Faculty Bibliography

In recognizing the critical role of vitamin D in bone metabolism and osseointegration, research aims to identify whether preoperative vitamin D deficiency serves as a risk factor for early implant failure. By analyzing patient outcomes and their serum vitamin D levels, studies seek to establish evidence-based recommendations for vitamin D assessment and management in the preoperative period, with the ultimate goal of enhancing implant success rates and patient outcomes in dental implantology. Given these insights, it is important for clinicians to incorporate the preoperative evaluation of vitamin D serum levels into their standard protocol for patients undergoing dental implant procedures. The objective of this study is to review and investigate the correlation between early dental implant failure (EDIF) and reduced serum levels of vitamin D, and to evaluate the potential benefits of preoperative screening and supplementation of vitamin D in patients undergoing dental implant surgery. A literature review was performed using a selected database-PubMed, Google Scholar, Cochrane, and SCOPUS-to assess the effect of vitamin D3 level on EDIF and biological factors (i.e., peri-implant bone level). Studies were limited to peer-reviewed, indexed journals. Subsequently, a hypothesis was proposed that vitamin D3 supplementation would mitigate the negative effect of vitamin D3 deficiency. The potential benefit of vitamin D3 supplementation-systemic and topical-was assessed in terms of bone-to-implant contact (BIC) and peri-implant bone level. The deleterious effects of low vitamin D serum levels on osseointegration of dental implants and immune system modulation are increasingly accepted. Evidence has displayed that deficiency of this vitamin can result in impaired peri-implant bone formation. Vitamin D deficiency resulted in nearly a fourfold increase in overall EDIF incidence. Presurgical supplementation of vitamin D3 demonstrated increased levels of implant osseointegration, increased bone-implant contact, enhanced bone level maintenance, and decreased EDIF even in at-risk demographics (i.e., diabetic subjects). The findings of this study reinforce the role of vitamin D in dental implant osseointegration. Our study, particularly, emphasizes the necessity of vitamin D supplementation for individuals with sub-physiologic vitamin D serum levels (≤ 30 ng/mL) and those within specific risk categories: smokers, diabetics, obese individuals, and those with compromised immune systems. Adopting a proactive management plan, including screening and supplementation in these patients, may substantially enhance the clinical outcomes in dental implant surgery.

Preclinical testing of tissue engineering modalities are commonly performed in a healthy wound bed. These conditions do not represent clinically relevant compromised oral wound environments due to radiation treatments seen clinically. This study aimed to characterize the bone regeneration outcomes in critical-sized mandibular defects using particulate grafting in an irradiated preclinical model of compromised wound healing. Sixteen New Zealand white rabbits were divided into two groups (n = 8/group), namely (i) irradiated (experimental) and (ii) non-irradiated (control). The rabbits in the experimental group received a total of 36 Gy radiation, followed by surgical intervention to create critical-sized (10 mm), full-thickness mandibular defects. The control group was subjected to the same surgical intervention. All defects were filled with bovine bone grafting material (Bio-Oss, Geistlich, Princeton, NJ, USA) and allowed to heal for 8 weeks. At the study endpoint, rabbits were euthanized, and their mandibles were harvested for micro-computed tomographic, histological, and histomorphometric processing and analysis. Qualitative histological analysis revealed increased levels of bone formation and bridging in the control group relative to the experimental group. This was accompanied by increased levels of soft tissue presence in the experimental group. Volumetric reconstruction showed a significantly higher degree of bone in the control group (27.59% ± 2.71), relative to the experimental group (22.02% ± 2.71) (p = 0.001). The irradiated rabbit model exhibited decreased bone regeneration capacity relative to the healthy subjects, highlighting its suitability as a robust compromised wound healing environment for further preclinical testing involving growth factors or customized, high-fidelity 3D printed tissue engineering scaffolds.

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.

BACKGROUND/UNASSIGNED:Polylactic acid (PLA) has been extensively used in tissue engineering. However, poor mechanical properties and low cell affinity have limited its pertinence in load bearing bone tissue regeneration (BTR) devices. OBJECTIVE/UNASSIGNED:Augmenting PLA with β-Tricalcium Phosphate (β-TCP), a calcium phosphate-based ceramic, could potentially improve its mechanical properties and enhance its osteogenic potential. METHODS/UNASSIGNED:Gels of PLA and β-TCP were prepared of different % w/w ratios through polymer dissolution in acetone, after which polymer-ceramic membranes were synthesized using the gel casting workflow and subjected to characterization. RESULTS/UNASSIGNED:Gel-cast polymer-ceramic constructs were associated with significantly higher osteogenic capacity and calcium deposition in differentiated osteoblasts compared to pure polymer counterparts. Immunocytochemistry revealed cell spreading over the gel-cast membrane surfaces, characterized by trapezoidal morphology, distinct rounded nuclei, and well-aligned actin filaments. However, groups with higher ceramic loading expressed significantly higher levels of osteogenic markers relative to pure PLA membranes. Rule of mixtures and finite element models indicated an increase in theoretical mechanical strength with an increase in β-TCP concentration. CONCLUSION/UNASSIGNED:This study potentiates the use of PLA/β-TCP composites in load bearing BTR applications and the ability to be used as customized patient-specific shape memory membranes in guided bone regeneration.

BACKGROUND/UNASSIGNED:performance of a novel electrospun composite scaffold coated in a recombinant variant of human bone morphogenetic protein-2 (OsteoAdapt) relative to a porcine-derived xenograft. Further, it sought to determine if OsteoAdapt would remain within the defect without a membrane in place, as this is not feasible with the particulate xenograft currently used in clinical practice. METHODS/UNASSIGNED:, bone regeneration was assessed through qualitative volumetric reconstruction, qualitative and quantitative histological analyses. RESULTS/UNASSIGNED:= 0.982, respectively). However, qualitative analysis of the histological micrographs demonstrated advanced bone healing characterized by an abundance of nucleation sites for regeneration to occur in defects treated with OA relative to the CTRL. Bone overgrowth beyond the limits of defect borders was observed in groups treated OA/ZM and OA/P/ZM. In contrast to the treatment groups, minimal woven bone was visualized in the CTRL group. CONCLUSION/UNASSIGNED:. This suggests that the novel combination of AMP-2 and a bioceramic/synthetic polymer-based electrospun scaffold is a suitable candidate for GBR procedures, without a barrier membrane to secure its place within a defect.

Bone nonunion following a fracture represents a significant global healthcare challenge, with an overall incidence ranging between 2 and 10% of all fractures. The management of nonunion is not only financially prohibitive but often necessitates invasive surgical interventions. This comprehensive manuscript aims to provide an extensive review of the published literature involving growth factors, stem cells, and novel delivery mechanisms for the treatment of fracture nonunion. Key growth factors involved in bone healing have been extensively studied, including bone morphogenic protein (BMP), vascular endothelial growth factor (VEGF), and platelet-derived growth factor. This review includes both preclinical and clinical studies that evaluated the role of growth factors in acute and chronic nonunion. Overall, these studies revealed promising bridging and fracture union rates but also elucidated complications such as heterotopic ossification and inferior mechanical properties associated with chronic nonunion. Stem cells, particularly mesenchymal stem cells (MSCs), are an extensively studied topic in the treatment of nonunion. A literature search identified articles that demonstrated improved healing responses, osteogenic capacity, and vascularization of fractures due to the presence of MSCs. Furthermore, this review addresses novel mechanisms and materials being researched to deliver these growth factors and stem cells to nonunion sites, including natural/synthetic polymers and bioceramics. The specific mechanisms explored in this review include BMP-induced osteoblast differentiation, VEGF-mediated angiogenesis, and the role of MSCs in multilineage differentiation and paracrine signaling. While these therapeutic modalities exhibit substantial preclinical promise in treating fracture nonunion, there remains a need for further research, particularly in chronic nonunion and large animal models. This paper seeks to identify such translational hurdles which must be addressed in order to progress the aforementioned treatments from the lab to the clinical setting.

The unique screw-shape design and microstructure of implants pose a challenge for mechanical debridement in removing biofilms. Biofilms exhibit increased resistance to antimicrobials relative to single planktonic cells, emphasizing the need for effective biofilm removal during periodontal therapy for peri-implantitis treatment. To tackle this issue, our team evaluated the effectiveness of low-temperature plasma (LTP) for disinfecting titanium discs contaminated with multispecies biofilms associated with peri-implantitis, specifically focusing on biofilms matured for 14 and 21 days as well as biofilms that had formed on Straumann^Ⓡ Ti-SLA implants for 21 days. The biofilms included Actinomyces naeslundii, Porphyromonas gingivalis, Streptococcus oralis, and Veillonella dispar, which were grown in anaerobic conditions. These biofilms were subjected to LTP treatment for 1, 3, and 5 min, using distances of 3 or 10 mm from the LTP nozzle to the samples. Control groups included biofilms formed on Ti discs or implants that received no treatment, exposure to argon flow at 3 or 10 mm of distance for 1, 3, or 5 min, application for 1 min of 14 μg/mL amoxicillin, 140 μg/mL metronidazole, or a blend of both, and treatment with 0.12% chlorhexidine (CHX) for 1 min. For the implants, 21-day-old biofilms were treated with 0.12% CHX 0.12% for 1 min and LTP for 1 min at a distance of 3 mm for each quadrant. Biofilm viability was assessed through bacterial counting and confocal laser scanning microscopy. The impact of LTP was investigated on reconstituted oral epithelia (ROE) contaminated with P. gingivalis, evaluating cytotoxicity, cell viability, and histology. The results showed that a 1 min exposure to LTP at distances of 3 or 10 mm significantly lowered bacterial counts on implants and discs compared to the untreated controls (p < 0.017). LTP exposure yielded lower levels of cytotoxicity relative to the untreated contaminated control after 12 h of contamination (p = 0.038), and cell viability was not affected by LTP (p ≥ 0.05); thus, LTP-treated samples were shown to be safe for tissue applications, with low cytotoxicity and elevated cell viability post-treatment, and these results were validated by qualitative histological analysis. In conclusion, the study's results support the effectiveness of 1 min LTP exposure in successfully disinfecting mature peri-implantitis multispecies biofilms on titanium discs and implants. Moreover, it validated the safety of LTP on ROE, suggesting its potential as an adjunctive treatment for peri-implantitis.

This study explores the novel application of pyronin Y for fluorescently labeling extracellular matrices (ECMs) and gelatin cryogels, providing a simple and reliable method for laser scanning confocal microscopy. Pyronin Y exhibited remarkable staining ability of the porous structures of gelatin cryogels, indicating its potential as a reliable tool for evaluating such biomaterials. Confocal imaging of pyronin Y-stained cryogels produced high signal-to-noise ratio images suitable for quantifying pores using Fiji/Image J. Importantly, pyronin Y enabled effective dual-color imaging of cryogel-labeled mesenchymal stem cells, expanding its utility beyond traditional RNA assays. Traditional staining methods like Mason's trichrome and Sirius Red have limitations in cryogel applications. Pyronin Y emerges as a powerful alternative due to its water solubility, minimal toxicity, and stability. Our results demonstrate pyronin Y's ability to specifically stain gelatin cryogel's porous structures, surpassing its weak staining of ECMs in 2D. Confocal imaging revealed enduring staining even under rigorous scanning, with no notable photobleaching observed. Furthermore, pyronin Y's combination with Alexa Fluor 647 for dual-color imaging showed promising results, validating its versatility in fluorescence microscopy. In conclusion, this study establishes pyronin Y as a cost-effective and rapid option for fluorescent staining of gelatin cryogels. Its simplicity, efficacy, and compatibility with confocal microscopy make it a valuable tool for characterizing and evaluating gelatin-based biomaterials, contributing significantly to the field of cryogel imaging. The study opens new avenues for dual-color imaging in biomaterial research and tissue engineering, advancing our understanding of cellular interactions within scaffolds. Key features • Fluorescent staining of gelatin-based cryogels with an inexpensive yet less time-consuming protocol. • Pyronin Y staining is suitable for dual-color confocal imaging by combining with far-red fluorophores (such as Alexa Fluor 647). • The method is conducted routinely. Graphical overview Gelatin cryogel staining using pyronin Y.

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.

Large osseous defects resulting from trauma, tumor resection, or fracture render the inherent ability of the body to repair inadequate and necessitate the use of bone grafts to facilitate the recovery of both form and function of the bony defect sites. In the United States alone, a large number of bone graft procedures are performed yearly, making it an essential area of investigation and research. Synthetic grafts represent a potential alterative to autografts due to their patient-specific customizability, but currently lack widespread acceptance in the clinical space. Early in their development, non-autologous bone grafts composed of metals such as stainless steel and titanium alloys were favorable due to their biocompatibility, resistance to corrosion, mechanical strength, and durability. However, since their inception, bioceramics have also evolved as viable alternatives. This review aims to present an overview of the fundamental prerequisites for tissue engineering devices using bioceramics as well as to provide a comprehensive account of their historical usage and significant advancements over time. This review includes a summary of commonly used manufacturing techniques and an evaluation of their use as drug carriers and bioactive coatings-for therapeutic ion/drug release, and potential avenues to further enhance hard tissue regeneration.