Abstract
The titanium mandibular modular endoprosthesis fixed with polymethylmethacrylate cement in the medullary space of the mandible has been introduced in previous studies. However, the internal parts of these devices have been found to be prone to loosening and wound dehiscence. The current study introduces a newly designed bioactive-coated cementless modular mandibular endoprosthesis, which was used for reconstruction in Macaca fascicularis . The devices were coated with hydroxyapatite (HA) and hydroxyapatite/bioglass (HA/BG) and implanted in unilateral mandibular segmental defects in nine monkeys for 6 months. Biomechanical testing found the reconstructed mandible to have a mean stiffness value of 110.43 N/mm. Histologically, there were both fibrous capsule and woven bone around the device body, and histomorphology analysis showed 64.17% bone contact to device stem surface. The percentage bone volume calculated from micro-computed tomography analysis around the stem surface was found to be superior to that reported in previous studies of cemented mandibular endoprostheses. Intermodular connection screw loosening has also been resolved with the dovetail interconnection. In conclusion, the current bioactive-coated cementless mandibular endoprosthesis is feasible for use in mandibular segmental reconstruction. However, insufficient load-bearing capability and a high rate of intraoral wound dehiscence were found in the majority of the study animals. Further device modifications and improvements in the surgical technique need to be addressed in future studies.
In orthopaedics, the use of a metallic endoprosthesis for skeletal reconstruction after segmental bone resection has been reported for several decades. A modular concept was introduced in the late 1980s, which has helped to eliminate the need for device customization. The prefabricated components of various modular sizes allow assembly during surgery. Both cemented and non-cemented methods have been used to fixate the device into the remaining bone. The cementless approach requires the use of materials that support the achievement of a good secondary fixation into the bone in order to avoid later loosening. Controversial failure and success data have been reported with the use of cementless orthopaedic devices. Abraham et al. found that the complication rate in the short-term outcomes of cementless modular endoprostheses to reconstruct the proximal femur, distal femur, and proximal tibia were relatively low compared to previously reported results of cemented implants.
In oral and maxillofacial reconstruction, a titanium-6 aluminium-4 vanadium (Ti6Al4V) modular endoprosthesis was introduced for mandibular segmental reconstruction by Lee et al. The devices were fixed into the remaining bone stumps in the mandible of Macaca fascicularis for 6 months using polymethylmethacrylate (PMMA) cement. The study showed an abundance of bone formation around the body of the modular endoprosthesis. Problems encountered included loosening of the module connections and infection. In addition, the soft tissue healing was not ideal, resulting in dehiscence and hardware exposure in some cases, while uneventful healing was experienced with a developed ramus/condyle replacement in a later study.
Based on the results of these previous studies, our research group modified the design of the endoprosthesis to better withstand the stresses from mastication forces. Therefore, the intermodular connection of the device was redesigned using mechanical testing and finite element analysis to prevent component loosening. The biomechanical stability was found to be firm under simulated functional forces without having excessive stresses beyond the material strength of bone or titanium alloy.
Further, the surface of the modular stems was modified to allow fixation into the mandibular bone without using bone cement, i.e. a cementless endoprosthesis. The bioactive surface coatings of hydroxyapatite (HA; Ca 10 (PO 4 ) 6 (OH) 2 ) and bioglass (BG; SiO 2 –Na 2 O–CaO–P 2 O 5 ) are selected for titanium surface modification to improve soft and hard tissue healing. HA and related calcium phosphates (CaP) are present in large amounts in bone. HA-based materials are basically not biodegradable, but are found to possess excellent bone biocompatibility and are widely used in clinical practice in both the orthopaedics and dental fields. HA coatings on dental implants have been shown to accelerate bone apposition, thereby shortening the waiting period for implant restoration. The additionally provided surface roughness increases the interface strength even further. As a consequence, higher survival rates have been reported than for just commercial pure-titanium and titanium-alloy implants.
BG is an inorganic component with a high bioactivity index and has the ability to bond to both soft and hard tissues. BG has been shown to increase the expression of vascular endothelial growth factor (VEGF) in vitro and to enhance vascularization in vivo , suggesting that BG might stimulate neovascularization.
The current study was designed to evaluate the effectiveness of a bioactive-coated cementless modular mandibular endoprosthesis for mandibular reconstruction in M. fascicularis . The device was coated with HA/BG at the modular body surface, while the stems were coated with HA. We hypothesized that the bioactive-coated cementless mandibular endoprosthesis would have: (1) sufficient load-bearing capability for masticatory function, (2) good bone and soft tissue healing at the reconstruction site, and (3) no loosening of the device components during the 6-month study period.
Materials and methods
Animals
Nine adult male M. fascicularis monkeys, aged 4–6 years, weighing 6–7 kg, were used in this study. All monkeys were pathogen-free, presented with full adult dentition, and were in a healthy condition. The experimental protocol was approved by the institutional animal care and use committee. The animal laboratory has been certified by the International Association for the Assessment of Laboratory Animal Care (IACUC), Singapore.
Ti6Al4V modular endoprosthesis
Design and characterization
The bioactive-coated cementless Ti6Al4V modular endoprosthesis is composed of two modular components, i.e. (1) anterior module and (2) posterior module. The connected device is 15 mm long, which was appropriate to replace and maintain the defect dimension. The device height was kept at 12 mm or 70% height of the original mandible, while the width was 6 mm at occlusal and 4 mm at the lower border, similar to the original size of the mandible. The two modules were joined together with a dovetail connection and secured with a vertical screw. The anterior and posterior stems consisted of tapered screws of 12 mm in length. The stems were non-self-cutting and therefore drilling of the cancellous bone of the mandibular stumps was required before their insertion ( Fig. 1 ).
Surface coating with hydroxyapatite (HA) and hydroxyapatite/bioglass (HA/BG)
The Ti6Al4V mandibular endoprosthesis was Al 2 O 3 grit-blasted (60 mesh). Hydroxyapatite granules (HA, particle size 0.5–1.0 mm, CAMCERAM; CAM Implants BV, Leiden, The Netherlands) and melt-derived bioglass crushed particles (Bioglass S53P4, particle size 30–315 μm, BonAlive; Vivoxid Ltd., Turku, Finland) were used for coating deposition on the implant surfaces.
HA and HA/BG coatings were made using a commercially available RF magnetron sputter deposition system (ESM100; Edwards, Crawley, West Sussex, UK). The target materials for the coating deposition were the HA granules and BG particles. The endoprostheses were mounted on a rotating water-cooled substrate holder. The distance with the targets was 80 mm. During deposition, the argon pressure was kept at 5 × 10 −3 mbar. The following coatings were created: (1) Endoprosthesis body modules coated with a mixture of HA/BG, at a discharge power of 100 W and 100 W, respectively, with a deposition time of 20 h, resulting in a coating with a thickness of 2 μm. (2) Endoprosthesis stems coated with HA, at a discharge power of 400 W for both targets, with a deposition time of 5 h, resulting in a coating with a thickness of 2 μm.
After deposition, the coated specimens were subjected to an additional heat-treatment for 2 h at 650 °C. The composition of the coatings was confirmed by X-ray diffraction and Fourier transform infrared (FTIR) analysis. The devices were sterilized by autoclave before placement in the experimental animals.
Surgical procedure
The animals underwent an overnight fast. Preoperatively, they received 0.05 mg/kg of atropine subcutaneously and 10 mg/kg of ketamine. Induction and maintenance of anaesthesia were performed by a veterinarian using 2% isoflurane. Endotracheal intubation was done using oral endotracheal tubes (3.5-mm gauge) that were secured around the upper premolar tooth with a ligature wire. Antibiotics (ampicillin/cloxacillin (Betamox; Norbrook Pharmaceuticals Worldwide, Newry, Northern Ireland) 6–8 mg/kg subcutaneous) were given on induction and analgesics were given at the end of surgery.
The operation site was disinfected with 1% cetrimide followed by 2% chlorhexidine and povidone iodine and draped for surgery. Using an intraoral approach, two vertical incisions were made, one between the second bicuspid and the first molar, and one behind the second molar. A horizontal incision 2–3 mm below the attached gingiva was made, connecting the two vertical incisions. The periosteum was reflected to expose the lower border of the mandible. A tapered fissure bur was employed to perform the resection, which included a 1.5-cm mandibular segment, containing the first and second permanent molars and the attached gingiva. Bleeding from the inferior mandibular canal was easily staunched. The anterior and posterior bone stumps were prepared with a 0.8-mm fissure bur to 10 mm depth of the cancellous bone. The device stems were inserted with manual rotation until they fitted tightly and the edge of the module body was flush with the bone margin of the mandibular stump. The size of the modular stems was selected to match the size of the mandibular bone stumps in each mandible. The modules were then connected and secured with the vertical screw at the superior aspect of the device ( Fig. 2 ).
