Mechanobiological predictions of fetal joint morphogenesis

This PhD thesis explores, through the use of a mechanobiological simulation of prenatal joint morphogenesis, the hypotheses on how fetal movements, shapes and position impact on the shape of the developing joint. A novel mechanoregulation algorithm specific for cartilage growth was developed and, for the first time, a 3D mechanobiological simulation of joint morphogenesis in which the effects of a range of movements and different initial joint shapes was proposed. Both pre- and post-cavitational phases of joint development were simulated and the effect of rigid paralysis on joint shape was also explored. This study concluded that the starting joint configuration and applied movement are fundamental for the development of specific and anatomically recognisable joint shapes. Moreover, for the first time, a mechanobiological simulation of prenatal hip joint morphogenesis was used to investigated the effects of reduced, or asymmetric, movement at various stages of fetal hip joint development. This study concluded that normal fetal movements are important for the emergence of a physiological hip joint shape and that movements during development tend to minimise the natural trend of decreasing stability. Results showed that reduced movements at an early stage of development lead to decreased sphericity and acetabular coverage of the femoral head, increasing the risk of subluxation or dislocation of the hip. It also shows that, in the case of mal-positioning or joint laxity in utero, movements may actually lead to an abnormal hip joint shape with characteristics of developmental dysplasia of the hip (DDH). This PhD thesis has advanced the basic understanding of prenatal joint shape development and the implication that different mechanical environments within the joint region, might have on developmental skeletal diseases such as DDH.