Actinomycotic osteomyelitis in the maxilla and the zygomatic bone: a case report and literature review / 口腔疾病防治

Objective@# To investigate the clinical features, diagnosis and treatment of osteomyelitis of the jaw caused by an actinomycotic infection and to provide a reference for clinical diagnosis and treatment.@*Methods@#A case of osteomyelitis in the bilateral maxilla and the left zygomatic bone and arch caused by a mixed bacterial infection dominated by Actinomycetes was reviewed and analyzed in combination with the literature. @*Results @#The patient had left upper posterior tooth pain with repeated left facial swelling for 7 months. The patient's left face was swollen before surgery, the left maxillary alveolar bone was necrotic, and the upper palate showed fistula discharge. A maxillofacial magnetic resonance imaging scan excluded tumors and other space-occupying lesions. According to CBCT images, the initial diagnoses were left infraorbital space infection and osteomyelitis of the bilateral maxillary, the left zygomatic bone, the left zygomatic arch and the lateral orbital wall. Necrosis of the left maxilla and the zygomatic bone was excised, the focus was cleared and the focal tooth was extracted under general anesthesia. Histopathological results confirmed osteomyelitis and actinomycotic infection. Anti-inflammatory therapy with penicillin sodium was given before surgery, and piperacillin sodium and tazobactam sodium, dexamethasone sodium phosphate, tranexamic acid and mecobalamine were given after surgery. The patients' 6-month follow-up results showed that the maxillofacial shape was basically symmetrical; no ulceration, pus or abnormal secretion was found in the skin or intraoral mucosa; and the surgical area showed good recovery. A review of the relevant literature showed that Actinomyces is an opportunistic pathogen, and factors such as trauma and dental infection have been implicated in the pathogenesis of osteomyelitis. In addition to surgery, antibiotics are used to treat the disease and multidisciplinary symptomatic treatment combined with supportive treatment is required to achieve a better prognostic effect. @*Conclusion @# Actinomycotic osteomyelitis occurring in the maxilla and the zygomatic bone is an extremely rare disease that can be diagnosed by clinical manifestations, bacteriological examination and biopsy. Appropriate and effective penicillin drugs should be given at the initial stage of treatment, more sensitive antibiotics should be selected according to the results of the drug sensitivity test, and the lesions should be surgically removed when the patient's condition improves. Active symptomatic and supportive treatment should be performed during the treatment period.

Recruited CD68+CD206+ macrophages orchestrate graft immune tolerance to prompt xenogeneic-dentin matrix-based tooth root regeneration.

Successful regenerative medicine strategies of xenogeneic extracellular matrix need a synergistic balance among inflammation, fibrosis, and remodeling process. Adaptive macrophage subsets have been identified to modulate inflammation and orchestrate the repair of neighboring parenchymal tissues. This study fabricated PPARγ-primed CD68+CD206+ M2 phenotype (M2γ), and firstly verified their anti-inflammatory and tissue-regenerating roles in xenogeneic bioengineered organ regeneration. Our results showed that Th1-type CD3+CD8+ T cell response to xenogeneic-dentin matrix-based bioengineered root complex (xeno-complex) was significantly inhibited by M2γ macrophage in vitro. PPARγ activation also timely recruited CD68+CD206+ tissue macrophage polarization to xeno-complex in vivo. These subsets alleviated proinflammatory cytokines (TNF-α, IFN-γ) at the inflammation site and decreased CD3+CD8+ T lymphocytes in the periphery system. When translated to an orthotopic nonhuman primate model, PPARγ-primed M2 macrophages immunosuppressed IL-1ß, IL-6, TNF-α, MMPs to enable xeno-complex to effectively escape immune-mediated rejection and initiate graft-host synergistic integrity. These collective activities promoted the differentiation of odontoblast-like and periodontal-like cells to guide pulp-dentin and cementum-PDLs-bone regeneration and rescued partially injured odontogenesis such as DSPP and periostin expression. Finally, the regenerated root showed structure-biomechanical and functional equivalency to the native tooth. The timely conversion of M1-to-M2 macrophage mainly orchestrated odontogenesis, fibrogenesis, and osteogenesis, which represents a potential modulator for intact parenchymal-stromal tissue regeneration of targeted organs.

Correction: Cumulative inactivation of Nell-1 in Wnt1 expressing cell lineages results in craniofacial skeletal hypoplasia and postnatal hydrocephalus.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Computational Fluid Dynamic Analysis of Different Velopharyngeal Closure Patterns.

OBJECTIVE: Velopharyngeal (VP) closure has high impact on the quality of life, especially in patients with cleft palate. For better understanding the VP closure, it is important to understand the airflow dynamics of different closure patterns, including circular, coronal, sagittal, and circular with a Passavant's ridge. The purpose of this study was to demonstrate the airflow characteristics of different velopharyngeal closure patterns. METHODS: Sixteen adults with no notable upper airway abnormality who needed multislice spiral computed tomography scans as part of their clinical care. Airways were reconstructed. A cylinder and a cuboid were used to replace the VP port in three models of VP port patterns. Flow simulations were carried using computational fluid dynamics. Airflow pressures in the VP orifice, oral cavity and nasal cavity, as well as airflow velocity through the velopharyngeal orifice, were calculated. RESULTS: The airflow dynamics at the velopharynx were different among different velopharyngeal patterns as the area of the velopharyngeal port increased from 0 to 25 mm2. The orifice areas of different closure conditions in four velopharyngeal closure patterns were significantly different. The maximal orifice area for adequate velopharyngeal closure was 7.57 mm2 in the coronal pattern and 6.21 mm2 in the sagittal pattern. CONCLUSIONS: Airflow dynamics of the velopharynx were correlated to the velopharyngeal closure patterns. Different closure patterns had different largest permitted orifice areas for getting the appropriate oral pressures for normal speech.

Cumulative inactivation of Nell-1 in Wnt1 expressing cell lineages results in craniofacial skeletal hypoplasia and postnatal hydrocephalus.

Upregulation of Nell-1 has been associated with craniosynostosis (CS) in humans, and validated in a mouse transgenic Nell-1 overexpression model. Global Nell-1 inactivation in mice by N-ethyl-N-nitrosourea (ENU) mutagenesis results in neonatal lethality with skeletal abnormalities including cleidocranial dysplasia (CCD)-like calvarial bone defects. This study further defines the role of Nell-1 in craniofacial skeletogenesis by investigating specific inactivation of Nell-1 in Wnt1 expressing cell lineages due to the importance of cranial neural crest cells (CNCCs) in craniofacial tissue development. Nell-1flox/flox; Wnt1-Cre (Nell-1Wnt1 KO) mice were generated for comprehensive analysis, while the relevant reporter mice were created for CNCC lineage tracing. Nell-1Wnt1 KO mice were born alive, but revealed significant frontonasal and mandibular bone defects with complete penetrance. Immunostaining demonstrated that the affected craniofacial bones exhibited decreased osteogenic and Wnt/ß-catenin markers (Osteocalcin and active-ß-catenin). Nell-1-deficient CNCCs demonstrated a significant reduction in cell proliferation and osteogenic differentiation. Active-ß-catenin levels were significantly low in Nell-1-deficient CNCCs, but were rescued along with osteogenic capacity to a level close to that of wild-type (WT) cells via exogenous Nell-1 protein. Surprisingly, 5.4% of young adult Nell-1Wnt1 KO mice developed hydrocephalus with premature ossification of the intrasphenoidal synchondrosis and widened frontal, sagittal, and coronal sutures. Furthermore, the epithelial cells of the choroid plexus and ependymal cells exhibited degenerative changes with misplaced expression of their respective markers, transthyretin and vimentin, as well as dysregulated Pit-2 expression in hydrocephalic Nell-1Wnt1 KO mice. Nell-1Wnt1 KO embryos at E9.5, 14.5, 17.5, and newborn mice did not exhibit hydrocephalic phenotypes grossly and/or histologically. Collectively, Nell-1 is a pivotal modulator of CNCCs that is essential for normal development and growth of the cranial vault and base, and mandibles partially via activating the Wnt/ß-catenin pathway. Nell-1 may also be critically involved in regulating cerebrospinal fluid homeostasis and in the pathogenesis of postnatal hydrocephalus.

Biomechanical analyses of common suspension sutures in primary cleft lip rhinoplasty.

BACKGROUND: For a better understanding of common suspension sutures during primary cleft lip nasal rhinoplasty, the biomechanical consequences of those sutures need to be demonstrated. METHODS: A finite element model of the infant specimen was established. The closure of cleft lip and four different specific suspension sutures were simulated by loading different forces on the model: 1. F1 to simulate the suture fastening both medial crura together; 2. F2 to simulate the suture which sewed both medial crura and the non-cleft-side upper lateral cartilage together; 3. F3 to simulate the suture elevating the alar cartilage cranially; 4. F4 to simulate the suture elevating the alar cartilage superiorly. The deformation and stress distribution consequent to each maneuver were analyzed in details. RESULTS: The deviation of columella was restored through the closure of cleft lip. Different suspension sutures had different biomechanical effects on the nasal structure. All suspension sutures had the function on elevating the alar cartilage. F2 had no function on restoring the collapse of the nasal tip. The suture which fastened both medial crura together leaded to the lowest stress on the skin envelope. CONCLUSIONS: Each suspension suture had its characteristics respectively. The simulation suggested that F1, the suture which fastened both medial crura, could be the most potential maneuver for cleft lip rhinoplasty because it can symmetrically restore the shape of the nose without incurring a significant increase in stress.

Functional stability analyses of maxillofacial skeleton bearing cleft deformities.

The symmetrically stable craniofacial bony structure supports the complex functions and delicate contour of the face. Congenital craniofacial deformities are often accompanied by bony defects and have been repetitively correlated with compromised dento-maxillary stability, but neither the extent nor the pattern of cleft-related maxillary instability has been explored in detail. Furthermore, it is largely unknown if the bony defect and related instability are correlated with secondary maxillary deformity common among patients with orofacial clefts. With the aid of finite element modeling, we studied the detailed relationship between cleft-related bony defect and maxillary stability under occlusal loading. Craniofacial models were generated based on cone-beam computed tomography data and loaded with mimicked bite forces along the axial axis of each tooth. Our data showed that all cleft models exhibited more asymmetrical deformations under mastication compared with the normal. Models with palatal cleft demonstrated greater asymmetry, greater dental arch contraction, and less maxillary protrusion compared to models with alveolar cleft only. For unilateral cleft models, alveolus on non-cleft side tended to be more protruded and lifted than the cleft side. For bilateral cleft models, the most prominent feature was the seriously contracted alveolar arch and curved and pitched premaxillae. These findings indicated cleft type-specific pattern of maxillary instability, which were largely in accordance with dentoalveolar morphological features among patients. Collectively, our study elucidated the detailed relationship between cleft bony defect and the pattern of maxillary instability, and suggested a prototype for studying the abnormal maxillary and dental arch growth among patients with craniofacial deformities.

Recapitulation of Unilateral Cleft Lip Nasal Deformity on Normal Nasal Structure: A Finite Element Model Analysis.

Cleft lip nasal deformity has been challenging to plastic surgeons. A better understanding of the biomechanical aspect of the cleft nose would contribute to a better correction. In this study, finite element model of a normal nose was constructed and loaded with forces to recapitulate the unilateral cleft lip nasal deformity. Tether at the alar base was simulated by a laterally directed force at the lateral crus, and tether at the columella base by a posteriorly directed force at the medial crus. The equivalent von-Mises stress and the total deformation consequent to different patterns of loading were captured. In accordance with clinical observations, unilaterally loaded forces caused deformation on both sides of the nose. A correlation between the patterns of loading and different cleft lip nasal deformities was documented in detail. When set at the same force magnitude, tether at the columella base led to more extensive changes in the nasal morphology and higher level of stress than at the alar base. Clear identification of major pathological tethers in the nasolabial region might lead to more accurate and stable correction of cleft lip nasal deformities.

Wnt7a induces satellite cell expansion, myofiber hyperplasia and hypertrophy in rat craniofacial muscle.

Craniofacial muscles drive critical functions in the head, including speech, feeding and expression. Compared with their counterparts in trunk and limbs, craniofacial muscles are of distinct embryonic origins, which might consequently lead to different growth patterns and regenerative potential. In this study, rat levator veli palatini muscle and masseter muscle were compared with tibialis anterior muscle in their response to exogenous Wnt7a stimulus, which has been proved effective in promoting muscle regeneration in the limbs. Histological, cellular and molecular analyses were performed both under basal condition and after a single dose injection of recombinant human Wnt7a. Under basal condition, levator veli palatini muscle demonstrated considerably more satellite cells than the others. After Wnt7a administration, regeneration-related activities, including satellite cell expansion, myofiber hyperplasia and hypertrophy were generally observed in all three muscles, but with obvious differences in the extent. The composition of fast/slow myofibers underwent substantial alterations, and the pattern varied among the three muscles. Location-specific alterations in the expression level of core components in planar cell polarity pathway, Akt/mTOR pathway and myostatin pathway were also observed. In conclusion, both craniofacial and limb muscles could be effectively expanded by exogenous Wnt7a stimulus, but muscle-to-muscle variations in response patterns existed.

Biomechanical simulation of correcting primary unilateral cleft lip nasal deformity.

For better outcomes of the primary correction of cleft lip nasal deformity, it is important to clarify the specific morphological and biomechanical consequences of major surgical maneuvers during cleft lip nose correction. In this study, a finite element model was established basing on the micro-MRI imaging of an infant specimen with unilateral complete cleft lip deformity. Alar base adduction was simulated as a medially-directed force on the lateral crus (F1); columella straightening was simulated as a laterally-directed force on the medial crus (F2); and nasal tip enhancement was simulated as an anteriorly-directed force on the intermediate crus (F3). The deformation and stress distribution consequent to each force vector or different force combinations were analyzed in details. Our biomechnical analyses suggested that W\when loaded alone, the three forces generated disparate morphological changes. The combination of different force loadings generated obviously different outcomes. F3 generated the most intensive stress when compared to F1 and F2. When F2 was loaded on top of F1-F3 combination, it further relieved nasal deviation without incurring significant increase in stress. Our simulation suggested that alar base adduction, columella straightening, and nasal tip elevation should all be included in a competent cleft lip nose correction.

Mechanical analyses of critical surgical maneuvers in the correction of cleft lip nasal deformity.

The relapse of nasal deformity is a challenge for modern correction of cleft lip. A comprehensive understanding in the biomechanical perspective of both the formation and correction of the cleft lip nasal deformity would lead to improved stability of the corrective outcome. In this study, a finite element model of secondary cleft lip nasal deformity was constructed, on which two critical corrective maneuvers were mimicked in the form of force-loading. The intercrural suture was simulated by a force loaded at the intermediate crus of the alar cartilage directing anteriorly and medially, and the suture suspending the alar cartilage to the upper lateral cartilage was simulated by a force loaded at the lateral crus directing superiorly and medially. The equivalent von-mises stress and the total deformation consequent to different patterns of loading were captured. Our biomechanical analyses suggested that the intercrural suture at the nasal tip might be more effective in generating widespread morphological change than the suspension suture, but left much higher level of stress within the skin envelope if placed too high. Synergistic effect was observed between the two sutures in both the resultant deformation and stress. In addition, our simulations were partially supported by clinical photogrammetry data.

Cell-derived micro-environment helps dental pulp stem cells promote dental pulp regeneration.

OBJECTIVES: The function of the dental pulp is closely connected to the extracellular matrix (ECM) structure, and ECM has received significant attention due to its biological functions for regulating cells. As such, the interaction between the ECM niche and cells is worth exploring for potential clinical uses. MATERIALS AND METHODS: In this study, dental pulp stem cell (DPSC)-derived ECM (DPM) was prepared through cell culture and decellularization to function as the cell niche, and changes in DPSC behaviour and histological analysis of dental pulp tissue regeneration were evaluated following the DPM culture. DPM promoted the replication of DPSCs and exhibited retention of their mineralization. Then, the DPM-based culture strategy under odontogenic culture medium was further investigated, and the mineralization-related markers showed that DPSCs were regulated towards odontogenic differentiation. Dental pulp-like tissue with well-arranged ECM was harvested after a 2-month subcutaneous implantation in nude mice with DPM application. Additionally, DPSCs cultured on the plastic culture surface showed the up-regulation of mineralization makers in vitro, but there was a disorder in matrix formation and mineralization when the cells were cultured in vivo. RESULTS AND CONCLUSIONS: DPM-based cultivation could serve as a cell niche and modulate DPSC behaviour, and this method also provided an alternative to harvest tissue-specific ECM and provided a strategy for ECM-cell interaction.

Xenogeneic Bio-Root Prompts the Constructive Process Characterized by Macrophage Phenotype Polarization in Rodents and Nonhuman Primates.

Tissue or organ regeneration using xenogeneic matrices is a promising approach to address the shortage of donor matrices for allotransplantation. Success of such approach has been demonstrated to correlate with macrophage-mediated fibrotic homeostasis and tissue remodeling. The previous studies have demonstrated that treated dentin matrix (TDM) could be a suitable bioactive substrate for allogeneic tooth root regeneration. This study constructed xenogeneic bioengineered tooth root (bio-root) via a combination of porcine TDM (pTDM) with allogeneic dental follicle cells (DFCs). Macrophage phenotypes are used to evaluate the remodeling process of xenogeneic bio-roots in vitro and in vivo. pTDM can facilitate odontoblast differentiation of human derived DFCs. Xenogeneic bio-roots in rat subcutaneous tissue prompt constructive response via M1 macrophage infiltration during early postimplantation stages and increase restorative M2 phenotype at later stages. After implantation of bio-roots into jaws of rhesus monkeys for six months, periodontal ligament-like fibers accompanied by macrophage polarization are observed, which are positive for COL-1, Periostin, ßIII-tubulin and display such structures as fibroblasts and blood vessels. The reconstructed bio-root possesses biomechanical properties for the dissipation of masticatory forces. These results support that xenogeneic bio-root could maintain fibrotic homeostasis during remodeling process and highlight the potential application of xenogeneic matrices in regenerative medicine.

CAD based design sensitivity analysis and shape optimization of scaffolds for bio-root regeneration in swine.

Tooth root supports dental crown and bears occlusal force. While proper root shape and size render the force being evenly delivered and dispersed into jawbone. Yet it remains unclear what shape and size of a biological tooth root (bio-root), which is mostly determined by the scaffold geometric design, is suitable for stress distributing and mastication performing. Therefore, this study hypothesized scaffold fabricated in proper shape and size is better for regeneration of tooth root with approving biomechanical functional features. In this study, we optimized shape and size of scaffolds for bio-root regeneration using computer aided design (CAD) modeling and finite element analysis (FEA). Statical structural analysis showed the total deformation (TD) and equivalent von-mises stress (EQV) of the restored tooth model mainly concentrated on the scaffold and the post, in accordance with the condition in a natural post restored tooth. Design sensitivity analysis showed increasing the height and upper diameter of the scaffold can tremendously reduce the TD and EQV of the model, while increasing the bottom diameter of scaffold can, to some extent, reduce the EQV in post. However, increase on post height had little influence on the whole model, only slightly increased the native EQV stress in post. Through response surface based optimization, we successfully screened out the optimal shape of the scaffold used in tissue engineering of tooth root. The optimal scaffold adopted a slightly tapered shape with the upper diameter of 4.9 mm, bottom diameter of 3.4 mm; the length of the optimized scaffold shape was 9.4 mm. While the analysis also suggested a height of about 9 mm for a metal post with a diameter of 1.4 mm suitable for crown restoration in bio-root regeneration. In order to validate the physiological function of the shape optimized scaffold in vivo, we transplanted the shape optimized treated dentin matrix (TDM) scaffold, seeding with dental stem cells, into alveolar bone of swine and further installed porcelain crown. Results showed that tooth root has not only been successfully regenerated histologically but also performed masticatory function and maintained stable for three months after crown restoration. Our results suggested that TDM scaffold with 9.4 mm in length and 4.9 mm/3.4 mm in upper/bottom diameter is a suitable biological scaffold for tooth root regeneration. These results also provided a recommendable design protocol for fabricating other scaffolds in tooth root reconstruction.

Combination of aligned PLGA/Gelatin electrospun sheets, native dental pulp extracellular matrix and treated dentin matrix as substrates for tooth root regeneration.

In tissue engineering, scaffold materials provide effective structural support to promote the repair of damaged tissues or organs through simulating the extracellular matrix (ECM) microenvironments for stem cells. This study hypothesized that simulating the ECM microenvironments of periodontium and dental pulp/dentin complexes would contribute to the regeneration of tooth root. Here, aligned PLGA/Gelatin electrospun sheet (APES), treated dentin matrix (TDM) and native dental pulp extracellular matrix (DPEM) were fabricated and combined into APES/TDM and DPEM/TDM for periodontium and dental pulp regeneration, respectively. This study firstly examined the physicochemical properties and biocompatibilities of both APES and DPEM in vitro, and further investigated the degradation of APES and revascularization of DPEM in vivo. Then, the potency of APES/TDM and DPEM/TDM in odontogenic induction was evaluated via co-culture with dental stem cells. Finally, we verified the periodontium and dental pulp/dentin complex regeneration in the jaw of miniature swine. Results showed that APES possessed aligned fiber orientation which guided cell proliferation while DPEM preserved the intrinsic fiber structure and ECM proteins. Importantly, both APES/TDM and DPEM/TDM facilitated the odontogenic differentiation of dental stem cells in vitro. Seeded with stem cells, the sandwich composites (APES/TDM/DPEM) generated tooth root-like tissues after being transplanted in porcine jaws for 12 w. In dental pulp/dentin complex-like tissues, columnar odontoblasts-like layer arranged along the interface between newly-formed predentin matrix and dental pulp-like tissues in which blood vessels could be found; in periodontium complex-like tissues, cellular cementum and periodontal ligament (PDL)-like tissues were generated on the TDM surface. Thus, above results suggest that APES and DPEM exhibiting appropriate physicochemical properties and well biocompatibilities, in accompany with TDM, could make up an ECM microenvironment for tooth root regeneration, which also offers a strategy for complex tissue or organ regeneration.