Background/Objectives: Surgical navigation has advanced maxillofacial surgery since the 1990s, bringing benefits for various indications. Traditional registration methods use fiducial markers that are either invasively bone-anchored or attached to a dental vacuum splint and offer high accuracy but necessitate additional imaging with increased radiation exposure. We propose a novel, non-invasive registration protocol using a CAD/CAM dental splint based on high-resolution intraoral scans. Methods: The effectiveness of this method was experimentally evaluated with an ex vivo 3D-printed skull measuring the target registration error (TRE). Surgical application is demonstrated in two clinical cases. Results: In the ex vivo model, the new CAD/CAM-splint-based method achieved a mean TRE across the whole facial skull of 0.97 ± 0.29 mm, which was comparable to traditional techniques like using bone-anchored screws (1.02 ± 0.23 mm) and dental vacuum splints (1.01 ± 0.33 mm), while dental anatomical landmarks showed a lower accuracy with a mean TRE of 1.84 ± 0.44 mm. Multifactorial ANOVA confirmed significant differences in TRE based on the registration method and the navigated level of the facial skull (p < 0.001). In clinical applications, the presented method demonstrated high accuracy for both midfacial and mandibular surgeries. Conclusions: Our results suggest that this non-invasive CAD/CAM-splint-based method is a viable alternative to traditional fiducial marker techniques, with the potential for broad application in maxillofacial surgery. This approach retains high accuracy while eliminating the need for supplementary imaging and reduces patient radiation exposure. Further clinical trials are necessary to confirm these findings and optimize splint design for enhanced navigational accuracy.
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