Ultrasonographic Diagnosis of Odontogenic Cutaneous Fistula: A CaseReport Demonstrating the Value of Multimodal Imaging Diagnostics

Pelvic fistulae are an abnormal communication among the genitourinary tract, the gastrointestinal tract, and the vagina or perineum. Genital tract fistulae have been described in the medical literature for the past several thousand years. Advancements in both the diagnosis and treatment of vaginal fistulae have been obtained over the past century as surgical interventions have become safer and surgical techniques have improved. The most common cause of fistulae worldwide is obstructed labor. In developed countries, fistulae most commonly occur after benign gynecologic surgery, but obstructed labor, malignancy, radiation exposure, and inflammatory bowel disease can also cause fistulae. Fistulae significantly affect quality of life. Diagnostic studies and radiologic imaging can help aid the diagnosis, but a thorough physical examination is the most important component in the evaluation and diagnosis of a fistula. Temporizing treatments are available to help ease patient suffering until surgical management can be performed. Surgical repairs can be performed using an abdominal, vaginal, or transanal approach. Although technically challenging, surgical repair is usually successful, but closure of the fistula tract does not guarantee continence of urine or feces, because there is often underlying damage to the bowel and bladder.

Left Ventricular Intramyocardial Dissecting Hematoma

ObjectiveAn exploratory phase II, multicenter, open-label, clinical trial (NCT03687632) was conducted to evaluate the safety and effectiveness in treating persistent corneal epithelial defects (PEDs) with ST266, a proprietary novel multi-cytokine platform biologic solution secreted by cultured Amnion-derived Multipotent Progenitor (AMP) cells.MethodsSubjects with a PED were treated with ST266 eye drops 4 times daily for 28 days, then followed for 1 week. Safety was assessed by monitoring of adverse events (AEs) and serious adverse events (SAEs). Efficacy was assessed by measuring the area of the PED by slit lamp biomicroscopy. Tolerability of ST266, percentage of eyes with complete healing, reduction in area of the epithelial defect, and maintenance of a reduction in the area of the epithelial defect 7 days after treatment were recorded.ResultsThirteen patients were enrolled into the trial at one of eight sites. The first patient withdrew after 5 days. The remaining 12 patients with PEDs with median duration of 39 days (range = 12 to 393 days) completed treatment. Ten of the 12 eyes had been refractory to treatment with various conventional therapies prior to enrollment. After 28 days of treatment, there was a significant decrease in mean PED area compared with baseline (66.4% ± 35.3%, P = 0.001). At follow-up, 1 week after completion of treatment, on day 35, the PED area was further reduced by 78.8% ± 37.5% (P = 0.01) compared with baseline. During 28 days of treatment, 5 eyes (41.7%) had complete wound closure. There were no AEs of concern thought to be related to the drug, and no SAEs were noted.ConclusionsIn this trial, we found ST266 eye drops might promote corneal epithelization, thereby reducing the PED area, including in refractory cases in a wide range of etiologies. ST266 was well-tolerated by most patients.

Purpose: To investigate the conventional ultrasound and contrast-enhanced ultrasound (CEUS) imaging features of pseudoangiomatous stromal hyperplasia (PASH).Methods: Retrospective analysis of clinical and imaging data of 29 patients diagnosed with PASH from June 2014 to June 2023.Results: The median age of the patients was 39 years. Linear/cystic hypoechoic areas could be detected within the lesion in 12 cases (41.4%), and in 17 cases, the lesions had extensive conventional ultrasound findings with no significant features. The ultrasound-measured lesion diameters were smaller than those measured in surgically resected lesions, and the statistical difference was highly significant (p < 0.01). Fifteen cases underwent CEUS examination, with 7 lesions (46.7%) demonstrating uniform enhancement and 8 lesions (53.3%) exhibiting nonuniform enhancement. Within the enhanced regions, perfusion defects were observed, all of which were of the patchy type. The areas of patchy perfusion defects corresponded to the linear/cystic hypoechoic regions observed in the conventional sonographic images of the lesions. The use of CEUS provided additional diagnostic clarity compared with conventional ultrasound. Specifically, the specificity for identifying PASH lesions increased from 35.7% with conventional ultrasound to 64.3% with CEUS, highlighting the value of CEUS in enhancing the diagnostic accuracy for PASH lesions.Conclusion: This study suggests that linear/cystic hypoechoic areas on sonography may serve as crucial clues for the ultrasound diagnosis of PASH. The presence of diffuse patchy perfusion defects in CEUS contributes to the accurate diagnosis of PASH.

This study was undertaken to evaluate the effects of different rhBMP-2 release profiles in defect areas around dental implants on osseointegration and bone regeneration. Four beagle dogs (13–15 kg) were used. The defect was 3 mm deep and there was a 1 mm gap around the implant. Each of the four implants was installed on the right and left mandibular alveolar ridges. After the implants were placed, experimental groups were applied to the surrounding defect area (n = 8 in each group, the control group was not treated). The inject group was injected with rhBMP-2 solution directly. In the gel group, rhBMP-2 mixed with a hydrogel matrix was applied. In the particle–gel group, rhBMP-2-embedded poly(lactic-co-glycolic acid)(PLGA) microparticles mixed with hydrogel matrix were applied to maintain consistent release. Sequential fluorescent labeling and histological analysis were performed to evaluate the new bone formation and osseointegration in the defect area. In the control group, larger marginal bone loss was detected as compared with the other groups (P < 0.05). The gel group showed significantly higher levels of BIC in the buccal and lingual defect areas compared with the other groups (P < 0.05). New-bone percentages in the inject and gel groups formed more new bone than in the particle–gel and control groups (P < 0.05). Despite the limitations of this study, the use of only hydrogel, which allows early release of rhBMP-2 followed by consistent extended release, showed better bone formation and osseointegration than simple injection or PLGA microparticles with hydrogel matrix.

The aims of the present study were to establish a new model for the study of biological events during bone regeneration using the principle of guided tissue regeneration and to study the effect of delta12-Prostaglandin J2 (delta12-PGJ2) on bone formation. Half-cylindrical shaped titanium tubes (8x1.5x2 mm) were placed and secured over transcortical defects (5x1.5 mm) at femoral bone in male Wistar rats. Healing periods of 3, 7, 21, 28 days were studied. Animals were injected with 5-Bromo-2'deoxy-uridine (BrdU) one hour before sacrifice in order to characterize cellular mitotic activity. Samples were processed for routine paraffin embedding, then stained with either H&amp;E or immunostained for COX-2, PDGF-B, IGF and BMP-6 expression. Bone regeneration occurred in both cortical defect area and supracortical area at day 7. The amount of the area of new bone was increased during healing period and reached about 56-60% of the defect area by day 28. Mitotic activity was found dominantly in each defect area before a large amount of bone would take placed. COX-2, PDGE-B and BMP-6, highly expressed early at day 3, were found to be important in the early stage of bone regeneration. COX-2 inhibitor (NS-398) decreased the area of new bone by 25% (p&lt;0.05) and both COX-2 and BMP-6 expression by 50-60% (p&lt;0.05) in this model. This study shows the early role of prostaglandins and some key growth factors in bone regeneration. The effect of a single application of delta12-PGJ2 on bone formation was studied in this model of bone regeneration. Four groups of the animals received a different concentration of delta12-PGJ2 (10 -9, 10 -7, 10 -5 and 10 -3 M). Ten mul of delta12-PGJ2 were loaded into a collagen sponge and then was placed inside the titanium chamber before placing on top of the defect. The contralateral defect served as a control without delta12-PGJ2. The animals were sacrificed 10 days after surgery. The amount of new boneformed and the proliferation rate in the cortical defects were determined histomorphometrically. The expression of PDGF, IGF, BMP-2 and BMP-6 was examined immunohistochemically in new bone regeneration. Bone formation in the defect area was significantly promoted by delta12-PGJ2 in a dosedependent manner. It was increased by 35% when the 10 -5 M concentration (54% of the defect area) or the 10 -3 M concentration (53%) were used, as compared with the bone formation observed with the control (40%). Statistically significant increases (2-3 folds) inthe area of PDGF-A and -B expression were seen at high doses of delta12-PGJ2. A significant increase in BMP-2 and BMP-6 expression (2-3 folds) was seen in the group receiving 10 -3 M of delta12-PGJ2. No significant difference was found in IGF expression and mitotic activity between the treatment and control groups. Single dose of delta12-PGJ2 (1x10 -5 and 1x10 -3 M) was also investigated for potential use in bone regeneration around implant. Screw-shaped titanium implants (1.35 mm in diameter and 1.5 mm in length) were inserted to femoral bones (2 implants for each femur). Five mul of carboxymethylcellulose, as carrier, alone (for control) or with delta12-PGJ2 were injected into surgically prepared holes before the insertion of implants. Rats were sacrificed at 3 and 8 weeks after surgery. The femoral bones with implants were embedded in methyl methacrylate resin and were prepared to make undecalcified sections. delta12-PGJ2 increased about 20% more new bone area in the space between thread at 8 week after surgery. Both vertical distance and the thickness of extended new bone regeneration surrounding the implant from endosteal surface were significantly increase (34% and 59% respectively) with delta12-PGJ2 at 8 week after surgery. The present findings indicate that a single application of delta12-PGJ2 promotes new bone formation in this model system. Moreover, PDGF-A and-B may be involved in the mechanism of delta12-PGJ2-induced bone formation as well as BMP-2 and -6

The authors present a novel mesh suture design aimed at minimizing the early laparotomy dehiscence that drives ventral hernia formation. The authors hypothesized that modulation of the suture-tissue interface through use of a macroporous structure and increased aspect ratio (width-to-height ratio) would decrease the suture pull-through that leads to laparotomy dehiscence. Incisional hernias were produced in 30 rats according to an established hernia model. The rat hernias were randomized to repair with either two 5-0 polypropylene sutures or two midweight polypropylene mesh sutures. Standardized photographs were taken before repair and 1 month after repair. Edge-detection software was used to define the border of the hernia defect and calculate the defect area. Histologic analysis was performed on all mesh suture specimens. Seventeen hernias were repaired with mesh sutures and 13 were repaired with conventional sutures. The mean area of the recurrent defects following repair with mesh suture was 177.8 ± 27.1 mm2, compared with 267.3 ± 34.1 mm2 following conventional suture repair. This correlated to a 57.4 percent reduction in defect area after mesh suture repair, compared with a 10.1 percent increase in defect area following conventional suture repair (p < 0.0007). None (zero of 34) of the mesh sutures pulled through the surrounding tissue, whereas 65 percent (17 of 26) of the conventional sutures demonstrated complete pull-through. Excellent fibrocollagenous ingrowth was observed in 13 of 17 mesh suture specimens. Mesh sutures better resisted suture pull-through than conventional polypropylene sutures. The design elements of mesh sutures may prevent early laparotomy dehiscence by more evenly distributing distracting forces at the suture-tissue interface and permitting tissue incorporation of the suture itself.

Endosseous dental implants with rough surfaces have been designed to improve early healing, especially in areas of poor bone or insufficient bone quantity. The aim of this study was to histomorphometrically assess the bone-to-implant contact on 3 different rough-surfaced implants following guided bone regeneration. Mandibular premolars and first molars were extracted in 12 dogs, and healing was allowed for 6 months. Six implant osteotomy sites were prepared, 3 per side, followed by the creation of 7.3 mm wide by 5 mm deep surgical defects in the coronal section of the osteotomy sites. Ten-mm long titanium screw-type implants with titanium plasma-sprayed (TPS), hydroxyapatite-coated (HA), or acid-etched (AE) surfaces were placed; the surrounding defects were filled with canine demineralized freeze-dried bone allograft; implants/grafts were covered with expanded polytetrafluoroethylene membranes; and the tissue was closed. Following a healing period of 4 months, the animals were sacrificed and mandibular blocks were harvested for histomorphometric analysis. The mean percentage of bone-to-implant contact in the defect and non-defect areas for the different implant surfaces was: AE 16.24% defect, and 28.78% non-defect; TPS 25.08% defect, and 16.96% non-defect; and HA 48.25% defect and 26.60% non-defect. Within the defect, the mean difference in the bone-to-implant contact was significant for HA compared to TPS (P < 0.0001) and HA versus AE (P < 0.0001); TPS versus AE was not significant (P = 0.063). In the non-defect areas, the mean difference in the bone-to-implant contact was significant for AE versus TPS (P = 0.010); all other comparisons were not significant. There were 18 membrane exposures in the 72 implant sites. Data were analyzed again to assess the impact of membrane complications. Using a 1-way analysis of variance, the bone-to-implant contact was compared between the sites with and without membrane complications. No significant differences were seen in the defect areas or in the non-defect areas between the sites with and without membrane complications. In this study, the bone-to-implant contact in regenerated bone was greatest when an HA-coated implant was used.

BackgroundOdontogenic cutaneous fistula appears as dimpling or a nodule with purulent discharge, usually in the chin or jaw. Affected patients usually seek help from dermatologists or surgeons rather than from dentists. However, clinical symptoms of facial skin fistula without dental problems can lead to misdiagnosis.ObjectiveThe purpose of this study was to investigate the clinical characteristics of patients with odontogenic cutaneous fistulas.MethodsThis retrospective observational study was performed at Chungbuk National University Hospital by analyzing patients who visited from April 1994 to September 2014. Following clinical and radiographic examinations, the paths and origins of sinus fistulas were determined. Investigated factors were gender, age, morphology, location, originating tooth, time to evolution, recurrence, and treatment method.ResultsThirty-three patients (22 males, 11 females; average age 49.2 years) were examined during the investigation period. Thirty-four fistulas were diagnosed as odontogenic cutaneous fistulas. The most common morphology was dimpling (n=14, 41.2%). The various locations observed were related to the originating tooth. The most common site was the mandibular body related to mandibular molars. The referral clinical diagnosis was of odontogenic origin in 6 cases (18.2%). The majority of patients had experienced recurrence after treatment in previous clinics that had failed to diagnose odontogenic cutaneous fistula. Surgical fistulectomy and/or tooth treatment were performed in all cases. All patients were followed-up for 1 year. None showed signs of recurrence.ConclusionExtraoral and dental examinations are required to make a diagnosis of odontogenic cutaneous fistula. Thus, cooperation between dermatologists and dentists is essential.

Electrohydraulic shockwave devices have been Food and Drug Administration-cleared for improved blood flow and connective tissue activation and have been used to treat erectile dysfunction (ED). In this study, the main focus was to evaluate improvement in erectile tissue quality after low intensity shockwave therapy (LiSWT). A single-blind, sham-controlled, randomized, prospective study, was performed in men with ED naïve to shockwave or radial ballistic pressure wave therapy. Participants were randomized 1:2 to simulated (sham) or active LiSWT treatment. After simulated treatments, participants in the Sham Arm were converted to active LiSWT, while participants initially in the Active Treatment Arm received no further treatment. Assessments were performed at baseline and two follow-up visits. Subjective parameters of erectile function (EF) were assessed by total and EF domain scores of the International Index of Erectile Function (IIEF) and sexual encounter profile (SEP). Objective parameters of penile erection were measurements of hypoechoic areas in images obtained by grayscale ultrasound (GUS) with high resolution 15.4 MHz probe and cavernosal artery peak systolic velocity (PSV) and end diastolic velocity (EDV) by color duplex Doppler ultrasound (DUS). Outcome measures for erectile and urinary function were also obtained. Simulated LiSWT did not significantly change any assessment parameter. Sham Arm participants who converted to active LiSWT had significantly increased mean IIEF total (P=0.02) and IIEF-EF scores that approached statistical significance (P=0.06), relative to baseline. Similarly, at the end of the study, Active Treatment Arm participants had significantly increased mean IIEF total (P=0.02) and IIEF-EF scores that approached statistical significance (P=0.07), relative to baseline. Additionally, at the end of the study, SEP3 success rates (erection lasting long enough for successful intercourse) approached statistical significance when Sham Arm participants were converted to active LiSWT (P=0.08) and reached statistical significance in the Active Treatment Arm (P=0.049). GUS assessments by visual grading were significantly correlated to IIEF-EF score (P=0.002) and were significantly increased relative to baseline in the Active Treatment Arm at follow-up Assessment 1 (P=0.03) and Assessment 2 (P=0.04). The greatest reduction in hypoechoic area after LiSWT occurred in the proximal penile shaft. EDV was also significantly reduced in the Active Treatment Arm at follow-up Assessment 1 (P=0.04) and Assessment 2 (P=0.04). LiSWT also resulted in improved prostate symptom scores, approaching significance in the Active Treatment Arm (P=0.055) with no changes in prostate-specific antigen. Treatment-related adverse events were limited and transient. In this prospective trial, LiSWT was safe and efficacious for erectile symptoms using GUS imaging as a novel, non-invasive method to assess improvements in corporal veno-occlusive function. Improved veno-occlusion and reduced hypoechoic area demonstrated by GUS imaging suggest that LiSWT decreases connective tissue content in penile erectile tissue. Lower urinary tract symptoms also improved with LiSWT. NCT06600893 on clinicaltrials.gov.

To compare the performance and safety of Inion GTR(TM) Biodegradable Membrane System and Geistlich resorbable bilayer Bio-Gide((R)) membrane in human bone regeneration. In a multicenter, split blind, comparative, randomized, prospective, pilot study 15 patients have been randomized at surgery whether to be treated either with Inion GTR(TM) Biodegradable Membrane System on one and Geistlich resorbable bilayer Bio-Gide((R)) membrane on the other side or vice versa after surgical removal of both fully impacted wisdom teeth. During the follow-up visits at week 1, 2 and 6 and at months 3 and 6 the general state, the wound, eventual adverse events and the medication of the patients were assessed. Computed Tomography (CT) scans were performed immediately and 3 months after the surgery, before biopsy collection. Semi-quantitative histological evaluation and histomorphometric analyses were performed according to the ISO 10993-6 standard. New bone formation and membrane integration were evaluated by CT scan measurements. Tissue healing was evaluated clinically and by photographs between the time on teeth extraction and during follow ups. Five patients were smokers, none drank alcohol. Mild adverse events like wound infection, haematoma or late swelling of the gums occurred in three patients. The trephine bur harvest of bone biopsies under local anaesthesia was uneventful. Whereas specimens from the sites treated with the Inion membrane yielded 17.0% (SD 24%), the Bio-Gide membrane sites yielded 13.5% (SD 15%) of bone tissue density. In sites treated with the Inion membrane, 9.5% of old bone density and 7.5% of newly formed bone could be found, whereas the Bio-Gide((R)) membrane sites showed 3.8% of old bone density and 9.8% of newly formed bone. There were no statistically significant differences between the two groups with respect to the two variables. The osteoid rim was more extended with the Bio-Gide((R)) (6.6 mm) than with the Inion membrane (5.1 mm) but the difference between the two treatments did not reach statistical significance. Highly significant reductions in the area of the defect with both membranes were detected with significant increases in CT density at the immediate inferio-buccal adjacent bone and in the surgical defect area with both membranes. However, there was neither significant change in CT density in the immediate inferior-lingual adjacent bone of the two membranes, nor significant difference between the membranes on any of the four measurements (area of defect: P=0.1354; CT density immediate inferio-buccal adjacent bone: P=0.7615; CT density surgical defect area: P=0.1876; CT density immediate inferio-lingual adjacent bone: P=0.4212). The overall clinical outcome was satisfying and the majority of the patients showed an uneventful healing phase. Both membranes presented similar capacities regarding their barrier function and were associated with analogous bone regeneration. No statistically valid evidence about the superiority of one particular membrane was obtained. For the patient the only difference is that one product is animal derived and the other synthetic.

Guided bone regeneration is a promising means for reconstructing bone defects in the cranium. The present study was performed to better define those factors that affect osteogenesis in the cranium. The authors studied a single animal model, investigating the contribution of the dura, the pericranium, and the adjacent calvarial bone in the process of calvarial regeneration in both mature and immature animals. Bilateral, 100-mm2, parietal calvariectomies were performed in immature (n = 16) and mature (n = 16) rabbits. Parietal defects were randomized to one of four groups depending on the differential blockade of the dura and/or the pericranium by expanded polytetrafluoroethylene membranes. Animals were humanely killed after 12 weeks, and histometric analysis was performed to quantitate the area of the original bone defect, new bone formation, and new bone density. Bone formation was quantified separately both at the periphery and in the center of the defects. Extrasite bone formation was also quantified both on the dural and on the pericranial sides of the barriers. Bone regeneration was incomplete in all groups over the 12-week study period, indicating that complete bone healing was not observed in any group. The dura was more osteogenic than the pericranium in mature and immature animals, as there was significantly more extrasite bone formed on the dural side in the double expanded polytetrafluoroethylene barrier groups. In both the dural and the double expanded polytetrafluoroethylene barrier groups, dural bone production was significantly greater in immature compared with mature animals. The dura appeared to be the source of central new bone, because dural blockade in the dural and double expanded polytetrafluoroethylene groups resulted in a significant decrease in central bone density in both mature and immature animals. Paradoxically, isolation of the pericranium in mature animals resulted in a significant reduction in total new bone area, whereas pericranial contact appeared to enhance peripheral new bone formation, with the control group having the greatest total new bone area. The present study establishes a model to quantitatively study the process of bone regeneration in calvarial defects and highlights differences in the contribution of the dura and pericranium to calvarial bone regeneration between infant and adult animals. On the basis of these findings, the authors propose that subsequent studies in which permeability of the expanded polytetrafluoroethylene membranes is altered to permit migration of osteoinductive proteins into the defect while blocking prolapse of adjacent soft tissues may help to make guided bone regeneration a realistic alternative for the repair of cranial defects.

Background:To assess and compare the effectiveness of two surgical procedures (Beagle's technique and modified Beagle's technique) for the reconstruction of the lost interproximal dental papilla.Materials and Methods:Twenty sites were selected based on the selection criteria which included patients within the age group of 20–50 years and the presence of Class I and Class II recession of the papilla in the maxillary anterior region. They were divided randomly into Group A and Group B. Group A sites were treated with modified Beagle's technique, whereas Group B sites were treated by the Beagle's technique. The patients were recalled at 1 week, 1 month, 3 months, and 6 months postsurgery. Parameters including classification of loss of papilla height (Nordland and Tarnow), change in vertical dimension, mesiodistal dimension and area of the papillary defect, and radiographic parameters (papilla height and bone crest-root apex distance) were recorded preoperatively and postoperatively.Results:At 6-month postsurgery, there was a statistically significant reduction in vertical dimension, mesiodistal dimension, and area of the papilla defect in Group A compared to Group B. At 6-month postsurgery, there was an increase in the height of the papilla in Group A, whereas there was a decrease in the height of the papilla in Group B. At 6-month postsurgery too, there was a reduction in the mean bone crest-root apex distance in both groups.Conclusion:Thus, the modified Beagle's technique is an easy and effective technique when compared to the Beagle's surgical technique for papilla reconstruction.

ObjectiveA bone defect rat model was established to investigate the osteogenic effect of local delivery two antibiotics (vancomycin and tobramycin powder) on bone regeneration.MethodsTwenty‐four Sprague–Dawley (SD) male rats (6 to 8 weeks, 200 to 250 g) were used in this study. All these rats were randomly divided into four groups. Based on dose conversion between rat and human via body surface area, the rat dose of two antibiotics was 88μg/g and 176 μg/g for vancomycin and tobramycin, respectively. Con group (no antibiotic), Van group (vancomycin, 88 μg/g), Tob group (tobramycin 176 μg/g), and Van+Tob group (vancomycin 88μg/g combined with tobramycin 176 μg/g). A 5.0‐mm full‐thickness standardized mandibular bone defect was performed with a drill in each rat and different antibiotic powders were placed over the bone defect space, respectively. All these animals were sacrificed after 12 weeks post‐operation. The mandible bones were harvested for further radiographic and histologic analysis. The bone volume/total volume (BV/TV) ratio, bone volume (BV), and bone fractional area (BFA) in the defect area via micro‐computed tomography (μCT scanning) were further analyzed. Then, we performed a histological assessment via hematoxylin and eosin (H&E) and Masson's trichrome staining to analyze bone regeneration and also analyze the number of osteoblasts per filed.ResultsThere were no postoperative deaths, signs of vancomycin‐related or tobramycin‐related toxicity, or signs of systemic illness in any of the four groups. All wounds healed well, and no complications or surgical site infection were observed in all rats. From the μCT scans analyses, there was less bone regeneration in the Van group than in the Con group (BV/TV: F = 64.29, R 2 = 0.9602; P = 0.0052; BFA: F = 76.17, R 2 = 0.9662, P = 0.0007; BV: F = 194.4, R 2 = 0.9865, P = 0.0022). However, when the tobramycin and vancomycin were combined, an increase in bone defect re‐ossification was found in the Van+Tob group than in the Van group (BV/TV: F = 64.29, R 2 = 0.9602, P = 0.0033; BFA: F = 76.17, R 2 = 0.9662, P = 0.0006; BV: F = 194.4, R 2 = 0.9865, P = 0.0033). Routine H&E and Masson staining supported the finding of μCT scanning. Quantitative indices confirmed that both the bone regeneration and the number of osteoblasts per filed in the defect area was higher in the Van+Tob group than in the Van group (percentage of bone tissue: F = 145.7, R 2 = 0.9562, P = 0.0008; number of osteoblasts per file; F = 67.3, R 2 = 0.9098, P < 0.0001). There was no significant difference between the Con group and the Van+Tob group on the number of osteoblasts each field (F = 145.7, R 2 = 0.9562, P > 0.9999).ConclusionFor bone defect, local application of vancomycin combined with tobramycin was recommended over vancomycin alone. This animal study presents data suggesting that the use of local delivery of vancomycin and tobramycin should be investigated further in clinical studies.

Repair of bone defects presents a serious clinical challenge as it is difficult to restore bone function and regenerate bone loss. In the present study, the effects of lentivirus-mediated transfection of bone marrow mesenchymal stem cells (BMSCs) with microRNA (miR)-26a on bone regeneration were investigated in a mouse bone defect repair model. Marker of proliferation Ki67 (Ki67) staining was employed to detect the cell proliferation capacity and alkaline phosphatase (ALP) staining was used to investigate osteogenic differentiation. A mouse model of cranial bone defects was established. β-tricalcium phosphate biomaterials co-cultured with the transfected BMSCs were implanted into the defect areas of mouse models. Micro-computed tomography, and hematoxylin and eosin and toluidine blue staining, were used to detect bone regeneration in the defect areas and the degradation of scaffolds. miR-26a expression, and the mRNA and protein expression of osteogenesis-associated cytokines, were detected using reverse transcription-quantitative polymerase chain reaction and western blot analysis. Separated and cultured BMSCs highly expressed CD29 and CD105, but not CD34 and CD45, as determined by flow cytometry. miR-26a expression and the positive cell rate of Ki67 and ALP staining in BMSCs transfected with pLVTHM-miR-26a were increased. The BMSC and negative control-transfected BMSC groups exhibited increased bone regeneration in the defect areas, increased bone volume of newly formed bones, and elevated mRNA and protein expression of runt-related transcription factor 2 (Runx2) and osteocalcin (OC), compared with the blank group. However, the miR-26a-transfected BMSC group exhibited further increases in bone regeneration and the volume of newly formed bones, and further elevations of the mRNA and protein expression levels of Runx2 and OC. The present findings demonstrated that lentivirus-mediated modification of BMSCs enhanced bone regeneration during the repair of cranial bone defects in mice.