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Fitzroy, Australia

Ladewig K.,University of Melbourne | Abberton K.,The OBrien Institute | Abberton K.,University of Melbourne | O'Connor A.J.,University of Melbourne
Journal of Biomaterials and Tissue Engineering | Year: 2012

Tissue engineering emerged in the early 1990s to address limitations in organ transplantation and synthetic tissue replacements, focusing on coupling cells and a biocompatible matrix known as a scaffold. Some clinical success has been achieved to date; primarily with hard or avascular tissue replacements (e.g., bone and cartilage replacements) and two-dimensional soft tissues (e.g., skin and cornea). The reconstruction of more complicated three-dimensional soft tissues (e.g., cardiovascular, adipose tissues) is far more challenging. Here the commonly taken route of seeding a scaffold with an appropriate progenitor cell type and culturing in a bioreactor in vitro followed by in vivo implantation often results in construct failure due to diffusion limitations causing substantial cell death in the interior of the scaffold. A lack of nutrients and oxygen and the accumulation of waste due to normal cell metabolism contribute to this phenomenon, which is one reason why the repair of large soft tissue defects through tissue engineering has so far eluded successful clinical translation. One emerging trend to circumvent this problem is to utilize in vivo bioreactors that provide intrinsic vascularization or induce in situ vascularization during tissue development. However, the design of in vivo bioreactors needs not only to consider ways to improve in situ vascularization, but also needs to include considerations familiar to many tissue engineering approaches such as biocompatibility of the construct material, biodegradability, and biochemical and biomechanical signaling. This review discusses the important design parameters for in vivo bioreactors for tissue engineering with a particular focus on engineering of soft tissues such as adipose, cardiovascular and muscle tissue. Specific examples of in vivo bioreactors currently under investigation clinically or pre-clinically are discussed with respect to their fundamental working principles, past and present developments, and proximity to clinic. © 2012 American Scientific Publishers. All rights reserved. Source

Worner M.,The OBrien Institute | Poore S.,The OBrien Institute | Poore S.,University of Wisconsin - Madison | Tilkorn D.,The OBrien Institute | And 2 more authors.
Artificial Organs | Year: 2014

We have designed a laboratory extracorporeal normothermic blood perfusion system for whole organs (e.g., kidney) that achieves pulsatile flow, low levels of hemolysis, and a blood priming volume of 60mL or less. Using this uniquely designed extracorporeal circuit, we have achieved perfusion of two isolated ex vivo constructs. In the first experiment, we successfully perfused a rabbit epigastric flap based on the femoral vessels. In the second experiment, we were able to perfuse the isolated rabbit kidney for 48h (range for all kidneys was 12-48h) with excellent urine output, normal arterial blood gasses at 24h, and normal ex vivo kidney histology at the conclusion of the experiments. These parameters have not been achieved before with any known or previously published laboratory extracorporeal circuits. The study has implications for prolonged organ perfusion prior to transplantation and for tissue engineering of vascularized tissues, such as by the perfusion of decellularized organs. © 2013 Wiley Periodicals, Inc. and International Center for Artificial Organs and Transplantation. Source

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