Stereolithography (SLA) is an interesting manufacturing technology to overcome limitations of commercially available particulated biomaterials dedicated to intra-oral bone regeneration applications. The purpose of this study was to evaluate the in vitro and in vivo biocompatibility and osteoinductive properties of two calcium-phosphate (CaP)-based scaffolds manufactured by SLA three-dimensional (3D) printing. Pellets and macro-porous scaffolds were manufactured in pure hydroxyapatite (HA) and in biphasic CaP (HA:60-TCP:40). Physico-chemical characterization was performed using micro X-ray fluorescence, scanning electron microscopy (SEM), optical interferometry, and microtomography (μCT) analyses. Osteoblast-like MG-63 cells were used to evaluate the biocompatibility of the pellets in vitro with MTS assay and the cell morphology and growth characterized by SEM and DAPI-actin staining showed similar early behavior. For in vivo biocompatibility, newly formed bone and biodegradability of the experimental scaffolds were evaluated in a subperiosteal cranial rat model using μCT and descriptive histology. The histological analysis has not indicated evidences of inflammation but highlighted close contacts between newly formed bone and the experimental biomaterials revealing an excellent scaffold osseointegration. This study emphasizes the relevance of SLA 3D printing of CaP-based biomaterials for intra-oral bone regeneration even if manufacturing accuracy has to be improved and further experiments using biomimetic scaffolds should be conducted. K E Y W O R D Sbone regeneration, bone scaffold, histology, microtomography, stereolithography

It has been shown that γδ T cells protect against the formation of squamous cell carcinoma (SCC) in several models. However, the role of γδ T cells in human papillomavirus (HPV)-associated uterine cervical SCC, the third-leading cause of death by cancer in women, is unknown. Here, we investigated the impact of γδ T cells in a transgenic mouse model of carcinogenesis induced by HPV16 oncoproteins. Surprisingly, γδ T cells promoted the development of HPV16 oncoprotein-induced lesions. HPV16 oncoproteins induced a decrease in epidermal Skint1 expression and the associated antitumor Vγ5 γδ T cells, which were replaced by γδ T-cell subsets (mainly Vγ6 γδCCR2CCR6) actively producing IL-17A. Consistent with a proangiogenic role, γδ T cells promoted the formation of blood vessels in the dermis underlying the HPV-induced lesions. In human cervical biopsies, IL-17A γδ T cells could only be observed at the cancer stage (SCC), where HPV oncoproteins are highly expressed, supporting the clinical relevance of our observations in mice. Overall, our results suggest that HPV16 oncoproteins induce a reorganization of the local epithelial-associated γδ T-cell subpopulations, thereby promoting angiogenesis and cancer development.

3D printing technologies are a promising approach to treat intra-oral bone defects, especially those with poor regenerative potential. However, there is a lack of evidence regarding the impact of internal design specifications on the bone regenerative potential. Here, an in silico approach to optimize the internal design of calcium phosphate-based scaffolds for bone regeneration is proposed. Based on an in silico model of neotissue formation, a gyroid 3D-printed scaffold is designed and manufactured using UV stereolithography of bioceramic materials. An orthogonal lattice structure 3D-printed scaffold and a particulate xenograft are used as control groups. The scaffolds are implanted subperiosteally under a shell on rat calvarium for 4 or 8 weeks and bone neoformation performances are investigated by nanofocus computed tomography and decalcified histology. After 8 weeks, the gyroid group is associated with a higher ingrowth potential of the bone and is characterized by signs of osteoinduction (newly formed bone islands). The bone to material contact is similar between the gyroid and the particulate groups. The present results reinforce this in silico modeling strategy to design calcium phosphate-based 3D scaffolds and the gyroid experimental internal architecture seems to be highly promising for intra-oral bone regeneration applications.

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Objectives To discern the effects of computer-aided design (CAD)/computer-aided manufactured (CAM) customized appliances and piezocision on orthodontic treatment (OT). Materials and Methods The study combined findings from two previously published randomized controlled trials: (1) standard OT vs piezocision-assisted standard OT, and (2) CAD/CAM OT vs piezocision-assisted CAD/CAM OT. Piezocision is a minimally invasive corticotomy surgical procedure used to accelerate orthodontic treatment and CAD/CAM refers to CAD/CAM customized brackets and archwires. The outcomes were the overall treatment time, and the durations of the alignment phase and fine-tuning phase. Clinical and radiological features also were evaluated. Results The combined study included 48 patients with similar baseline characteristics. Compared to the standard treatment, CAD/CAM technology alone significantly decreased the overall median OT time from 543 to 394 days (P < .001) and from 543 to 254 days (P < .0001) when combined with piezocision. Although piezocision significantly reduced the duration of the alignment phase in the mandible and maxilla, CAD/CAM technology considerably shortened the fine-tuning phase. All periodontal and radiographic parameters remained stable from the start to the end of treatment in all groups. Conclusions CAD/CAM technology combined with piezocision accelerates the entire OT process, during the alignment phase for piezocision and during the fine-tuning phase for CAD/CAM, with a global reduction of the overall treatment time of more than 50%.

BackgroundPeriodontitis is a chronic inflammatory gum disease associated with systemic diseases such as cardiovascular diseases.AimTo investigate the association of systemic blood biomarkers, C-reactive protein (CRP), levels of lipopolysaccharide (LPS), and IgG levels against periodontal pathogens Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) with the stability, based on the aortic diameter, the growth rate and the eligibility for surgical intervention, of patients with abdominal aortic aneurysm (AAA).MethodsPatients with stable AAA (n = 30) and unstable AAA (n = 31) were recruited. The anti-A. actinomycetemcomitans and anti-P. gingivalis IgG levels were analyzed by ELISA, the LPS analysis was performed by using the limulus amebocyte lysate (LAL) test, and plasma levels of CRP were determined using an immune turbidimetric method. The association between these blood systemic biomarkers, AAA features, periodontal clinical parameters and oral microbial profiles were explored. Regression models were used to test the relationship between variables.ResultsThe presence of antibodies against Pg and Aa, LPS and high CRP concentrations were found in all AAA patients. The IgG levels were similar in patients with stable and unstable AAA (both for Aa and Pg). Among investigated blood biomarkers, only CRP was associated with AAA stability. The amount of LPS in saliva, supra, and subgingival plaque were significantly associated with the systemic LPS (p <0.05).ConclusionsThis post-hoc study emphasizes the presence of antibodies against Pg and Aa, LPS and high CRP concentrations in all AAA patients. The presence of Pg in saliva and subgingival plaque was significantly associated with the blood LPS levels. For further studies investigating periodontitis and systemic diseases, specific predictive blood biomarkers should be considered instead of the use of antibodies alone.

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