Novel approaches to enhance osseointegration using titanium-based materials

UoM administered thesis: Phd

  • Authors:
  • Juan Shong Khaw

Abstract

Titanium (Ti) and Ti alloys are widely used as medical implant materials due to their remarkable biocompatibility and corrosion resistance properties. Thanks to their great durability and high strength to weight ratio, Ti-based devices are often chosen as a skeletal replacement therapy to improve quality of life of patients suffering from bone fracture and osteolysis. Researchers around the globe have tried multiple approaches to increase the unmet needs of cost-effectiveness, to improve restorative time and the osseointegration of Ti-based implants. This thesis aims to investigate the optimisation of Ti-based materials through surface coating, nanostructured modifications, and electrical stimulation for use in bone and dental applications. Surface coating using osteoinductive coating materials such as hydroxyapatite (HA), brushite and other orthophosphates can enhance bone growth and osseointegration. In collaboration with the University of Bath and Plasma Coatings Ltd., the alloyed Ti (Ti-6Al-4V) substrates were modified to investigate the biocompatibility of the commercially viable thin layer calcium orthophosphates coatings on metal substrates using different coating methodologies: thermal spraying HA, grit-blasting, HA via brushite conversion, and electro-precipitating brushite. A more uniform coating layer with sophisticated morphology was achieved using electrodeposition techniques, which presented approximately 6 times thinner coating thickness in comparison to thermally coated samples. However, the subsequent biocompatibility test using MC3T3-E1 osteoblastic cells revealed the possible dissociation of undesirable ions and structural instability of thinly coated brushite and converted HA samples, as opposed to more biocompatible and morphologically stable thermal coated HA and grit-blasted samples. Surface nanostructuring using electrochemical anodisation techniques has gained increasing interest due to its ability to create uniform titania (TiO2) nanotube arrays that provide a nanoengineered biomimetic environment to promote osteogenesis and bone cell mineralisation. This section provides a methodological optimisation of the anodisation device to gain enough specimens to be able to meet statistically informed decisions on the suitability of this surface modification technique in biomedical applications. An average of approximately 7.5-fold increase in cost and time efficiency was attained with regards to the reproducible and consistent generation of 20, 50 and 100 nm pore diameter nanotube via anodising pure Ti and Ti-6Al-4V. The optimised device allows the manufacturing of a high number of anodised specimens with customisable specimen shape and tunable pore diameters for use in in-vitro assessments. The biocompatibility and functional assays closed the gaps present in the literature regarding the effect of different nanotube pore diameter on different human cell lineage, revealing that human mesenchymal progenitors exhibited high differentiation rate on 20 nm pore diameter TiO2 nanotubes; while osteoblast lineage differentiates better on TiO2 nanotube specimens with 50 nm pore diameter. Electrical stimulation (ES) can control cell growth, orientation and bone remodelling appreciated by the electrical signals as important stimuli. Combining pure Ti and ES, this section involves software modelling of the electric field (EF) and current density in different bioreactor designs. The novel ES bioreactor with capacitive stimulation delivery system features long-term stimulation with homogeneous EF, biocompatible, sterilisable and cost-effective in the manufacturing process. A continuous capacitive stimulation regime on Ti with 200 mV/mm simulated EF could influence stem cell orientation and promote nuclei elongation, proliferation, differentiation and matrix production as compared to non-stimulated controls. The three approaches investigated in this thesis provide novel engineering approaches to influence cell activities. In addition to filling the gaps present in the literature, the interaction of the cells and materials was also explored to elucidate the underlying mechanisms affecting the cellular behaviours. As a whole, the novel methodologies introduced in this research provide a thoughtful fundamental basis for future studies in the area of biomaterials and regenerative medicine.

Details

Original languageEnglish
Awarding Institution
Supervisors/Advisors
Award date1 Aug 2019