Isadora Breseghello

Scopus Publications

Titanium Implants Functionalized with Zoledronic Acid Associated with Ruterpy Accelerate Peri-Implant Repair in Healthy and Osteoporotic Rats
Laura Vidoto Paludetto, Isadora Breseghello, Sabrina Cruz Tfaile Frasnelli, Fábio Roberto de Souza Batista, Paulo Roberto Botacin, Cristina Antoniali, Paulo Noronha Lisboa-Filho, Roberta Okamoto
Biomimetics, 2025
Osteoporosis compromises bone quality and impairs implant osseointegration. Since an adequate bone bed is essential for implant stability and success, this study evaluated the effects of implant surface functionalization with zoledronic acid (ZOL), alone or combined with ruterpy (TERPY), on peri-implant bone healing in healthy (SHAM) and osteoporotic (OVX) rats. ZOL has antiresorptive properties, while TERPY exhibits osteoinductive potential. The hypothesis was that ZOL + TERPY would act synergistically by inhibiting bone resorption and promoting new bone formation. Sixty-six female Wistar rats (3 months old) were divided into six groups (n = 11) according to systemic condition (SHAM or OVX) and implant type: conventional (CONV), ZOL, or ZOL + TERPY. Surgeries (sham or bilateral ovariectomy) were performed on day 0, and implants were placed in the tibial metaphysis on day 90. Fluorochromes were administered on days 104 (calcein) and 114 (alizarin), and euthanasia was performed on day 118. Samples were analyzed histologically via confocal microscopy and micro-computed tomography (Micro-CT). The ZOL + TERPY groups demonstrated significantly accelerated peri-implant bone repair, showing greater bone formation and organization; improved BV/TV, Tb.N, and I.S.; and reduced Tb.Sp and Po.Tot compared to CONV and ZOL-alone groups. In conclusion, ZOL + TERPY enhances and speeds bone healing, even under osteoporotic conditions.
Effect of Er:YAG laser bone bed milling, with or without photobiomodulation, on the bone repair process of additive manufacturing implants in rats
Fernando Costa Neto, Isadora Breseghello, Laura Vidoto Paludetto, Sabrina Cruz Tfaile Frasnelli, Fábio Roberto de Souza Batista, Alberto Blay, Armando Boni, Fernando Costa Júnior, Roberta Okamoto
Journal of Photochemistry and Photobiology, 2025
The preparation of the bone bed for implant placement is a critical factor for successful osseointegration and is influenced by surgical techniques and instrumentation. In this context, a study was conducted to compare bone bed milling using an Er:YAG laser, with or without photobiomodulation, to conventional milling combined with Nd:YAG laser photobiomodulation. To assess the effects of Er:YAG laser milling, with or without photobiomodulation, on bone bed preparation and its potential to enhance osseointegration, 28 male rats underwent implant placement in their tibial metaphyses and were divided into four groups: conventional milling (CM), photobiomodulation + conventional milling (PBM + CM), Er:YAG laser milling (Er:YAG), and photobiomodulation + Er:YAG laser milling (PBM + Er:YAG). Euthanasia was performed 28 days after implant placement. Reverse torque testing and real-time PCR (RT-PCR) analysis were conducted to evaluate the expression of osteogenic markers, including ALP, IBSP, OCN, and RUNX2. Data were analyzed using the Shapiro-Wilk test, followed by one-way ANOVA and Tukey's post hoc test, where applicable, with a significance level of p ≤ 0.05. The Er:YAG group exhibited a significantly higher implant removal torque compared to the CM group. Additionally, the expression of genes associated with bone maturation (OCN), differentiation (RUNX2), and osteoblastic activity (ALP and IBSP) was significantly increased in both the Er:YAG and PBM + Er:YAG groups, indicating enhanced osteogenic potential. Thus, Er:YAG laser milling, with or without photobiomodulation using the Nd:YAG laser, may represent a promising alternative for bone bed preparation in implant procedures. However, further studies are required to better characterize bone healing and its long-term consolidation.
Phthalocyanine derivative attenuates TNF-α production in macrophage culture and prevents alveolar bone loss in experimental periodontitis
Isadora Breseghello, Pedro Luiz Rosalen, Rafaela Franco Dias Bruzadelli, Leonardo Pereira de Araújo, Henrique Ballassini Abdalla, Josy Goldoni Lazarini, Isadora Marques Paiva, Bruno Bueno‐Silva, Márcia Regina Cordeiro, Severino Matias de Alencar, Fabiano Vieira Vilhena, Thiago Mattar Cunha, Leandro Araújo Fernandes, Masaharu Ikegaki, Marcelo Franchin
Journal of Periodontal Research, 2025
AimThis study investigated the activity and mechanism of action of the iron tetracarboxyphthalocyanine (FeTcPc) on tumor necrosis factor alpha (TNF‐α) production and its impact on experimental periodontitis.MethodsRAW 264.7 macrophages were treated with FeTcPc, activated with lipopolysaccharide (LPS) at 10 ng/mL, and the TNF‐α levels were measured, as well as the nuclear factor kappa B (NF‐κB) activation. Subsequently, a mouth gel containing 1% FeTcPc was topically administered to the gingival tissue of mice with periodontitis‐induced ligatures. Bone loss and the gene expression of Tnfα, p65 (NF‐κB), and receptor‐activating nuclear factor kappa B ligand (Rankl) were quantified in gingival tissue. Finally, the systemic toxicity of FeTcPc was estimated in Galleria mellonella larvae.ResultsIn an activated RAW 264.7 macrophage culture, 100 μM FeTcPc reduced TNF‐α release and NF‐κB activation. Regarding experimental periodontitis, topical application of mouth gel containing 1% FeTcPc blocked alveolar bone loss. Additionally, 1% FeTcPc reduced the expression of Tnfα, p65 (NF‐κB), and Rankl in gingival tissue. Finally, administration FeTcPc at doses ranging from 1 to 1000 mg/kg did not cause acute systemic toxicity in G. mellonella.ConclusionOverall, we demonstrated the potential of mouth gel containing FeTcPc as a therapeutic strategy for managing osteolytic inflammatory disorders, such as periodontitis.
Smart Delivery of Biomolecules Interfering with Peri-Implant Repair in Osteoporotic Rats
Laura Vidoto Paludetto, Naara Gabriela Monteiro, Isadora Breseghello, Fábio Roberto de Souza Batista, Cristina Antoniali, Paulo Noronha Lisboa-Filho, Roberta Okamoto
International Journal of Molecular Sciences, 2024
Bisphosphonates are widely used for the treatment of postmenopausal osteoporosis; however, they cause several long-term side effects, necessitating the investigation of local ways to improve osseointegration in compromised bone tissue. The purpose of this study was to evaluate peri-implant bone repair using implants functionalized with zoledronic acid alone (OVX ZOL group, n = 11), zoledronic acid + teriparatide (OVX ZOL + TERI group, n = 11), and zoledronic acid + ruterpy (OVX ZOL + TERPY group, n = 11) compared to the control group (OVX CONV, n = 11). Analyses included computer-assisted microtomography, qualitative histologic analysis, and real-time PCR analysis. Histologically, all functionalized surfaces improved peri-implant repair, with the OVX ZOL + TERI group standing out. Similar results were found in computerized microtomography analysis. In real-time PCR analysis, however, the OVX ZOL and OVX ZOL + TERPY groups showed better results for bone formation, with the OVX ZOL + TERPY group standing out, while there were no statistical differences between the OVX CONV and OVX ZOL + TERI groups for the genes studied at 28 postoperative days. Nevertheless, all functionalized groups showed a reduced rate of bone resorption. In short, all surface functionalization groups outperformed the control group, with overall better results for the OVX ZOL + TERI group.
Correction to: Progress and promise of alternative animal and non-animal methods in biomedical research (Archives of Toxicology, (2023), 97, 9, (2329-2342), 10.1007/s00204-023-03532-1)
Irlan Almeida Freires, David Fernando Colon Morelo, Lélio Fernando Ferreira Soares, Isabela Silva Costa, Leonardo Pereira de Araújo, Isadora Breseghello, Henrique Ballassini Abdalla, Josy Goldoni Lazarini, Pedro Luiz Rosalen, Suzane Cristina Pigossi, Marcelo Franchin
Archives of Toxicology, 2023
Progress and promise of alternative animal and non-animal methods in biomedical research
Irlan Almeida Freires, David Fernando Colon Morelo, Lélio Fernando Ferreira Soares, Isabela Silva Costa, Leonardo Pereira de Araújo, Isadora Breseghello, Henrique Ballassini Abdalla, Josy Goldoni Lazarini, Pedro Luiz Rosalen, Suzane Cristina Pigossi, Marcelo Franchin
Archives of Toxicology, 2023
Cell culture and invertebrate animal models reflect a significant evolution in scientific research by providing reliable evidence on the physiopathology of diseases, screening for new drugs, and toxicological tests while reducing the need for mammals. In this review, we discuss the progress and promise of alternative animal and non-animal methods in biomedical research, with a special focus on drug toxicity.
A Study on the Anti-NF-кB, Anti-Candida, and Antioxidant Activities of Two Natural Plant Hormones: Gibberellin A4 and A7
Bruno Dias Nani, Pedro Luiz Rosalen, Josy Goldoni Lazarini, Janaína de Cássia Orlandi Sardi, Diego Romário-Silva, Leonardo Pereira de Araújo, Mateus Silva Beker dos Reis, Isadora Breseghello, Thiago Mattar Cunha, Severino Matias de Alencar, Nelson José Freitas da Silveira, Marcelo Franchin
Pharmaceutics, 2022
Introduction: Gibberellins (GA) are terpenoids that serve as important plant hormones by acting as growth and response modulators against injuries and parasitism. In this study, we investigated the in vitro anti-NF-κB, anti-Candida, and antioxidant activity of gibberellin A4 (GA4) and A7 (GA7) compounds, and further determined their toxicity in vivo. Methods: GA4 and GA7 in vitro toxicity was determined by MTT method, and nontoxic concentrations were then tested to evaluate the GA4 and GA7 anti-NF-κB activity in LPS-activated RAW-luc macrophage cell culture (luminescence assay). GA4 in silico anti-NF-κB activity was evaluated by molecular docking with the software “AutoDock Vina”, “MGLTools”, “Pymol”, and “LigPlot+”, based on data obtained from “The Uniprot database”, “Protein Data Bank”, and “PubChem database”. The GA4 and GA7 in vitro anti-Candida effects against Candida albicans (MYA 2876) were determined (MIC and MFC). GA7 was also evaluated regarding the viability of C. albicans preformed biofilm (microplate assay). In vitro antioxidant activity of GA4 and GA7 was evaluated against peroxyl radicals, superoxide anions, hypochlorous acid, and reactive nitrogen species. GA4 and GA7 in vivo toxicity was determined on the invertebrate Galleria mellonella larvae model. Results: Our data show that GA4 at 30 µM is nontoxic and capable of reducing 32% of the NF-κB activation on RAW-luc macrophages in vitro. In vitro results were confirmed via molecular docking assay (in silico), since GA4 presented binding affinity to NF-κB p65 and p50 subunits. GA7 did not present anti-NF-κB effects, but exhibited anti-Candida activity with low MIC (94 mM) and MFC (188 mM) values. GA7 also presented antibiofilm properties at 940 mM concentration. GA4 did not present anti-Candida effects. Moreover, GA4 and GA7 showed antioxidant activity against peroxyl radicals, but did not show scavenging activity against the other tested radicals. Both compounds did not affect the survival of G. mellonella larvae, even at extremely high doses (10 g/Kg). Conclusion: Our study provides preclinical evidence indicating that GA4 and GA7 have a favorable low toxicity profile. The study also points to GA4 and GA7 interference with the NF-κB via, anti-Candida activity, and a peroxyl radical scavenger, which we argue are relevant biological effects.