Nerve and Bone Interaction During Osseointegration by Investigating the Regulatory Roles of Neuronal Factors
Doctor of Philosophy
Barbara D. Boyan
Jennifer L. Puetzer
Vamsi K. Yadavalli
Orthopaedic, spinal, or dental Implant performance can be hindered by various compromised diseases and certain medications. This study explores the role of neuronal factors in improving osseointegration by investigating nerve and bone interactions.
The study revealed that semaphorin 3C (sema3C), an originally identified axon guidance protein, is produced by osteoblast lineage cells and regulated by microstructured titanium surface properties. It serves as a coupling factor to inhibit osteoclast differentiation and resorption activities during the surface-mediated bone remodeling stage. Meanwhile, sema3C inhibited angiogenesis but did not affect macrophage polarization, highlighting its potential as a factor to balance homeostasis with the presence of titanium implants.
This project reported a decreased bone-to-implant contact in compromised bone models, including nerve dysfunction models (neurectomy, and botulinum toxin A injection (Botox)), and type 2 diabetes model (T2DM) and also proposed strategies to enhance osseointegration, including biomimetic implants and identifying local regulatory coupling factors that improve cellular communication. Semaphorin 3A (sema3A), from the same semaphorin class as sema3C, has been identified as an osteoprotective factor that facilitates the bone formation and inhibits bone resorption, indicating its therapeutic potential to be used to improve osseointegration in our compromised models. Our studies showed that sema3A treatment enhanced bone-to-implant contact in both T2DM and Botox models and further enhanced bone regenerative potential and integration when used in combination with biomimetic multiscale micro/nanotextured titanium implants in the Botox model.
© 2023 Jingyao Deng
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Available for download on Tuesday, May 09, 2028
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