Faculty Bibliography

Osseointegration is critical for the long-term success of endosteal implants, as it is influenced by factors such as implant design, material selection, and site of implantation. Considering the structural and vascular properties of trabecular bone, it is reasonable to hypothesize that osseointegration could be enhanced in this region. However, emerging evidence indicates that cortical bone frequently offers a more favorable environment for osseointegration. The objective was to conduct a systematic review of preclinical translational studies comparing osseointegration outcomes around implants placed in cortical and trabecular bone. Preclinical studies comparing bone-to-implant contact (BIC) and bone area fraction occupied (BAFO) between cortical and trabecular regions in animals with solid endosteal implants were retrieved from the PubMed, EMBASE, and Cochrane databases. We included randomized and nonrandomized preclinical translational trials published in English between 2014 and 2024 that reported at least one outcome of interest. Exclusion criteria comprised in vitro or ex vivo experiments, research involving human subjects, studies using powder, liquid, or plasma implants, abstracts, technical descriptions, and narrative or systematic reviews. The systematic review comprised 15 studies, which included a total of 298 animals and 877 implants. The mean follow-up period ranged between 4 and 17 weeks. In 13 studies, the cortical bone region demonstrated higher BIC values, with differences in BIC between cortical and trabecular bone ranging from 5.55% to 49.55% during the first 4 weeks, 1.80% to 51.30% between 4 and 8 weeks, and 9.65% to 35.41% following the 8-week healing period. Regarding BAFO values, data were reported in three studies, all of which indicated elevated values in cortical bone. The mean difference in the first 4 weeks ranged from 15.83% to 29.92%, and from 26.33% to 60.11% after 4 weeks of healing. These findings suggest that cortical regions exhibit enhanced short- and long-term osseointegration outcomes compared to trabecular bone regions. Impact Statement The specific site of implantation significantly influences the degree and rate of osseointegration. Trabecular bone, characterized by its high porosity and larger surface area relative to volume, facilitates the diffusion of nutrients and oxygen from the surrounding marrow and blood vessels. Nevertheless, emerging evidence indicates that cortical bone, due to its greater density and superior mechanical properties, often provides a more stable environment for osseointegration compared to trabecular bone. This systematic review of preclinical studies represents the first comprehensive effort to evaluate and compare osseointegration in cortical versus trabecular bone.

In an effort to improve bone response, predictably regenerate lost tissue, and provide an anatomically pleasing ridge contour for biomechanically favorable and prosthetically driven implant placement, guided bone regeneration (GBR) procedures have been indicated. This study provides the first direct in vivo comparison of the biocompatibility of an experimental porcine-derived collagen membrane (CMI, Regenity Biosciences, Paramus, NJ, USA) and a commercially available bovine-derived collagen membrane (CopiOs, ZimVie, Palm Beach Gardens, FL, USA) in a beagle mandibular model for the purposes of GBR. Four bilateral defects of 10 mm × 10 mm through the mandibular thickness were placed in each of n = 16 adult beagle dogs. Defects were filled with a deproteinized porcine-derived particulate graft and were covered either with CMI or CopiOs to allow compartmentalized healing. Animals were euthanized after 4, 8, 12, or 16 weeks post-operatively (n = 4 beagles/time point). Bone regenerative capacity, graft, and soft tissue presence were evaluated by histomorphometric and microtomographic analyses. Outcome variables were compared using a mixed model analysis with fixed factor variables of time and material. Qualitatively, no histomorphological differences in healing were observed between the membrane groups at any time point. Histomorphometrically, CMI and CopiOs presented statistically significant differences in bone (mean ± SD: 38.27% ± 15.20 vs. 17.43% ± 15.49, respectively, p = 0.016) and soft tissue presence (mean ± SD: 50.88% ± 11.83 vs. 68.21% ± 16.98, respectively, p = 0.026) at 8 weeks. These results might influence treatment timing in clinical practice, by enabling early implant placement or shorter healing intervals. No significant differences were detected in these parameters at any other healing time point (p > 0.05). CMI and CopiOs showed no signs of adverse immune response and led to similar trends in bone regeneration after 16 weeks of permitted healing. Both membranes minimized soft tissue infiltration and maintained defect stability over the observed healing periods without adverse events such as inflammation and/or foreign body reaction.

Peri-implant disease and gingival recession may be partially attributed to inadequate keratinized tissue. Soft tissue augmentation procedures utilizing non-autologous biomaterials, such as porcine-derived collagen membranes, have been gaining prominence and exogenous crosslinking is being actively investigated to improve the collagen membrane's stability and potential for keratinized tissue gain. The aim of this preclinical study was to evaluate the performance of a novel, crosslinked porcine collagen membrane (Zderm^TM, Osteogenics Biomedical, Lubbock, TX, USA) relative to an established, commercially available, non-crosslinked counterpart (Mucograft^®, Geistlich Pharma North America Inc., Princeton, NJ, USA) in a canine mandibular model. Bilateral split-thickness mucosal defects were created in adult beagles (n = 17), with each site receiving one membrane. Qualitative and quantitative histomorphometric analyses of groups were performed after 4, 8, and 12 weeks of healing and compared to unoperated, positive controls from the same subject. No significant differences in membrane presence were observed between Zderm^TM and Mucograft^® at 4, 8, and 12 weeks of permitted healing (p > 0.05). Similarly, the average keratinized tissue (KT) length between Zderm^TM and Mucograft^® groups was statistically equivalent across all healing times (p > 0.05). However, qualitative histological evaluation revealed greater rete ridge morphology amongst defects treated with Zderm^TM in comparison to Mucograft^®. Nevertheless, both membranes exhibited excellent biocompatibility and are well-suited for soft tissue augmentation procedures in the oral cavity.

Effective surface treatment of implants is essential for enhancing osseointegration outcomes. This study assessed the influence of alcohol decontamination both with and without secondary argon-based non-thermal plasma (NTP) treatment on osseointegration of endosteal implants in a large translational (sheep) model. Ti6Al4V dental implants were utilized either as received (CTRL), or subjected to ethanol cleaning (for 60 s) followed by NTP (for 60 s) (Clean+Plasma); or treated with NTP alone (Plasma) for 60 s. X-ray photoelectron spectroscopy was used for surface elemental analysis, followed by interferometry and sessile drop tests to measure changes in surface roughness and surface energy, respectively. Twelve sheep received implants (one implant per group per sheep) in the iliac crest, and bone healing was evaluated after 3 and 12 weeks using histomorphometric analysis (six sheep/time point). No significant differences in surface roughness (arithmetic mean (Sa) and root mean square (Sq) height: p > 0.161 and p > 0.173, respectively) or topographies were detected between implant surfaces. However, both NTP treated groups presented higher surface energies and lower water contact angle values relative to CTRL surface (p < 0.001). Compared to the CTRL, both NTP-treated groups exhibited reduced levels of Carbon and elevated levels of Oxygen. No significant differences in Bone-to-Implant Contact (BIC) or Bone Area Fractional Occupancy (BAFO) were observed among groups at 3 weeks. At the 12-week time point, Plasma implants demonstrated significantly higher BAFO (p = 0.014) compared to the CTRL group, as well as an increase in both BIC and BAFO over time (3 vs. 12 weeks in vivo) (p = 0.041 and p = 0.043, respectively). Building on the existing literature, the current study suggests that NTP treatment alone may be adequate to successfully enhance osseointegration while minimizing contamination risks, thereby eliminating the need for additional cleaning protocols.

Achieving the appropriate primary stability for immediate or early loading in areas with low-density bone, such as the posterior maxilla, is challenging. A three-dimensional (3D) stabilization implant design featuring a tapered body with continuous cutting flutes along the length of the external thread form, with a combination of curved and linear geometric surfaces on the thread's crest, has the capacity to enhance early biomechanical and osseointegration outcomes compared to implants with traditional buttressed thread profiles. Commercially available implants with a buttress thread design (TP), and an experimental implant that incorporated the 3D stabilization trimmed-thread design (TP 3DS) were used in this study. Six osteotomies were surgically created in the ilium of adult sheep (N = 14). Osteotomy sites were randomized to receive either the TP or TP 3DS implant to reduce site bias. Subjects were allowed to heal for either 3 or 12 weeks (N = 7 sheep/time point), after which samples were collected en bloc (including the implants and surrounding bone) and implants were either subjected to bench-top biomechanical testing (e.g., lateral loading), histological/histomorphometric analysis, or nanoindentation testing. Both implant designs yielded high insertion torque (ITV ≥ 30 N⋅cm) and implant stability quotient (ISQ ≥ 70) values, indicative of high primary stability. Qualitative histomorphological analysis revealed that the TP 3DS group exhibited a continuous bone-implant interface along the threaded region, in contrast to the TP group at the early, 3-week, healing time point. Furthermore, TP 3DS's cutting flutes along the entire length of the implant permitted the distribution of autologous bone chips within the healing chambers. Histological evaluation at 12 weeks revealed an increase in woven bone containing a greater presence of lacunae within the healing chambers in both groups, consistent with an intramembranous-like healing pattern and absence of bone dieback. The TP 3DS macrogeometry yielded a ~66% increase in average lateral load during pushout testing at baseline (T = 0 weeks, p = 0.036) and significantly higher bone-to-implant contact (BIC) values at 3 weeks post-implantation (p = 0.006), relative to the traditional TP implant. In a low-density (Type IV) bone model, the TP 3DS implant demonstrated improved performance compared to the conventional TP, as evidenced by an increase in baseline lateral loading capacity and increased BIC during the early stages of osseointegration. These findings indicate that the modified implant configuration of the TP 3DS facilitates more favorable biomechanical integration and may promote more rapid and stable bone anchorage under compromised bone quality conditions. Therefore, such improvements could have important clinical implications for the success and longevity of dental implants placed in regions with low bone density.

The aim of the study was to assess the effect of bulk material on the reliability and failure modes of narrow-diameter implants. Narrow implants (Ø3.5 × 10 mm - 11° internal conical connection) were manufactured from three different bulk materials: commercially pure titanium grade-IV (CP4), cold-worked titanium (CW), and 4Titude (4Ti), and were evaluated under fatigue testing. Eighteen samples per group were tested under step-stress accelerated life testing through 30° off-axis load application in mild, moderate, and aggressive loading profiles. The number of cycles and load at failure were used to calculate use-level probability curves and reliability for missions of 100,000 cycles up to 200 N, followed by fractographic analyses. Beta values suggested that damage accumulation dictated failures. Reliability analyses at 80, 120, and 150 N evidenced high reliability for narrow implants independent of bulk material. At 200 N, a decrease in reliability was observed for all groups (∼46%). Failure mode analysis depicted similar failures for all groups and comprised implant fracture, abutment fracture, and implant + abutment fractures. Narrow implants presented high reliability for physiologic masticatory forces in the anterior region. Characteristic strength, reliability, and failure modes were similar regardless of bulk material, suggesting that fatigue damage accumulation at thin wall implants dictated failure over bulk material strength.

Giant cell tumors (GCTs) are benign but locally aggressive bone neoplasms that primarily affect skeletally mature individuals. They are characterized by a tendency for recurrence and being associated with significant morbidity. Traditional treatment has focused on surgical resection; however, the role of medical therapies, such as Denosumab, a bone anti-resorptive drug, which has been Food and Drug Administration (FDA)-approved for unresectable GCTs since 2013, recently has gained prominence. Denosumab is a human monoclonal antibody that inhibits receptor activator of nuclear factor kappa B ligand (RANKL). This article aims to consolidate the current literature on Denosumab's efficacy in treating GCTs, highlighting its mechanism of action, clinical evidence, and potential complications. Clinical studies have demonstrated that Denosumab effectively reduces tumor size improving patient outcomes. Yet, some clinicians maintain concerns and reservations regarding local recurrence and malignant transformation. This review discusses the biochemical background of GCTs, current treatment guidelines, challenges, and future directions for research. Ultimately, Denosumab represents a potentially viable advancement in the management of GCTs, particularly in cases where surgical options are limited.

To evaluate the effect of silanized filler particles and blue light-sensitive photoinitiator system on the internal and marginal fit of 3D printed resin crowns as well as the volume of provisional cement space. This study evaluated three commercially available 3D-printing resins (Smart Print Temp/SP, Resilab 3D Temp/RL, and Cosmos Temp/CT). The experimental groups consisted of the addition of 30% by weight (30 wt%) of silanized filler particles and a blue light-sensitive Ternary Photoinitiator System (TPS). Samples were printed for each group (n = 10) and evaluated for internal and marginal fit and volume of cement space using a micro-computed tomography (μCT). The obtained data were analyzed by Generalized Linear Models (α = 0.05). The incorporation of TPS and filler particles to the 3D printing resins altered the internal fit and the marginal fit, increasing the cement space at the occlusal face and decreasing the cement space of the axial walls for all tested materials. The volume was significantly affected too, especially for RL and CT. Internal misfit was significantly higher with the addition of TPS, and marginal misfit with the addition of filler particles. In general, the incorporation of TPS and 30 wt% of filler particles promoted an increase in the volume of cement space, as well as an increase in occlusal space and marginal space and a decrease in the axial walls' spaces.

Sodium-glucose transporter-2 inhibitor (SGLT2i) drugs are widely used for lowering blood glucose levels independent of insulin. Beyond this, these drugs induce various metabolic changes, including weight loss and impaired bone integrity. There is a significant gap in understanding SGLT2i-induced skeletal changes, as SGLT2 is not expressed in osteoblasts or osteocytes, which use glucose to remodel the bone matrix. We studied the impact of 1, 3, or 6 months of canagliflozin (CANA), an SGLT2i treatment, on the skeleton of 6-month-old genetically heterogeneous UM-HET3 mice. Significant metabolic adaptations to CANA were evident as early as 1.5 months post-treatment, specifically in male mice. CANA-treated male mice exhibited notable reductions in body weight and decreased proinflammatory and bone remodeling markers associated with reduced cortical bone remodeling indices. Bone tissue metabolome indicated enrichment in metabolites related to amino acid transport and tryptophan catabolism in CANA-treated male mice. In contrast, CANA-treated female mice showed increases in nucleic acid metabolism. An integrOmics approach of source-matched bone tissue metabolome and bone marrow RNAseq indicated a positive correlation between the two omics data sets in male mice. Three clusters of transcripts and metabolites involved in energy metabolism, oxidative stress response, and cellular proliferation and differentiation were reduced in CANA-treated male mice. In conclusion, CANA affects bone metabolism mainly via the 'glucose restriction state' it induces and impacts bone cell proliferation and differentiation. These findings underline the effects of SGLT2i on bone health and highlight the need to consider sex-specific responses when developing clinical treatments that alter substrate availability.