A novel surgical model for the preclinical assessment of the osseointegration of dental implants: a surgical protocol and pilot study results

Abstract

Background: Dental implants are considered the gold standard replacement for missing natural teeth. The successful clinical performance of dental implants is due to their ability to osseointegrate with the surrounding bone. Most dental implants are manufactured from Titanium and it alloys. Titanium does however have some shortcomings so alternative materials are frequently being investigated. Effective preclinical studies are essential to transfer the innovations from the benchtop to the patients. Many preclinical studies are carried out in the extra-oral bones of small animal models to assess the osseointegration of the newly developed materials. This does not simulate the oral environment where the dental implants are subjected to several factors that influence osseointegration; therefore, they can have limited clinical value.

Aim: This study aimed to develop an appropriate in-vivo model for dental implant research that mimic the clinical setting. The study evaluated the applicability of the new model and investigated the impact of the surgical procedure on animal welfare.

Materials and methods: The model was developed in male New Zealand white rabbits. The implants were inserted in the extraction sockets of the secondary incisors in the maxilla. The model allows a split-mouth comparative analysis. The implants' osseointegration was assessed clinically, radiographically using micro-computed tomography (µ-CT), and histologically. A randomised, controlled split-mouth design was conducted in 6 rabbits. A total of twelve implants were inserted. In each rabbit, two implants; one experimental implant on one side, and one control implant on the other side were applied. Screw-shaped implants were used with a length of 8 mm and a diameter of 2 mm.

Results: All the rabbits tolerated the surgical procedure well. The osseointegration was confirmed clinically, histologically and radiographically. Quantitative assessment of bone volume and mineral density was measured in the peri-implant bone tissues. The findings suggest that the new preclinical model is excellent, facilitating a comprehensive evaluation of osseointegration of dental implants in translational research pertaining to the human application.

Conclusion: The presented model proved to be safe, reproducible and required basic surgical skills to perform.

Keywords: Dental implants; In vivo study; Osseointegration; Preclinical investigation; Surgical model.

Fig. 1

Cadaveric maxilla of rabbit. a Illustration of position of the secondary incisors behind the primary incisors. b The proposed implant positions in the sockets of the extracted secondary incisors

Fig. 2

Operative protocol. a Secondary incisors (arrows). b Secondary incisors luxated with a 19-gauge. c H-shape flap design. d Extraction performed using root forceps. e Alternative extraction method using college tweezers. f Extraction sockets (arrows) and extracted secondary incisors at upper left corner. g Final placement of implants in the maxilla. h Reflected flap closed primarily using bio-absorbable sutures

Fig. 3

Chart of individual bodyweight of rabbits during the study period

Fig. 4

Clinical image demonstrating complete healing with healthy gingival coverage in one of the cases postoperatively

Fig. 5

Gross examination of the retrieved bone sample. a Close-up of lateral view of explanted anterior maxilla of one of the cases illustrating the complete bone coverage of both implants. b Close-up view showing no bone overgrowth nor marginal bone resorption around both implants. c Superior view showing intact bone with no bone perforation by the implants

Fig 6

The radiographic images demonstrating the position of the implants in the presented model. a Three-dimensional reconstruction of the model in cadaveric rabbit using X-ray computed tomography system (XCT). b Representative microtomographic axial slice of the µ-CT image from rabbit maxilla. c Representative microtomographic sagittal slice of the µ-CT image from rabbit maxilla in colour scale. d Representative microtomographic coronal slice of the µ-CT image

Fig. 7

The Quantitative µ-CT analysis. a Bone mineral density (BMD) data are presented as mean ± SD and were analyzed with paired t-test. No statistical differences were seen between the two types of dental implants. b Results of paired t-tests of BMD demonstrating the pattern of the relationship between the experimental and titanium implants. The pair of implants inserted in anterior maxilla of each rabbit are connected by a line. c Data are presented as mean ± SD and were analyzed with paired t-test. No statistical differences were seen between the two types of dental implants. d Results of paired t-tests of BV/TV demonstrating the pattern of the relationship between the experimental and titanium implants. The pair of implants inserted in anterior maxilla of each rabbit are connected by a line, ns = not significant