Research Spotlight

Pandya, M., Saxon, M., Bozanich, J., Tillberg, C., Luan, X. and Diekwisch, T.G.H. (2021). “The Glycoprotein/Cytokine Erythropoietin Promotes Rapid Alveolar Ridge Regeneration In Vivo by Promoting New Bone Extracellular Matrix Deposition in Conjunction with Coupled Angiogenesis/Osteogenesis.” Int J Mol Sci 22(6).

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The loss of bone following tooth extraction poses a significant clinical problem for maxillofacial esthetics, function, and future implant placement. In the present study, the efficacy of an erythropoietin-impregnated collagen scaffold as an alveolar ridge augmentation material versus a conventional collagen scaffold and a BioOss inorganic bovine bone xenograft was examined. The collagen/Erythropoietin (EPO) scaffold exhibited significantly more rapid and complete osseous regeneration of the alveolar defect when compared to bone xenograft and the collagen membrane alone. The new EPO induced extracellular matrix was rich in Collagen I, Collagen III, Fibronectin (Fn) and E-cadherin, and featured significantly increased levels of the osteogenic transcription factors Runt-related transcription factor 2 (Runx2) and Osterix (Osx). Histomorphometric evaluation revealed a significant two-fold increase in the number of capillaries between the EPO and the BioOss group. Moreover, there was a highly significant 3.5-fold higher level of vascular endothelial growth factor (VEGF) in the collagen/EPO-treated group compared to controls. The significant effect of EPO on VEGF, FN, and RUNX2 upregulation was confirmed in vitro, and VEGF pathway analysis using VEGF inhibitors confirmed that EPO modulated extracellular matrix protein expression through VEGF even in the absence of blood vessels. Together, these data demonstrate the effectiveness of an EPO-impregnated collagen scaffold for bone regeneration as it induces rapid matrix production and osseoinduction adjacent to new capillaries via VEGF.

Wang, C.I., Cho, S.H., Ivey, A., Reddy, L.V. and Sinada, N. (2021). “Combined bone- and mucosa-supported 3D-printed guide for sinus slot preparation and prosthetically driven zygomatic implant placement.” J Prosthet Dent Mar 29;S0022-3913(21)00107-4. [Epub ahead of print].

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The use of zygomatic implants to rehabilitate the severely atrophic maxilla has been well documented since first being introduced by Brånemark. Placement of zygomatic implants is technically complex, with catastrophic complications and numerous prosthetic challenges resulting from imprecise placement. The purpose of this report was to demonstrate a technique that allows transfer of the preoperatively planned sinus slot position to the surgical field by using cone beam computed tomography (CBCT) and an implant planning software program to fabricate a combined bone- and mucosa-supported 3D-printed surgical guide. This facilitates optimal zygomatic implant positioning and promotes favorable biomechanics with a predictable prosthetic outcome.

Yan, F., Cheng, Y.L., Katabi, N., Nguyen, S.A., Chen, H.S., Morgan, P., Zhang, K. and Chi, A.C. (2021). “Interobserver Variation in Evaluating Perineural Invasion for Oral Squamous Cell Carcinoma: Phase 2 Survey Study.” Head Neck Pathol.

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In a previous study, we found interobserver agreement among 88 board-certified pathologists evaluating perineural invasion (PNI) in oral squamous cell carcinoma (OSCC) was fair, and participants most often used the following criteria: (1) tumor invading the perineurium, (2) tumor surrounding a nerve. In this study, we aimed to determine whether application of these most commonly used criteria may improve interobserver agreement. 512 pathologists were invited to participate in a web-based survey. Participants were asked to assess the presence/absence of PNI in a set of OSCC photomicrographs by applying each of the two criteria above. The survey was completed by 84 board-certified pathologists [mean age: 52 years (range 31-81), mean years in practice: 19 (range 1-56)]. Interobserver agreement was moderate (k = 0.46, 95% CI 0.45-0.46) when using definition #1 (tumor invading the perineurium) and fair (k = 0.24, 95% CI 0.23-0.25) when using definition #2 (tumor surrounding a nerve). By comparison, interobserver agreement was fair (k = 0.36, 95% CI 0.35-0.37) among phase 1 participants asked to evaluate these photomicrographs as they would in their pathology practice. Differences in kappa between definition #1 and phase 1, definition #2 and phase 2, and definition #1 and #2 were statistically significant (p < 0.001). Compared to our prior study based on pathologists' personal views, the current study shows improved interobserver agreement with application of the criterion, "tumor invading the perineurium." However, further work is needed to delineate concise, objective, and more reproducible criteria for histopathologic assessment of PNI.

Geshay, D., Campbell, P., Tadlock, L., Schneiderman, E., Kyung, H.M. and Buschang, P. (2021). “Stability of immediately loaded 3 mm long miniscrew implants: a feasibility study.” Dental Press J Orthod 26(1): e2119155.

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INTRODUCTION: Shorter miniscrew implants (MSIs) are needed to make orthodontics more effective and efficient. OBJECTIVE: To evaluate the stability, insertion torque, removal torque and pain associated with 3 mm long MSIs placed in humans by a novice clinician. METHODS: 82 MSIs were placed in the buccal maxillae of 26 adults. Pairs of adjacent implants were immediately loaded with 100g. Subjects were recalled after 1, 3, 5, and 8 weeks to verify stability and complete questionnaires pertaining to MSI-related pain and discomfort. RESULTS: The overall failure rate was 32.9%. The anterior and posterior MSIs failed 35.7% and 30.0% of the time, respectively. Excluding the 10 MSIs (12.2%) that were traumatically dislodged, the failure rates in the anterior and posterior sites were 30.1% and 15.2%, respectively; the overall primary failure rate was 23.6%. Failures were significantly (p= 0.010) greater (46.3% vs 19.5%) among the first 41 MSIs than the last 41 MSIs that were placed. Excluding the traumatically lost MSIs, the failures occurred on or before day 42. Subjects experienced very low pain (2.2% of maximum) and discomfort (5.5% of maximum) during the first week only. CONCLUSIONS: Shorter 3 mm MSIs placed by a novice operator are highly likely to fail. However, failure rates can be substantially decreased over time with the placement of more MSIs. Pain and discomfort experienced after placing 3 mm MSIs is minimal and temporary.

Siebert, M., Hedrick, B.N., Zide, J.R., Thomas, D.M., Shivers, C., Pierce, W.A., Kanaan, Y., Harris, M.C. and Riccio, A.I. (2021). “Do We Really Need to Worry About Calcaneocuboid Subluxation During Lateral Column Lengthening for Planovalgus Foot Deformity?” J Pediatr Orthop 41(3): e246-e251.

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BACKGROUND: Although lengthening of the lateral column through an osteotomy of the anterior calcaneus is an integral component of flatfoot reconstruction in younger patients with flexible planovalgus deformities, the procedure has been implicated in iatrogenic calcaneocuboid (CC) subluxation and subsequent degenerative changes at the CC articulation. The purpose of this study is to characterize alterations at the CC joint after lateral column lengthening (LCL) and determine if Steinmann pin stabilization of the CC joint before distraction maintains a normal relationship. METHODS: Seven matched pairs of fresh-frozen cadaveric feet underwent preprocedure plain radiography and cross-sectional computed tomography (CT) imaging. LCL by osteotomy through the anterior calcaneus was then performed. One foot of each matched pair had a single smooth Steinmann pin placed centrally across the CC joint before osteotomy distraction. Distraction across each osteotomy was then performed and maintained with a 12-mm porous titanium wedge. Repeat imaging was obtained and compared with preprocedure studies to quantify sagittal and rotational differences at the CC articulation. RESULTS: Following LCL, plain radiography demonstrated statistically significant increases in the percentage of the calcaneal articular surface dorsal to the superior aspect of the cuboid in both the pinned (8.2% vs. 17.6%, P=0.02) and unpinned (12.5% vs. 16.3%, P=0.04) specimens. No difference in the percentage of subluxation was found between the 2 groups after LCL. CT imaging demonstrated statistically significant increases in rotation between the calcaneus and cuboid after LCL in both the pinned (7.6±5.6 degrees, P=0.01) and unpinned (17±12.3 degrees, P=0.01) specimens. The degree of rotation was greater in unpinned specimens after LCL (P=0.043). CONCLUSIONS: Both sagittal and rotatory subluxation seem to occur at the CC joint after LCL regardless of pin stabilization. As a single pin would be expected to limit pure translation while having little effect on rotation, it is possible that the rotational changes identified on 3-dimensional imaging are interpreted as dorsal translation when viewed 2 dimensionally using plain radiography. Consideration should therefore be given to CC stabilization with 2 pins during LCL to prevent this rotatory subluxation. LEVEL OF EVIDENCE: Level V-cadaver study.