Abstract
Magnesium (Mg) was originally developed as a degradable metallic biomaterial for orthopaedic application in the mid 1800s. The theory behind the use of a biodegradable metal is that it would allow the complete elimination of the orthopaedic device after healing, removing the need for a second surgery for implant removal. Additionally, Mg exhibits a high strength to weight ratio and an elastic modulus similar to bone, which are favourable characteristics for optimal fracture fixation and healing. These properties also minimise complications such as stress shielding and the resultant osteopenia. Although, investigations of Mg as orthopaedic implants were hindered by its highly reactive nature and unpredictable corrosive behaviour. However, recent technological advancements in the processing, manufacture, and modification of Mg have warranted renewed interest in Mg as a biomaterial. The main focus of this study is using a novel coating method to control Mg corrosion, whilst maintaining or improving the biocompatibility of the material. To address this aim, the calcium phosphates (CaP), brushite and monetite, were developed as coatings on Mg. These coatings were then assessed both in vitro and in vivo for corrosion and biocompatibility .
The initial investigations were carried out using in vitro techniques to assess the suitability of these coatings for advancement to in vivo assessment. Both the brushite and monetite coating showed corrosion protection in a range of physiological solutions exhibiting mass loss ranges of 4.39-6.39% and 2.76- 4.39% respectively over 28 days compared to the uncoated range of 5.1%- 10.1%. In vitro biocompatibility tests using a murine fibroblastic cell line (L929) and a human osteosarcoma cell line (SaOS-2) assessed the proliferation/viability of cells on the coatings using a standard LIVE/DEAD® assay. Western blotting was also used to identify the bone markers, osteopontin, osteonectin, osteocalcin, and bone-sialo protein. ALP activity was also used to assess the osteopotentive properties of the coatings. The results indicated good biocompatibility for both the brushite and monetite coatings when compared to uncoated Mg and inert titanium.
The in vitro findings supported the further investigation of the coatings in an in vivo environment. Accordingly, a small animal model, the Lewis rat, was selected for preliminary corrosion and biocompatibility investigation in a subcutaneous environment. In these investigations, the brushite- and monetite-coated Mg displayed enhanced corrosion protection compared to an uncoated control, more so in the case of the latter coating. The range of mass loss seen between uncoated, brushite and monetite coated were 2.46-7.11%, 1.89-5.14% and 1.42-3.78% respectively. No differences were seen in the inflammatory responses to coated Mg samples when compared to uncoated samples, supporting their biocompatibility in an in vivo location. The corrosion and biocompatibility data further validated the exploration of these coatings in a bony location in a larger animal model. Accordingly, the Romney-Cross sheep was selected for the evaluation of brushite and monetite coatings in both cortical and cancellous bone. The data obtained was conflicting and provided varied support for the use of brushite and monetite coatings for fracture fixation applications. The coatings, when compared to uncoated controls, provided no significant corrosion protection in cancellous bone although some initial protection was apparent in a cortical location. Moreover, the biocompatibility of the coated Mg paralleled the uncoated controls. However, the relationships between the assessed parameters (corrosion, bone-implant contact, bone deposition, and hydrogen production) suggest and support the further consideration of these coatings for fracture fixation applications.