Embryonic joint development is a complex process with several distinct stages. The first step occurs in the cartilage anlage, where chondrocytes at the presumptive joint site stop proliferating and become compacted to form what is called the interzone. From the interzone, the synovial cavity develops. Once the cavity has been initiated, the surfaces of the opposing cartilage rudiments undergo gradual shape morphogenesis so that the ends of the two bones form a functioning, friction-minimising contact surface, i.e. a synovial joint. It has been shown that mechanical forces are essential for normal cavitation of the joint, while it is not yet clear whether mechanical forces are an essential influence for moulding of the articular surfaces. If embryos are immobilised prior to cavitation, the process does not occur, while if immobilisation is induced after the cavity has formed, the cavity regresses and the elements can become fused. In this application, I propose a computational simulation of joint development, modelling cavitation of the joint and morphogenesis of the articular surfaces based on the interactions between mechanical and biological factors. The aims of the project are to 1) characterise the developing joint in 3-D in the embryonic chick; 2) calculate the forces and biophysical stimuli active in the joint over several stages; 3) create 2-D model of simple joint, 4) alter mechanical state to corroborate model predictions; 5) investigate mechanosensitive molecules and genes, and 6) upgrade model to 3-D. Such a simulation will lead to a better understanding of joint development which would have significant consequences for medical applications such as osteoarthritis and tissue engineering. This project will enable me to become an expert at the interface between developmental biology and bioengineering, and equip me to become a successful researcher and principal investigator as a specialist in the mechanobiology of the developing limb.
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