Michigan Technological University Digital Commons @ Michigan Tech Dissertations, Master's Theses and Master's Reports 2016 Enhancing Osseointegration of Orthopaedic Implants with Titania Nanotube Surfaces Erin A. Baker Michigan Technological University, [email protected] Copyright 2016 Erin A. Baker Recommended Citation Baker, Erin A., "Enhancing Osseointegration of Orthopaedic Implants with Titania Nanotube Surfaces", Open Access Dissertation, Michigan Technological University, 2016. https://doi.org/10.37099/mtu.dc.etdr/255 Follow this and additional works at: https://digitalcommons.mtu.edu/etdr Part of the Biomaterials Commons ENHANCING OSSEOINTEGRATION OF ORTHOPAEDIC IMPLANTS WITH TITANIA NANOTUBE SURFACES By Erin A. Baker A DISSERTATION Submitted in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY In Mechanical Engineering-Engineering Mechanics MICHIGAN TECHNOLOGICAL UNIVERSITY 2016 © 2016 Erin A. Baker 1 This dissertation has been approved in partial fulfillment of the requirements for the Degree of DOCTOR OF PHILOSOPHY in Mechanical Engineering-Engineering Mechanics. Department of Mechanical Engineering-Engineering Mechanics Dissertation Advisor: Craig Friedrich, Ph.D., P.E. Committee Member: Paul Fortin, M.D. Committee Member: Gregory Odegard, Ph.D. Committee Member: Tolou Shokuhfar, Ph.D. Department Chair: William Predebon, PhD 2 To my sons— Everett Charles, Miles Anden and Hadden Stuart 3 Table of Contents LIST OF FIGURES .......................................................................................................... 6 LIST OF TABLES ............................................................................................................ 7 PREFACE.......................................................................................................................... 8 ACKNOWLEDGMENTS .............................................................................................. 11 ABSTRACT ..................................................................................................................... 14 CHAPTER 1: INTRODUCTION................................................................................. 16 CHAPTER 2: SPECIFIC CONSIDERATIONS OF ORTHOPAEDIC IMPLANTS FOR OSSEOINTEGRATION APPLICATIONS........................................................ 19 2.1 INTRODUCTION......................................................................................................... 19 2.2 BONE FORMATION FOR INGROWTH AND ONGROWTH OF ORTHOPAEDIC IMPLANTS . 19 2.3 MATERIAL SELECTION OF ORTHOPAEDIC IMPLANTS FOR OSSEOINTEGRATION ........ 24 CHAPTER 3: TITANIA NANOTUBE SURFACES FOR ORTHOPAEDIC IMPLANT APPLICATIONS ........................................................................................ 27 3.1 INTRODUCTION......................................................................................................... 27 3.1.1 Previous In Vitro Studies of Titania Nanotube Surfaces for Osseointegration Applications .............................................................................................................. 29 3.1.2 Previous In Vivo Studies of Titania Nanotube Surfaces for Osseointegration Applications .............................................................................................................. 32 3.2 TITANIA NANOTUBE SURFACE MORPHOLOGIES ....................................................... 34 3.3 MATERIAL PROCESSING OF TITANIA NANOTUBE SURFACES .................................... 35 CHAPTER 4: IN VITRO ASSESSMENT OF BONE MARROW-DERIVED CELLS ON TITANIA NANOTUBE SURFACES....................................................... 38 4.1 INTRODUCTION......................................................................................................... 38 4.2 EXPERIMENTAL METHODS ....................................................................................... 39 4.2.1 Bone Marrow Isolation .................................................................................... 39 4.2.2 Bone Marrow Cell-Seeding.............................................................................. 39 4.2.3 Cell Attachment and Morphology .................................................................... 40 4.2.4 Cell Proliferation and Differentiation ............................................................. 41 4.3 RESULTS................................................................................................................... 45 4.3.1 Cell Attachment and Morphology .................................................................... 45 4.3.2 Cell Proliferation and Differentiation ............................................................. 50 4.4 DISCUSSION AND CONCLUSIONS .............................................................................. 54 CHAPTER 5: IN VIVO ASSESSMENT OF BIOCOMPATIBILITY TITANIA NANOTUBE SURFACES IN A RAT MODEL OF INTRAMEDULLARY FIXATION....................................................................................................................... 58 5.1 INTRODUCTION......................................................................................................... 58 4 5.2 EXPERIMENTAL METHODS ....................................................................................... 58 5.2.1 Implantation Procedure ................................................................................... 59 5.2.2 General Health Assessment ............................................................................. 61 5.2.3 Hematologic Analysis ...................................................................................... 61 5.2.4 Metal Ion Analysis ........................................................................................... 62 5.2.5 Undecalcified Histologic Analysis ................................................................... 62 5.3 RESULTS................................................................................................................... 63 5.4 DISCUSSION AND CONCLUSIONS .............................................................................. 70 CHAPTER 6: IN VIVO ASSESSMENT OF OSSEOINTEGRATION OF TITANIA NANOTUBE SURFACES IN A RAT MODEL OF INTRAMEDULLARY FIXATION....................................................................................................................... 73 6.1 INTRODUCTION......................................................................................................... 73 6.2 EXPERIMENTAL METHODS ....................................................................................... 73 6.2.1 Implantation Procedure ................................................................................... 73 6.2.2 Imaging Analysis.............................................................................................. 74 6.2.2.1 Microcomputed Tomography Analysis ..................................................... 74 6.2.2.2 Backscattered Electron Analysis............................................................... 77 6.2.3 Undecalcified Histologic Analysis ................................................................... 78 6.2.4 Biomechanical Analysis ................................................................................... 79 6.3 RESULTS................................................................................................................... 81 6.4 DISCUSSION AND CONCLUSIONS .............................................................................. 93 CHAPTER 7: FUTURE WORK .................................................................................. 99 7.1 INTRODUCTION......................................................................................................... 99 7.2 PROPOSED CONCEPT 1: LOCAL DELIVERY OF SDF-1Β VIA TITANIA NANOTUBE SURFACES ...................................................................................................................... 99 7.2.1 Specific Aims .................................................................................................. 100 7.2.2 Study Design .................................................................................................. 101 7.2.2.1 Aim 1: Hep-DOPA Functionalization of TiNT Implants and SDF-1β Release Kinetics .................................................................................................. 101 7.2.2.2 Aim 2: Comparison of In Vivo Osteogenicity of SDF-1β-functionalized TiNT Implants ..................................................................................................... 103 7.2.3 Anticipated Outcomes .................................................................................... 104 7.2.4 Study Status .................................................................................................... 105 7.3 PROPOSED CONCEPT 2: ASSESSING BIOCOMPATIBILITY OF TITANIA NANOTUBES VIA MURINE AIR POUCH MODEL........................................................................................ 108 7.4. PROPOSED CONCEPT 3: BONE FORMATION AND BIOCOMPATIBILITY STUDIES IN HIGHER PHYLOGENETIC ORDER SPECIES ..................................................................... 111 CHAPTER 8: CONCLUSIONS ................................................................................. 114 REFERENCES.............................................................................................................. 118 5 List of Figures Figure 2.1. Illustration of the cycle of osteoblatic differentiation at the cellular level .....22 Figure 2.2. Digital and scanning electron