Purpose: This pilot study was conducted to develop a novel test setup for the in vitroassessment of the primary stability of dental implants. This was achieved by characterising their long-term behaviour based on the continuous recording of micromotions resulting from dynamic and cyclic loading. Methods: Twenty screw implants, each 11 mm in length and either 3.8 mm (for premolars) or 4.3 mm (for molars) in diameter, were inserted into the posterior region of 5 synthetic mandibular models. Physiological masticatory loads were simulated by superimposing cyclic buccal-lingual movement of the mandible with a vertically applied masticatory force. Using an optical 3-dimensional (3D) measuring system, the micromotions of the dental crowns relative to the alveolar bone resulting from alternating off-centre loads were concurrently determined over 10,000 test cycles. Results: The buccal-lingual deflections of the dental crowns significantly increased from cycle 10 to cycle 10,000 (P<0.05). The deflections increased sharply during the first 500 cycles before approaching a plateau. Premolars exhibited greater maximum deflections than molars. The bone regions located mesially and distally adjacent to the loaded implants demonstrated deflections that occurred synchronously and in the same direction as the applied loads. The overall spatial movement of the implants over time followed an hourglassshaped loosening pattern with a characteristic pivot point 5.5±1.1 mm from the apical end. Conclusions: In synthetic mandibular models, the cyclic reciprocal loading of dental implants with an average masticatory force produces significant loosening. The evasive movements observed in the alveolar bone suggest that its anatomy and yielding could significantly influence the force distribution and, consequently, the mechanical behaviour of dental implants. The 3D visualisation of the overall implant movement under functionalPurpose: This pilot study was conducted to develop a novel test setup for the in vitroassessment of the primary stability of dental implants. This was achieved by characterising their long-term behaviour based on the continuous recording of micromotions resulting from dynamic and cyclic loading. Methods: Twenty screw implants, each 11 mm in length and either 3.8 mm (for premolars) or 4.3 mm (for molars) in diameter, were inserted into the posterior region of 5 synthetic mandibular models. Physiological masticatory loads were simulated by superimposing cyclic buccal-lingual movement of the mandible with a vertically applied masticatory force. Using an optical 3-dimensional (3D) measuring system, the micromotions of the dental crowns relative to the alveolar bone resulting from alternating off-centre loads were concurrently determined over 10,000 test cycles. Results: The buccal-lingual deflections of the dental crowns significantly increased from cycle 10 to cycle 10,000 (P<0.05). The deflections increased sharply during the first 500 cycles before approaching a plateau. Premolars exhibited greater maximum deflections than molars. The bone regions located mesially and distally adjacent to the loaded implants demonstrated deflections that occurred synchronously and in the same direction as the applied loads. The overall spatial movement of the implants over time followed an hourglassshaped loosening pattern with a characteristic pivot point 5.5±1.1 mm from the apical end. Conclusions In synthetic mandibular models, the cyclic reciprocal loading of dental implants with an average masticatory force produces significant loosening. The evasive movements observed in the alveolar bone suggest that its anatomy and yielding could significantly influence the force distribution and, consequently, the mechanical behaviour of dental implants. The 3D visualisation of the overall implant movement under functional cyclic loading complements known methods and can contribute to the development of implant designs and surgical techniques by providing a more profound understanding of dynamic bone-implant interactions.

Purpose: This pilot study was conducted to develop a novel test setup for the in vitroassessment of the primary stability of dental implants. This was achieved by characterising their long-term behaviour based on the continuous recording of micromotions resulting from dynamic and cyclic loading. Methods: Twenty screw implants, each 11 mm in length and either 3.8 mm (for premolars) or 4.3 mm (for molars) in diameter, were inserted into the posterior region of 5 synthetic mandibular models. Physiological masticatory loads were simulated by superimposing cyclic buccal-lingual movement of the mandible with a vertically applied masticatory force. Using an optical 3-dimensional (3D) measuring system, the micromotions of the dental crowns relative to the alveolar bone resulting from alternating off-centre loads were concurrently determined over 10,000 test cycles. Results: The buccal-lingual deflections of the dental crowns significantly increased from cycle 10 to cycle 10,000 (P<0.05). The deflections increased sharply during the first 500 cycles before approaching a plateau. Premolars exhibited greater maximum deflections than molars. The bone regions located mesially and distally adjacent to the loaded implants demonstrated deflections that occurred synchronously and in the same direction as the applied loads. The overall spatial movement of the implants over time followed an hourglassshaped loosening pattern with a characteristic pivot point 5.5±1.1 mm from the apical end. Conclusions: In synthetic mandibular models, the cyclic reciprocal loading of dental implants with an average masticatory force produces significant loosening. The evasive movements observed in the alveolar bone suggest that its anatomy and yielding could significantly influence the force distribution and, consequently, the mechanical behaviour of dental implants. The 3D visualisation of the overall implant movement under functionalPurpose: This pilot study was conducted to develop a novel test setup for the in vitroassessment of the primary stability of dental implants. This was achieved by characterising their long-term behaviour based on the continuous recording of micromotions resulting from dynamic and cyclic loading. Methods: Twenty screw implants, each 11 mm in length and either 3.8 mm (for premolars) or 4.3 mm (for molars) in diameter, were inserted into the posterior region of 5 synthetic mandibular models. Physiological masticatory loads were simulated by superimposing cyclic buccal-lingual movement of the mandible with a vertically applied masticatory force. Using an optical 3-dimensional (3D) measuring system, the micromotions of the dental crowns relative to the alveolar bone resulting from alternating off-centre loads were concurrently determined over 10,000 test cycles. Results: The buccal-lingual deflections of the dental crowns significantly increased from cycle 10 to cycle 10,000 (P<0.05). The deflections increased sharply during the first 500 cycles before approaching a plateau. Premolars exhibited greater maximum deflections than molars. The bone regions located mesially and distally adjacent to the loaded implants demonstrated deflections that occurred synchronously and in the same direction as the applied loads. The overall spatial movement of the implants over time followed an hourglassshaped loosening pattern with a characteristic pivot point 5.5±1.1 mm from the apical end. Conclusions In synthetic mandibular models, the cyclic reciprocal loading of dental implants with an average masticatory force produces significant loosening. The evasive movements observed in the alveolar bone suggest that its anatomy and yielding could significantly influence the force distribution and, consequently, the mechanical behaviour of dental implants. The 3D visualisation of the overall implant movement under functional cyclic loading complements known methods and can contribute to the development of implant designs and surgical techniques by providing a more profound understanding of dynamic bone-implant interactions.

Purpose: This pilot study was conducted to develop a novel test setup for the in vitroassessment of the primary stability of dental implants. This was achieved by characterising their long-term behaviour based on the continuous recording of micromotions resulting from dynamic and cyclic loading. Methods: Twenty screw implants, each 11 mm in length and either 3.8 mm (for premolars) or 4.3 mm (for molars) in diameter, were inserted into the posterior region of 5 synthetic mandibular models. Physiological masticatory loads were simulated by superimposing cyclic buccal-lingual movement of the mandible with a vertically applied masticatory force. Using an optical 3-dimensional (3D) measuring system, the micromotions of the dental crowns relative to the alveolar bone resulting from alternating off-centre loads were concurrently determined over 10,000 test cycles. Results: The buccal-lingual deflections of the dental crowns significantly increased from cycle 10 to cycle 10,000 (P<0.05). The deflections increased sharply during the first 500 cycles before approaching a plateau. Premolars exhibited greater maximum deflections than molars. The bone regions located mesially and distally adjacent to the loaded implants demonstrated deflections that occurred synchronously and in the same direction as the applied loads. The overall spatial movement of the implants over time followed an hourglassshaped loosening pattern with a characteristic pivot point 5.5±1.1 mm from the apical end. Conclusions: In synthetic mandibular models, the cyclic reciprocal loading of dental implants with an average masticatory force produces significant loosening. The evasive movements observed in the alveolar bone suggest that its anatomy and yielding could significantly influence the force distribution and, consequently, the mechanical behaviour of dental implants. The 3D visualisation of the overall implant movement under functionalPurpose: This pilot study was conducted to develop a novel test setup for the in vitroassessment of the primary stability of dental implants. This was achieved by characterising their long-term behaviour based on the continuous recording of micromotions resulting from dynamic and cyclic loading. Methods: Twenty screw implants, each 11 mm in length and either 3.8 mm (for premolars) or 4.3 mm (for molars) in diameter, were inserted into the posterior region of 5 synthetic mandibular models. Physiological masticatory loads were simulated by superimposing cyclic buccal-lingual movement of the mandible with a vertically applied masticatory force. Using an optical 3-dimensional (3D) measuring system, the micromotions of the dental crowns relative to the alveolar bone resulting from alternating off-centre loads were concurrently determined over 10,000 test cycles. Results: The buccal-lingual deflections of the dental crowns significantly increased from cycle 10 to cycle 10,000 (P<0.05). The deflections increased sharply during the first 500 cycles before approaching a plateau. Premolars exhibited greater maximum deflections than molars. The bone regions located mesially and distally adjacent to the loaded implants demonstrated deflections that occurred synchronously and in the same direction as the applied loads. The overall spatial movement of the implants over time followed an hourglassshaped loosening pattern with a characteristic pivot point 5.5±1.1 mm from the apical end. Conclusions In synthetic mandibular models, the cyclic reciprocal loading of dental implants with an average masticatory force produces significant loosening. The evasive movements observed in the alveolar bone suggest that its anatomy and yielding could significantly influence the force distribution and, consequently, the mechanical behaviour of dental implants. The 3D visualisation of the overall implant movement under functional cyclic loading complements known methods and can contribute to the development of implant designs and surgical techniques by providing a more profound understanding of dynamic bone-implant interactions.

Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.