A review on mechanobiology of cell adhesion networks in different stages of sporadic colorectal cancer to explain its tumorigenesis.

Sporadic colorectal cancer (CRC) is strongly linked to extraneous factors, like poor diet and lifestyle, but not to inherent factors like familial genetics. The changes at the epigenomics and signalling pathways are known across the sporadic CRC stages. The catch is that temporal information of the onset, the feedback loop, and the crosstalk of signalling and noise are still unclear. This makes it challenging to diagnose and treat colon cancer effectively with no relapse. Various microbial cells and native cells of the colon, contribute to sporadic CRC development. These cells secrete autocrine and paracrine for their bioenergetics and communications with other cell types. Imbalances of the biochemicals affect the epithelial lining of colon. One side of this epithelial lining is interfacing the dense colon tissue, while the other side is exposed to microbiota and excrement from the lumen. Hence, the epithelial lining is prone to tumorigenesis due to the influence of both biochemical and mechanical cues from its complex surrounding. The role of physical transformations in tumorigenesis have been limitedly discussed. In this context, cellular and tissue structures, and force transductions are heavily regulated by cell adhesion networks. These networks include cell anchoring mechanism to the surrounding, cell structural integrity mechanism, and cell effector molecules. This review will focus on the progression of the sporadic CRC stages that are governed by the underlaying cell adhesion networks within the epithelial cells. Additionally, current and potential technologies and therapeutics that target cell adhesion networks for treatments of sporadic CRC will be incorporated.

Design and validation of a bi-axial loading bioreactor for mechanical stimulation of engineered cartilage.

A mechanical-conditioning bioreactor has been developed to provide bi-axial loading to three-dimensional (3D) tissue constructs within a highly controlled environment. The computer-controlled bioreactor is capable of applying axial compressive and shear deformations, individually or simultaneously at various regimes of strain and frequency. The reliability and reproducibility of the system were verified through validation of the spatial and temporal accuracy of platen movement, which was maintained over the operating length of the system. In the presence of actual specimens, the system was verified to be able to deliver precise bi-axial load to the specimens, in which the deformation of every specimen was observed to be relatively homogeneous. The primary use of the bioreactor is in the culture of chondrocytes seeded within an agarose hydrogel while subjected to physiological compressive and shear deformation. The system has been designed specifically to permit the repeatable quantification and characterisation of the biosynthetic activity of cells in response to a wide range of short and long term multi-dimensional loading regimes.