Fabrication of Calcium Phosphate Scaffolds Via Honeycomb Extrusion
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Fabrication of Calcium Phosphate Scaffolds via Honeycomb Extrusion By: Mohammed Elbadawi A thesis submitted in partial fulfilment of the requirements for the degree of Doctor of Philosophy The University of Sheffield Faculty of Engineering Department) of Mechanical Engineering August 2018 I Acknowledgements I would like to thank my project supervisors Dr. James Meredith and Prof. Ian Reaney for their continued guidance and inspiration. I would like to thank many of the staff as their assistance was very much appreciated. Thanks go to Michael Jackson, Richard Kay, Austin Lafferty, Lisa Holland, Dean Haylock, Ben Palmer, Michael Bell, Andrew Mould, Robert Moorehead and The Sorby Centre staff for going above and beyond your duty. Thanks also go to my colleagues Lynne, Hande, Rod, Ben, Phil, Whitney, Jen, Zuheir, Edgar, Ed and Altair, and the many more in G-floor and J-loor. I am privileged to have worked beside you all. Special thanks to Carl, Moss and Shbeh. I hope our collaborations continue for many years to come. Above all, I wish to thank my family as this PhD would not be complete without their support. II Declarations This thesis represents my original research work. Where others have contributed, their content was duly acknowledged in the text. I declare the following publications related to this project: ‘Progress in Bioactive Metal and Ceramic Implants for Load-Bearing Application’ by M. Elbadawi, J. Meredith, L. Hopkins and I. Reaney DOI: 10.5772/62598 ‘Porous hydroxyapatite scaffolds fabricated from nano-sized powder via honeycomb extrusion’ by M. Elbadawi, J. Meredith. M.Mosalagae and I. Reaney DOI: 10.5185/amlett.2016.7063 ‘Guar gum: A novel binder for ceramic extrusion’ by M. Elbadawi, M. Mosalagae, I. Reaney and J. Meredith DOI: 10.1016/j.ceramint.2017.09.066 ‘High strength yttria-reinforced HA scaffolds fabricated via ceramic honeycomb extrusion’ by M. Elbadawi and M. Shbeh DOI: 10.1016/j.jmbbm.2017.10.09 ‘Porous hydroxyapatite-bioactive glass hybrid scaffolds fabricated via ceramic honeycomb extrusion’ Accepted – Journal of American Ceramic Society ‘Investigation of the processing and biocompatibility of Ti-HA biocomposite foams’ Submitted Mohammed Elbadawi III Abstract For Hydroxyapatite (HA) bone graft substitutes, the choice of fabrication technique is an important aspect of design. Using HA ceases concerns with regards to biocompatibility, however other facets of design need to be addressed, particularly achieving high porosity and high mechanical properties. These two facets are mutually exclusive, however, if porosity can be achieved in a controlled manner, then it is possible for them to coincide. Honeycomb extrusion is a technique capable of achieving the aforementioned feat, with the added advantage of a high degree of pore interconnectivity. Extrusion is also relatively simple, inexpensive, and can achieve large-sized scaffolds. Thus, it was hypothesised that the aforementioned advantages can be translated to bone tissue engineering. Dynamic mechanical analysis revealed that ceramic pastes formulated using guar gum and Methocel™ (MC) binders, required a shear modulus of 10-1 and 101 MPa, respectively, for extrusion. A higher solids loading was achieved with MC, by 7.6 vol%, and accordingly was used for further studies. The extrusion setup favoured calcined powders for maximising scaffold compressive strength. Initially, a calcined -tricalcium (-TCP) and uncalcined HA scaffolds has compressive strengths of 23.6 5.7 and 29.8 8.6 MPa, respectively. When HA was calcined, the strength soared to 105.9 12.2. Calcined powders were less susceptible to both agglomeration and enhanced densification, which resulted in higher solids loading and a higher thermal stability. The calcined powders all possessed a surface area < 10 m2/g, which was regarded as the ideal value to ensure sufficient binder coating of the ceramic primary particles. HA was also composited with 10 wt% Bioglass® (BG) and 10 wt% canasite glass (CAN), which have been documented to possess improved biological properties over the ceramic. A maximum compressive strength of 30.3 3.9 and 11.4 3.1 MPa, for BG and CAN, respectively, were achieved, and hence revealed that BG was the stronger compositing glass. The calcium oxide (CaO) content in raw BG was then increased by 5 wt%, which resulted in a maximum strength of 56.7 6.9 MPa. The increased CaO was found to lessen the effect of glass-induced HA phase transformation into the mechanically weaker -TCP, from a -TCP:HA ratio of 1.01 to 0.84, as determined by XRD; and thus demonstrating that a 5 wt% change was able to have a profound effect on scaffold strength. The compressive strength values obtained herein are a considerable improvement on traditional and commercially-available products, thereby demonstrating the potential of honeycomb extrusion for fabricating porous scaffolds. IV Table of Contents Acknowledgements ......................................................................................................... II Declarations .................................................................................................................. III Abstract ......................................................................................................................... IV List of Figures ............................................................................................................... XI List of Tables ....................................................................................................... XXVIII CHAPTER 1 : PROJECT INTRODUCTION ............................................................. 1 1.1 AIMS AND OBJECTIVES OF THE PROJECT ............................................................................ 2 CHAPTER 2 : BACKGROUND ................................................................................... 4 1.1 INTRODUCTION ................................................................................................................... 4 2.1 THE SKELETON AND BONE PHYSIOLOGY ........................................................................... 4 2.1.1 The Skeleton ................................................................................................................ 4 1.1.1.1 Gross Anatomy of Long Bone ........................................................................................................... 5 2.1.1.1 Microscopic Anatomy ........................................................................................................................ 7 2.1.1.2 Compositional Difference Between Trabecular and Cortical Bone ................................................... 8 2.1.2 Mediators of Remodelling ........................................................................................... 9 2.1.2.1 Osteoclasts ....................................................................................................................................... 10 2.1.2.2 Osteoblasts ....................................................................................................................................... 10 2.1.2.3 Osteocytes ........................................................................................................................................ 11 2.1.2.4 Bone lining cells .............................................................................................................................. 11 2.1.2.5 Bone Matrix ..................................................................................................................................... 12 2.1.3 Bone Growth, Modelling and Remodelling ............................................................... 16 2.1.3.1 Bone Growth and Modelling ............................................................................................................ 16 2.1.3.2 Bone Remodelling ........................................................................................................................... 16 2.1.4 Determinants of Bone Strength ................................................................................. 18 2.1.5 Fracture Healing ....................................................................................................... 18 2.1.5.1 Direct fracture healing ..................................................................................................................... 19 2.1.5.1.1 Contact healing ........................................................................................................................ 19 2.1.5.1.2 Gap Healing ............................................................................................................................. 19 2.1.5.2 Indirect fracture healing ................................................................................................................... 20 2.1.5.2.1 Acute Inflammatory Response ................................................................................................. 20 2.1.5.2.2 Recruitment of Mesenchymal Stem Cells ................................................................................ 20 2.1.5.2.3 Generation of Cartilaginous and Periosteal Bony Callus ......................................................... 20 2.1.5.2.4 Revascularisation and Neoangiogensis .................................................................................... 21 2.1.5.2.5 Mineralisation and Resorption of Cartilaginous Callus ........................................................... 21 2.1.5.2.6 Bone Remodelling ..................................................................................................................