Development of absorbable magnesium bone-fixation plate

Abstract

Background and purpose of study Titanium (Ti) is currently the most widely used material in bone fixation devices for craniofacial bone surgery. However, the Ti fixation device is permanent and thus increases the risk of infection due to prolonged metal exposure. Moreover, in children, there is an increased risk that the inserted fixation plate or screws will become incorporated into the bone, necessitating removal with additional surgery. Polymer-based bone fixation devices have certain advantages with respect to bioresorption

however, the strength of the polymer is still far lower than that of the Ti device. Unlike Ti and polymer, magnesium (Mg) can provide a balance of strength and an appropriate rate of degradation. The degradation of Mg reduces the risk of long-term infection, eliminates the need for removal surgery, and can promote healing through Mg ion release. Furthermore, its elastic modulus and compressive strength are similar to those of human bone. For these reasons, Mg is being explored for various craniofacial and orthopedic applications. However, rapid degradation of Mg can cause excessive hydrogen gas formation, which can ultimately hinder clinical success. In addition, although Mg has better mechanical properties than polymer, it still has poorer mechanical properties than Ti. The purpose of the present study was to improve the mechanical strength and control the absorption rate of Mg material and to develop an absorbable metallic plate for craniofacial application.

Methods Chapter 1: Development and evaluation of strength-enhanced pure Mg plate The tensile strength and flexural strength of a Ti plate and an untreated pure Mg plate were evaluated. Pure Mg plates for the in vivo test were treated with a bi-axial rolling process to enhance the mechanical strength. Mg plates were inserted above the cranial bones of Sprague-Dawley rats (rat calvarium). In the control group (non-coated Mg group), non-coated Mg plates were inserted into 25 rats and, and five rats were sacrificed each at 2, 4, 6, 8, and 12 weeks. In the experimental group (HA-coated Mg group), hydroxyapatite (HA)-coated Mg plates were inserted into 30 rats, and five rats were sacrificed each at 2, 4, 6, 8, 12, and 24 weeks. The presence of inflammation, infection, hydrogen gas formation, wound dehiscence, and plate exposure was examined at the time of sacrifice. The absorption pattern and tensile strength of the retrieved Mg plate were examined after micro-computed tomography (µCT).

Chapter 2: Development and evaluation of Mg alloy bone-fixation plate-ZK60 Alloying is an innovative approach to improve the mechanical properties of pure Mg. In order to overcome the limitation of the poor mechanical strength of pure Mg, ZK60 was selected, which has a higher mechanical strength than pure Mg. In addition, ZK60 was expected to be absorbed in the body fluid at a similar rate as pure Mg

poly-L-lactic acid (PLLA) coating was used to slow the absorption. The PLLA-coated ZK60 plate was evaluated using a LeFort I osteotomy canine model of two beagle dogs. Four L-shaped plates were fixed at the anterior buttresses and posterior buttress with 16 screws. The presence of wound dehiscence, plate exposure, gas formation, occlusion, inflammation, pus formation, food intake, and fistula formation was evaluated weekly. Both dogs were sacrificed after 10 weeks, and µCT was performed. Gas formation and the absorption rate of the plates and screws were evaluated with the µCT images.

Chapter 3: Development and evaluation of Mg alloy bone-fixation plate-WE43 ZK60, which is a Mg alloy, had good mechanical properties but exhibits too rapid absorption. Thus, other types of material having slower absorption were sought. WE43 has slower absorption than ZK60. However, WE43 has low mechanical strength and is difficult to use clinically as it requires additional strength enhancement, which can be accomplished by an extrusion process. A WE43 Mg alloy rod was pre-treated with an extrusion process to increase its strength (extruded WE43). The biocompatibility of WE43 was evaluated using an osteoblast cell line (MC3T3-E1). The static immersion test in the simulated body fluid (SBF) was performed to observe the corrosion rate of the alloys over a period of 60 days. A three-point flexural test and a tensile test were performed on the Ti plate, pure Mg plate, and WE43 plate. The extruded WE43 plate was evaluated using a LeFort I osteotomy canine model of 10 beagle dogs. Dogs were divided into two groups: five dogs in the experimental group and five dogs in the control group. Clinical evaluation was performed in the same manner as was described for the animal study using the ZK60 plate. µCT was acquired at 4, 12, and 24 weeks. The absorption of the plates and the change in the surrounding bone were evaluated. At 24 weeks after the operation, all animals were sacrificed, and histologic evaluation was performed.

Results Chapter 1: Development and evaluation of strength-enhanced pure Mg plate The Mg plate had lower flexural strength and tensile strength than the Ti plate. In the non-coated Mg group, gas formation and plate exposure were observed starting at 2 weeks. In the HA-coated Mg group, gas formation was not observed until 12 weeks and was also observed at 24 weeks. The HA-coated Mg group showed slower absorption of the plate compared to the non-coated Mg group. The tensile strength of HA-coated Mg plates was maintained until 12 weeks (>190 MPa).

Chapter 2: Development and evaluation of Mg alloy bone-fixation plate-ZK60 Neither of the dogs experienced any specific problem during the surgical procedure. Plate exposure, gas formation, and external fistula were not observed, and occlusion remained stable. However, the wound dehiscence that occurred after 2 weeks was not healed during the observation period. The inflammatory symptoms continued after 2 weeks. All plates were not seen in the µCT images, and only a few screw bodies fixed in the bone remained after 10 weeks.

Chapter 3: Development and evaluation of Mg alloy bone-fixation plate-WE43 There was no difference in cell attachment or proliferation between pure Mg and WE43. The corrosion rate of WE43 remained constant for 60 days and was slow compared to that of ZK60. Approximately 60% of the initial mass remained at 60 days. The flexural strength and tensile strength of the extruded WE43 were higher than those of casted WE43. Swelling and gas formation were observed in three dogs in the experimental groups at 8 weeks. From 12 weeks, infraorbital fistula and inflammation were observed in three dogs in the experimental group, which gradually decreased and disappeared at 24 weeks. The plate that separated from the bone showed rapid absorption, but the screw fixed inside the bone showed slow absorption. Two dogs showed less gas formation at 12 weeks compared to the other dogs. The plates were completely absorbed, and gas formation was not observed at 24 weeks in these two dogs. In the control group, plates and screws were maintained as they were at their initial position without any problem. Osteoblastic lining and woven bone were observed around the screw threads in both groups. New bone was well formed around the plates and screws in both groups. Histologic examination showed no specific differences between the experimental group and control group.

Conclusion The mechanical strength of pure Mg was improved by a bi-axial process

however, the tensile strength did not exceed 200 MPa. The tensile strength of ZK60 exceeded 300 MPa, but the absorption was too rapid for clinical application. The mechanical strength of extruded WE43 was sufficient for mid-facial application. Absorption of WE43 showed disadvantageous gas formation, but it was thought that the absorption rate could be optimized with a surface treatment such as coating. Plates made with appropriately treated WE43 have the potential to be useful clinically.