Tissue-engineered bone construct promotes early osseointegration of implants with low primary stability in oversized osteotomy.

OBJECTIVES: To evaluate the histological parameters and bone mechanical properties around implants with low primary stability (PS) in grafted bone substitutes within an oversized osteotomy. MATERIALS AND METHODS: An oversized osteotomy penetrating the double cortical bone layers was made on both femora of 24 New Zealand white rabbits. Bilaterally in the femur of all animals, 48 implants were installed, subdivided into four groups, corresponding to four prepared tissue-engineering bone complexes (TEBCs), which were placed between the implant surface and native bone wall: A: tricalcium phosphate ß (TCP-ß); B: autologous adipose derived-stem cells with TCP-ß (ASCs/TCP-ß); C: ASCs transfected with the enhanced-GFP gene with TCP-ß (EGFP-ASCs/TCP-ß); D: ASCs transfected with the BMP-2 gene with TCP-ß (BMP2-ASCs/TCP-ß). Trichrome fluorescent labeling was conducted. Animals were sacrificed after eight weeks. The trichromatic fluorescent labeling (%TFL), area of new bone (%NB), residual material (%RM), bone-implant contact (%BIC), and the removal torque force (RTF, N/cm) were assessed. RESULTS: ASCs were successfully isolated from adipose tissue, and the primary ASCs were induced into osteogenic, chondrogenic, and adipogenic differentiation. The BMP-2 overexpression of ASCs sustained for ten days and greatly enhanced the expression of osteopontin (OPN). At eight weeks post-implantation, increased %NB and RTF were found in all groups. The most significant value of %TFL, %BIC and lowest %RM was detected in group D. CONCLUSION: The low PS implants osseointegrate with considerable new bone in grafted TEBCs within an oversized osteotomy. Applying BMP-2 overexpressing ASCs-based TEBC promoted earlier osseointegration and more solid bone mechanical properties on low PS implants. Bone graft offers a wedging effect for the implant with low PS at placement and promotes osteogenesis on their surface in the healing period.

Local delivery of simvastatin maintains tooth anchorage during mechanical tooth moving via anti-inflammation property and AMPK/MAPK/NF-kB inhibition.

Simvastatin (SMV) could increase tooth anchorage during orthodontic tooth movement (OTM). However, previous studies on its bone-specific anabolic and anti-inflammation properties were based on static in vitro and in vivo conditions. AMPK is a stress-activated kinase that protects tissue against serious damage from overloading inflammation. Rat periodontal ligament cells (PDLCs) were subjected to a serial of SMV concentrations to investigate the optimization that promoted osteogenic differentiation. The PDLCs in static and/or tensile culturing conditions then received the proper concentration SMV. Related factors expression was measured by the protein array, real-time PCR and Western blot. The 0.05UM SMV triggered osteogenic differentiation of PDLCs. The inhibition of AMPK activation through a pharmacological approach (Compound C) caused dramatic decrease in osteogenic/angiogenic gene expression and significant increase in inflammatory NF-κB phosphorylation. In contrast, pharmacological activation of AMPK by AICAR significantly inhibited inflammatory factors expression and activated ERK1/2, P38 MAPK phosphorylation. Moreover, AMPK activation induced by SMV delivery significantly attenuated the osteoclastogenesis and decreased the expression of pro-inflammatory TNF-α and NF-κB in a rodent model of OTM. The current studies suggested that SMV could intrigue intrinsic activation of AMPK in PDLCs that promote attenuate the inflammation which occurred under tensile irritation through AMPK/MAPK/NF-kB Inhibition.

Using rigidly fixed autogenous tooth graft to repair bone defect: an animal model.

OBJECTIVE: This study describes a new approach to regenerate bone defect using autogenous tooth. MATERIALS AND METHODS: Freshly extracted teeth were used as autogenous grafts. Teeth were sectioned, cut into desired shape, and disinfected. The grafts were rigidly fixed to the mandibular defects in eighteen rabbits using titanium screws to achieve good stability. Every six rabbits were stochastically sacrificed at 1, 3, and 6 months after implantation, respectively. For all specimens, clinical, radiographical, and histological measurements were performed. RESULTS: The boundaries of the grafts were distinctly visible in the implanted area during the first and third month. However, the teeth grafts were fully covered by new bone by the sixth month. The radiograph demonstrated the progressive change in the bone and grafted tooth interface from radiolucency to radiopacity during different time periods. Histologically, vascularization led to a temporary fibrous integration in the graft-bone interface. The bone contact rate of 1 and 3 months was significantly lower than that of the 6 months. During this period, grafts were gradually resorbed and replaced by new bone. CONCLUSION: Rigid fixation of autogenous tooth could serve as a novel approach for the repair of bone defect.

A generalizable sensing platform based on molecularly imprinted polymer-aptamer double recognition and nanoenzyme assisted photoelectrochemical-colorimetric dual-mode detection.

Developing highly sensitive and selective methods that incorporate specific recognition elements is crucial for detecting small molecules because of the limited availability of small molecule antibodies and the challenges in obtaining sensitive signals. In this study, a generalizable photoelectrochemical-colorimetric dual-mode sensing platform was constructed based on the synergistic effects of a molecularly imprinted polymer (MIP)-aptamer sandwich structure and nanoenzymes. The MIP functionalized peroxidase-like Fe3O4 (Fe3O4@MIPs) and alkaline phosphatase mimic Zr-MOF labeled aptamer (Zr-mof@Apt) were used as the recognition elements. By selectively accumulating dibutyl phthalate (DBP), a small molecule target model, on Fe3O4@MIPs, the formation of Zr-MOF@Apt-DBP- Fe3O4@MIPs sandwich structure was triggered. Fe3O4@MIPs oxidized TMB to form blue-colored oxTMB. However, upon selective accumulation of DBP, the catalytic activity of Fe3O4@MIPs was inhibited, resulting in a lighter color that was detectable by the colorimetric method. Additionally, Zr-mof@Apt effectively catalyzed the hydrolysis of L-Ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AAPS), generating ascorbic acid (AA) that could neutralize the photogenerated holes to decrease the photocurrent signals for PEC sensing and reduce oxTMB for colorimetric testing. The dual-mode platform showed strong linearity for different concentrations of DBP from 1.0 pM to 10 µM (PEC) and 0.1 nM to 0.5 µM (colorimetry). The detection limits were 0.263 nM (PEC) and 30.1 nM (colorimetry) (S/N = 3), respectively. The integration of dual-signal measurement mode and sandwich recognition strategy provided a sensitive and accurate platform for the detection of small molecules.

Hybrid system with stable structure of hard/soft tissue substitutes induces re-osseointegration in a rat model of biofilm-mediated peri-implantitis.

Re-osseointegration of an infected/contaminated dental implant poses major clinical challenges. We tested the hypothesis that the application of an antibiotic-releasing construct, combined with hard/soft tissue replacement, increases the efficacy of reconstructive therapy. We initially fabricated semi-flexible hybrid constructs of ß-TCP/PHBHHx, with tetracycline (TC) (TC amounts: 5%, 10%, and 15%). Thereafter, using in vitro assays, TC release profile, attachment to rat bone marrow-derived stem cells (rBMSCs) and their viability as well as anti-bacterial activity were determined. Thereafter, regenerative efficacies of the three hybrid constructs were assessed in a rat model of peri-implantitis induced by Aggregatibacter actinomycetemcomitans biofilm; control animals received ß-TCP/Bio-Gide and TC injection. Eight weeks later, maxillae were obtained for radiological, histological, and histomorphometric analyses of peri-implant tissues. Sulcus bleeding index was chronologically recorded. Serum cytokines levels of IL-6 and IL-1ß were also evaluated by enzyme-linked immunosorbent assay. Substantial amounts of tetracycline, from hybrid constructs, were released for 2 weeks. The medium containing the released tetracycline did not affect the adhesion or viability of rBMSCs; however, it inhibited the proliferation of A. actinomycetemcomitans. Osteogenesis and osseointegration were more marked for the 15% hybrid construct group than the other two groups. The height of attachment and infiltration of inflammatory cells within fibrous tissue was significantly reduced in the experimental groups than the control group. Our protocol resulted in re-osseointegration on a biofilm-contaminated implant. Thus, an antibiotic releasing inorganic/organic construct may offer a therapeutic option to suppress infection and promote guided tissue regeneration thereby serving as an integrated multi-layer substitute for both hard/soft tissues.

A 12-Year-Old Girl Presenting With Recurrent Dyspnea and Pulmonary Ground-Glass Opacities.

CASE PRESENTATION: A 12-year-old girl presented with shortness of breath with exercise for 2 weeks. Her oxygen saturation was 85% during exercise. Birth and family histories were unremarkable. The girl was healthy until 7.1 years of age, when she suffered a "pneumonia" with fever, dyspnea, and hypoxemia, which diminished after a 19-day treatment with antibiotics and methylprednisolone. These symptoms relapsed 8 months later, and she was diagnosed with rapidly progressive interstitial lung disease (ILD) and a Mycoplasma pneumoniae infection. At that time, her symptoms failed to respond to a course of antibiotic therapy but resolved with IV methylprednisolone at 2.7 mg/kg/day. She remained on a tapering dose of methylprednisolone plus methotrexate for the next 18 months until withdrawal of these medications because of return of almost normal lung imaging. She had never had myalgia, muscle weakness, arthritis, rashes, mechanic's hands, Raynaud's phenomenon, dry mouth, or dry eyes.

The circadian expression of osteogenic factors in periodontal tissue loading mechanical force: new concepts of the personalized orthodontic care.

OBJECTIVE: The need for orthodontic treatment continues to increase. Strategies that shorten the treatment course and reduce discomfort are most welcome in clinic. Circadian rhythm plays important role in various physiological processes, including bone formation. This study intended to depict a possible circadian releasing property of the osteogenic factors within the periodontal tissue during orthodontic treatment, which may direct a more efficient and satisfactory orthodontic treatment to the patient. METHODS: Primary periodontal ligament cells (PDLCs) were obtained from the Sprague-Dawley (SD) rats. An equibiaxial strain value of 12% was applied on rat PDLCs (rPDLCs). After 2 h stimuli of 10-7 M dexamethasone (DX), the osteogenic genes' expressions were detected by real-time polymerase chain reaction (RT-PCR) at Zeitgeber times 0, 4, 8, 12, 16, 20, and 24. An orthodontic appliance was placed on 45 SD rats. Animals were maintained under 12-h light/dark periods and euthanized at 9 time points over the diurnal cycle. The orthodontic sensitive tissues of the mesial root of the maxillary first molar were collected for RT-PCR and immunohistological assay. RESULTS: The rPDLCs displayed typical fibroblastic spindle shape, and subcultured steadily in vitro. Induced by DX, the mRNA expression of Col-1, OPN, and IBSP within the loaded/unloaded rPDLCs oscillated as that of the main clock gene Per-1. The osteogenic genes' expressions as well as the protein releases sustained a circadian oscillation trend in vivo. CONCLUSIONS: This study indicates the existence of a circadian rhythm of the osteogenic factors within the orthodontic sensitive tissues, which highlights the importance of precise timing of force loading in further orthodontic treatment. Thus, a periodicity pattern of orthodontic traction at night may prove a more efficient tooth movement while minimizing the treatment window and discomfort complains.

Demineralized Dentin as a Semi-Rigid Barrier for Guiding Periodontal Tissue Regeneration.

BACKGROUND: Guided tissue regeneration (GTR) is an accepted approach in the correction of periodontal bone loss. Nonetheless, the deficiencies of commonly applied absorbable membrane, such as flexibility and limited osteoconductive and osteoinductive capability, still leave much room for improvement. Thus, the feasibility of applying demineralized dentin tissue to improve the therapeutic effect of GTR in periodontal regeneration was explored. METHODS: Demineralized dentin was harvested after acid treatment, and its physiochemical properties were assessed in terms of mineralization density, contact angle, three-point test, and cell attachment. Because of its similar characteristics with bone tissue, dentin that had been acid-treated for 6 hours was chosen to repair a periodontal defect using an induced-periodontitis canine model. Histologic measurements were taken to compare its therapeutic effects to an absorbable membrane group and an untreated group. RESULTS: The demineralized dentin displayed continually decreased hardness and density as the acid etching time was prolonged. Enhanced attachment and spreading of bone marrow mesenchymal stem cells were observed on the 6-hour processed dentin. Furthermore, in the demineralized dentin group, more periodontal tissues were newly formed compared with the biomembrane and untreated groups. CONCLUSION: Acid etching represents an easy and promising approach to obtain demineralized dentin with desirable properties, similar to bone, for clinical application to promote periodontal tissue regeneration.

[The effect of stress distribution and displacement by two kinds of different distract directions on mandibular body].

OBJECTIVE: To establish a three-dimensional finite element model of mandibular distraction osteogenesis (DO) in order to study the influence of distraction orientations to mandibular DO. METHODS: By using the two finite element models, Von Mises stress and the displacement under different loads were measured. RESULTS: The maximum stress in the distract equipment paralleled to the mandibular corpus was two times of that when the distract equipment paralleled to the sagittal axis. Von Mises stress concentration mainly occurred in the loading position and the condylar ante inferior. This phenomenon may lead to partial bone resorption, consequently lead to screw loose and affect the stability of distraction device. When the displacement increased in the model, the maximum stress and displacement showed linear relation. CONCLUSION: The counterforce produced by the device makes lateral displacement in tail. The reaction force could be reduced to a minimum degree when the traction device parallel to the sagittal axis. This study provides theoretical basis for the position of distract equipment and distraction orientations in clinical application.