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result(s) for
"Garcia, Franklin"
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Nanoparticles in Bone Regeneration: A Narrative Review of Current Advances and Future Directions in Tissue Engineering
by
Farjaminejad, Samira
,
Garcia-Godoy, Franklin
,
Farjaminejad, Rosana
in
Allografts
,
Angiogenesis
,
Autografts
2024
The rising demand for effective bone regeneration has underscored the limitations of traditional methods like autografts and allografts, including donor site morbidity and insufficient biological signaling. This review examines nanoparticles (NPs) in tissue engineering (TE) to address these challenges, evaluating polymers, metals, ceramics, and composites for their potential to enhance osteogenesis and angiogenesis by mimicking the extracellular matrix (ECM) nanostructure. The methods involved synthesizing and characterizing nanoparticle-based scaffoldsand integrating hydroxyapatite (HAp) with polymers to enhance mechanical properties and osteogenic potential. The results showed that these NPs significantly promote cell growth, differentiation, and bone formation, with carbon-based NPs like graphene and carbon nanotubes showing promise. NPs offer versatile, biocompatible, and customizable scaffolds that enhance drug delivery and support bone repair. Despite promising results, challenges with cytotoxicity, biodistribution, and immune responses remain. Addressing these issues through surface modifications and biocompatible molecules can improve the biocompatibility and efficacy of nanomaterials. Future research should focus on long-term in vivo studies to assess the safety and efficacy of NP-based scaffolds and explore synergistic effects with other bioactive molecules or growth factors. This review underscores the transformative potential of NPs in advancing BTE and calls for further research to optimize these technologies for clinical applications.
Journal Article
Induction of synthetic lethality in IDH1-mutated gliomas through inhibition of Bcl-xL
by
Canoll, Peter
,
Bianchetti, Elena
,
Zhang, Yiru
in
692/4028/67/1922
,
692/4028/67/70
,
Aniline Compounds - therapeutic use
2017
Certain gliomas often harbor a mutation in the activity center of IDH1 (R132H), which leads to the production of the oncometabolite 2-R-2-hydroxyglutarate (2-HG). In six model systems, including patient-derived stem cell-like glioblastoma cultures, inhibition of Bcl-xL induces significantly more apoptosis in IDH1-mutated cells than in wild-type IDH1 cells. Anaplastic astrocytoma samples with mutated IDH1 display lower levels of Mcl-1 than IDH1 wild-type tumors and specific knockdown of Mcl-1 broadly sensitizes glioblastoma cells to Bcl-xL inhibition-mediated apoptosis. Addition of 2-HG to glioblastoma cultures recapitulates the effects of the IDH mutation on intrinsic apoptosis, shuts down oxidative phosphorylation and reduces ATP levels in glioblastoma cells. 2-HG-mediated energy depletion activates AMPK (Threonine 172), blunting protein synthesis and mTOR signaling, culminating in a decline of Mcl-1. In an orthotopic glioblastoma xenograft model expressing mutated IDH1, Bcl-xL inhibition leads to long-term survival. These results demonstrate that IDH1-mutated gliomas are particularly vulnerable to Bcl-xL inhibition.
Glioblastoma (GBM) cells are often characterized by the presence of the IDH1 R132H mutation and high expression of anti-apoptotic proteins. Here, the authors show that the inhibition of Bcl-xL is synthetically lethal in IDH1-mutated GBM models and that this effect is mediated by the oncometabolite, 2-HG, which reduces Mcl-1 protein levels.
Journal Article
Emerging technologies for salivaomics in cancer detection
by
Garcia‐Godoy, Franklin
,
Wei, Fang
,
Kaczor‐Urbanowicz, Karolina Elżbieta
in
Biomarkers
,
Biopsy
,
Biosensors
2017
Salivary diagnostics has great potential to be used in the early detection and prevention of many cancerous diseases. If implemented with rigour and efficiency, it can result in improving patient survival times and achieving earlier diagnosis of disease. Recently, extraordinary efforts have been taken to develop non‐invasive technologies that can be applied without complicated and expensive procedures. Saliva is a biofluid that has demonstrated excellent properties and can be used as a diagnostic fluid, since many of the biomarkers suggested for cancers can also be found in whole saliva, apart from blood or other body fluids. The currently accepted gold standard methods for biomarker development include chromatography, mass spectometry, gel electrophoresis, microarrays and polymerase chain reaction‐based quantification. However, salivary diagnostics is a flourishing field with the rapid development of novel technologies associated with point‐of‐care diagnostics, RNA sequencing, electrochemical detection and liquid biopsy. Those technologies will help introduce population‐based screening programs, thus enabling early detection, prognosis assessment and disease monitoring. The purpose of this review is to give a comprehensive update on the emerging diagnostic technologies and tools for the early detection of cancerous diseases based on saliva.
Journal Article
Oral Pathogens’ Substantial Burden on Cancer, Cardiovascular Diseases, Alzheimer’s, Diabetes, and Other Systemic Diseases: A Public Health Crisis—A Comprehensive Review
by
Garcia-Godoy, Franklin
,
Coffman, Jonathan A.
,
Murray, Peter E.
in
Alzheimer Disease - epidemiology
,
Alzheimer Disease - microbiology
,
Alzheimer's disease
2024
This review synthesizes the findings from 252 studies to explore the relationship between the oral pathogens associated with periodontitis, dental caries, and systemic diseases. Individuals with oral diseases, such as periodontitis, are between 1.7 and 7.5 times (average 3.3 times) more likely to develop systemic diseases or suffer adverse pregnancy outcomes, underscoring the critical connection between dental and overall health. Oral conditions such as periodontitis and dental caries represent a significant health burden, affecting 26–47% of Americans. The most important oral pathogens, ranked by publication frequency, include the herpes virus, C. albicans, S. mutans, P. gingivalis, F. nucleatum, A. actinomycetemcomitans, P. intermedia, T. denticola, and T. forsythia. The systemic diseases and disorders linked to oral infections, ranked similarly, include cancer, respiratory, liver, bowel, fever, kidney, complications in pregnancy, cardiovascular bacteremia, diabetes, arthritis, autoimmune, bladder, dementia, lupus, and Alzheimer’s diseases. Evidence supports the efficacy of dental and periodontal treatments in eliminating oral infections and reducing the severity of systemic diseases. The substantial burden that oral pathogens have on cancer, cardiovascular diseases, Alzheimer’s, diabetes, and other systemic diseases poses a significant public health crisis.
Journal Article
Effect of crown stiffness and prosthetic screw absence on the stress distribution in implant-supported restoration: A 3D finite element analysis
by
Garcia-Godoy, Franklin
,
Ausiello, Pietro
,
Mendes Tribst, João Paulo
in
B spline functions
,
Biology and Life Sciences
,
Biomechanics
2023
This in-silico investigation evaluated the mechanical impact of Morse tape implant-abutment interface and retention system (with and without screw) and restorative materials (composite block and monolithic zirconia) by means of a three-dimensional finite element analysis (3D-FEA). Four 3D models were designed for the lower first molar. A dental implant (4.5 × 10 mm B&B Dental Implant Company) was digitized (micro CT) and exported to computer-aided design (CAD) software. Non-uniform rational B-spline surfaces were reconstructed, generating a 3D volumetric model. Four different models were generated with the same Morse-type connection, but with a different locking system (with and without active screw) and a different crown material made of composite block and zirconia. The D2 bone type, which contains cortical and trabecular tissues, was designed using data from the database. The implants were juxtaposed inside the model after Boolean subtraction. Implant placement depth was simulated for the implant model precisely at crestal bone level. Each acquired model was then imported into the finite element analysis (FEA) software as STEP files. The Von Mises equivalent strains were calculated for the peri-implant bone and the Von Mises stress for the prosthetic structures. The highest strain values in bone tissue occurred in the peri-implant bone interface and were comparable in the four implant models (8.2918e-004–8.6622e-004 mm/mm). The stress peak in the zirconia crown (64.4 MPa) was higher than in the composite crown (52.2 MPa) regardless of the presence of the prosthetic screw. The abutment showed the lowest stress peaks (99.71–92.28 MPa) when the screw was present (126.63–114.25 MPa). Based on this linear analysis, it is suggested that the absence of prosthetic screw increases the stress inside the abutment and implant, without effect on the crown and around the bone tissue. Stiffer crowns concentrate more stress on its structure, reducing the amount of stress on the abutment.
Journal Article
Narrative Review of Endodontic Biomaterials
by
Garcia-Godoy, Alexander
,
Farjaminejad, Samira
,
Garcia-Godoy, Franklin
in
Acids
,
Antimicrobial agents
,
bioceramics
2026
Advancements in biomaterials have transformed the field of endodontics, shifting treatment approaches from mechanical interventions to biologically driven regenerative therapies. This narrative review explores the evolving landscape of endodontic biomaterials, emphasizing their roles in disinfection, obturation, root repair, surgical procedures, and regenerative endodontics. Key materials such as mineral trioxide aggregate (MTA), Biodentine, and calcium-enriched mixture (CEM) cement demonstrate superior sealing, biocompatibility, and osteogenic potential compared to traditional materials. The integration of nanotechnology, bioactive components, and smart drug delivery systems has further enhanced antimicrobial properties and tissue interaction. Clinical applications, including regenerative procedures using platelet-rich fibrin and case-based biomaterial usage, are discussed to illustrate their relevance and effectiveness in real-world practice. Despite significant progress, challenges such as regulatory hurdles, economic limitations, and translational gaps persist. Emerging trends such as 3D printing, personalized medicine, and multifunctional scaffolds offer promising directions for future endodontic care. Continued interdisciplinary collaboration is essential to overcome current barriers and facilitate widespread adoption of next-generation biomaterials. Unlike prior reviews that categorize endodontic biomaterials descriptively by material class or technological advancement, this review introduces an indication-based comparative framework aligning biomaterial properties with specific clinical decision points and corresponding levels of evidence. By integrating biological mechanisms, translational considerations, and clinical application within a structured decision-oriented model, the manuscript offers analytical synthesis rather than a purely descriptive overview.
Journal Article
EZH2 Inhibition Sensitizes IDH1R132H-Mutant Gliomas to Histone Deacetylase Inhibitor
2024
Isocitrate Dehydrogenase-1 (IDH1) is commonly mutated in lower-grade diffuse gliomas. The IDH1R132H mutation is an important diagnostic tool for tumor diagnosis and prognosis; however, its role in glioma development, and its impact on response to therapy, is not fully understood. We developed a murine model of proneural IDH1R132H-mutated glioma that shows elevated production of 2-hydroxyglutarate (2-HG) and increased trimethylation of lysine residue K27 on histone H3 (H3K27me3) compared to IDH1 wild-type tumors. We found that using Tazemetostat to inhibit the methyltransferase for H3K27, Enhancer of Zeste 2 (EZH2), reduced H3K27me3 levels and increased acetylation on H3K27. We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.
Journal Article
Relationships between Flexural and Bonding Properties, Marginal Adaptation, and Polymerization Shrinkage in Flowable Composite Restorations for Dental Application
by
Teixeira, Erica Cappelletto Nogueira
,
Maruo, Yukinori
,
Nishigawa, Goro
in
Adaptation
,
Addition polymerization
,
Adhesives
2021
To evaluate the flexural and bonding properties, marginal adaptation, and polymerization shrinkage in flowable composite restorations and their relationships, four new generation flowable composites, one conventional, and one bulk-fill flowable composite were used in this study. Flexural properties of the composites and shear bond strength to enamel and dentin for flowable restorations were measured immediately and 24 h after polymerization. Marginal adaptation, polymerization shrinkage, and stress were also investigated immediately after polymerization. The flexural properties, and bond strength of the flowable composites to enamel and dentin were much lower immediately after polymerization than at 24 h, regardless of the type of the composite. Polymerization shrinkage and stress varied depending on the material, and bulk-fill flowable composite showed much lower values than the others. The marginal adaptation and polymerization shrinkage of the composites appeared to have a much stronger correlation with a shear bond strength to dentin than to enamel. The weak mechanical properties and bond strengths of flowable composites in the early stage after polymerization must be taken into account when using them in the clinic. In addition, clinicians should be aware that polymerization shrinkage of flowable composites can still lead to the formation of gaps and failure of adaptation to the cavity regardless of the type of composite.
Journal Article
Substituted Nano-Hydroxyapatite Toothpastes Reduce Biofilm Formation on Enamel and Resin-Based Composite Surfaces
by
Ottobelli, Marco
,
Garcia-Godoy, Franklin
,
Ionescu, Andrei C.
in
Bioactive compounds
,
biofilm(s)
,
Biofilms
2020
Background: Toothpastes containing nano-hydroxyapatite (n-HAp) substituted with metal ions provide calcium and phosphate ions to dental hard tissues, reducing demineralization, and promoting remineralization. Few data are available about the effect of these bioactive compounds on oral microbiota. Methods: This in vitro study evaluated the influence of two commercially-available substituted n-HAp-based toothpastes (α: Zn-carbonate substituted n-HAp; β: F, Mg, Sr-carbonate substituted n-HAp) on early colonization (EC, 12 h) and biofilm formation (BF, 24 h) by oral microbiota. Controls were brushed with distilled water. Artificial oral microcosm and Streptococcus mutans biofilms were developed using human enamel and a resin-based composite (RBC) as adherence surfaces. Two test setups, a shaking multiwell plate and a modified drip-flow reactor (MDFR), were used to simulate clinical conditions during the night (low salivary flow and clearance) and daytime, respectively. Energy-dispersive X-ray spectrometry (EDS) was used to evaluate specimens’ surfaces after toothpaste treatment. Fluoride release from β toothpaste was evaluated. Viable adherent biomass was quantified by MTT assay, and biofilms’ morphology was highlighted using confocal microscopy. Results: EDS showed the presence of remnants from the tested toothpastes on both adherence surfaces. β toothpaste showed significantly lower EC and BF compared to control using the artificial oral microcosm model, while α toothpaste showed lower EC and BF compared to control, but higher EC and BF compared to β toothpaste. The effect shown by β toothpaste was, to a minimal extent, due to fluoride release. Interestingly, this result was seen on both adherence surfaces, meaning that the tested toothpastes significantly influenced EC and BF even on RBC surfaces. Furthermore, the effect of toothpaste treatments was higher after 12 h than 24 h, suggesting that toothbrushing twice a day is more effective than brushing once. Conclusions: The efficacy of these treatments in reducing microbial colonization of RBC surfaces may represent a promising possibility in the prevention of secondary caries.
Journal Article
The Role of Tissue Engineering in Orthodontic and Orthognathic Treatment: A Narrative Review
by
Sayahpour, Babak
,
Farjaminejad, Samira
,
Garcia-Godoy, Franklin
in
Aesthetics
,
Angiogenesis
,
Antimicrobial agents
2025
Background: Orthodontics and orthognathic surgery present challenges such as extended treatment durations, patient discomfort, and complications like root resorption. Recent advancements in tissue engineering and nanotechnology offer promising solutions by improving bone regeneration, periodontal repair, and biomaterial integration. Objectives: This review explores the integration of scaffold-based tissue engineering and nanotechnology in orthodontics, focusing on their roles in accelerating bone regeneration, reducing treatment times, and minimizing adverse effects to enhance the predictability and success of orthodontic interventions. Methods: Relevant literature was selected from PubMed, Scopus, and Web of Science, focusing on studies related to scaffold technology, biomaterials, and nanotechnology in orthodontics. Keywords included “tissue engineering”, “orthodontics”, “biomaterials”, “scaffolds”, “nanotechnology”, and “bone regeneration”. Priority was given to peer-reviewed original studies, systematic reviews, and meta-analyses addressing innovative treatment approaches and clinical outcomes. Results: Findings indicate that scaffolds enhance bone regeneration and periodontal repair, while nanoparticles improve biomaterial integration and drug delivery efficiency. These advancements contribute to faster, more predictable orthodontic treatments with reduced complications. However, challenges such as high costs, regulatory hurdles, and the need for long-term clinical validation remain barriers to widespread adoption. Conclusions: Tissue engineering and nanotechnology offer minimally invasive, biologically driven solutions for orthodontic treatment. While significant progress has been made, further clinical studies, cost-effective strategies, and regulatory approvals are needed to integrate these innovations into routine practice.
Journal Article