Abstract
Tissue expansion is a technique used by plastic and restorative surgeons to cause the body to grow additional skin, bone or other tissues. For example, distraction osteogenesis has been widely applied in lower limb surgery (trauma / congenital), and congenital upper limb reconstruction (e.g. radial dysplasia). This complex and tightly regulated expansion process can thus far only be optimised by long-term animal or human experimentation.
Here the intent is to develop an in vitro model of tissue expansion that will allow to both optimise the extension regime (µm/h, continuous/ intermittent) and investigate using proteomic techniques which molecular pathways are involved in its regulation. Cells cultured onto sheets of polymer (PCL) can be stretched at very low, adjustable speeds, using a stepper motor and various 3D printed and laser cut designs. The system utilises plastic flow of the polymer, enabling the material to stay extended upon strain being released.
Tensile tests have displayed the plastic behaviour of the polymer sheet when stretched, and digital image correlation (DIC) has been used to analyse homogeneity of the strain field. Further analysis involving nuclear localisation of yes-associated protein (YAP) aims to link cell response to this strain field.
Nuclear orientation analysis has demonstrated a morphological response to strain (1 mm/day) in comparison to not being stretched, and this is in the process of being linked to nanoscale changes of the substrate (using atomic force microscopy) during the stretching regime. Future work will identify how strain is affecting the cell cycle, before a mass tagging approach is used to identify protein changes induced by strain.
