Development of a displacement-controlled uniaxial-strain bioreactor for high-throughput, dynamic in vitro cell culture

Abstract

1Bone is a dynamic tissue that experiences a wide range of forces during regular daily locomotion. This environment of dynamic strain strongly influences the architecture of the extracellular matrix, and it can impact the rate that bone adapts or recovers after an injury [1], [2]. Cell research is commonly performed in mechanically static conditions in the base of well plates, yet this is a far cry from the conditions natural to osteoblasts. To better understand the behaviours of osteoblasts, it is important to ensure that platforms are available to perform cell culture experiments in mechanically dynamic environments [3]-[5]. For this reason, we have designed a bioreactor system that imparts tensile strain onto flat, cell-seeded scaffold constructs in vivo within custom well plates. The bioreactor system has 36 separated wells spread across four mechanical actuation units and can apply up to 30% tensile strain to a 15 by 9 mm area of the constructs, operating within an incubator. The wider body of mechanostimulation research also shows that different many cell types, from neurons [6] to cardiac tissue [7], [8] and more [2], [6], [9]-[11], can be stimulated with a range of stimulus and have a wide array of responses, and it is expected that the bioreactor will also be useful for this research. To be accessible to research groups, the bioreactor has predominantly been constructed from widely available components and materials. Most parts fabricated using 3D printing, and all of the electronics can be found within a typical 3D printer DIY assembly kit. The device was validated for use in a 28 day in-vitro dynamic culture of osteoblasts on melt-electrowritten polycaprolactone scaffolds. The cell constructs were strained to 4% at 0.5 Hz on days 25-27 and removed on the 28th day. Cells were observed to elongate and align within some regions of high local strain following the 3 days of stimulation.