The Development of Cell Gym and its Applications to Tissue Engineering

Abstract

Tendon injuries are a common clinical problem and damaged tendon tissue heals very slowly and rarely regains its structural integrity and mechanical strength; thus re-tear rates and post-surgery are high. The development of new treatment options for injured tendons has been hindered by a limited understanding of basic tendon biology. Therefore, in this PhD research, an advanced mechanical cell stretcher was developed to enhance our understanding of tendon mechanobiology. A customized cell stretching device named the Cell Gym was developed. The device could generate a sufficient force and speed to stimulate tenocytes. The Cell Gym could also fit under a microscope during operation allowing simultaneous examination. Additionally, micro-channels of 10 μm in width by 5 μm in height were developed to align tenocytes onto the silicone culture dishes. A customized clamping mechanism was designed to couple the silicone culture dishes to the device. This mechanical system was validated top down from the device to the cellular level. The Cell Gym induced cyclic mechanical loading to the tenocytes attached on the silicone culture dishes. From these studies, tenocytes under mechanical loading exhibited better proliferation and expressed an increase in the COX-2 gene, a mechanotransduction mediator. Furthermore, the Cell Gym successfully mimicked in vivo knee extension exercises. In a subsequent study, the Cell Gym was also used to investigate dermal fibroblasts. This study demonstrated that the SCX gene was affected by substrate geometries. The Cell Gym is a versatile tool that enables researchers to investigate cell mechanobiological behaviour. It is currently being used in a tissue engineering study to investigate the behaviour of chondrocytes cultured in 3D agarose gel under cyclic stretching.