We evaluated the in vivo therapeutic efficacy and tolerability of BI-3406-mediated pharmacological inhibition of SOS1 in comparison to genetic ablation of this universal Ras-GEF in various KRAS-dependent experimental tumor settings. Contrary to the rapid lethality caused by SOS1 genetic ablation in SOS2 ^KO mice, SOS1 pharmacological inhibition by its specific inhibitor BI-3406 did not significantly affect animal weight/viability nor cause noteworthy systemic toxicity. Allograft assays using different KRAS ^mut cell lines showed that treatment with BI-3406 impaired RAS activation and RAS downstream signaling and decreased tumor burden and disease progression as a result of both tumor-intrinsic and -extrinsic therapeutic effects of the drug. Consistent with prior genetic evidence and the KRAS ^mut allografts assays in immunocompromised mice, our analyses using an in vivo model of KRAS ^G12D -driven lung adenocarcinoma (LUAD) in immunocompetent mice showed that single, systemic BI-3406 treatment impaired tumor growth and downmodulated protumorigenic components of the tumor microenvironment comparably to SOS1 genetic ablation or to treatment with the specific KRAS ^G12D inhibitor MRTX1133. Furthermore, markedly stronger, synergistic antitumor effects were observed upon concomitant treatment with BI-3406 and MRTX1133 in the same in vivo LUAD mouse model. Our data confirm SOS1 as an actionable therapy target in RAS-dependent cancers and suggest that BI-3406 treatment may yield clinical benefit both as monotherapy or as a potential combination partner for multiple RAS-targeting strategies.

The aim of this work was to analyze and compare the removal capability, conical internal hex implant-abutment connection damage and thermal effect using ultrasonic and drilling techniques for the extraction of fractured abutment screws. Twenty abutment screws were randomly fractured into twenty dental implants and randomly extracted using the following removal techniques: Group A: drilling technique without irrigation (n = 10) (DT) and Group B: ultrasonic technique without irrigation (n = 10) (UT). The dental implants were submitted to a preoperative and postoperative micro-computed tomography (micro-CT) scan to obtain a Standard Tessellation Language (STL) digital file that determined the wear comparison by morphometry. Moreover, the thermographic effects generated by the DT and UT removal techniques were registered using a thermographic digital camera. Comparative analysis was performed by comparing the volumetric differences (mm³) between preoperative and postoperative micro-CT scans and thermographic results (°C) using the Student t test. The DT extracted 8/10 and the US 9/10 abutment screws. The pairwise comparison revealed statistically significant differences between the volumetric differences of postoperative and preoperative micro-CT scans of the DT (− 0.09 ± − 0.02mm³) and UT (− 0.93 ± − 0.32mm³) study groups (p = 0.0042); in addition, the pairwise comparison revealed statistically significant differences between the thermographic values of the DT (38.12 ± − 10.82 °C) and UT (78.52 ± 5.43 °C) study groups (p < 0.001). The drilling technique without irrigation provides a less removal capability, less conical internal hex implant-abutment connection damage and less thermal effect than ultrasonic technique for the extraction of fractured abutment screws; however, the ultrasonic technique resulted more effective for the extraction of fractured abutment screws.

Background/Objectives: The therapeutic approach to bone mass loss and bone’s limited self-regeneration is a major focus of research, emphasizing new biomaterials and cell therapy. Tissue bioengineering emerges as a potential alternative to conventional treatments. In this study, an experimental model of a critical bone lesion in rats was used to investigate bone regeneration by treating the defect with biomaterials Evolution^® and Gen-Os^® (OsteoBiol^®, Turín, Italy), with or without mesenchymal stromal cells from dental pulp (DP-MSCs). Methods: Forty-six adult male Wistar rats were subjected to a 5-mm critical bone defect in the right mandible, which does not regenerate without intervention. The rats were randomly assigned to a Simulated Group, Control Group, or two Study Groups (using Evolution^®, Gen-Os^®, and DP-MSCs). The specimens were euthanized at three or six months, and radiological, histological, and ELISA tests were conducted to assess bone regeneration. Results: The radiological results showed that the DP-MSC group achieved uniform radiopacity and continuity in the bone edge, with near-complete structural defect restitution. Histologically, full bone regeneration was observed, with well-organized, vascularized lamellar bone and no lesion edges. These findings were supported by increases in endoglin, transforming growth factor-beta 1 (TGF-β1), protocollagen, parathormone, and calcitonin, indicating a conducive environment for bone regeneration. Conclusions: The use of DP-MSCs combined with biomaterials with appropriate three-dimensional matrices is a promising therapeutic option for further exploration.

The increase in the rate and prevalence of diseases associated with the localized and general loss of bone mass calls for an investigation into therapeutic alternatives that largely involve the de-velopment of new biomaterials and cell therapy, converting tissue bioengineering into a prom-ising option. An experimental model of a critical mandibular lesion in rats has been used to study bone re-generation by treating the ostectomy with the biomaterials Evolution® and Gen-Os® (OsteoBiol®, Italy) combined, or not, with dental pulp stem cells (DP-MSC). The results obtained through the Micro-CT and histological study reveal the almost complete re-covery of the lesion in the group with DP-MSC. These results are supported by increases in endoglin, TGF-β, protocollagen I, parathormone, and calcitonin, generating an environment of bone generation and development when combining Evolution® and Gen-Os® (OsteoBiol®, Italy) with DP-MSC. These promising results confirm the transcendental role of DP-MSC in combina-tion with osteogenic biomaterials for bone regeneration, and warrant further studies, including its assessment in clinical trials.