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Angiogenesis, the formation of capillaries from pre-existing blood vessels, is a key process in tissue engineering. If blood supply cannot be established rapidly, there is insufficient oxygen and nutrient transport and necrosis of the implanted tissue will occur. Recent studies indicate that the human dental pulp contains precursor cells, named dental pulp stem cells (hDPSC) that show self-renewal and multilineage differentiation capacity. Since these cells can be easily isolated, cultured and cryopreserved, they represent an attractive stem cell source for tissue engineering. Until now, only little is known about the angiogenic abilities and mechanisms of the hDPSC. In this study, the angiogenic profile of both cell lysates and conditioned medium of hDPSC was determined by means of an antibody array. Numerous pro-and anti-angiogenic factors such as vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) and endostatin were found both at the mRNA and protein level. hDPSC had no influence on the proliferation of the human microvascular endothelial cells (HMEC-1), but were able to significantly induce HMEC-1 migration in vitro. Addition of the PI3K-inhibitor LY294002 and the MEK-inhibitor U0126 to the HMEC-1 inhibited this effect, suggesting that both Akt and ERK pathways are involved in hDPSC-mediated HMEC-1 migration. Antibodies against VEGF also abolished the chemotactic actions of hDPSC. Furthermore, in the chicken chorioallantoic membrane (CAM) assay, hDPSC were able to significantly induce blood vessel formation. In conclusion, hDPSC have the ability to induce angiogenesis, meaning that this stem cell population has a great clinical potential, not only for tissue engineering but also for the treatment of chronic wounds, stroke and myocardial infarctions.

Background Titanium and its alloys have been widely employed for bone tissue repair and implant manufacturing. The rapid development of three-dimensional (3D) printing technology has allowed fabrication of porous titanium scaffolds with controllable microstructures, which is considered to be an effective method for promoting rapid bone formation and decreasing bone absorption. The purpose of this systematic review was to evaluate the osteogenic potential of 3D-printed porous Ti6Al4V (Ti64) scaffold for repairing long bone defects in animal models and to investigate the influential factors that might affect its osteogenic capacity. Methods Electronic literature search was conducted in the following databases: PubMed, Web of Science, and Embase up to September 2021. The SYRCLE's tool and the modified CAMARADES list were used to assess the risk of bias and methodological quality, respectively. Due to heterogeneity of the selected studies in relation to protocol and outcomes evaluated, a meta-analysis could not be performed. Results The initial search revealed 5858 studies. Only 46 animal studies were found to be eligible based on the inclusion criteria. Rabbit was the most commonly utilized animal model. A pore size of around 500–600 µm and porosity of 60–70% were found to be the most ideal parameters for designing the Ti64 scaffold, where both dodecahedron and diamond pores optimally promoted osteogenesis. Histological analysis of the scaffold in a rabbit model revealed that the maximum bone area fraction reached 59.3 ± 8.1% at weeks 8–10. Based on micro-CT assessment, the maximum bone volume fraction was found to be 34.0 ± 6.0% at weeks 12. Conclusions Ti64 scaffold might act as a promising medium for providing sufficient mechanical support and a stable environment for new bone formation in long bone defects. Trail registration The study protocol was registered in the PROSPERO database under the number CRD42020194100.

Objectives We review the evidence for tranexamic acid (TXA) for the treatment and prevention of bleeding caused by surgery, trauma and bleeding disorders. We highlight therapeutic areas where evidence is lacking and discuss safety issues, particularly the concern regarding thrombotic complications. Methods An electronic search was performed in PubMed and the Cochrane Library to identify clinical trials, safety reports and review articles. Findings TXA reduces bleeding in patients with menorrhagia, and in patients undergoing caesarian section, myomectomy, hysterectomy, orthopedic surgery, cardiac surgery, orthognathic surgery, rhinoplasty, and prostate surgery. For dental extractions in patients with bleeding disorders or taking antithrombotic drugs, as well as in cases of idiopathic epistaxis, tonsillectomy, liver transplantation and resection, nephrolithotomy, skin cancer surgery, burn wounds and skin grafting, there is moderate evidence that TXA is effective for reducing bleeding. TXA was not effective in reducing bleeding in traumatic brain injury and upper and lower gastrointestinal bleeding. TXA reduces mortality in patients suffering from trauma and postpartum hemorrhage. For many of these indications, there is no consensus about the optimal TXA dose. With certain dosages and with certain indications TXA can cause harm, such as an increased risk of seizures after high TXA doses with brain injury and cardiac surgery, and an increased mortality after delayed administration of TXA for trauma events or postpartum hemorrhage. Whereas most trials did not signal an increased risk for thrombotic events, some trials reported an increased rate of thrombotic complications with the use of TXA for gastro-intestinal bleeding and trauma. Conclusions TXA has well-documented beneficial effects in many clinical indications. Identifying these indications and the optimal dose and timing to minimize risk of seizures or thromboembolic events is work in progress.

The use of high quality facemasks is indispensable in the light of the current COVID pandemic. This study proposes a fully automatic technique to design a face specific mask. Through the use of stereophotogrammetry, computer-assisted design and three-dimensional (3D) printing, we describe a protocol for manufacturing facemasks perfectly adapted to the individual face characteristics. The face specific mask was compared to a universal design of facemask and different filter container’s designs were merged with the mask body. Subjective assessment of the face specific mask demonstrated tight closure at the nose, mouth and chin area, and permits the normal wearing of glasses. A screw-drive locking system is advised for easy assembly of the filter components. Automation of the process enables high volume production but still allows sufficient designer interaction to answer specific requirements. The suggested protocol can be used to provide more comfortable, effective and sustainable solution compared to a single use, standardized mask. Subsequent research on printing materials, sterilization technique and compliance with international regulations will facilitate the introduction of the face specific mask in clinical practice as well as for general use.

The purpose of this study was to report root remodeling/resorption percentages of maxillary teeth following the different maxillary osteotomies; i.e. one-piece, two-pieces, three-pieces Le Fort I, surgically assisted rapid palatal expansion (SARPE). The possibility of relationships between root remodeling and various patient- and/or treatment-related factors were further investigated. A total of 110 patients (1075 teeth) who underwent combined orthodontic and orthognathic surgery were studied retrospectively. The sample size was divided into: 30 patients in one-piece Le Fort I group, 30 patients in multi-pieces Le Fort I group, 20 patients in SARPE group and 30 patients in orthodontic group. Preoperative and 1 year postoperative cone beam computed tomography (CBCT) scans were obtained. A validated and automated method for evaluating root remodeling and resorption in three dimensions (3D) was applied. SARPE group showed the highest percentage of root remodeling. Spearman correlation coefficient revealed a positive relationship between maxillary advancement and root remodeling, with more advancement contributing to more root remodeling. On the other hand, the orthodontic group showed a negative correlation with age indicating increased root remodeling in younger patients. Based on the reported results of linear, volumetric and morphological changes of the root after 1 year, clinical recommendations were provided in the form of decision tree flowchart and tables. These recommendations can serve as a valuable resource for surgeons in estimating and managing root remodeling and resorption associated with different maxillary surgical techniques.

Silver-based nanoparticles and biomaterials have extensive biomedical applications owing to their unique antimicrobial properties. Thus, green and facile synthesis of such materials is highly desirable. This study reports an antibacterial hydrogel based on polyvinyl alcohol/sodium alginate network with the incorporation of silver nanoparticles (AgNPs), which is greenly synthesized by reductive metabolites obtained from the leaves of green tea. The 'flower-shape' AgNPs were acquired, it formed a mono-disperse system with a distinct uniform interparticle separation. The average size of AgNPs varied from 129.5 to 243.6 nm, which could be regulated by using different volumes of the green tea extract. Zeta potentials of the AgNPs were from −39.3 mV to −20.3 mV, indicating the moderate stability of the particles in water. In the next stage, the antibacterial polyvinyl alcohol/sodium alginate hydrogels were fabricated by incorporating prepared AgNPs. Scanning Electron Microscopy (SEM) images showed that the porous structure was obtained, and Energy Dispersive X-Ray (EDX) analysis confirmed that the AgNPs were uniformly dispersed in the polymer network. The hydrogels exhibited superior water absorption properties, which were characterized by a high swelling ratio (500-900%) and fast equilibrium. The hydrogels also exhibited good antimicrobial activity in assays with Gram-positive bacteria Escherichia coli and Gram-negative bacteria Staphylococcus aureus. To sum up, a process for the green preparation of antibacterial hydrogels based on AgNPs derived from tea leaves as a conveniently available cheap local agricultural product was established.

Condylar resorption is a feared complication of orthognathic surgery. This study investigated condylar resorption in a cohort of 200 patients This allowed for a powerful update on incidence and risk factors. 9.5% of patients developed resorption. These patients had on average, 17% volume loss with 3.9 mm ramal height loss and 3.1 mm posterior mandibular displacement. 2% of patients had bilateral resorption. Univariable analysis identified a younger age, a bimaxillary + genioplasty procedure, larger mandibular advancements, upward movements of the distal segment, a higher counterclockwise pitch of the distal segment, smaller preoperative condylar volumes and a higher anterior/posterior lower facial height ratio as risk factors on a patient level. Univariable analysis on a condylar level also identified compressive movements of the ramus and a higher mandibular plane angle as risk factors. Using machine learning for the multivariable analysis, the amount of mandibular advancement was the most important predictor for condylar resorption. There were no differences in preoperative mandibular, ramal or condylar shape between patients with or without resorption. These findings suggest condylar resorption may be more common than thought. Identifying risk factors allows surgical plans to be adjusted to reduce the likelihood of resorption, and patients can be more selectively screened postoperatively.

The purpose of the presented Artificial Intelligence (AI)-tool was to automatically segment the mandibular molars on panoramic radiographs and extract the molar orientations in order to predict the third molars’ eruption potential. In total, 838 panoramic radiographs were used for training (n = 588) and validation (n = 250) of the network. A fully convolutional neural network with ResNet-101 backbone jointly predicted the molar segmentation maps and an estimate of the orientation lines, which was then iteratively refined by regression on the mesial and distal sides of the segmentation contours. Accuracy was quantified as the fraction of correct angulations (with predefined error intervals) compared to human reference measurements. Performance differences between the network and reference measurements were visually assessed using Bland−Altman plots. The quantitative analysis for automatic molar segmentation resulted in mean IoUs approximating 90%. Mean Hausdorff distances were lowest for first and second molars. The network angulation measurements reached accuracies of 79.7% [−2.5°; 2.5°] and 98.1% [−5°; 5°], combined with a clinically significant reduction in user-time of >53%. In conclusion, this study validated a new and unique AI-driven tool for fast, accurate, and consistent automated measurement of molar angulations on panoramic radiographs. Complementing the dental practitioner with accurate AI-tools will facilitate and optimize dental care and synergistically lead to ever-increasing diagnostic accuracies.

The trigeminal system is one of the most complex cranial nerve systems of the human body. Research on it has vastly grown in recent years and concentrated more and more on molecular mechanisms and pathophysiology, but thorough reviews on this topic are lacking, certainly on the normal physiology of the trigeminal sensory system. Here we review the current literature on neurophysiology of the trigeminal nerve from peripheral receptors up to its central projections toward the somatosensory cortex. We focus on the most recent scientific discoveries and describe historical relevant research to substantiate further. One chapter on new insights of the pathophysiology of pain at the level of the trigeminal system is added. A database search of Medline, Embase and Cochrane was conducted with the search terms ‘animal study’, ‘neurophysiology’, ‘trigeminal’, ‘oral’ and ‘sensory’. Articles were manually selected after reading the abstract and where needed the article. Reference lists also served to include relevant research articles. Fifty-six articles were included after critical appraisal. Physiological aspects on mechanoreceptors, trigeminal afferents, trigeminal ganglion and central projections are reviewed in light of reference works. Embryologic and anatomic insights are cited where needed. A brief description of pathophysiology of pain pathways in the trigeminal area and recent advances in dental stem cell research are also discussed. Neurophysiology at the level of the central nervous system is not reviewed. The current body of knowledge is mainly based on animal and cadaveric studies, but recent advancements in functional imaging and molecular neuroscience are elucidating the pathways and functioning of this mixed nerve system. Extrapolation of animal studies or functioning of peripheral nerves should be warranted.

Purpose Implant-supported prosthetic rehabilitation in the resorbed maxilla is a great challenge. The aim of this study was to determine the survival rate of conventional anterior implants placed in combination with zygomatic implants according to the Brånemark technique, and to identify risk factors for implant failure. Methods We collected data retrospectively from 72 consecutive patients who received treatment from 1998 to 2018 at our center, according to Brånemark’s original technique. Kaplan–Meier analysis was conducted to assess survival rate, and a survival regression model was used with the patient as the random factor, applying the Weibull distribution. Results A total of 236 maxillary anterior implants were included, with a mean follow-up of 12.1 years. Kaplan–Meier analysis showed overall cumulative survival rates of 95.3% at 1 year, 94.8% at 2 years, 93.0% at 5 years, 90.5% at 10 years, 81.6% at 15 years, and 67.7% at 20 years. Survival regression showed an association between bruxism and implant failure as well as implants bearing an overdenture. Implants with length ≤ 10 mm had a significantly lower survival time. No significant association was found between the number of anterior implants and survival rate. Conclusions We found acceptable long-term anterior conventional implant survival. Significant risk factors for failure were bruxism, overdentures, and implants shorter than 10 mm.