Bioreactor design for perfusion-based, highly-vascularized organ regeneration

Abstract

Bioartificial or laboratory-grown organs is a growing field centered on developing replacement organs and tissues to restore body function and providing a potential solution to the shortage of donor organs for transplantation. With the entry of engineered planar tissues, such as bladder and trachea, into clinical studies, an increasing focus is being given to designing complex, three-dimensional solid organs. As tissues become larger, thicker and more complex, the vascular network becomes crucial for supplying nutrients and maintaining viability and growth of the neo-organ. Perfusion decellularization, the process of removing cells from an entire organ, leaves the matrix of the vascular network intact. Organ engineering requires a delicate process of decellularization, sterilization, reseeding with appropriate cells, and organ maturation and stimulation to ensure optimal development. The design of bioreactors to facilitate this sequence of events has been refined to the extent that some bioartificial organs grown in these systems have been transplanted into recipient animals with sustained, though limited, function. This review focuses on the state-of-art in bioreactor development for perfusion-based bioartificial organs and highlights specific design components in need of further refinement.

Keywords: Bioreactors; Tissue engineering; bioartificial organs; organ transplantation; perfusion decellularization; regenerative medicine.

Figure 1 (and Graphical abstract)

This illustration depicts the process of bioartificial organ engineering. Cells are removed from non-transplantable organs in a decellularization bioreactor. The resulting extracellular matrix scaffold is then reseeded within a specialized perfusion culture system that mimics the in vivo environment and provides for optimal organ development.

Figure 2

General bioreactor layout and design. A) Typical process flow diagram for a bioreactor circuit with sensors before, within or after the bioreactor system. B) Circular bioreactor. C) Dynamic reactor adapted from a CSTR. A stir bar is located in the bottom to mix the liquid.