Exploring Cellular Biomechanics at Calvarial Suture - A Soft-Hard Tissue Interface

As the most abundant cells in bone, osteocytes are the control centre to process biomechanical stimulus and to regulate remodelling events through their extensive Lacuno-Canaliculi Network (LCN). While the key factors governing the arrangement of osteocyte LCN remain unclear, mechanical loading is found capable of alternating cellular and network topology. These characteristics of LCN are found closely associated with extracellular matrix (ECM) mineralisation, through which nanoscopic mineral particles are embedded in organic collagen matrix. The different amounts, sizes, and arrangements of mineral particles contribute to bone material properties through a hierarchical structure in bone. In return, these ECM mineral conditions affect consequential remodelling events. Continuous effectors have been dedicated to understanding the interaction among biomechanical loading, LCN characteristics, and ECM mineral conditions in long bone, and their interaction is believed as indicative for pathological conditions, such as osteoporosis, osteoarthritis, and osteoarthrosis.

Compared to the emerging findings of LCN characteristics and ECM mineral conditions in long bone, very little is yet known for other types of bone, such as in calvaria. The calvaria bones are joined by fibrous sutures (Sharpey's fibres). Not only providing the cranial flexibility during birth, this soft-hard (suture-bone) tissue interface is also the primary site of intramembranous bone growth to accommodate the rapid expansion of neurocranium through embryonic development and early postnatal growth. These sutures transmit biomechanical signals and balance the proliferation of osteogenic cells and their differentiation to form new bone. Interestingly, sutures must keep their patency from ossification to maintain their functionalities in extending calvaria bone fronts. Premature closure of sutures (craniosynostosis) by ossification affects approximately 1 out of 2000 newborns, and can lead to abnormal facial and cranial appearances; in the worse scenarios, it will cause the increased intracranial pressure leading to visual damage, sleeping disorder, masticatory malfunction, impaired mental development, and even sudden death. Another major clinical challenge is bone flap resorption and cranioplastic failure following decompressive craniectomy, affecting both infants and adults. Investigating into the mechanical stimulation-cell-mineral interaction can provide some temporal and spatial insights in suture morphogenesis and bone formation, which potentially helps elucidating possible mechanisms involving these clinical conditions.

This project is structured to answer the following two closely related fundamental questions.

1) How do fibrous tissues in sutures connect the calvaria bone in a 3D manner and how is the biomechanical stimulus distribution across this tissue interface?

2) As the primary growth site, what are the spatial and temporal effects of a suture on osteocyte LCN arrangement and ECM mineralisation, along and further away from a suture?

To answer these questions, the student will be required to perform

-microCT imaging, confocal microscopy, back-scattered imaging

-image segmentation and analysis

-reverse engineering modelling

-finite element analysis for mechanical status