Bone Multiscale Mechanics
Skeletal Fragility: Using animal models of different types of Osteogenesis Imperfecta (OI or brittle bone disease) we explore how small length scale abnormalities ramify at larger length scales, causing bone fragility (supported by a NSF CAREER Award). To date, there is no cure for OI and very little is known about the development of bone fragility during skeletal growth, and the efficacy of current treatments to rescue OI brittle bones. We have been developing an advanced platform to explore how bone fractures at all of its structural levels in mouse diaphyseal bone and to enhance preclinical testing of therapies that can help restore toughness in bone and reduce its fracture risk. We use highly interdisciplinary studies that combine classical fracture mechanics with synchrotron microtomography to image bone at sub-micron resolution and genetics approaches to investigate how healthy mouse bone develops its toughness and what mechanisms make OI bone brittle, thus to identify the interaction of multi-scale mechanisms involved when small molecular alterations cause whole bone deficiencies.
Gold standard Therapies for Brittle Bone: Using our advanced platform for examining toughness and fragility in mouse bones, we are currently examining the effect of gold standard treatment, such as bisphosphonates, on young OI bones using mouse models of the disease (supported by a NSF CAREER Award).
New Therapies for Brittle Bone: Because of the high need for better therapeutic approaches to OI and other bone fragilities, we launched a novel initiative to develop high through-put zebrafish models and methods for skeletal drug studies for bone fragility (supported by a NIH grant). We have adapted the methodologies we normally use for studying mouse bone to examine the multiscale mechanics of zebrafish bones. They set standards for the analysis of bone fragility in these small animal models. We are now investigating the efficacy of synthetic collagen hybridizing peptides as carrier to reduce endoplasmic reticulum stress in OI osteoblasts, and improve bone material properties. (Collaborator: Dr. Antonella Forlino (University of Pavia)
Hearing Loss in Brittle Bone Disease: Here we aim to determine whether the hearing loss in OI is related to bone fragility (supported by a NSF CAREER Award). Using the synchrotron imaging approaches we developed, we have identified numerous bony changes in the middle and inner ear in OI mice that appear to compromise hearing, including increased otic capsule thickness and bone porosity and evidence of matrix damage (microscopic cracks in the solid bone material). We are now investigating the nature of these changes in relation to hearing loss in these mice. (Collaborators: Claus-Peter Richter (Northwestern University) and Luis Cardoso (CCNY))
Nanoscale Porosity in Bone: We are investigating the effect of lacunar-canalicular morphology to cell mechanosensing and fragility by analyzing bone and fluid flow in the pericanalicular space using a parametric fluid-structure-interaction computational model of an osteocyte surrounded by bone extracellular matrix (supported by a NSF CAREER Award). (Collaborator: Luis Cardoso (CCNY)).
These studies evolved from our multiscale imaging studies to study the role of bone cellular and sub-cellular porosity network connectomics on transport and homeostasis (supported by The Human Frontier Research Program). (Collaborators: Dr. Kathryn Grandfield (McMaster University) and Dr. Aurelien Gourrier (University of Grenoble)).
Bone mechano-adaptation
Mechanomedicine for Growing Bones with altered gait: Our skeletal growth studies investigated how altered gaits apply abnormal loads on the developing bones, thus leading to bone deformities in children. Combining clinical imaging and gait data, we classified gaits in children with muscle spasticity, and examined the relationship between gait characteristic and bone deformities in children with cerebral palsy. Combining clinical data with musculoskeletal and finite element modeling, we then estimate muscle and joint forces on bone, and finally developed new models to simulate bone growth according to the loads applied on bone by the different gaits. We are currently studying the effect of selective neurosurgical ablations, which have shown to improve motor function after surgery, on limb loading and bone deformities in children with cerebral palsy (supported by a seed grant from the Shriner’s Hospital for Children). (Collaborators: Drs. Jean-Pierre Farmer (Shriner’s Hospital in Montreal) and Elizabeth Zimmerman (McGill University).
Mechanomedicine for Infants with hip dysplasia: Combining musucloskeltal theories of static and dynamic bone and cartilage growth we are developing new models to simulate hip growth to investigate the effect of mechanical therapies for hip dysplasia (supported by a seed grant from the International Hip Dysplasia Institute).
New Software and Technologies
Mechanically Targeting Skeletal Growth: Our studies on the musculoskeletal biomechanics and mechanobiology during growth have focused on the development of novel, lightweight and biomechanically sound exoskeletons for gait assistance that can be easily adapted for children (supported by a (NSF collaborative grant with Dr. Hao Su, formerly in the CCNY Mechanical Engineering Department,).
Advanced Imaging Analysis: As a part of our advanced platform to investigate bone fracture toughness, we developed the software FiberO to calculate fibers orientation and organization in fibrous tissue like bone (supported by a NSF CAREER Award).
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