Towards the design of biomimetic dental implants: defining the natural periodontal ligament’s structure and a scoping review of soft tissue interfaces

Background: Tooth loss is one of the most prevalent oral diseases. Usually, tooth loss is treated either by removable, fixed, or implant-supported prosthesis. While osseointegrated dental implants represent a largely successful treatment option, they still have anatomical, biological, physiological, and mechanical shortcomings. Most of these shortcomings are attributed to the lack of periodontal ligament (PDL) around dental implants. Surprisingly, the literature lacks proper understanding of the PDL due to difficulty in imaging and studying this part in its 3D geometry. It is a clinical necessity to improve treatment for tooth loss by re-establishing the PDL and its associated functions around an implant. Proper understanding of the PDL is paramount to achieving this goal.Objectives: i) to define the PDL’s natural 3D structure while in its anatomical position utilizing contrast enhanced nano-computed tomography imaging and ii) to perform a scoping review of research areas working towards building a biomimetic dental implant or interfaces between implants and investing tissues.Materials and Methods: C57Bl/6 mice (n=5), aged 28-35 days were euthanized. Ten half-mandible samples were prepared and fixed in Bouin’s solution for 24h, then stored in the refrigerator. The samples were stained with either iodine potassium iodide (IKI), phosphotungstic acid (PTA), phosphomolybdic acid (PMA), mercury chloride (HgCl), or no stain. Then, the samples were mounted in agarose before scanning. The Zeiss Xradia 520 versa nano-computed tomography imaging unit was used. Images processing was performed using dragonfly software.For the scoping review, Medline, Embase, Scopus, and Compendex were searched with the help of a librarian from the McGill University library. Deduplication were completed on endnote. Two blinded reviewers completed the Initial inclusion/exclusion by screening of titles and abstracts using Rayyan. The full text was reviewed in the next stage to reach the final included records. Eligibility criteria included i) English language, ii) biologically induced growth of an attachment between bone and biocompatible implant, iii) scaffold or other engineered construct to act as an interface between bone and biocompatible implant, iv) in-vivo and in-vitro studies.Results: The PDL was imaged successfully in the stained samples but not the unstained ones. However, the collagen fibers were not visible even after staining. The physical size of the samples should be minimized to reduce total imaging time. Staining time should range from 24h (IKI) to 48h (PTA, PMA, HgCl). PTA and PMA would exhibit the optimum contrast. Scanning parameters should be optimized to maximize contrast and resolution. Proposed parameters are voltage  40kV, current  70A, pixel size  0.7m, optical magnification at 10X, and exposure time  20 seconds. In the scoping review, the initial stage yielded 9,562 records. After screening of titles, abstracts, and full text, 82 articles satisfied the defined inclusion criteria. The included studies were classified as PDL regeneration (n=77) or PDL substitution (n=5). The studies were also categorized by experimental approach: Ti implant (n=25), PEEK implant (n=1), cell & cell sheets (n=27), and scaffolds (n=29). Of the 82 included studies, 22 studies were in-vitro, 59 were animal study and only 1 was performed on human participants. 54 articles reported ordered PDL regeneration.Conclusion: Imaging of this part of the tooth is particularly challenging as it is surrounded by mineralized tissues. Careful selection of sample size, staining protocol and scanning parameter are essential for proper tissue visualization. The knowledge obtained from the different studies which aimed to restore the PDL reflect the need for further experiments to achieve this goal. Deeper understanding of the structural components of the PDL will improve the chances to successfully develop biomimetic dental implants

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