Dissertations and Theses
Date of Award
2025
Document Type
Thesis
Department
Biomedical Engineering
First Advisor
Alessandra Carriero
Keywords
Bone quality, Homeostasis, Permeability, Fracture toughness, Lacunar-canalicular network, Interstitial fluid flow
Abstract
Healthy bones are strong and tough, able to resist plastic deformations and withstand crack propagation. These essential mechanical properties emerge from a complex hierarchical structure and the activity of osteocytes, bone cells residing in tiny cavities within the matrix. The lacunar canalicular network surrounds these cells and forms a porous system allowing fluid to flow through interconnected spaces. This interstitial fluid movement enables nutrient delivery, cell signaling, and mechanosensation, which regulate bone remodeling and adaptation to mechanical demands. Bone’s ability to maintain structure, function, and quality depends on a delicate balance among mechanical forces, fluid flow, and cellular responses, all working together to maintain bone homeostasis. When this balance is disturbed by aging, disease, or abnormal loading, changes in bone structure and composition impair fluid transport and mechanoadaptation, leading to reduced bone quality and increased fracture risk.
Understanding how these factors interact is critical, especially in pathological contexts where bone fragility increases. This dissertation explores how bone homeostasis, permeability, and fracture toughness are linked through experimental imaging, computational modeling, and mechanical testing across multiple length scales. To understand bone fragility origins, we focus on osteogenesis imperfecta, a genetic disorder marked by defective collagen, abnormal mineralization, and increased porosity. Our findings indicate that osteogenesis imperfecta presents distinct features depending on biological sex, and that in healthy individuals, structural and compositional differences between sexes lead to comparable levels of fracture toughness. In osteogenesis imperfecta, disrupted collagen organization, mineral deposition, and elevated vascular and lacunar porosities with more spherical lacunae reduce fracture toughness, leading to greater bone fragility in females. We also show that antiresorptive therapies, which are commonly used in children with osteogenesis imperfecta to increase bone mass, fail to restore resistance to fracture, emphasizing the need for treatments that improve bone quality rather than focusing solely on increasing bone quantity.
To investigate how lacunar porosity changes seen in osteogenesis imperfecta affect mechanoadaptation and fragility, we developed computational fluid-structure interaction models simulating load-induced interstitial fluid flow at the osteocyte microscale. These models show that variations in lacunar shape and canalicular organization affect mechanical strain and fluid dynamics within the network. Our findings reveal that elongated lacunae with radially arranged canaliculi reduce bone matrix strain while increasing fluid velocity and osteocyte deformation, creating a mechanical environment supporting osteocyte activation, nutrient delivery, and tissue integrity.
Beyond pathological conditions, bone also dynamically adapts to normal metabolic challenges that affect homeostasis, such as the calcium demands during lactation. To investigate these adaptations, we applied advanced imaging methods and found that lactation causes region-specific cortical thinning, lacunar enlargement, and increased nanoporous structures, particularly in the posterior region of the femoral midshaft, suggesting localized calcium mobilization and altered permeability. These adaptations were partially reversed after weaning, indicating a transient yet coordinated remodeling process that balances systemic mineral requirements with preservation of skeletal integrity. We identified a novel nanoporous compartment likely critical for mineral exchange and fluid transport, a previously underexplored component of bone remodeling and homeostasis.
Recommended Citation
Munoz, Asier, "The Interplay Between Bone Homeostasis, Permeability, and Fracture Toughness" (2025). CUNY Academic Works.
https://academicworks.cuny.edu/cc_etds_theses/1250
