The role of perfusion bioreactors in bone tissue engineering

Abstract

Tissue engineering has emerged as a possible alternative to current treatments for bone injuries and defects. However, the common tissue engineering approach presents some obstacles to the development of functional tissues, such as insufficient nutrient and metabolite transport and non-homogenous cell distribution. Culture of bone cells in three-dimensional constructs in bioreactor systems is a solution for those problems as it improves mass transport in the culture system. For bone tissue engineering spinner flasks, rotating wall vessels and perfusion systems have been investigated, and based on these, variations that support cell seeding and mechanical stimulation have also been researched. This review aims at providing an overview of the concepts, advantages and future applications of bioreactor systems for bone tissue engineering with emphasis on the design of different perfusion systems and parameters that can be optimized.

Keywords: bioreactor; bone; perfusion; shear stress; tissue engineering.

Figure 1. Schematic of the perfusion system described by Bancroft et al. (A) Top view of the perfusion chamber with six scaffold holders. (B) Representation of the complete system with the scaffold represented in gray, press-fit between the two O-rings, in black. The two medium reservoirs, 1 and 2, allow for complete medium change when the connection between the two is closed. Arrows represent medium flow.

Figure 2. Schematic of the perfusion system described by Janssen et al. (A) Top view of the perforated lid and bottom, (B) detail of the perfusion chamber (scaffolds in gray and O-rings in black) and (C) representation of the complete system. Oxygen sensors are placed before and after the perfusion chamber.

Figure 3. (A) Representation of the perfusion chamber described by Grayson et al. The media goes in through one end and it is distributed equally by the six individual chambers (each holding one scaffold shown in gray) and finally goes out through the opposite end. (B) Representation of the system described by Cartmell et al. The perfusion block is composed by eight individual chambers (each holding one scaffold, entrance of the chamber shown in gray). Each chamber is fed individually by a tube that comes from the reservoir.