Publications
59 results found
Verbruggen SVW, Oyen M, Phillips A, et al., 2017, Function and failure of the fetal membrane: Modelling the mechanics of the chorion and amnion, PLOS One, Vol: 12, ISSN: 1932-6203
The fetal membrane surrounds the fetus during pregnancy and is a thin tissue composed of two layers, the chorion and the amnion. While rupture of this membrane normallyoccurs at term, preterm rupture can resultin increased risk of fetal mortality and morbidity, as well as danger of infection in the mother. Although structural changes have been observed in the membrane in such cases, the mechanical behaviour of the human fetal membrane in vivoremains poorly understoodand is challenging to investigate experimentally.Therefore,the objectiveof this study wasto developsimplifiedfinite element models toinvestigatethe mechanical behaviourand ruptureof the fetal membrane, particularlyits constituent layers,under variousphysiological conditions.It was found that modelling the chorion and amnion as a single layer predicts remarkably different behaviourcompared with a more anatomically-accurate bilayer, significantly underestimating stress in the amnion and under-predicting the risk ofmembrane rupture. Additionally,reductions in chorion-amnion interface lubrication and chorion thickness (reported in cases of preterm rupture)both resultedin increasedmembrane stress. Interestingly, the inclusion of a weak zone in the fetal membrane that has been observed to develop overlying the cervix would likelycause it to fail atterm,during labour. Finally, these findings support the theory that the amnion is the dominant structural component of the fetal membrane and is required to maintain its integrity. The results provide a novel insight into the mechanical effect of structural changes in the chorion and amnion, in cases of bothnormal andpreterm rupture.
Verbruggen SW, Nowlan NC, 2017, Ontogeny of the Human Pelvis., Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology, Vol: 300, Pages: 643-652, ISSN: 1932-8486
The human pelvis has evolved over time into a remarkable structure, optimised into an intricate architecture that transfers the entire load of the upper body into the lower limbs, while also facilitating bipedal movement. The pelvic girdle is composed of two hip bones, os coxae, themselves each formed from the gradual fusion of the ischium, ilium and pubis bones. Unlike the development of the classical long bones, a complex timeline of events must occur in order for the pelvis to arise from the embryonic limb buds. An initial blastemal structure forms from the mesenchyme, with chondrification of this mass leading to the first recognisable elements of the pelvis. Primary ossification centres initiate in utero, followed post-natally by secondary ossification at a range of locations, with these processes not complete until adulthood. This cascade of events can vary between individuals, with recent evidence suggesting that fetal activity can affect the normal development of the pelvis. This review surveys the current literature on the ontogeny of the human pelvis.
Nowlan NC, Rolfe RA, Iatridis JC, et al., 2017, Abnormal fetal muscle forces result in defects in spinal curvature and alterations in vertebral segmentation and shape, Journal of Orthopaedic Research, Vol: 35, Pages: 2135-2144, ISSN: 1554-527X
The incidence of congenital spine deformities, including congenital scoliosis, kyphosis and lordosis, may be influenced by the in utero mechanical environment, and particularly by fetal movements at critical time-points. There is a limited understanding of the influence of fetal movements on spinal development, despite the fact that mechanical forces have been shown to play an essential role in skeletal development of the limb. This study investigates the effects of muscle forces on spinal curvature, vertebral segmentation and vertebral shape by inducing rigid or flaccid paralysis in the embryonic chick. The critical time-points for the influence of fetal movements on spinal development were identified by varying the time of onset of paralysis. Prolonged rigid paralysis induced severe defects in the spine, including curvature abnormalities, posterior and anterior vertebral fusions and altered vertebral shape, while flaccid paralysis did not affect spinal curvature or vertebral segmentation. Early rigid paralysis resulted in more severe abnormalities in the spine than later rigid paralysis. The findings of this study support the hypothesis that the timing and nature of fetal muscle activity are critical influences on the normal development of the spine, with implications for the understanding of congenital spine deformities.
Chandaria VV, McGinty J, Nowlan NC, 2016, Characterising the effects of in vitro mechanical stimulation on morphogenesis of developing limb explants, Journal of Biomechanics, Vol: 49, Pages: 3635-3642, ISSN: 1873-2380
Mechanical forces due to fetal movements play an important role in joint shape morphogenesis, and abnormalities of the joints relating to abnormal fetal movements can have long-term health implications. While mechanical stimulation during development has been shown to be important for joint shape, the relationship between the quantity of mechanical stimulation and the growth and shape change of developing cartilage has not been quantified. In this study, we culture embryonic chick limb explants in vitro in order to reveal how the magnitude of applied movement affects key aspects of the developing joint shape. We hypothesise that joint shape is affected by movement magnitude in a dose-dependent manner, and that a movement regime most representative of physiological fetal movements will promote characteristics of normal shape development. Chick hindlimbs harvested at seven days of incubation were cultured for six days, under either static conditions or one of three different dynamic movement regimes, then assessed for joint shape, cell survival and proliferation. We demonstrate that a physiological magnitude of movement in vitro promotes the most normal progression of joint morphogenesis, and that either under-stimulation or over-stimulation has detrimental effects. Providing insight into the optimal level of mechanical stimulation for cartilage growth and morphogenesis is pertinent to gaining a greater understanding of the etiology of conditions such as developmental dysplasia of the hip, and is also valuable for cartilage tissue engineering.
Ford CA, Nowlan NC, Thomopoulos S, et al., 2016, Effects of imbalanced muscle loading on hip joint development and maturation, Journal of Orthopaedic Research, Vol: 35, Pages: 1128-1136, ISSN: 1554-527X
The mechanical loading environment influences the development and maturation of joints. In this study, the influence of imbalanced muscular loading on joint development was studied using localized chemical denervation of hip stabilizing muscle groups in neonatal mice. It was hypothesized that imbalanced muscle loading, targeting either Gluteal muscles or Quadriceps muscles, would lead to bilateral hip joint asymmetry, as measured by acetabular coverage, femoral head volume and bone morphometry, and femoral-acetabular shape. The contralateral hip joints as well as age-matched, uninjected mice were used as controls. Altered bone development was analyzed using micro-computed tomography, histology, and image registration techniques at post-natal days (P) 28, 56, and 120. This study found that unilateral muscle unloading led to reduced acetabular coverage of the femoral head, lower total volume, lower bone volume ratio, and lower mineral density, at all three time points. Histologically, the femoral head was smaller in unloaded hips, with thinner triradiate cartilage at P28 and thinner cortical bone at P120 compared to contralateral hips. Morphological shape changes were evident in unloaded hips at P56. Unloaded hips had lower trabecular thickness and increased trabecular spacing of the femoral head compared to contralateral hips. The present study suggests that decreased muscle loading of the hip leads to altered bone and joint shape and growth during post-natal maturation. Statement of Clinical Significance: Adaptations from altered muscle loading during postnatal growth investigated in this study have implications on developmental hip disorders that result from asymmetric loading, such as patients with limb-length inequality or dysplasia. This article is protected by copyright. All rights reserved.
Lai J, Nowlan N, Vaidyanathan R, et al., 2016, Fetal movements as a predictor of health, Acta Obstetricia et Gynecologica Scandinavica, Vol: 95, Pages: 968-975, ISSN: 1600-0412
The key determinant to a fetus maintaining its health is through adequate perfusion and oxygen transfer mediated by the functioning placenta. When this equilibrium is distorted, a number of physiological changes including reduced fetal growth occur to favour survival. Technologies have been developed to monitor these changes with a view to prolong intrauterine maturity whilst reducing the risks of stillbirth. Many of these strategies involve complex interpretation, for example Doppler ultrasound for fetal blood flow and computerisedcomputerized analysis of fetal heart rate changes. However, even with these modalities of fetal assessment to determine the optimal timing of delivery, fetal movements remain integral to clinical decision making. In high risk cohorts with fetal growth restriction, the manifestation of a reduction in perceived movements may warrant an expedited delivery. Despite this, there remains has been little evolution in the development of technologies to objectively define evaluate normal fetal movement behavior for behavior, and where there has, there has been no linkage to clinical useapplication. In tThis review we is an attempt to understand synthesize currently available literature on the value of fetal movement analysis as a method of assessing fetal wellbeing, and show how interdisciplinary developments in this area may aid in improvements to clinical outcomes.
Verbruggen SW, Loo JHW, Hayat TTA, et al., 2015, Modeling the biomechanics of fetal movements, Biomechanics and Modeling in Mechanobiology, Vol: 15, Pages: 995-1004, ISSN: 1617-7959
Fetal movements in the uterus are a natural part of development, and are known to play an important role in normal musculoskeletal development. However, very little is known about the biomechanical stimuli that arise during movements in utero, despite these stimuli being crucial to normal bone and joint formation. Therefore the objective of this study is to create a series of computational steps by which the forces generated during a kick in utero could be predicted from clinically observed fetal movements using novel cine-MRI data of three fetuses, aged 20-22 weeks. A custom tracking software was designed to characterise the movements of joints in utero, and average uterus deflection of 6.95 ± 0.41 mm due to kicking was calculated. These observed displacements provided boundary conditions for a finite element model of the uterine environment, predicting an average reaction force of 0.52 ± 0.15 N generated by a kick against the uterine wall. Finally, these data were applied as inputs for a musculoskeletal model of a fetal kick, resulting in predicted maximum forces in the muscles surrounding the hip joint of approximately 8 N, while higher maximum forces of approximately 21 N were predicted for the muscles surrounding the knee joint. This study provides a novel insight into the closed mechanical environment of the uterus, with an innovative method allowing elucidation of the biomechanical interaction of the developing fetus with its surroundings.
Nowlan NC, Giorgi M, Shefelbine SJ, et al., 2015, Effects of normal and abnormal loading conditions on morphogenesis of the prenatal hip joint: application to hip dysplasia, Journal of Biomechanics, Vol: 48, Pages: 3390-3397, ISSN: 1873-2380
Joint morphogenesis is an important phase of prenatal joint development during which the opposing cartilaginous rudiments acquire their reciprocal and interlocking shapes. At an early stage of development, the prenatal hip joint is formed of a deep acetabular cavity that almost totally encloses the head. By the time of birth, the acetabulum has become shallower and the femoral head has lost substantial sphericity, reducing joint coverage and stability. In this study, we use a dynamic mechanobiological simulation to explore the effects of normal (symmetric), reduced and abnormal (asymmetric) prenatal movements on hip joint shape, to understand their importance for postnatal skeletal malformations such as developmental dysplasia of the hip (DDH). We successfully predict the physiological trends of decreasing sphericity and acetabular coverage of the femoral head during fetal development. We show that a full range of symmetric movements helps to maintain some of the acetabular depth and femoral head sphericity, while reduced or absent movements can lead to decreased sphericity and acetabular coverage of the femoral head. When an abnormal movement pattern was applied, a deformed joint shape was predicted, with an opened asymmetric acetabulum and the onset of a malformed femoral head. This study provides evidence for the importance of fetal movements in the prevention and manifestation of congenital musculoskeletal disorders such as DDH.
Giorgi M, Carriero A, Shefelbine SJ, et al., 2015, The role of fetal movement in prenatal hip joint morphogenesis, INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Vol: 96, Pages: A12-A12, ISSN: 0959-9673
Bowles C, Nowlan NC, Hayat TTA, et al., 2015, Machine learning for the automatic localisation of foetal body parts in cine-MRI scans, Medical Imaging 2015: Image Processing, Publisher: Society of Photo-optical Instrumentation Engineers (SPIE), ISSN: 0277-786X
Nowlan NC, 2015, BIOMECHANICS OF FOETAL MOVEMENT, EUROPEAN CELLS & MATERIALS, Vol: 29, Pages: 1-21, ISSN: 1473-2262
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- Citations: 46
Nowlan NC, Chandaria V, Sharpe J, 2014, Immobilized Chicks as a Model System for Early-Onset Developmental Dysplasia of the Hip, JOURNAL OF ORTHOPAEDIC RESEARCH, Vol: 32, Pages: 777-785, ISSN: 0736-0266
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- Citations: 35
Nowlan NC, Sharpe J, 2014, Joint shape morphogenesis precedes cavitation of the developing hip joint, JOURNAL OF ANATOMY, Vol: 224, Pages: 482-489, ISSN: 0021-8782
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- Citations: 23
Giorgi M, Carriero A, Shefelbine SJ, et al., 2014, Mechanobiological simulations of prenatal joint morphogenesis, JOURNAL OF BIOMECHANICS, Vol: 47, Pages: 989-995, ISSN: 0021-9290
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- Citations: 45
Rolfe RA, Nowlan NC, Kenny EM, et al., 2014, Identification of mechanosensitive genes during skeletal development: alteration of genes associated with cytoskeletal rearrangement and cell signalling pathways, BMC GENOMICS, Vol: 15, ISSN: 1471-2164
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- Citations: 58
Nowlan NC, Jepsen KJ, Morgan EF, 2011, Smaller, weaker, and less stiff bones evolve from changes in subsistence strategy, Publisher: SPRINGER LONDON LTD, Pages: 1967-1980, ISSN: 0937-941X
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- Citations: 11
Nowlan NC, Jepsen KJ, Morgan EF, 2011, Smaller, Weaker and Less Stiff Bones Evolve from Changes in Lifestyle, Osteoporosis International, Vol: 22, Pages: 1967-1980
Nowlan NC, Dumas G, Tajbaksh S, et al., 2011, Biophysical stimuli generated by passive movements contribute to the mechanoregulation of skeletogenesis, Biomechanics and Modeling in Mechanobiology
Nowlan NC, Bourdon C, Dumas G, et al., 2010, Developing Bones are Differentially Affected by Compromised Skeletal Muscle Formation, Bone, Vol: 46, Pages: 1275-1285
Nowlan NC, Sharpe J, Roddy KA, et al., 2010, Mechanobiology of Embryonic Skeletal Development: Insights from Animal Models, Birth Defects Research Part C: Embryo Today Reviews, Vol: 90, Pages: 203-213
Nowlan NC, Prendergast PJ, Tajbakhsh S, et al., 2009, Identifying candidate mechanoregulators of skeletal development, Proceedings of the ASME Summer Bioengineering Conference 2009, SBC2009, Pages: 149-150
Roddy KA, Nowlan NC, Prendergast PJ, et al., 2009, 3D representation of the developing chick knee joint: a novel approach relating multiple components, Journal of Anatomy, Vol: 214, Pages: 374-387
Nowlan NC, Murphy P, Prendergast PJ, 2008, A Dynamic Pattern of Mechanical Stimulation Promotes Ossification in Avian Embryonic Long Bones, Journal of Biomechanics, Vol: 41, Pages: 249-258
Nowlan NC, Prendergast PJ, Murphy P, 2008, Identification of Mechanoregulatory Genes in vivo during Embryonic Bone Formation, PLoS Computational Biology, Vol: 4
Foolen J, van Donkelaar CC, Murphy P, et al., 2008, Collagen orientation in periosteum and perichondrium is aligned with preferential directions of tissue growth, Journal of Orthopaedic Research, Vol: 26, Pages: 1263-1268
Nowlan NC, Murphy P, Prendergast PJ, 2007, Mechanical stimuli resulting from embryonic muscle contractions promote avian periosteal bone collar formation, Proceedings of the ASME Summer Bioengineering Conference 2007, SBC 2007, Pages: 833-834
Nowlan NC, Murphy P, Prendergast PJ, 2007, Mechanobiology of Embryonic Limb Development, Annals of the New York Academy of Sciences, Vol: 1101, Pages: 389-411
Nowlan NC, Prendergast PJ, 2005, Evolution of Mechanoregulation of Bone Growth Will Lead to Non-optimal Bone Phenotypes, Journal of Theoretical Biology, Vol: 235, Pages: 408-418
Prendergast PJ, Nowlan NC, Lally C, 2005, Experiment and computation in mechanobiology, with new applications in cardiology and evolution, Tissue Remodelling, Centre of Excellence for Applied Biomedical Modelling and Diagnostics, Warsaw, Pages: 219-240
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