ABM CDT Osseointegration of graphene coated implants

Supervisors:

Main Supervisor: Prof. L Biant

Supporting Supervisors: Prof. J Gough, Dr K Kostarelos, Mr M McNicholas

Currently, titanium-based orthopaedic implants may fail due to insufficient integration into the surrounding bone when utilised in a press fit manner for arthroplasty and “best fit” to the endosteal surface in fracture fixation. To address this issue, coating implant surfaces with bioactive substances has been shown to effectively improve the biocompatibility and bioactivity of implants, promote bone tissue regeneration, and improve bonding strength and osseointegration at the implant/bone interface. Due to its desirable biocompatibility, antibacterial property and excellent mechanical properties, GO has attracted enormous research interest in recent years. The project aims to examine GO beyond osteogenic capacity and assess osseointegration as a standalone coating and within a composite compared to conventional coatings.

The University of Manchester is a world leader in Advanced Materials in Medicine. The supervisory team are all internationally renowned researchers working within the Royce Institute, the Graphene Institute, Division of Cell Matrix Biology and Regenerative Medicine with experience utilising GO coatings in orthopaedic devices. This project is an expansion of this work and aims to further assess the benefit of GO coatings in orthopaedic applications. 

Background:

Osseointegration (OI) is the direct anchorage of a metal implant into bone, allowing for the connection of a prosthesis to the skeleton. This is better researched in oral and craniofacial surgery than orthopaedic surgery. The successful process of metal integration into host bone demands synergy between the host bone, the metal implant, and the bone-implant interface. Bridging of gaps (1-2 mm) between the bone and implant by nascent bone, is dependent on the surface coating of the implant. Metals and metal alloys are primarily used to manufacture OI implants due to their strength and toughness. Hydroxyapatite (HA) coatings have been shown to be superior to titanium alloy coating for stimulating implant bone ingrowth from the native bone. However, loosening of intramedullary implants over time remains a problem for both intramedullary fracture fixation and cementless arthroplasty particularly with osteoporotic bone. Also, HA is not routinely used for OI because the highly osteophilic surface created by HA can result in a stronger bone-HA layer and this layer separates from the titanium surface over time. Graphene oxide (GO) and reduced graphene oxide (RGO) has been investigated for its OI potential in implantology. In a recent animal model study by Li et al, implantation of a graphene coated titanium alloy scaffold in bone demonstrated an improved osteogenic rate and volumetric growth of new bone tissue compared to the uncoated implant. We believe that GO may be a far superior substrate for cell attachment, proliferation, and differentiation on orthopaedic implants than conventional surface coatings. 

Questions to be answered:

1. Do GO coated implants demonstrate an improved osteogenic rate and volumetric growth of new bone tissue compared to current HA coatings, composite coating, and non-coated implants?
2. Do GO coated implants demonstrate earlier implant fixation compared to current HA coatings, composite coatings, and non-coated implants?
3. Do GO coated implants demonstrate reduce implant loosening with cyclic loading over time compared to current HA coatings, composite coated and non-coated implants?

These questions will be evaluated using the following biomaterial analyses for in-vitro and potentially in-vivo animal models following chemical vapour deposition of graphene on intra-medullary devices.

• Ultrasonication testing to assess stability of coatings
• Histological assessment of new bone formation (Van Gieson staining, light microscopy and scanning electron microscopy)
• Assessment of mesenchymal stem cell attachment and cell distribution
• Biomechanical assessment of implant fixation using “push-out” experiments
• Micro-CT to analyse the new bone volume and trabecular bone density surrounding the implant materials
• Post mortem analyses to assess for systemic leaching of GO coating