A pilot study comparing the disinfecting effects of commercialized stable ClO2 solution (free of activation) with conventional H2O2 on dental unit waterlines in the dental practice setting.

Disinfection of dental unit waterlines (DUWLs) plays a key role in control and prevention of nosocomial infection in a dental clinic. The most conventional disinfectant is hydrogen peroxide (H2O2), while chlorine dioxide (ClO2) has been considered however was limited by the "activation" procedures. With the availability of commercialized stable ClO2 solution (free of activation), direct application of ClO2 in the dental practice became possible. This study was designed to compare the disinfecting effects of stable 5 ppm of ClO2 solution with conventional 0.24% of H2O2 on DUWLs in dental practice. Studies of colony-forming units (CFUs), confocal laser scanning microscopy (CLSM) and scanning electron microscope (SEM) were employed for evaluation. In CFUs studies, we found that the efficiency of ClO2 was no less than those of H2O2. In the morphological studies, the stronger disinfecting effects of ClO2 was verified by both CLSM and SEM studies for removal and prevention of biofilm. Importantly, ClO2 solution achieved a better disinfecting efficiency not only at the surface of bacterial biofilm, but also, it has penetrating effects, presented disinfecting effects from the surface to the bottom of the biofilm. This pilot study provided evidence regarding the efficiency of stable ClO2 solution on disinfection of DUWLs in the dental practice setting. Application of stable ClO2 solution in dental practice is therefore become possible.

A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns. Shared decision-making (SDM) is an approach that involves patients and healthcare providers in making decisions about treatment options. This study aims to assess the effectiveness of a novel SDM tool for anticoagulation management in AF. METHODS: The study will be a prospective, cluster randomized controlled trial involving 440 patients with AF in 8 community health service centers (clusters) in Shanghai, China. The SDM group will receive anticoagulation management through the novel SDM tool, while the control group will receive standard care. The follow-up period will be at least 2 years. The primary outcome will be any bleeding event, while secondary outcomes include the accordance of stroke prophylaxis for AF according to the current guidelines, time in therapeutic range (TTR), the occurrences of major bleeding and thrombosis events, and patient knowledge, adherence, and satisfaction. DISCUSSION: This study will provide evidence of the effectiveness of shared decision-making in improving the appropriateness of OAC use in Chinese AF patients. The findings may inform the development of guidelines and policies for the management of AF and anticoagulation therapy in China and other countries. TRIAL REGISTRATION: ChiCTR ChiCTR2200062123. Registered on 23 July 2022.

Hypersensitive C-reactive protein as a potential indicator for predicting left ventricular hypertrophy in elderly community-dwelling patients with hypertension.

BACKGROUND: The aim of this study was to investigate the relationship between Hypersensitive C-reactive protein (hs-CRP) and left ventricular hypertrophy (LVH) in elderly community-dwelling patients with hypertension. METHODS: A cross-sectional study was conducted, involving the recruitment of 365 elderly hypertensive residents ≥ 65 years of age from five communities. The participants were divided into two groups: an LVH group (n = 134) and a non-LVH group (n = 231), based on the left ventricular mass index (LVMI) determined by echocardiography. Spearman correlation analysis was used to assess the relationship between hs-CRP and LVH. Univariate and Multivariate analysis was performed to detect variables associated with LVH. The diagnostic value of hs-CRP for LVH was expressed as the area under the receiver operating characteristic (ROC) curve. RESULTS: The incidence of LVH in elderly hypertension patients in the community was 36.7%. The hs-CRP levels were significantly higher in subjects with LVH compared to those without LVH (1.9 [0.8, 2.9] vs. 0.7 [0.4, 1.4], P = 0.002). Spearman correlation analysis demonstrated a positive correlation between hs-CRP and LVMI (r = 0.246, P < 0.001), as well as with IVST (r = 0.225, P < 0.001) and LVPWT (r = 0.172, P = 0.001). Among elderly hypertensive residents in the community, the cut-off value of hs-CRP for diagnosing LVH was 1.25 mg/L (sensitivity: 57.5%; specificity: 78.4%), and the area under the ROC curve for hs-CRP to predict LVH was 0.710 (95%CI: 0.654-0.766; P < 0.001). In the final model, hs-CRP ≥ 1.25 mg/L (OR = 3.569; 95%CI, 2.153-5.916; P<0.001) emerged as an independent risk factor for LVH. This association remained significant even after adjusting for various confounding factors (adjusted OR = 3.964; 95%CI, 2.323-6.765; P < 0.001). CONCLUSIONS: This community-based cohort of elderly hypertensive individuals demonstrates a strong association between hs-CRP levels and the presence of LVH. The hs-CRP ≥ 1.25 mg/L may serve as an independent predictor for LVH in hypertensive subjects and exhibit good diagnostic efficacy for LVH.

With two episodes of right retromandibular angle subcutaneous emphysema during right upper molar crown preparation: A case report.

BACKGROUND: Subcutaneous emphysema is a well-known complication of oral surgery, especially during mandibular wisdom tooth extraction. However, subcutaneous emphysema secondary to dental procedures such as crown preparation is rare. The main symptom of emphysema is swelling and crepitus on palpation. Uncontrolled emphysema may spread along the fascial planes and cause deep space infections or a pneumomediastinum. CASE SUMMARY: In this paper, we report a 34-year-old female who underwent upper molar tooth preparation for crowns and subsequently developed extensive subcutaneous emphysema on the retromandibular angle on two different occasions. The treatment plan for this patient involved close observation of the airway, and administration of dexamethasone and antibiotics via intravenous drip or orally. Ice bag compression was quickly applied and medication was prescribed to alleviate discomfort and promote healing. Although the main reason is unclear, the presence of a fissure in the molar is an important clue which may contribute to the development of subcutaneous emphysema during crown preparation. It is imperative for dental professionals to recognize such pre-disposing factors in order to minimize the risk of complications. CONCLUSION: This case highlights the need for prompt diagnosis and management of subcutaneous emphysema because of the risk of much more serious complications. Awareness of relatively "benign" subcutaneous emphysema during any dental procedure is critical not only for inexperienced dentists, but also for those who work in rural and remote settings as members of surgical teams. In this study, we review the clinical presentation, mechanism, and differential diagnosis of subcutaneous emphysema.

Galactosylation of xyloglucan is essential for the stabilization of the actin cytoskeleton and endomembrane system through the proper assembly of cell walls.

Xyloglucan, a major hemicellulose, interacts with cellulose and pectin to assemble primary cell walls in plants. Loss of the xyloglucan galactosyltransferase MURUS3 (MUR3) leads to the deficiency of galactosylated xyloglucan and perturbs plant growth. However, it is unclear whether defects in xyloglucan galactosylation influence the synthesis of other wall polysaccharides, cell wall integrity, cytoskeleton behaviour, and endomembrane homeostasis. Here, we found that in mur3-7 etiolated seedlings cellulose was reduced, CELLULOSE SYNTHASE (CESA) genes were down-regulated, the density and mobility of cellulose synthase complexes (CSCs) were decreased, and cellulose microfibrils become discontinuous. Pectin, rhamnogalacturonan II (RGII), and boron contents were reduced in mur3-7 plants, and B-RGII cross-linking was abnormal. Wall porosity and thickness were significantly increased in mur3-7 seedlings. Endomembrane aggregation was also apparent in the mur3-7 mutant. Furthermore, mutant seedlings and their actin filaments were more sensitive to Latrunculin A (LatA) treatment. However, all defects in mur3-7 mutants were substantially restored by exogenous boric acid application. Our study reveals the importance of MUR3-mediated xyloglucan galactosylation for cell wall structural assembly and homeostasis, which is required for the stabilization of the actin cytoskeleton and the endomembrane system.

Genomics assisted functional characterization of Bacillus velezensis E as a biocontrol and growth promoting bacterium for lily.

Lily (Lilium spp.) is one of the most famous ornamental flowers globally. Lily basal rot (also known as root rot or stem rot) and lily gray mold have seriously affected the yield and quality of lily, resulting in huge economic losses. In this study, bacterial strain E was isolated from a continuous lily cropping field. Strain E displayed high control efficiency against lily basal rot and gray mold, caused by Fusarium oxysporum and Botrytis cinerea respectively, and promoted the occurrence of scale bulblets. Strain E displayed strong inhibitory effects against several other plant pathogenic fungi and two pathogenic bacteria in dual culture and disc diffusion assays, respectively. Whole genome sequencing revealed that strain E contained a 3,929,247 bp circular chromosome with 4,056 protein-coding genes and an average GC content of 47.32%. Strain E was classified as Bacillus velezensis using genome-based phylogenetic analysis and average nucleotide identity and digital DNA-DNA hybridization analyses. A total of 86 genes and 13 secondary metabolite biosynthetic gene clusters involved in antifungal and antibacterial activity, plant growth promotion, colonization, nutrient uptake and availability were identified in the genome of strain E. In vitro biochemical assays showed that strain E produced siderophores, proteases, cellulases, biofilms, antifungal and antibacterial substances, and exhibited organic phosphate solubilization and swimming and swarming motility, which were consistent with the results of the genome analysis. Colonization analysis showed that strain E could colonize the root of the lily, but not the leaf. Overall, these results demonstrate that B. velezensis strain E can be used as a potential biofertilizer and biocontrol agent for lily production.

Exposure to BDE-47 and BDE-209 impaired antioxidative defense mechanisms in Brachionus plicatilis.

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs) that pose serious challenges to aquatic animals and environments. Compared with BDE-47 which was one of the most toxic congeners known to date, BDE-209 is less toxic with higher abundance in biotic and abiotic samples. In this study, we have explored the effects of BDE-47 and BDE-209 at different concentrations on the radical oxygen species (ROS) levels and the antioxidant defense system of Brachionus plicatilis. Antioxidant indexes were measured, including total protein content (TSP), the activities of antioxidant enzymes, lipid peroxidation and DNA damage. The results indicated that while low concentrations of PBDEs could activate the antioxidant defense mechanisms, prolonged exposure to higher concentrations of PBDEs could impair the antioxidative capacity of B.plicatilis (P < 0.05). The overwhelming of the B.plicatilis antioxidant defense mechanism led to an accumulation of free radicals, resulting in the overactivation of lipid peroxidation and the increased frequency of DNA damage (P < 0.05). By studying the toxicity of PBDEs and the detoxification mechanism of B.plicatilis, our research has revealed useful indexes for detecting and monitoring the level of BDE-47 and BDE-209 in the future. Altogether, this study holds immense value in the field of ecotoxicology and environmental safety and will aid in the proper management of PBDEs pollution.

Spatiotemporal variations of air pollution and population exposure in Shandong Province, eastern China, 2014-2018.

To clarify the characteristics and interannual variation of air pollution since the implementation of China's clean air actions, hourly in situ measurements of six gaseous and particulate criteria pollutants at 100 sites in Shandong Province were studied during 2014-2018. General decreasing trends in the concentrations of PM2.5, PM10, NO2, SO2, and CO were observed, while O3 increased continuously. In 2018, the annual average PM2.5, PM10, NO2, SO2, and CO concentration in Shandong was 50, 100, 35, 16 µg m-3, and 1.5 mg m-3, representing decreases of 39%, 30%, 24%, 73%, and 35% from 2014, respectively. These decreases occurred throughout the province. Seven "2 + 26" cities (in Beijing-Tianjin-Hebei and its surrounds) in western Shandong had higher average concentrations and greater reductions than other areas. In contrast, O3 concentration rose, with occurrences of the 90th percentile of all daily maximum 8-h averages increasing by 12% from 159 to 181 µg m-3, during 2014-2018. From May to September, O3 pollution dominated as the sole primary pollutant on non-attainment days, and PM2.5 contributed to more than 90% of polluted days in wintertime months. Population exposures were investigated based on high-resolution monitoring data and population distribution, and high exposure to pollution was displayed. The population-weighted exposure to PM2.5 in Shandong was 50 µg m-3, a decrease of 33%. Eighty-nine percentage of the provincial population was exposed to PM2.5 > 35 µg m-3, while for 99.2% of population in the seven "2 + 26" cities, PM2.5 exposure exceeded 50 µg m-3.

The Epithelial-Mesenchymal Transition Influences the Resistance of Oral Squamous Cell Carcinoma to Monoclonal Antibodies via Its Effect on Energy Homeostasis and the Tumor Microenvironment.

Oral squamous cell carcinoma (OSCC) is a major type of cancer that accounts for over 90% of all oral cancer cases. Recently developed evidence-based therapeutic regimens for OSCC based on monoclonal antibodies (mAbs), such as cetuximab, pembrolizumab, and nivolumab, have attracted considerable attention worldwide due to their high specificity, low toxicity, and low rates of intolerance. However, the efficacy of those three mAbs remains poor because of the low rate of responders and acquired resistance within a short period of time. The epithelial-mesenchymal transition (EMT) process is fundamental for OSCC growth and metastasis and is also responsible for the poor response to mAbs. During EMT, cancer cells consume abundant energy substrates and create an immunosuppressive tumor microenvironment to support their growth and evade T cells. In this review, we provide an overview of the complex roles of major substrates and signaling pathways involved in the development of therapeutic resistance in OSCC. In addition, we summarize potential therapeutic strategies that may help overcome this resistance. This review aims to help oral oncologists and researchers aiming to manage OSCC and establish new treatment modalities.

Overview of Evidence-Based Chemotherapy for Oral Cancer: Focus on Drug Resistance Related to the Epithelial-Mesenchymal Transition.

The increasing incidence of resistance to chemotherapeutic agents has become a major issue in the treatment of oral cancer (OC). Epithelial-mesenchymal transition (EMT) has attracted a great deal of attention in recent years with regard to its relation to the mechanism of chemotherapy drug resistance. EMT-activating transcription factors (EMT-ATFs), such as Snail, TWIST, and ZEB, can activate several different molecular pathways, e.g., PI3K/AKT, NF-κB, and TGF-ß. In contrast, the activated oncological signal pathways provide reciprocal feedback that affects the expression of EMT-ATFs, resulting in a peritumoral extracellular environment conducive to cancer cell survival and evasion of the immune system, leading to resistance to multiple chemotherapeutic agents. We present an overview of evidence-based chemotherapy for OC treatment based on the National Comprehensive Cancer Network (NCCN) Chemotherapy Order Templates. We focus on the molecular pathways involved in drug resistance related to the EMT and highlight the signal pathways and transcription factors that may be important for EMT-regulated drug resistance. Rapid progress in antitumor regimens, together with the application of powerful techniques such as high-throughput screening and microRNA technology, will facilitate the development of therapeutic strategies to augment chemotherapy.

Bioactive Regeneration Potential of the Newly Developed Uncalcined/Unsintered Hydroxyapatite and Poly-l-Lactide-Co-Glycolide Biomaterial in Maxillofacial Reconstructive Surgery: An In Vivo Preliminary Study.

Uncalcined/unsintered hydroxyapatite (HA) and poly-l-lactide-co-glycolide (u-HA/PLLA/PGA) are novel bioresorbable bioactive materials with bone regeneration characteristics and have been used to treat mandibular defects in a rat model. However, the bone regenerative interaction with the periosteum, the inflammatory response, and the degradation of this material have not been examined. In this study, we used a rat mandible model to compare the above features in u-HA/PLLA/PGA and uncalcined/unsintered HA and poly-l-lactic acid (u-HA/PLLA). We divided 11 male Sprague-Dawley rats into 3- and 16-week groups. In each group, we assessed the characteristics of a u-HA/PLLA/PGA sheet covering the right mandibular angle and a u-HA/PLLA sheet covering the left mandibular angle in three rats each, and one rat was used as a sham control. The remaining three rats in the 16-week group were used for a degradation assessment and received both sheets of material as in the material assessment subgroup. At 3 and 16 weeks after surgery, the rats were sacrificed, and mandible specimens were subjected to micro-computed tomography, histological analysis, and immunohistochemical staining. The results indicated that the interaction between the periosteum and u-HA/PLLA/PGA material produced significantly more new bone regeneration with a lower inflammatory response and a faster resorption rate compared to u-HA/PLLA alone. These findings may indicate that this new biomaterial has ideal potential in treating maxillofacial defects of the midface and orbital regions.

Feasibility of Application of the Newly Developed Nano-Biomaterial, ß-TCP/PDLLA, in Maxillofacial Reconstructive Surgery: A Pilot Rat Study.

This study was performed to examine the applicability of the newly developed nano-biocomposite, ß-tricalcium phosphate (ß-TCP)/u-HA/poly-d/l-lactide (PDLLA), to bone defects in the oral and maxillofacial area. This novel nano-biocomposite showed several advantages, including biocompatibility, biodegradability, and osteoconductivity. In addition, its optimal plasticity also allowed its utilization in irregular critical bone defect reconstructive surgery. Here, three different nano-biomaterials, i.e., ß-TCP/PDLLA, ß-TCP, and PDLLA, were implanted into critical bone defects in the right lateral mandible of 10-week-old Sprague-Dawley (SD) rats as bone graft substitutes. Micro-computed tomography (Micro-CT) and immunohistochemical staining for the osteogenesis biomarkers, Runx2, osteocalcin, and the leptin receptor, were performed to investigate and compare bone regeneration between the groups. Although the micro-CT results showed the highest bone mineral density (BMD) and bone volume to total volume (BV/TV) with ß-TCP, immunohistochemical analysis indicated better osteogenesis-promoting ability of ß-TCP/PDLLA, especially at an early stage of the bone healing process. These results confirmed that the novel nano-biocomposite, ß-TCP/PDLLA, which has excellent biocompatibility, bioresorbability and bioactive/osteoconductivity, has the potential to become a next-generation biomaterial for use as a bone graft substitute in maxillofacial reconstructive surgery.

Comparison of the Bone Regenerative Capacity of Three-Dimensional Uncalcined and Unsintered Hydroxyapatite/Poly-d/l-Lactide and Beta-Tricalcium Phosphate Used as Bone Graft Substitutes.

This study compared the in vivo applicability of three-dimensional uncalcined and unsintered hydroxyapatite/poly-d/l-lactide (3D-HA/PDLLA) with beta-tricalcium phosphate (ß-TCP). 3D-HA/PDLLA is a newly developed bioactive, osteoconductive, bioresorbable bone regenerative composite. We performed critical-defect surgery on the mandible body of rats; the defects were filled with one of two bone graft substitutes. After a 4-week follow-up period, the mandibular specimens were examined using hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) staining and micro-computed tomography (micro-CT). The H&E staining showed an increase in newly formed bone in both groups from week 1 to 4. The difference in the Runx2 IHC optical density (OD) scores of 3D-HA/PDLLA and ß-TCP was not statistically significant (p > 0.05); however, the osteocalcin IHC OD scores of the groups differed significantly (p < 0.05). Micro-CT demonstrated a similar trabecular thickness, trabecular spacing, and bone volume per total volume in the two groups (p > 0.05), indicating that bone formation in the two groups was nearly the same from a macro-perspective of bone regeneration. These results demonstrated that a different bone regeneration pattern and earlier osteoblast differentiation occurred in 3D-HA/PDLLA compared with ß-TCP. In conclusion, our study demonstrates that 3D-HA/PDLLA is feasible for clinical application as a new bioactive, osteoconductive/bioresorbable bone graft substitute for maxillofacial surgery.

A Narrative Review of u-HA/PLLA, a Bioactive Resorbable Reconstruction Material: Applications in Oral and Maxillofacial Surgery.

The advent of bioresorbable materials to overcome limitations and replace traditional bone-reconstruction titanium-plate systems for bone fixation, thus achieving greater efficiency and safety in medical and dental applications, has ushered in a new era in biomaterial development. Because of its bioactive osteoconductive ability and biocompatibility, the forged composite of uncalcined/unsintered hydroxyapatite and poly L-lactic acid (u-HA/PLLA) has attracted considerable interest from researchers in bone tissue engineering, as well as from clinicians, particularly for applications in maxillofacial reconstructive surgery. Thus, various in vitro studies, in vivo studies, and clinical trials have been conducted to investigate the feasibility and weaknesses of this biomaterial in oral and maxillofacial surgery. Various technical improvements have been proposed to optimize its advantages and limit its disadvantages. This narrative review presents an up-to-date, comprehensive review of u-HA/PLLA, a bioactive osteoconductive and bioresorbable bone-reconstruction and -fixation material, in the context of oral and maxillofacial surgery, notably maxillofacial trauma, orthognathic surgery, and maxillofacial reconstruction. It simultaneously introduces new trends in the development of bioresorbable materials that could used in this field. Various studies have shown the superiority of u-HA/PLLA, a third-generation bioresorbable biomaterial with high mechanical strength, biocompatibility, and bioactive osteoconductivity, compared to other bioresorbable materials. Future developments may focus on controlling its bioactivity and biodegradation rate and enhancing its mechanical strength.

Bone Regeneration Capacity of Newly Developed Uncalcined/Unsintered Hydroxyapatite and Poly-l-lactide-co-glycolide Sheet in Maxillofacial Surgery: An In Vivo Study.

Uncalcined/unsintered hydroxyapatite and poly-l-lactide-co-glycolide (u-HA/PLLA/PGA) is a new bioresorbable nanomaterial with superior characteristics compared with current bioresorbable materials, including appropriate mechanical properties, outstanding bioactive/osteoconductive features, and remarkably shorter resorption time. Nevertheless, the bone regeneration characteristics of this nanomaterial have not been evaluated in maxillofacial reconstructive surgery. In this study, we used a rat mandible model to assess the bone regeneration ability of u-HA/PLLA/PGA material, compared with uncalcined/unsintered hydroxyapatite and poly-l-lactide acid (u-HA/PLLA) material, which has demonstrated excellent bone regenerative ability. A 4-mm-diameter defect was created at the mandibular angle area in 28 Sprague Dawley male rats. The rats were divided into three groups: u-HA/PLLA/PGA (u-HA/PLLA/PGA graft + defect), u-HA/PLLA (u-HA/PLLA graft + defect), and sham control (defect alone). At 1, 3, 8, and 16 weeks after surgeries, the rats were sacrificed and assessed by micro-computed tomography, histological analysis with hematoxylin and eosin staining, and immunohistochemical analyses. The results confirmed that the accelerated bone bioactive/regenerative osteoconduction of u-HA/PLLA/PGA was comparable with that of u-HA/PLLA in the rat mandible model. Furthermore, this new regenerative nanomaterial was able to more rapidly induce bone formation in the early stage and had great potential for further clinical applications in maxillofacial reconstructive surgery.

The Role of Carcinogenesis-Related Biomarkers in the Wnt Pathway and Their Effects on Epithelial-Mesenchymal Transition (EMT) in Oral Squamous Cell Carcinoma.

As oral squamous cell carcinoma (OSCC) can develop from potentially malignant disorders (PMDs), it is critical to develop methods for early detection to improve the prognosis of patients. Epithelial-mesenchymal transition (EMT) plays an important role during tumor progression and metastasis. The Wnt signaling pathway is an intercellular pathway in animals that also plays a fundamental role in cell proliferation and regeneration, and in the function of many cell or tissue types. Specific components of master regulators such as epithelial cadherin (E-cadherin), Vimentin, adenomatous polyposis coli (APC), Snail, and neural cadherin (N-cadherin), which are known to control the EMT process, have also been implicated in the Wnt cascade. Here, we review recent findings on the Wnt signaling pathway and the expression mechanism. These regulators are known to play roles in EMT and tumor progression, especially in OSCC. Characterizing the mechanisms through which both EMT and the Wnt pathway play a role in these cellular pathways could increase our understanding of the tumor genesis process and may allow for the development of improved therapeutics for OSCC.

Bone Regeneration Potential of Uncalcined and Unsintered Hydroxyapatite/Poly l-lactide Bioactive/Osteoconductive Sheet Used for Maxillofacial Reconstructive Surgery: An In Vivo Study.

Uncalcined and unsintered hydroxyapatite/poly l-lactide (u-HA/PLLA) material has osteoconductive characteristics and is available for use as a maxillofacial osteosynthetic reconstruction device. However, its bone regeneration ability in the maxillofacial region has not been fully investigated. This study is the first to assess the bone regenerative potential of osteoconductive u-HA/PLLA material when it is used for repairing maxillofacial bone defects. A total of 21 Sprague-Dawley male rats were divided into three groups-the u-HA/PLLA, PLLA, or sham control groups. A critical size defect of 4 mm was created in the mandible of each rat. Then, the defect was covered with either a u-HA/PLLA or PLLA sheet on the buccal side. The rats in each group were sacrificed at 2, 4, or 8 weeks. The rats' mandibles were sampled for histological analysis with hematoxylin and eosin staining, histomorphometry, and immunohistochemistry with Runx2 and osteocalcin (OCN) antibody. The amount of newly formed bone in the u-HA/PLLA group was significantly higher than that of the PLLA group. The expression of Runx2 and OCN in the u-HA/PLLA group was also significantly higher. These results demonstrate that the u-HA/PLLA material has excellent bone regenerative ability and confirm its applicability as a reconstructive device in maxillofacial surgery.

Efficacy of Bacterial Cellulose as a Carrier of BMP-2 for Bone Regeneration in a Rabbit Frontal Sinus Model.

If the alveolar bone height of patients requiring dental implants in the maxillary molar region is inadequate, it is difficult to achieve satisfactory outcomes using existing bone graft materials. We previously reported the possible utility of bacterial cellulose (BC) as a new dental treatment material. BC has a high absorptive capacity, good mechanical strength, and good volume retention. BC loaded with bone morphogenetic protein-2 (BMP-2) might allow effective alveolar bone augmentation. We created critical frontal bone defect models in 12 male Japanese white rabbits and divided them into four groups: sham; BC (BC grafting only); BMP-2 (treated with BMP-2 solution only); and BC+BMP-2 (grafted with BC loaded with BMP-2). Newly formed bone volume was calculated via hematoxylin-eosin staining evaluation. The proliferating cell nuclear antigen and osteocalcin levels were determined by the immunohistochemical staining analysis. All measured indices of the BC+BMP-2 group were significantly superior to those of the other groups (all p < 0.05). BC maintained the graft space and released BMP-2 in a sustained manner, promoting optimal bone formation. The BC+BMP-2 combination enhanced bone regeneration and shows promise as a useful means of clinical pre-dental implant bone augmentation in the maxillary sinus.

Application of a Bioactive/Bioresorbable Three-Dimensional Porous Uncalcined and Unsintered Hydroxyapatite/Poly-D/L-lactide Composite with Human Mesenchymal Stem Cells for Bone Regeneration in Maxillofacial Surgery: A Pilot Animal Study.

A novel three-dimensional (3D) porous uncalcined and unsintered hydroxyapatite/poly-d/l-lactide (3D-HA/PDLLA) composite demonstrated superior biocompatibility, osteoconductivity, biodegradability, and plasticity, thereby enabling complex maxillofacial defect reconstruction. Mesenchymal stem cells (MSCs)-a type of adult stem cell-have a multipotent ability to differentiate into chondrocytes, adipocytes, and osteocytes. In a previous study, we found that CD90 (Thy-1, cluster of differentiation 90) and CD271 (low-affinity nerve growth factor receptor) double-positive cell populations from human bone marrow had high proliferative ability and differentiation capacity in vitro. In the present study, we investigated the utility of bone regeneration therapy using implantation of 3D-HA/PDLLA loaded with human MSCs (hMSCs) in mandibular critical defect rats. Microcomputed tomography (Micro-CT) indicated that implantation of a 3D-HA/PDLLA-hMSC composite scaffold improved the ability to achieve bone regeneration compared with 3D-HA/PDLLA alone. Compared to the sufficient blood supply in the mandibular defection superior side, a lack of blood supply in the inferior side caused delayed healing. The use of Villanueva Goldner staining (VG staining) revealed the gradual progression of the nucleated cells and new bone from the scaffold border into the central pores, indicating that 3D-HA/PDLLA loaded with hMSCs had good osteoconductivity and an adequate blood supply. These results further demonstrated that the 3D-HA/PDLLA-hMSC composite scaffold was an effective bone regenerative method for maxillofacial boney defect reconstruction.

Feasibility of a Three-Dimensional Porous Uncalcined and Unsintered Hydroxyapatite/poly-d/l-lactide Composite as a Regenerative Biomaterial in Maxillofacial Surgery.

This study evaluated the feasibility of a novel three-dimensional (3D) porous composite of uncalcined and unsintered hydroxyapatite (u-HA) and poly-d/l-lactide (PDLLA) (3D-HA/PDLLA) for the bony regenerative biomaterial in maxillofacial surgery, focusing on cellular activities and osteoconductivity properties in vitro and in vivo. In the in vitro study, we assessed the proliferation and ingrowth of preosteoblastic cells (MC3T3-E1 cells) in 3D-HA/PDLLA biomaterials using 3D cell culture, and the results indicated enhanced bioactive proliferation. After osteogenic differentiation of those cells on 3D-HA/PDLLA, the osteogenesis marker genes runt-related transcription factor-2 (Runx2), and Sp7 (Osterix) were upregulated. For the in vivo study, we evaluated the utility of 3D-HA/PDLLA biomaterials compared to the conventional bone substitute of beta-tricalcium phosphate (ß-TCP) in rats with critical mandibular bony defects. The implantation of 3D-HA/PDLLA biomaterials resulted in enhanced bone regeneration, by inducing high osteoconductivity as well as higher ß-TCP levels. Our study thus showed that the novel composite, 3D-HA/PDLLA, is an excellent bioactive/bioresorbable biomaterial for use as a cellular scaffold, both in vitro and in vivo, and has utility in bone regenerative therapy, such as for patients with irregular maxillofacial bone defects.