Expanding the Surgeon's Armamentarium: Use of the Tubing Technique to Preserve the Inferior Alveolar Nerve During Transposition Procedure.

Severe edentulous posterior mandible atrophy with inadequate bone height superior to the inferior alveolar canal may increase the risk of neurosensory impairment and other complications during inferior alveolar nerve (IAN) transposition (IANT) prior to dental implant insertion. The current report describes the tubing technique as a practical and feasible procedure that ensures IAN preservation during IANT. The technique involves wrapping a standard suction catheter around the exposed nerve to facilitate full coverage. This work presents a retrospective review of 31 patients undergoing IANT procedures followed by immediate placement of dental implants between January 2015 and January 2020. IANT was performed either unilaterally or bilaterally on all patients, followed by IAN tubing before implant placement. A total of 46 IANT procedures involving the tubing technique were performed. Overall, 149 dental implants were inserted during IANT surgeries, with a success rate of 98.6%. Sensory disturbance was documented in 47.8% of the treated sites (left/right mandible) at 1 month (22/46 sites), 21.7% at 3 months (10/46 sites), 6.5% at 6 months (3/46 sites), and 2.2% at 12 months (1/46 sites) postimplantation. In total, except for 1 case, sensory disturbance was fully resolved by the end of the 12-month follow-up period. Taken together, the tubing technique described herein is a practical and reproducible method for protecting the IAN during transposition.

Injectable Hydrogels Based on Inter-Polyelectrolyte Interactions between Hyaluronic Acid, Gelatin, and Cationic Cellulose Nanocrystals.

The present work dealt with the development of physically cross-linked injectable hydrogels with potential applications in tissue engineering. The hydrogels were composed of a ternary mixture of a polyanion and a polyampholyte, hyaluronic acid (HA) and gelatin, respectively, bridged by cationic cellulose nanocrystals (cCNCs). A 3D network is formed by employing attractive electrostatic interactions and hydrogen bonding between these components under physiological conditions. The hydrogels demonstrated low viscosity at high stresses, enabling easy injection, structural stability at low stresses (<15 Pa), and nearly complete structure recovery within several minutes. Increasing the cCNC content (>3%) reduced hydrogel swelling and decelerated the degradation in phosphate-buffered saline as compared to that in pure HA and HA-gelatin samples. Biological evaluation of the hydrogel elutions showed excellent cell viability. The proliferation of fibroblasts exposed to elutions of hydrogels with 5% cCNCs reached ∼200% compared to that in the positive control after 11 days. Considering these results, the prepared hydrogels hold great potential in biomedical applications, such as injectable dermal fillers, 3D bioprintable inks, or 3D scaffolds to support and promote soft tissue regeneration.

Forty-One Plant Extracts Screened for Dual Antidiabetic and Antioxidant Functions: Evaluating the Types of Correlation between -Amylase Inhibition and Free Radical Scavenging.

Dysregulation of glucose homeostasis followed by chronic hyperglycemia is a hallmark of diabetes mellitus (DM), a disease spreading as a worldwide pandemic for which there is no satisfactory dietary treatment or cure. The development of glucose-controlling drugs that can prevent complications of DM, such as hyperglycemia and oxidative stress, which contribute to the impairment of the key physiological processes in the body, is of grave importance. In pursuit of this goal, this study screened 41 plant extracts for their antidiabetic and antioxidant activities by employing assays to test for α-amylase inhibition and free radical scavenging activity (FRSA) and by measuring glucose uptake in L6-GLUT4myc cells. While extracts of Rhus coriaria, Punica granatum, Olea europaea, Pelargonium spp., Stevia rebaudiana, and Petroselinum crispum demonstrated significant α-amylase inhibition, the extracts of Rhus coriaria and Pelargonium spp. also demonstrated increased FRSA, and the extract of Rhus coriaria stimulated glucose uptake. These natural extracts, which are believed to have fewer side effects because they are prepared from edible plants, interfere with the process in the small intestine that breaks down dietary carbohydrates into monosaccharide and disaccharide derivatives, and thereby suppress increases in diet-induced blood glucose; hence, they may have clinical value for type 2 diabetes management. The Pelargonium spp. and Rhus coriaria extracts demonstrated the highest antidiabetic and antioxidant activities. Both plants may offer valuable medical benefits, especially because they can be taken as dietary supplements by patients with diabetes and can serve as sources of new, natural-based antidiabetic drug candidates. The enhancement of cellular glucose uptake stimulated by Rhus coriaria extract could lead to the development of clinical applications that regulate blood glucose levels from within the circulatory system. Isolating bioactive substances from these plant extracts and testing them in diabetic mice will significantly advance the development of natural drugs that have both antidiabetic and free radical-scavenging properties, likely with lesser side effects.

Vaccine hesitancy: the next challenge in the fight against COVID-19.

Vaccine hesitancy remains a barrier to full population inoculation against highly infectious diseases. Coincident with the rapid developments of COVID-19 vaccines globally, concerns about the safety of such a vaccine could contribute to vaccine hesitancy. We analyzed 1941 anonymous questionnaires completed by healthcare workers and members of the general Israeli population, regarding acceptance of a potential COVID-19 vaccine. Our results indicate that healthcare staff involved in the care of COVID-19 positive patients, and individuals considering themselves at risk of disease, were more likely to self-report acquiescence to COVID-19 vaccination if and when available. In contrast, parents, nurses, and medical workers not caring for SARS-CoV-2 positive patients expressed higher levels of vaccine hesitancy. Interventional educational campaigns targeted towards populations at risk of vaccine hesitancy are therefore urgently needed to combat misinformation and avoid low inoculation rates.

Storage effect on viability and biofunctionality of human adipose tissue-derived stromal cells.

BACKGROUND AIMS: In our recent studies, the transplantation of human adipose tissue-derived stromal cells (ASCs) has shown promise for treatment of diseases related to bone and joint disorders. METHODS: For the current clinical applications, ASCs were formulated and suspended in PlasmaLyte A supplemented with heparin, glucose and human serum albumin, balanced to pH 7.4 with sodium bicarbonate. This cell solution constitutes 20% of the overall transplanted mixture and is supplemented with hyaluronic acid (60%) and OraGraft particles (20%). We intended to investigate the effect of this transplantation mixture on the viability and biofunctionality of ASCs in bone formation. Freshly harvested cells were resuspended and incubated in the indicated mixture for up to 48 h at 4°C. Cell viability was assessed using trypan blue and AlamarBlue, and cell functionality was determined by quantifying their adhesion rate in vitro and bone formation in an ectopic mouse model. RESULTS: More than 80% of the ASCs stored in the transplantation mixture were viable for up to 24 h. Cell viability beyond 24 h in storage decreased to approximately 50%. In addition, an equal degree of bone formation was observed between the cells transplanted following incubation in transplantation mixture for up to 24 h and zero-time non-incubated cells (control). CONCLUSIONS: The viability and functionality of ASCs stored in the presented formulation will make such cell therapy accessible to larger and more remote populations.

Arthroscopic discopexy is effective in managing temporomandibular joint internal derangement in patients with Wilkes stage II and III.

PURPOSE: Disc repositioning for temporomandibular joint (TMJ) internal derangement (ID) is a well-established surgical technique with variable success. The purpose of the present study was to assess the outcomes after arthroscopic disc repositioning (discopexy) for TMJ ID. PATIENTS AND METHODS: This was a prospective, cohort, single-institutional clinical study. The study included patients with TMJ ID in whom diagnostic arthroscopy had failed. These patients were presented and treated at Miami Oral and Maxillofacial Surgery, Baptist Hospital (Miami FL). The predictive variable was the Wilkes diagnostic categories, presented in 2 groups: II and III versus IV and V. The primary outcome variable was the absence of joint pain at 12 months postoperatively. The secondary outcome variables included joint function, maximum interincisal opening, medication use, joint loading sign, and muscle pain. The patients were followed for 1 year postoperatively. The statistical analyses included paired and independent sample Student's t test, χ(2) test, and logistic regression analysis. RESULTS: A total of 32 subjects (42 joints), with a mean age of 31 years, were included in the present study; 28 (87.5%) were women. Of the 42 joints, 71.4% were classified as Wilkes stage II and III. A successful outcome was seen in 69% of the studied subjects and in 86.7% of the Wilkes II and III group versus 25% of the Wilkes IV and V group (P = .001). CONCLUSION: The results of the present study have shown that TMJ arthroscopic discopexy is an effective and predictable treatment of patients with TMJ ID in whom primary TMJ arthroscopy failed. Our results have also shown that patients with Wilkes II or III TMD will have the most successful outcome.

Altered sensation following extrusion of an endodontic file treated by intentional replantation: case report and treatment recommendations.

OBJECTIVE: An altered sensation during endodontic treatment can occur due to the extrusion of endodontic materials. This study aims to discuss intentional replantation to address paresthesia resulting from an endodontic file penetrating the inferior alveolar nerve canal (IANC) and provide a protocol for managing nerve injuries in such incidents. CASE PRESENTATION: A 12-year-old girl developed paresthesia when an endodontic file separated and was inadvertently pushed through the apical foramen into IANC during root canal treatment of the mandibular left first molar. A CBCT scan revealed the file penetrating the canal towards the inferior border of the mandible. After considering the treatment options, intentional replantation was deemed suitable. The tooth was a-traumatically extracted and preserved in sterile saline. The surgeon then carefully cleaned and irrigated the socket. The radiographic assessment confirmed successful file removal from the socket. The Root ends were resected, and retrograde preparation and obturation were conducted using ultrasonic tips and MTA. The tooth was then replanted into the socket. Successful replantation was confirmed by tooth stability and an audible click. The patient was prescribed antibiotics and steroids. Subsequently, after completing the endodontic treatment. a stainless-steel crown was cemented. The successful intentional replantation procedure resulted in rapid improvement in the patient's condition. The normal sensation had been restored, indicating nerve recovery. At the 15-month follow-up, Periapical bone healing and the eruption of the adjacent second molar were observed, affirming the treatment protocol's overall success. CONCLUSION: Prompt intervention and immediate intentional replantation facilitated direct inspection of the separated file within the socket. Collaboration between an oral maxillofacial surgeon and an endodontist ensures expedited and targeted treatment, leading to favorable outcomes.

Computer-Assisted Evaluation Confirms Spontaneous Healing of Donor Site One Year following Bone Block Harvesting from Mandibular Retromolar Region-A Cohort Study.

Bone augmentation prior to dental implant placement is a common scenario in the dental implantology field. Among the important intraoral harvesting sites to obtain bone blocks is the ramus/retromolar region that has a high success rate and long-lasting alveolar ridge augmentation. Preserving the bone volume and quality at the donor site is crucial for preventing further complications or to serve as a site for re-harvesting. Healing of the intraoral donor sites has been described in the maxillofacial field. This study aimed to evaluate the spontaneous healing of the mandibular retromolar donor site utilizing computer-assisted quantification 6 and 12 months after bone harvesting. MATERIALS AND METHODS: The study was conducted on patients who underwent an alveolar ridge augmentation using an intraoral retromolar bone graft. Three CBCT scans were performed-intraoperative, and at six months and one year after the surgical procedure. By using the Materialise Mimics Innovation Suite software 26.0 features segmentation by thresholding, Hounsfield unit averaging, and superimposition of the tomographies, we could precisely quantify the healing process utilizing spatial and characteristic measures. RESULTS: In all cases, the computer-aided quantification showed that six months following surgery, the donor site had recovered up to 64.5% ± 4.24 of its initial volume, and this recovery increased to 89.2% ± 2.6 after one year. Moreover, the Hounsfield unit averaging confirmed dynamic bone quality healing, starting at 690.3 ± 81 HU for the bone block, decreasing to 102 ± 27.8 HU at six months postoperatively, and improving to 453.9 ± 91.4 HU at the donor site after a year. CONCLUSIONS: This study demonstrates that there is no need for additional replanting at the donor site following retromolar bone block harvesting, whether autogenous or allograft, since spontaneous healing occurs 12 months following the surgery.

Evaluation of the osteoconductive potential of bone substitutes embedded with schneiderian membrane- or maxillary bone marrow-derived osteoprogenitor cells.

AIM: Sinus augmentation procedures commonly employ osteoconductive scaffolding materials to stimulate and support bone formation. The aim of this study was to develop a simple screening methodology for the evaluation of the osteoconductive potential of various bone graft materials prior to clinical use. MATERIALS AND METHODS: Materials tested were Bio-Oss, Bi-Ostetic, OraGraft, and ProOsteon. These Simple and composite bone substitutes were embedded with osteoprogenitor cells derived from either the human maxillary sinus schneiderian membrane (hMSSM) or from maxillary tuberosity bone marrow and then monitored both in vitro and in vivo. RESULTS: Cell adherence and proliferation was most pronounced in OraGraft, followed by ProOsteon. In vivo bone formation, within the bone graft, was also observed, with most marked results in OraGraft and ProOsteon grafts. CONCLUSIONS: The proposed osteoconductivity testing method proved simple, informative, and reliable for the purpose of screening candidate biomaterials for sinus lifting or sinus augmentation.

Enhanced socket preparation during autotransplantation: a new treatment protocol.

OBJECTIVE: Tooth autotransplantation (AT) is a viable option for the replacement of unrestorable or missing teeth. Recently, the use of a 3D replica of a donor tooth constructed from CBCT scans was described. The model is made to assess the recipient site's size and minimize the required extraoral time of the donor tooth after extraction. The aim of the paper was to describe a new technique for AT using the 3D replica as a socket preparation tool. CASE REPORT: A 13-year-old boy who presented with hypodontia was referred for consultation and treatment. The treatment plan included combined orthodontic treatment and AT of the mandibular left second premolar into the site of the congenitally missing maxillary right canine. A titanium 3D model of the donor tooth was printed by a direct metal laser 3D printer utilizing the model from the CBCT scan. An intrasulcular flap was elevated, and the edentulous maxillary ridge was prepared using implant trephine burs with increasing diameters. A surgical mallet was utilized to apply vertical forces to the 3D-printed model, which was inserted into the prepared socket to allow a perfect fit for the donor tooth. After atraumatic extraction of the mandibular left second premolar, the donor tooth was inserted into the ready socket and splinted. Follow-up examinations at 1, 3, and 6 months, and 1 year after surgery demonstrated a successful outcome. CONCLUSION: The titanium replica was successfully used for precise preparation of the recipient site, minimizing the extraoral time of the procedure to 4 minutes, and thereby improving the expected outcome. (Quintessence Int 2023;54:142-148; doi: 10.3290/j.qi.b3649031).

Recommendations on the Use of Oral Orthotic Occlusal Appliance Therapy for Temporomandibular Joint Disorders: Current Evidence and Clinical Practice.

Background: 'Temporomandibular joint disorders (TMDs)' denote an umbrella term that includes arthritic, musculoskeletal and neuromuscular conditions involving the temporomandibular joint, the masticatory muscles, and the associated tissues. Occlusal devices are one of the common treatment modalities utilized in the conservative management of TMDs. The indications for the available 'oral splints' or 'oral orthotic occlusal devices' remain ambiguous. Methods: A joint international consortium was formulated involving the subject experts at TMJ Foundation, to resolve the current ambiguity regarding the use of oral orthotic occlusal appliance therapy for the temporomandibular joint disorders based on the current scientific and clinical evidence. Results: The recommendations and the conclusion of the clinical experts of the joint international consort has been summarized for understanding the indications of the various available oral orthotic occlusal appliances and to aid in the future research on oral occlusal orthotics. Conclusion: The use of the oral orthotic occlusal appliances should be based on the current available scientific evidence, rather than the archaic protocols.

Priming integrin alpha5 promotes human mesenchymal stromal cell osteoblast differentiation and osteogenesis.

Adult human mesenchymal stromal cells (hMSCs) have the potential to differentiate into chondrogenic, adipogenic, or osteogenic lineages, providing a potential source for tissue regeneration. An important issue for efficient bone regeneration is to identify factors that can be targeted to promote the osteogenic potential of hMSCs. Using transcriptome analysis, we found that integrin alpha5 (ITGA5) expression is up-regulated during dexamethasone-induced osteoblast differentiation of hMSCs. Gain-of-function studies showed that ITGA5 promotes the expression of osteoblast phenotypic markers and in vitro osteogenesis of hMSCs. Down-regulation of endogenous ITGA5 using specific shRNAs blunted osteoblast marker gene expression and osteogenic differentiation. Molecular analyses showed that the enhanced osteoblast differentiation induced by ITGA5 was mediated by activation of focal adhesion kinase/ERK1/2-MAPKs and PI3K signaling pathways. Remarkably, activation of endogenous ITGA5 using agonists such as a specific antibody that primes the integrin or a peptide that specifically activates ITGA5 was sufficient to enhance ERK1/2-MAPKs and PI3K signaling and to promote osteoblast differentiation and osteogenic capacity of hMSCs. Importantly, we demonstrated that hMSCs engineered to overexpress ITGA5 exhibited a marked increase in their osteogenic potential in vivo. Taken together, these findings not only reveal that ITGA5 is required for osteoblast differentiation of adult hMSCs but also provide a targeted strategy using ITGA5 agonists to promote the osteogenic capacity of hMSCs. This may be used for tissue regeneration in bone disorders where the recruitment or capacity of hMSCs is compromised.

Distraction osteogenesis for tracheostomy dependent children with severe micrognathia.

Obstructive sleep apnea (OSA) in pediatric populations is often associated with congenital craniofacial malformations resulting in decreased pharyngeal airway, which in severe cases leads to tracheostomy dependence. The purpose of this study was to use distraction osteogenesis to improve the airway and decannulate the tracheostomy. This study involved 11 OSA tracheostomy-dependent patients (age range, 4 months to 6 years) who underwent bilateral distraction in the mandibular body using extraoral distraction devices. Following a latency period of 4 days, gradual distraction at a rate of 1 mm/d was performed followed by a consolidation period of 10 weeks. Three-dimensional computed tomography reconstruction of the face and neck before and after the mandibular lengthening aided in quantitative volumetric evaluation of mandibular volume and airway volume. The results demonstrated mandibular elongation of a mean of 30 mm on each side, an increase in mandibular volume by an average of 29.19%, and increase in pharyngeal airway by an average of 70.53%. Two to 3 months following the last lengthening, all 11 patients were decannulated with improvement of signs and symptoms of OSA and elimination of oxygen requirement. Mean follow-up was 2.0 years. The oxygen saturation level rose to more than 95%, and the apnea index respiratory disturbance index was less than 2 episodes per hour for all patients. Bilateral mandibular distraction is a useful method in younger children to decannulate permanent tracheostomy expanding the hypoplastic mandible and concomitantly advance the base of tongue and hyoid bone increasing the pharyngeal airway.

Comparisons between lysis and lavage, intra-articular steroid injections, and three-point subsynovial steroid injections using operative single-cannula arthroscopy - A retrospective analysis.

The aim of this study is to compare the effectiveness of intra-articular and three-point sub-synovial steroid injections. In this retrospective Cohort study an OSCA lysis and lavage, intra-articular and threepoint sub-synovial steroid injections were performed and the maximal interincisinal opening (MIO), pain using 10- point visual analog scale (VAS) and quality of life (QOL) were measured one week before the procedure and 1, 3, 6, 12 months, and 2 and 3years after surgery. Sixty-five patients suffering from internal derangement refractory to conservative treatment charts were reviewed. successfully lowered pain (p value = 0.0012), and improved mouth opening (p value = 0.023), and quality of life (QoL) (p value = 0.003) for up to 6 months after surgery. OSCA with intra-articular CS injections effectively lowered pain (p value = 0.0025), and improved mouth opening (p value = 0.03) and QoL (p value = 0.004) for 12 months. In comparison, OSCA with sub-synovial steroid injections was significantly effective in lowering pain (p value = 0.000002), improving mouth opening (p value = 0.000004), and QoL (p value p = 0.000006) for the duration of the 36-month follow-up period within the limitations of the study it seems that the OSCA technique with site-specific, sub-synovial CS injections should be the preferred treatment approach when the priority is long-term success concerning pain relief, increased mouth opening and improved quality of life in Wilkes II-IV patients.

Decline in Maxillofacial Injuries during the Pandemic: The Hidden Face of COVID-19.

Maxillofacial injuries result from a variety of daily activities. Traffic accidents, interpersonal violence, and falls represent some of the most common etiological factors behind maxillofacial fractures. During the COVID-19 outbreak, the social distancing measures imposed by healthcare authorities aimed at abolishing the spread of the viral infection. This study aimed to evaluate the effect of social distancing measures on the incidence of maxillofacial injuries. METHODS: Data were retrieved from the medical file registry at the Galilee Medical Center, Nahariya, Israel. Incidence, gender, age, etiology, and cost of hospitalization during the COVID-19 lockdown and the previous periods were retrieved. RESULTS: A decrease in maxillofacial fractures was registered during the 2020 lockdown; younger patients had the largest share of maxillofacial traumas during this period. The midface was the most involved facial region in both periods, and a reduction of 62.3% in the cost of OMF fracture treatment was observed during the COVID-19 era. CONCLUSIONS: The occurrence, etiology, and cost of treatment of maxillofacial injuries during the COVID-19 period were different from those in the corresponding period in the pre-COVID-19 era. These results can provide a guide to help design programs for the prevention of OMF trauma.

3D Printing and Virtual Surgical Planning in Oral and Maxillofacial Surgery.

Compared to traditional manufacturing methods, additive manufacturing and 3D printing stand out in their ability to rapidly fabricate complex structures and precise geometries. The growing need for products with different designs, purposes and materials led to the development of 3D printing, serving as a driving force for the 4th industrial revolution and digitization of manufacturing. 3D printing has had a global impact on healthcare, with patient-customized implants now replacing generic implantable medical devices. This revolution has had a particularly significant impact on oral and maxillofacial surgery, where surgeons rely on precision medicine in everyday practice. Trauma, orthognathic surgery and total joint replacement therapy represent several examples of treatments improved by 3D technologies. The widespread and rapid implementation of 3D technologies in clinical settings has led to the development of point-of-care treatment facilities with in-house infrastructure, enabling surgical teams to participate in the 3D design and manufacturing of devices. 3D technologies have had a tremendous impact on clinical outcomes and on the way clinicians approach treatment planning. The current review offers our perspective on the implementation of 3D-based technologies in the field of oral and maxillofacial surgery, while indicating major clinical applications. Moreover, the current report outlines the 3D printing point-of-care concept in the field of oral and maxillofacial surgery.

The Modulatory Effect of Adipose-Derived Stem Cells on Endometrial Polyp Fibroblasts.

Endometrial polyps (EPs) are benign overgrowths of the endometrium, with the potential to cause severe complications, ranging from discomfort to inflammation and infertility. Dysfunction of endometrial fibroblasts may be a critical component leading to the development of polyps. Although surgical intervention is the common remedy for severe cases, it comes with drawbacks, including infection, bleeding, and risk of damage to the cervix and adjacent tissues. Adipose-derived mesenchymal stromal cells (ASCs) are at the focus of modern medicine, as key modulators of tissue homeostasis, inflammation, and tissue repair, rendering them prime candidate agents for tissue regeneration and cell-based therapies. In this study, EPs were isolated from patients admitted to the OB/GYN department at the Galilee Medical Center and extracted fibroblasts (endometrial polyp fibroblasts, EPFs) were isolated and characterized. ASCs were isolated from healthy patients. The effect of EPF- and ASC-conditioned media (CM) on polyp-derived fibroblasts was evaluated, in both 2D and 3D assays, as well as on the expression of matrix-related gene expression. Herein, EPFs exposed to ASC-CM exhibited reduced migration, invasion, contraction of hydrogels, and extracellular matrix deposition, compared with those exposed to EPF-CM. Altogether, this study suggests that ASCs may have a modulating effect on fibroblasts involved in forming EPs and may serve as the basis for conservative treatment strategies aimed at treating severe cases of EPs.

COVID-19 knowledge and adherence of dental practitioners to health authority safety guidelines during a pandemic.

OBJECTIVES: This study aimed to assess the degree of dental practitioner adherence to recommendations made during the COVID-19 pandemic. METHOD AND MATERIALS: An online questionnaire was distributed via social media among dental practitioners in Israel who worked during the COVID-19 outbreak. RESULTS: In total, 144 dental practitioners completed the survey; it was found that dental practitioner adherence to all the official PPE use recommendations was 69.8%, whereas 36.8% of dental practitioners reported the use of N95 when needed. Knowledge of self-protection against COVID-19 was rated as "very good" by 37.5% of responders. However, only 25.7% felt "highly protected" by personal protective equipment. Interestingly, many dental practitioners (46.8%) reported adherence to extra protection in addition to the required PPE communicated by the Ministry of Health guidelines. CONCLUSION: Stricter regimens should be applied for dealing with the current challenging pandemic, especially in clinical work with a higher risk for viral transmission. Specific strategies should be followed to ensure good practice to improve dental practitioners' and patients' safety.

A Multichamber Gas System to Examine the Effect of Multiple Oxygen Conditions on Cell Culture.

The classic bone tissue engineering model for bone regeneration combines three elements: scaffolds, biomaterials, and mesenchymal stem cells (MSCs). Incorporation of MSCs and growth factors into a scaffold implanted into the area of bone injury is a proven strategy to achieve successful bone regeneration as demonstrated in the literature. However, a major limitation of using bone grafts or scaffolds is oxygen (O2) deprivation in the inner sections of the construct, due to lack of adequate vascularization. To address this limitation, we proposed two treatment strategies for MSC-seeded constructs or adipose tissue scaffolds before implantation: (1) O2 enrichment and (2) acclimation to hypoxia. Based on previous studies, the significance of the different O2 concentrations on MSC biological characteristics remains controversial. Therefore, the optimal O2 condition for engineered bone tissues should be determined. Thus, we designed an innovative multichamber gas system aimed to simultaneously assess the effects of different O2 levels on cell culture. This system was assembled using three isolated chambers integrated into a single incubator. To explore the efficacy of our method, we investigated the effect of hyperoxia, normoxia, and hypoxia, (50-60%, 21%, and 5-7.5% O2, respectively) on the biological characteristics of human adipose-derived MSCs: immunophenotyping, adhesion, proliferation, and osteogenic, and angiogenic differentiation. Our findings demonstrated that hypoxic adipose-derived mesenchymal stem cells (ASCs) conditions exhibited significantly lower levels of CD34 (p = 0.014), with significantly higher osteogenic and angiogenic differentiation capacities (p = 0.023 and p = 0.0042, respectively) than normoxia. Conversely, hyperoxia-cultured ASCs demonstrated significantly higher levels of CD73 and CD90 expression than both normoxic ASCs (p = 0.006 and p = 0.025, respectively) and hypoxic ASCs (p = 0.003 and p = 0.003, respectively). In addition, hyperoxic ASCs showed significantly reduced proliferation capacity by day 11 (p = 0.032) and significantly enhanced migration rates after 48 h (p = 0.044). The newly developed controllable multichamber gas system was cost-effective and easy to use. Different assays can be performed concurrently while preserving all other conditions identical, and the use of other ranges of O2 concentrations is feasible and also necessary to determine the ideal O2 concentration. Furthermore, the multichamber gas system has the potential for wide application, including other cell cultures, grafts, or scaffolds for in vitro and in vivo experimentation. This study was approved by the Galilee Medical Center Helsinki Committee (No. 0009-19-NHR). Impact statement The introduced multichamber gas system provides a custom-made setup for simultaneous control of three oxygen (O2) levels in a single incubator. The use of our innovative multichamber gas system is essential to determine the ideal O2 levels for engineered tissues by examining multiple O2 concentrations on cells in vitro. The determined ideal O2 concentration will then be used through this system to investigate the engrafted cell survival ex vivo, to ensure successful integration of the engineered tissues and tissue regeneration in vivo. Use of this method may promote a therapeutic tool for a major limitation in tissue engineering due to the problematic O2 insufficiency in tissue scaffolds.

The power of three-dimensional printing technology in functional restoration of rare maxillomandibular deformity due to genetic disorder: a case report.

BACKGROUND: Thalassemia is an inherited autosomal recessive blood disorder causing abnormal formation of hemoglobin, known as a syndrome of anemia with microcytic erythrocytes. It is the most common genetic disorder worldwide, with a high prevalence among individuals of Mediterranean descent. The state of homozygosity of the beta-globin mutated gene is known as beta-thalassemia major, and these patients require regular blood transfusions and iron chelation therapy for survival. The rapid loss of red blood cells among affected individuals activates compensatory mechanisms of excessive medullary and extramedullary hematopoiesis, leading to severe skeletal bone deformity. CASE PRESENTATION: We present the case of a 39-year-old Bedouin male, diagnosed with beta-thalassemia major at infancy, with diagnosed homozygosity for the intervening sequence 2-1 (guanine > adenine) mutation. Since early infancy, he started receiving blood transfusions with a gradual increase in treatment frequency through adulthood due to the severe clinical progression of the disease. He was referred to the oral and maxillofacial surgery department at Galilee Medical Center to evaluate his facial deformity in the upper jaw and treat his severe periodontal disease. The patient presented maxillary overgrowth, and severe dental deformity resulted in progressive disfigurement and difficulty chewing, swallowing, and speaking. To address the challenge of surgical treatment, we utilized the advantage of three-dimensional planning and printing technology to simulate the optimal result. Resection of maxillary bone overgrowth and insertion of custom-made subperiosteal implants were followed by rehabilitation of both jaws to the patients' satisfaction at 3-year follow-up. CONCLUSIONS: The ongoing implementation of state-of-the-art technologies such as virtual reality and three-dimensional printing has become a prominent component in surgical toolsets. Comprehensive case simulation and accurate planning before surgery will improve surgical results and patient satisfaction. This approach is highly advocated when approaching a case of rare maxillofacial deformity associated with either genetic or orphan diseases.