The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis-apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

Elucidating Cathodic Corrosion Mechanisms with Operando Electrochemical Transmission Electron Microscopy.

Cathodic corrosion represents an enigmatic electrochemical process in which metallic electrodes corrode under sufficiently reducing potentials. Although discovered by Fritz Haber in the 19th century, only recently has progress been made in beginning to understand the atomistic mechanisms of corroding bulk electrodes. The creation of nanoparticles as the end-product of the corrosion process suggests an additional length scale of complexity. Here, we studied the dynamic evolution of morphology, composition, and crystallographic structural information of nanocrystal corrosion products by analytical and four-dimensional electrochemical liquid-cell scanning transmission electron microscopy (EC-STEM). Our operando/in situ electron microscopy revealed, in real-time, at the nanometer scale, that cathodic corrosion yields significantly higher levels of structural degradation for heterogeneous nanocrystals than bulk electrodes. In particular, the cathodic corrosion of Au nanocubes on bulk Pt electrodes led to the unexpected formation of thermodynamically immiscible Au-Pt alloy nanoparticles. The highly kinetically driven corrosion process is evidenced by the successive anisotropic transition from stable Pt(111) bulk single-crystal surfaces evolving to energetically less-stable (100) and (110) steps. The motifs identified in this microscopy study of cathodic corrosion of nanocrystals are likely to underlie the structural evolution of nanoscale electrocatalysts during many electrochemical reactions under highly reducing potentials, such as CO2 and N2 reduction.

A Modified Minimally Invasive Approach for the Treatment of Mandibular Condylar Fracture.

ABSTRACT: In this study, we introduced a small "V" shaped incision around the ear lobe modified from fact-lift approach to treat the mandibular condylar neck and subcondylar fractures to further minimize and hide the postsurgical scars. A total of 15 cases with mandibular condylar fractures from low levels of condylar neck to high levels of subcondylar region were treated by this approach. An incision was designed from the posterior rim of the tragus down to the anterior skin wrinkle to the ear lobe, surrounding it, continually up and backward for a little distance, forming a "V"-like shape. After cutting and elevation of the skin flap, the remaining steps were the same as those in trans-parotid mini-invasive approaches. The surgical scars introduced in this study were more hidden than those in other mini-invasive approaches and all patients were satisfied with their aesthetic appearances. We suggested that the modified "V" shaped mini-invasive approach has an advantage in achieving aesthetic results and could be an alternative incision in treating some types of mandibular condylar and subcondylar fractures.

Cricoid-mental distance-based versus weight-based criteria for size selection of classic laryngeal mask airway in adults: a randomized controlled study.

The optimal size selection of laryngeal mask airway (LMA) based on body weight is not always applicable. This study was prospectively conducted to evaluate the efficacy of cricoid-mental distance-based method versus weight-based method in optimal size selection of LMA in adults. Seventy-four patients (aged from 18 to 65) undergoing ophthalmic surgery were randomly assigned into cricoid-mental (CM) distance-based group or weight-based group to select appropriate size of LMA. The primary outcome was oropharyngeal leak pressure (OLP). Secondary outcomes included overall insertion success rate, number of insertion attempts, time to successful insertion, ease of insertion, score of fiber-optic view, peak inspiratory pressure during mechanical ventilation and postoperative pharyngolaryngeal morbidity. The OLP was significantly higher in CM distance-based group than that in weight-based group (19.38 ± 3.52 vs. 17.50 ± 3.18, P = 0.022). The successful placement at the first attempt in CM distance-based group was dramatically increased as compared with weight-based group (89.2% vs. 62.2%, P = 0.005). The overall success rate of LMA insertion in CM distance-based group was slightly increased in comparison with the weight-based group (100% vs. 91.9%, P = 0.240). There were no significant differences in score of fiber-optic view and postoperative pharyngolaryngeal morbidity between both groups (all P > 0.05). CM distance-based criteria is an alternative choice for optimizing size selection of classic LMA in adults.

Garlic-Derived Exosome-like Nanovesicles-Based Wound Dressing for Staphylococcus aureus Infection Visualization and Treatment.

Garlic-derived exosome-like nanovesicles (GELNs) could function in interspecies communication and may serve as natural therapeutics to regulate the inflammatory response or as nanocarriers to efficiently deliver specific drugs. Staphylococcus aureus (S. aureus) is able to hide within host cells to evade immune clearance and antibiotics, leading to life-threatening infections. On-site detection and efficient treatment of intracellular S. aureus infection in wounds remain challenging. Herein, we report a thermosensitive, injectable, visible GELNs-based wound dressing, Van@GELNs/F127 hydrogel (gel Van@GELNs), which is H2O2-responsive and can slowly release vancomycin into host cells forS. aureus infection visualization and treatment in wounds. GELNs show inherent antibacterial activity, which is significantly enhanced after loading vancomycin. Both GELNs and Van@GELNs have the ability to be internalized by cells, so Van@GELNs are more effective than free vancomycin in killing S. aureus in RAW 264.7 macrophages. When applied to an S. aureus-infected wound on a mouse, the colorless HRP&ABTS/Van@GELNs/F127 solution immediately changes to a green hydrogel and shows better therapeutic effect than vancomycin. Thus, direct visualization by the naked eye and effective treatment of S. aureus infection in wounds are achieved by gel Van@GELNs. We anticipate gel Van@GELNs be applied for the theranostics of S. aureus infection diseases in the clinic in the near future.

Hyaluronic acid/PEO electrospun tube reduces tendon adhesion to levels comparable to native tendons - An in vitro and in vivo study.

A major problem after tendon injury is adhesion formation to the surrounding tissue leading to a limited range of motion. A viable strategy to reduce adhesion extent is the use of physical barriers that limit the contact between the tendon and the adjacent tissue. The purpose of this study was to fabricate an electrospun bilayered tube of hyaluronic acid/polyethylene oxide (HA/PEO) and biodegradable DegraPol® (DP) to improve the anti-adhesive effect of the implant in a rabbit Achilles tendon full laceration model compared to a pure DP tube. Additionally, the attachment of rabbit tenocytes on pure DP and HA/PEO containing scaffolds was tested and Scanning Electron Microscopy, Fourier-transform Infrared Spectroscopy, Differential Scanning Calorimetry, Water Contact Angle measurements, and testing of mechanical properties were used to characterize the scaffolds. In vivo assessment after three weeks showed that the implant containing a second HA/PEO layer significantly reduced adhesion extent reaching levels comparable to native tendons, compared with a pure DP implant that reduced adhesion formation only by 20 %. Tenocytes were able to attach to and migrate into every scaffold, but cell number was reduced over two weeks. Implants containing HA/PEO showed better mechanical properties than pure DP tubes and with the ability to entirely reduce adhesion extent makes this implant a promising candidate for clinical application in tendon repair.

Sunflower pollen-derived microcapsules adsorb light and bacteria for enhanced antimicrobial photothermal therapy.

Bacterial infection is one of the most serious clinical complications, with life-threatening outcomes. Nature-inspired biomaterials offer appealing microscale and nanoscale architectures that are often hard to fabricate by traditional technologies. Inspired by the light-harvesting nature, we engineered sulfuric acid-treated sunflower sporopollenin exine-derived microcapsules (HSECs) to capture light and bacteria for antimicrobial photothermal therapy. Sulfuric acid-treated HSECs show a greatly enhanced photothermal performance and a strong bacteria-capturing ability against Gram-positive bacteria. This is attributed to the hierarchical micro/nanostructure and surface chemistry alteration of HSECs. To test the potential for clinical application, an in situ bacteria-capturing, near-infrared (NIR) light-triggered hydrogel made of HSECs and curdlan is applied in photothermal therapy for infected skin wounds. HSECs and curdlan suspension that spread on bacteria-infected skin wounds of mice first capture the local bacteria and then form hydrogels on the wound upon NIR light stimulation. The combination shows a superior antibacterial efficiency of 98.4% compared to NIR therapy alone and achieved a wound healing ratio of 89.4%. The current study suggests that the bacteria-capturing ability and photothermal properties make HSECs an excellent platform for the phototherapy of bacteria-infected diseases. Future work that can fully take advantage of the hierarchical micro/nanostructure of HSECs for multiple biomedical applications is highly promising and desirable.

Multifunctional Droplets Formed by Interfacially Self-Assembled Fluorinated Magnetic Nanoparticles for Biocompatible Single Cell Culture and Magnet-Driven Manipulation.

The ability to encapsulate and manipulate droplets with a picoliter volume of samples and reagents shows great potential for practical applications in chemistry, biology, and materials science. Magnetic control is a promising approach for droplet manipulation due to its ability for wireless control and its ease of implementation. However, it is challenged by the poor biocompatibility of magnetic materials in aqueous droplets. Moreover, current droplet technology is problematic because of the molecule leakage between droplets. In the paper, we propose multifunctional droplets with the surface coated by a layer of fluorinated magnetic nanoparticles for magnetically actuated droplet manipulation. Multifunctional droplets show excellent biocompatibility for cell culture, nonleakage of molecules, and high response to a magnetic field. We developed a strategy of coating the F-MNP@SiO2 on the outer surface of droplets instead of adding magnetic material into droplets to enable droplets with a highly magnetic response. The encapsulated bacteria and cells in droplets did not need to directly contact with the magnetic materials at the outer surface, showing high biocompatibility with living cells. These droplets can be precisely manipulated based on magnet distance, the time duration of the magnetic field, the droplet size, and the MNP composition, which well match with theoretical analysis. The precise magnetically actuated droplet manipulation shows great potential for accurate and sensitive droplet-based bioassays like single cell analysis.

Glycolytic reprogramming controls periodontitis-associated macrophage pyroptosis via AMPK/SIRT1/NF-κB signaling pathway.

Glycolysis has been demonstrated as a crucial metabolic process in bacteria infected diseases via modulating the activity of pyroptosis. Macrophages are the most abundant immune cells that infiltrated in the infected periodontal tissues, which significantly influence the outcome of periodontitis (PD). However, the effect of glycolysis in regulating macrophage pyroptosis during PD development remains unknown. This study aimed to explore the role of glycolysis in PD-associated macrophage pyroptosis and periodontal degeneration. Clinical specimens were used to determine the emergence of macrophage pyroptosis and glycolysis in periodontal tissues by immunohistochemical analysis and western blot. For an in-depth understanding of the regulatory effect of glycolysis in the progression of macrophage pyroptosis associated periodontitis, both in vivo PD model and in vitro PD model were treated with 2-DG (2-Deoxy-d-glucose), a glycolysis inhibitor. The data showed that the blockade of glycolysis could significantly suppress the lipopolysaccharide (LPS) induced macrophage pyroptosis, resulting in an attenuation of the inflammatory response and bone resorption in periodontal lesions. Furthermore, we revealed that the regulatory effect of glycolysis on macrophage pyroptosis can be mediated via AMPK/SIRT1/NF-κB signaling pathway. Our study unveiled that suppressed glycolysis restrains the activity of PD-associated macrophage pyroptosis, osteoclastogenesis, and subsequent periodontal tissue destruction. These findings extend our knowledge of glycolysis in regulating PD-associated macrophage pyroptosis and provide a potential novel target for PD therapy.

Application of Plastic Sheet Barrier and Video Intubating Stylet to Protect Tracheal Intubators During Coronavirus Disease 2019 Pandemic: A Taiwan Experience.

Since its outbreak in China, the Coronavirus disease 2019 (COVID-19) pandemic has caused worldwide disaster. Globally, there have been 71,581,532 confirmed cases of COVID-19, including 1,618,374 deaths, reported to World Health Organization (data retrieved on December 16, 2020). Currently, no treatment modalities for COVID-19 (e.g., vaccines or antiviral drugs) with confirmed efficacy and safety are available. Although the possibilities and relevant challenges of some alternatives (e.g., use of stem cells as immunomodulators) have been proposed, the personal protective equipment is still the only way to protect and lower infection rates of COVID-19 among healthcare workers and airway managers (intubators). In this article, we described the combined use of a plastic sheet as a barrier with the intubating stylet for tracheal intubation in patients needing mechanical ventilation. Although conventional or video-assisted laryngoscopy is more popular and familiar to other groups around the world, we believe that the video-assisted intubating stylet technique is much easier to learn and master. Advantages of the video stylet include the creation of greater working distance between intubator and patient, less airway stimulation, and less pharyngeal space needed for endotracheal tube advancement. All the above features make this technique reliable and superior to other devices, especially when a difficult airway is encountered in COVID scenario. Meanwhile, we proposed the use of a flexible and transparent plastic sheet to serve as a barrier against aerosol and droplet spread during airway management. We demonstrated that the use of a plastic sheet would not interfere or hinder the intubator's maneuvers during endotracheal intubation. Moreover, we demonstrated that the plastic sheet was effective in preventing the spread of mist and water spray in simulation models with a mannequin. In our experience, we found that this technique most effectively protected the intubator and other operating room personnel from infection during the COVID-19 pandemic.

Development and Validation of a Prognostic Nomogram for Postoperative Recurrence-Free Survival of Ameloblastoma.

PURPOSE: Ameloblastoma is a benign odontogenic neoplasm with a high local recurrence rate if the operation is not thorough. However, a useful clinical tool for the quantitative assessment of the prognosis and risk of postoperative recurrence of ameloblastoma has not yet been constructed. This study aims to develop a prognostic nomogram model for ameloblastoma of the jaw to assist surgeons in surgical decision-making. PATIENTS AND METHODS: Patients who underwent initial surgery for ameloblastoma in our department from October 2004 to March 2020 were enrolled and randomly divided into training and validation sets. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify the independent prognostic factors, from which a nomogram for predicting 3-, 5- and 10-year recurrence-free survival (RFS) of ameloblastoma was constructed using the training set and internally validated using the validation set. The model performance was assessed by Harrell's concordance index (C-index) and calibration curves. RESULTS: A total of 302 eligible patients with ameloblastoma were enrolled, 54 of whom were confirmed to relapse during the follow-up period of 6 to 191 months. Four independent predictors, including cortical bone perforation, root(s) resorption, WHO classification, and treatment pattern, were identified and included in the construction of a nomogram for recurrence-free survival (RFS), which showed promising calibration performance and discrimination in the training set (C-index 0.790, 95% confidence interval [CI] 0.735-0.845) and the validation set (C-index 0.734, 95% CI 0.599-0.869). CONCLUSION: A favorable nomogram was developed that accurately predicted the RFS of patients with ameloblastoma based on individual characteristics. Risk stratification using the nomogram could optimize tailored therapy and follow-up.

Early Percutaneous Vertebroplasty Improves Bone-Cement Integration and Reduces Adjacent Fractures.

BACKGROUND: Percutaneous vertebroplasty (PVP) is widely used for treatment of osteoporotic vertebral compression fractures (VCFs). However, the influence of PVP timing (early vs. late) on development of adjacent vertebral fractures has rarely been discussed. This retrospective cohort study aimed to evaluate bone-cement binding for thoracolumbar fractures (T8-L3) using a new assessment method to predict risk for adjacent vertebral fractures. METHODS: Patients with a single-level T-score ≤ -1.0 of lumbar bone mineral density and a primary osteoporotic VCF in the thoracolumbar region (T8-L3) who underwent PVP from October 2016 to February 2018 at our medical university-affiliated hospital were included. Patients were divided into refracture and non-refracture groups. All patients underwent computed tomography after vertebroplasty. Bone-cement distribution patterns were evaluated using standardized axial computed tomography images of each cemented vertebra by 4 independent observers with ImageJ software. The smoothness index was calculated as a percentage of smooth margins. RESULTS: Of 51 VCFs, 15 (29.4%) and 36 (70.6%) were refracture and non-refracture VCFs, respectively. The mean smoothness index (MSI) was higher in the refracture group than in the non-refracture group (P < 0.01), with an increased refracture risk that corresponded to increased MSI values (P = 0.004). Spearman correlation coefficient (0.375) showed a positive correlation between the fracture-vertebroplasty interval and MSI (P = 0.01). CONCLUSIONS: Axial computed tomography images were used to characterize bone-cement binding properties. Patients who underwent early PVP had a lower MSI, better bone-cement integration, and fewer adjacent fractures.

Sensory denervation increases potential of bisphosphonates to induce osteonecrosis via disproportionate expression of calcitonin gene-related peptide and substance P.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious side effect of systematic administration of bisphosphonates (BPs). Sensory innervation is crucial for bone healing. We established inferior alveolar nerve injury (IANI) and inferior alveolar nerve transection (IANT) models characterized by disorganized periosteum, increased osteoclasts, and unbalanced neuropeptide expression. Zoledronate injection disrupted neuropeptide expression in the IANI and IANT models by decreasing calcitonin gene-related peptide (CGRP) and increasing substance P (SP); associated with this, BRONJ prevalence was significantly higher in the IANT model, followed by the IANI model and the sham control. CGRP treatment significantly reduced BRONJ occurrence, whereas SP administration had the opposite effect. In vitro, RAW 264.7 cells were treated with BPs and then CGRP and/or SP to study changes in zoledronate toxicity; combined application of CGRP and SP decreased zoledronate toxicity, whereas CGRP or SP applied alone showed no effects. These results demonstrate that sensory denervation facilitates the occurrence of BRONJ and that CGRP used therapeutically may prevent BRONJ progression, provided that SP is also present. Further studies are necessary to determine the optimal ratio of CGRP to SP for promoting bone healing and to uncover the mechanism by which CGRP and SP cooperate.

Charge-reversal nanomedicine based on black phosphorus for the development of A Novel photothermal therapy of oral cancer.

Driven by the lifestyle habits of modern people, such as excessive smoking, drinking, and chewing betel nut and other cancer-causing foods, the incidence of oral cancer has increased sharply and has a trend of becoming younger. Given the current mainstream treatment means of surgical resection will cause serious damage to many oral organs, so that patients lose the ability to chew, speak, and so on, it is urgent to develop new oral cancer treatment methods. Based on the strong killing effect of photothermal therapy on exposed superficial tumors, we developed a pH-responsive charge reversal nanomedicine system for oral cancer which is a kind of classic superficial tumor. With excellent photothermal properties of polydopamine (PDA) modified black phosphorus nanosheets (BP NSs) as basal material, then used polyacrylamide hydrochloride-dimethylmaleic acid (PAH-DMMA) charge reversal system for further surface modification, which can be negatively charged at blood circulation, and become a positive surface charge in the tumor site weakly acidic conditions due to the breaking of dimethylmaleic amide. Therefore, the uptake of oral cancer cells was enhanced and the therapeutic effect was improved. It can be proved that this nanomedicine has excellent photothermal properties and tumor enrichment ability, as well as a good killing effect on oral cancer cells through in vitro cytotoxicity test and in vivo photothermal test, which may become a very promising new model of oral cancer treatment.

Tumor vasculature-targeting PEGylated peptide-drug conjugate prodrug nanoparticles improve chemotherapy and prevent tumor metastasis.

Metastasis is the main cause of death in cancer patients; therefore, new strategies or technologies that can inhibit the growth of primary tumors and their metastatic spread are extremely valuable. In this study, we selected an E-selectin-binding peptide as a targeting ligand and an inhibitor of metastasis, and conjugated this peptide with SN38 and PEG to produce an amphiphilic PEGylated peptide-drug conjugate (PDC). Novel self-assembled nanoparticles were then formed by the amphiphilic conjugate. The particles were actively targeted to the tumor vasculature by the peptide and passively to the tumor site by the enhanced permeability and retention (EPR) effect. As a nano-prodrug, this multifunctional conjugate (PEG-Pep-SN38) could reduce tumor growth, with an effect similar to that of irinotecan. Moreover, it could prolong the survival of mice bearing primary HCT116 tumors, which was not observed for its parent drug, SN38, nor the clinical prodrug of SN38 (irinotecan). Furthermore, this PDC prodrug prevented B16-F10 colonization in the lungs of mice. This study describes a new tumor vasculature-targeting PDC nano-prodrug with convenient preparation and high potential for cancer therapy, with the potential to be applied to other chemotherapeutic drugs.

Development and Analytical Validation of a 29 Gene Clinical Pharmacogenetic Genotyping Panel: Multi-Ethnic Allele and Copy Number Variant Detection.

To develop a novel pharmacogenetic genotyping panel, a multidisciplinary team evaluated available evidence and selected 29 genes implicated in interindividual drug response variability, including 130 sequence variants and additional copy number variants (CNVs). Of the 29 genes, 11 had guidelines published by the Clinical Pharmacogenetics Implementation Consortium. Targeted genotyping and CNV interrogation were accomplished by multiplex single-base extension using the MassARRAY platform (Agena Biosciences) and multiplex ligation-dependent probe amplification (MRC Holland), respectively. Analytical validation of the panel was accomplished by a strategic combination of > 500 independent tests performed on 170 unique reference material DNA samples, which included sequence variant and CNV accuracy, reproducibility, and specimen (blood, saliva, and buccal swab) controls. Among the accuracy controls were 32 samples from the 1000 Genomes Project that were selected based on their enrichment of sequence variants included in the pharmacogenetic panel (VarCover.org). Coupled with publicly available samples from the Genetic Testing Reference Materials Coordination Program (GeT-RM), accuracy validation material was available for the majority (77%) of interrogated sequence variants (100% with average allele frequencies > 0.1%), as well as additional structural alleles with unique copy number signatures (e.g., CYP2D6*5, *13, *36, *68; CYP2B6*29; and CYP2C19*36). Accuracy and reproducibility for both genotyping and copy number were > 99.9%, indicating that the optimized panel platforms were precise and robust. Importantly, multi-ethnic allele frequencies of the interrogated variants indicate that the vast majority of the general population carries at least one of these clinically relevant pharmacogenetic variants, supporting the implementation of this panel for pharmacogenetic research and/or clinical implementation programs.

A polymer-based capacitive sensing array for normal and shear force measurement.

In this work, we present the development of a polymer-based capacitive sensing array. The proposed device is capable of measuring normal and shear forces, and can be easily realized by using micromachining techniques and flexible printed circuit board (FPCB) technologies. The sensing array consists of a polydimethlysiloxane (PDMS) structure and a FPCB. Each shear sensing element comprises four capacitive sensing cells arranged in a 2 × 2 array, and each capacitive sensing cell has two sensing electrodes and a common floating electrode. The sensing electrodes as well as the metal interconnect for signal scanning are implemented on the FPCB, while the floating electrodes are patterned on the PDMS structure. This design can effectively reduce the complexity of the capacitive structures, and thus makes the device highly manufacturable. The characteristics of the devices with different dimensions were measured and discussed. A scanning circuit was also designed and implemented. The measured maximum sensitivity is 1.67%/mN. The minimum resolvable force is 26 mN measured by the scanning circuit. The capacitance distributions induced by normal and shear forces were also successfully captured by the sensing array.

Effects of nerve growth factor delivery via a gel to inferior alveolar nerve in mandibular distraction osteogenesis.

Inferior alveolar nerve (IAN) injury is a concern in mandible distraction osteogenesis (DO). We have previously demonstrated that repeated local injections of human nerve growth factor beta (NGF-beta) have significantly enhanced the histologic recovery of the IAN in a rabbit model of DO. This study was to further test the effect of a single injection of human NGF-beta delivered via a collagen/nanohydroxyapatite/kappa-carrageenan gel to the recovery of the IAN in DO. Rabbits underwent mandibular DO at a rate of 0.75 mm/12 h for 6 days. At the end of the distraction period, injections were performed near the IAN percutaneously as follows: group 1, human NGF-beta in the gel; group 2, human NGF-beta in saline; group 3, the gel alone; and group 4, saline alone. At 14 days after the end of distraction, IAN histologic findings and histomorphometric parameters were evaluated. Histologically, there were less myelin debris and more abundant regenerating nerve fibers in group 1 than the other groups. Both the myelinated fiber density and the myelinated axon area in group 1 were significantly higher than groups 3 and 4 (P < 0.01); the myelinated axon area in the group 1 was significantly higher than group 2 (P < 0.01). In conclusion, the delivery of human NGF-beta in the gel leads to a better acceleration of the IAN injury recovery over the saline delivery. It provides a possible way to enhance the recovery of nerve injuries in craniofacial DO clinically.

Inferior alveolar nerve transection disturbs innate immune responses and bone healing after tooth extraction.

Coordination between the nervous and innate immune systems to maintain bone homeostasis is largely uncharacterized. The present study investigated the sensory-immune interaction in resting alveolar bone and healing socket by surgical sensory denervation. Bone histomorphometry and immunohistochemistry showed that sensory denervation resulted in moderate suppression of bone remodeling, with a proinflammatory milieu manifested by increased neutrophil recruitment and possible alternations in macrophage phenotypes along the resting bone surface. This denervation effect intensified when bone remodeling was triggered by tooth extraction, as revealed by disrupted temporospatial variations in macrophage subpopulations and neutrophil infiltration, which were closely associated with a dramatic decline in socket bone filling and residual ridge height. Antagonism of calcitonin gene-related peptide (CGRP) brought about similar antianabolic and proinflammatory effects as sensory denervation, suggesting that sensory nerves may monitor the bony milieu by CGRP. Depletion of macrophages, rather than neutrophils, ruled out CGRP effects, illustrating that macrophages were the primary immune mechanism that linked sensory innervation, innate immunity, and bone. The data support that sensory innervation is required for control of innate immune responses and maintenance of bone homeostasis. Sensory neuropeptides, such as CGRP, are a possible target for the development of proanabolic treatments in bone disease by modulating innate immune responses.