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Development of a Biomimetic Phosphoserine Modified Calcium Phosphate Adhesive for the Regeneration of Bone Defects

Tzagiollari, Antzela orcid logoORCID: 0000-0001-6157-6378 (2024) Development of a Biomimetic Phosphoserine Modified Calcium Phosphate Adhesive for the Regeneration of Bone Defects. PhD thesis, Dublin City University.

Abstract
Phosphoserine is a ubiquitous molecule found in numerous proteins and demonstrates the ability to generate an adhesive biomaterial capable of stabilising and repairing bone fractures. This study aimed to develop phosphoserine-modified calcium phosphates (PM-CPC), which incorporate phosphoserine, with alpha-tricalcium phosphate (α-TCP) and calcium silicate for bone stabilisation and regeneration. The PM-CPC formulation was characterised and optimised using Design of Experiments (DoE) with the following inputs: grinding cycles of α-TCP, liquid-to-powder ratio (LPR) and the molar ratios of phosphoserine and calcium silicate. Also, a dual syringe-mixed PM-CPC adhesive was developed and assessed. The optimal PM-CPC formulation either hand-mixed or through the mixing system, necessitated a mixing time of 20 s and displayed an initial setting time between 3-4 min, and a bone-to-bone bond strength of 1.05±0.3 MPa under a wet environment providing suitable properties for surgeons to apply and stabilise bone fractures. Cell viability >70% and cell proliferation were obtained after an indirect cytotoxicity study in both PM-CPC adhesives. The in vivo study in mini pigs demonstrated the ability of PM-CPC to stabilise dental implants with implant stability quotient (ISQ) values of 65–85 after 15 min which indicates the level of stability and osseointegration in dental implants. The PM-CPC-bone-implant interface was sufficiently mature enough to have a measurable mechanical effect (pull-out force=287 N, torque strength=80 Ncm) at 8 weeks post-surgery. Qualitative histological analysis on an in vivo study of trabecular bone demonstrated newly formed bone around the implants and in the adhesive bone interface. The design, characterisation and development of the proposed bone adhesive and associated delivery device represent a major step forward in both orthopaedic and dental injuries and have the potential to improve patient outcomes.
Metadata
Item Type:Thesis (PhD)
Date of Award:August 2024
Refereed:No
Supervisor(s):Dunne, Nicholas, Levingstone, Tanya and Clarkin, Owen
Subjects:Engineering > Materials
Engineering > Biomedical engineering
Medical Sciences > Biomechanics
Medical Sciences > Health
Medical Sciences > Performance
DCU Faculties and Centres:DCU Faculties and Schools > Faculty of Engineering and Computing > School of Mechanical and Manufacturing Engineering
Use License:This item is licensed under a Creative Commons Attribution-NonCommercial-No Derivative Works 4.0 License. View License
Funders:Irish Research Council, PBC Biomed Ltd.
ID Code:30180
Deposited On:19 Nov 2024 14:41 by Nicholas Dunne . Last Modified 19 Nov 2024 14:41
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