Design of a high-throughput flow perfusion bioreactor system for tissue engineering

Abstract

Flow perfusion culture is used in many areas of tissue engineering and offers several key advantages. However, one challenge to these cultures is the relatively low-throughput nature of perfusion bioreactors. Here, a flow perfusion bioreactor with increased throughput was designed and built for tissue engineering. This design uses an integrated medium reservoir and flow chamber in order to increase the throughput, limit the volume of medium required to operate the system, and simplify the assembly and operation.

FIG. 1.

(A) Schematic of assembled bioreactor unit with the integrated medium reservoir and flow chamber. (B) Image of assembled bioreactor unit.

FIG. 2.

Scaffold holder and stainless steel 316 support mesh. Ten scaffolds, 3 mm in diameter, are distributed axisymmetrically and pressfit into position. A support mesh slides into place to prevent the movement of scaffolds during culture.

FIG. 3.

The scaffold holder is easily adaptable to other scaffold sizes and numbers. Shown here from left to right are scaffold holders designed to support twenty 2-mm scaffolds, ten 3-mm scaffolds, ten 5-mm scaffolds, and four 8-mm scaffolds.

FIG. 4.

Representative histological sections of electrospun poly(ɛ-caprolactone) scaffolds with bovine chondrocytes cultured for 14 days under (A) static and (B) flow perfusion conditions. Images show histological sections stained with Safranin O to visualize cartilaginous matrix. Extracellular matrix proteoglycans are stained red, and representative examples are indicated with yellow arrows. Representative examples of poly(ɛ-caprolactone) fibers are marked with blue arrows. Scale bar represents 100 μm in both images. These images demonstrate the significant increase in cartilage-like matrix as a result of perfusion culture.