients undergoing liver failure, (2) development of a new generation of skin regeneration templates that reduce scarring and speed up wound healing in burn patients, and (3) modulation of metabolism to reduce loss of lean body mass and improve immunity in patients suffering from muscle wasting syndromes found in trauma, AIDS, diabetes, and cancer.

Metabolic anomalies exist in most severe injuries and chronic diseases such as cancer and AIDS. They are often manifested as wasting syndromes leading to a severe loss of lean body mass, sometimes called cachexia. Our objective is to account quantitatively for the underlying metabolic alterations. Because the metabolic changes are so broad and complex, we are using a systems approach combining metabolomics, proteomics, and genomics to characterize the evolution of the metabolic states of the key organs, as well as elucidate the regulatory mechanisms. Furthermore, we apply bioinformatics analytical techniques and optimization tools to determine the best therapeutic targets to alleviate these metabolic derangements, which will yield therapies combining both nutrition and more conventional drugs that modulate the regulation of the response.

Our bio-artificial liver work revolves around microfabricated hepatocyte bioreactors that overcome the major transport-related shortcomings of hollow fiber-based systems previously tested in the clinic. Recent scale-up and in vivo testing of this design have yielded dramatic, positive results. Because such devices will most likely serve as a bridge to transplantation, we are also addressing the severe shortage of donor livers by recovering livers rejected from the donor pool due to metabolic abnormalities, such as excessive fat content or prolonged lack of oxygen. In these studies, we perfuse these organs with appropriate solutions that restore the metabolic energy production and promote repair processes.

In the bioartificial skin area, we are using various strategies to modulate the local growth factor environment of the wound. Deep wounds have a high propensity to heal as unappealing scars that can restrict joint motion, and often require repeated surgical revisions. We have developed a number of genetically modified skin grafts for local delivery of growth factors to promote and modulate the wound healing response in cases of severe burn injury or skin ulcers. We are also investigating the effect of factors that repel immune cells in an attempt to mimic the wound environment in the fetus, which can heal without scar. Our results show that we can modulate the proliferation of cells in the dermis and epidermis, as well as the recruitment of inflammatory cells in the wound to obtain better and faster wound healing in animal models.