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Title: Enhancing host cell responses via lipid-functionalisation of orthopaedic titanium
Author: Blackburn , Julia
ISNI:       0000 0004 5921 0627
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2014
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Total joint replacement surgery is an excellent treatment for arthritis. Unfortunately around 10% of these prostheses will fail due to aseptic loosening and require revision surgery that is both expensive and less successful for patients. One way of reducing revision surgery could include steps to enhance human osteoblast (hOB) maturation at biomaterial surfaces by modifying existing implant materials. The aim of this research therefore was to create a lipid-functionalised titanium surface that encourages maturation of hOBs, a key event for successfuI osseo integration. Lysophosphatidic acid (LPA) refers to a family of structurally-related bioactive lipids. One of these molecules, oleoyl-LPA, had already been shown to enhance vitamin D3-induced hOB formation and maturation in vitro. Novel results presented within this thesis indicate that LPA members and structurally related synthetic lipids exhibit different potencies with regard to vitamin D3-induced hOB maturation. In summary the finding ofthis thesis indicate that the synthetic compounds are especially efficacious in securing vitamin D3-induced hOB maturation. When developing bioactive titanium surfaces for orthopaedic applications it is important to examine hOB responses to the selected agent(s) in combination with factors central to skeletal health. In this thesis, initial studies focused on an important local mediator, transforming growth factor ~ (TGF~) . In addition research extended to two widely recognised systemic factors, parathyroid hormone (PTH) and oestradiol. Interestingly TGF~ bolstered the maturation of hOBs to LPA and vitamin D3 via a mechanism that may involve an autocrine/paracrine platelet-derived growth factor (PDGF) loop. In contrast oestradiol and parathyroid hormone (PTH) appeared to be without influence on the maturation responses of hOBs to LPA. In light of the risk of prosthetic joint infections, it is also important to consider whether any surface modification promotes or deters the growth of microorganisms. Whilst oleoyl-LPA lacked appreciable antimicrobial actions, it did not promote bacterial growth. In contrast, palmitoyl-LPA appeared to have greater antimicrobial activity and may therefore be an interesting molecule to investigate further in developing multifunctional bone biomaterials that combine host tissue biocompatibility with an antibacterial surface finish . In considering titanium surface functionalisation with LPA (or indeed related lipids) the potential for self-assembly of lipid bi-Iayered structure presented itself as an attractive and facile means of modification. To this end titanium was initially treated with an alkanephosphonate (octadecylphosphonic acid) that served as a tethering point for LPA via tail -tail - hydrophobic interactions akin to the arrangement of phospholipids in cell membranes. The findings of this thesis support the successful functionalisation oftitanium using this simple approach . Future research should continue in exploring the stability and biocompatibility of these novel titanium modifications.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available