Development and assessment of calcium phosphate bone substitutes for orthopaedic applications

  • Caroline Frances Newe

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

The need to restore or replace damaged, traumatised or lost bone tissue is a major clinical and socioeconomic concern. Shortcomings associated with traditional bone graft materials have lead to the development of synthetic materials which show promise for use in bone substitution. The development of bone substitutes with architectural and biological properties comparable to healthy bone is a challenge. Porous scaffolds based on calcium phosphate (CaP) ceramics such as hydroxyapatite (HA) and (3-tricalcium phosphate (P-TCP) have potential in the treatment of injured and diseased bone.

Degradation of CaP’s in vivo occurs as a result of osteoclastic resorption and dissolution due to their solubility in physiological solutions. Their degradation rate should be in line with tissue regeneration, ensuring the scaffold has disappeared completely once the tissue has fully matured. The rate can be altered by modifying HA:P-TCP ratio, scaffold surface area and porosity. In vitro dissolution experiments have the potential to provide a valuable method of predicting in vivo degradation.

The aim of this research was to identify optimal strategies for CaP scaffold manufacture, allowing the influence of HA:P-TCP content and architecture on dissolution to be investigated. Experimental methods were designed to assess the effect of pH and flow condition on scaffold dissolution, following which a rabbit model was adopted to assess in vivo efficacy over a 20 week period. Scaffolds were produced which demonstrated desirable architectural properties including 392.2pm average diameter pores and 64.24% porosity. In vitro dissolution was shown to be more strongly influenced by architecture than HA:P-TCP composition. Suitability of scaffolds for bone tissue replacement applications was suggested by their tolerance and degradation in vivo. Comparison of in vitro and in vivo data indicated laboratory-based experiments have potential in estimating degradation in vivo and further developments in this area could lead to a reduction in in vivo testing.
Date of AwardMay 2012
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SupervisorNicholas Dunne (Supervisor), Fraser Buchanan (Supervisor) & Gavin Walker (Supervisor)

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