Bone healing in rabbit calvarial critical-sized defects filled with stem cells and growth factors combined with granular or solid scaffolds.

PURPOSE: In pediatric neurosurgery, decompressive craniectomy and correction of congenital cranial anomalies can result in major cranial defects. Corrective cranioplasty for the repair of these critical-sized defects is not only a cosmetic issue. The limited availability of suitable autogenous bone and the morbidity of donor site harvesting have driven the search for new approaches with biodegradable and bioactive materials. This study aimed to assess the healing of rabbit calvarial critical-sized defects filled with osteogenic material, either with bioactive glass scaffolds or tricalcium phosphate granules in various combinations with adipose stem cells or bone marrow stem cells, BMP-2, BMP-7, or VEGF to enhance osteogenesis. METHODS: Eighty-two bicortical full thickness critical-sized calvarial defects were operated. Five defects were left empty as negative control defects. The remaining 77 defects were filled with solid bioactive glass scaffolds or tricalcium phosphate granules seeded with adipose or bone marrow derived stem cells in combination with BMP-2, BMP-7, or VEGF. The defects were allowed to heal for 6 weeks before histologic and micro-CT analyses. RESULTS: Micro-CT examination at the 6-week post-operative time point revealed that defects filled with stem cell-seeded tricalcium phosphate granules resulted in new bone formation of 6.0 %, whereas defects with bioactive glass scaffolds with stem cells showed new bone formation of 0.5 to 1.7 %, depending on the growth factor used. CONCLUSIONS: This study suggests that tricalcium phosphate granules combined with stem cells have osteogenic potential superior to solid bioactive glass scaffolds with stem cells and growth factors.

Matrix metalloproteinase-8 regulates transforming growth factor-ß1 levels in mouse tongue wounds and fibroblasts in vitro.

Matrix metalloproteinase-8 (MMP-8)-deficient mice (Mmp8-/-) exhibit delayed dermal wound healing, but also partly contradicting results have been reported. Using the Mmp8-/- mice we investigated the role of MMP-8 in acute wound healing of the mobile tongue, and analyzed the function of tongue fibroblasts in vitro. Interestingly, in the early phase the tongue wounds of Mmp8-/- mice healed faster than those of wild type (wt) mice resulting in significant difference in wound widths (P=0.001, 6-24h). The Mmp8-/- wounds showed no change in myeloperoxidase positive myeloid cell count, but the level of transforming growth factor (TGF)-ß1 was significantly increased (P=0.007) compared to the wt tongues. Fibroblasts cultured from wt tongues expressed MMP-8 and TGF-ß1. However, higher TGF-ß1 levels were detected in Mmp8-/- fibroblasts, and MMP-8 treatment decreased phosphorylated Smad-2 levels and α-smooth muscle actin expression in these fibroblasts suggesting reduced TGF-ß1 signaling. Consistently, a degradation of recombinant TGF-ß1 by MMP-8 decreased its ability to activate the signaling cascade in fibroblasts. Moreover, collagen gels with Mmp8-/- fibroblasts reduced more in size. We conclude that MMP-8 regulates tongue wound contraction rate and TGF-ß1 levels. In vitro analyses suggest that MMP-8 may also play a role in regulating TGF-ß1 signaling of stromal fibroblasts.

Healing of rabbit calvarial critical-sized defects using autogenous bone grafts and fibrin glue.

PURPOSE: This study aimed to evaluate ossification of cranial bone defects comparing the healing of a single piece of autogenous calvarial bone representing a bone flap as in cranioplasty compared to particulated bone slurry with and without fibrin glue to represent bone collected during cranioplasty. These defect-filling materials were then compared to empty control cranial defects. METHODS: Ten White New Zealand adult male rabbits had bilateral critical-sized calvarial defects which were left either unfilled as control defects or filled with a single full-thickness piece of autogenous bone, particulated bone, or particulated bone combined with fibrin glue. The defects were left to heal for 6 weeks postoperatively before termination. CT scans of the calvarial specimens were performed. Histomorphometric assessment of hematoxylin-eosin- and Masson trichrome-stained specimens was used to analyze the proportion of new bone and fibrous tissue in the calvarial defects. RESULTS: There was a statistically significant difference in both bone and soft tissue present in all the autogenous bone-grafted defect sites compared to the empty negative control defects. These findings were supported by CT scan findings. While fibrin glue combined with the particulated bone seemed to delay ossification, the healing was more complete compared to empty control non-grafted defects. CONCLUSIONS: Autogenous bone grafts in various forms such as solid bone flaps or particulated bone treated with fibrin glue were associated with bone healing which was superior to the empty control defects.

Tent-pole approach to treat severely atrophic fractured mandibles using immediate or delayed protocols: preliminary case series.

PURPOSE: To investigate the outcomes of patients with severely resorbed fractured mandibles who were managed with a modified tent-pole procedure. PATIENTS AND METHODS: Four edentulous patients (2 male and 2 female; mean age, 59.5 years; range, 52 to 64 years) with a severely atrophic fractured mandible and less than 10 mm of vertical height of the body of the mandible were treated with an immediate or a delayed protocol (n=2 in each group). In the immediate group, a transcutaneous submental approach was used to provide open reduction with rigid fixation, immediate dental implant placement in the anterior mandible, and an autogenous particulate iliac bone grafting harvested from the posterior iliac crest. In the delayed protocol group, the fractures were treated with an open reduction and rigid fixation. Six months after fracture treatment, the fixation hardware was removed and a tent-pole approach was used to place the dental implants to the anterior mandible with an autogenous bone graft harvested from the posterior iliac crest. Implant fixtures were loaded at 3 months as the patients were fitted with healing caps, and the dental implants were loaded using provisional screw-retained acrylic resin prostheses and bar-retained overdentures afterward. The mean follow-up was 19.8 months (range, 13 to 28 months). RESULTS: The postoperative course and healing of the 4 patients was uneventful, without any fracture nonunion. The average alveolar augmentation±standard deviation was 7.5±1.17 mm (range, 6.6 to 9.0 mm). There was no bone resorption around any of the endosseous implants on follow-up. All 4 patients wore their dental implant-supported prosthesis comfortably. CONCLUSIONS: This preliminary evidence indicates that the modified tent-pole technique may be a safe and effective method to manage the fractured severely resorbed mandible using an immediate or a delayed protocol. Much larger-scale prospective evidence is required to further validate this observation.

Navigation-assisted Le Fort I osteotomy with midpalatal split to treat compressive pathologies of the craniovertebral junction.

This report describes the management of the case of an 11-year-old girl with serious compressive pathology of the craniocervical junction using a navigation-guided Le Fort I level maxillotomy and midline split. In this pediatric case, image guidance significantly enhanced intraoperative orientation and helped to determine the correct location of the horizontal osteotomy lines at the Le Fort I level.

Outcome of treatment of implant-retained overdenture in patients with extreme mandibular bone resorption treated with bone grafts using a modified tent pole technique.

PURPOSE: To evaluate the outcome (prosthetic maintenance, survival of implants, patient satisfaction, and quality of life) of prosthetic treatment using an implant-retained overdenture and a modified tent pole procedure for severe mandibular resorption. MATERIAL AND METHODS: Seventeen edentulous patients (mean age, 68 yr; range, 54 to 77 yr) with severely resorbed mandibles were treated with autogenous bone grafts using a modified tent pole technique and implant overdentures. A bar was used to splint the implants and the final prostheses with implant connection were completed approximately 7 months after surgery. The mean follow-up time was 5 years (1.5 to 7.4 yr). Patients filled out the Oral Health Impact Profile-14 questionnaire concerning their oral health-related quality of life, and then panoramic radiographs were taken during clinical examination. RESULTS: The stability of the overdenture was good in 58.8% of cases and retention was good in 64.7%. The most usual prosthetic complication was loosening of the attachment component, which occurred in 7 cases (41.2%). The amount of plaque and bleeding was more remarkable on the lingual surface of the implants and less remarkable on the buccal surface. Pocket depth around the implants seemed to correspond to intraoral implantation. The radiographs depicted excellent grafted bone survival. The patients' oral health-related quality of life was found to be good after treatment. CONCLUSIONS: Implant placement with bone grafting using a modified tent pole technique enables the achievement of a good prosthetic solution and the rehabilitation of occlusion, thereby improving the functionality of the prostheses and quality of life.

Long-term follow-up of severely resorbed mandibles reconstructed using tent pole technique without platelet-rich plasma.

PURPOSE: To investigate the results of edentulous patients with severely resorbed mandibles who were treated with a modified tent pole procedure. PATIENTS AND METHODS: Twenty-two edentulous patients (3 men, 19 women; mean age, 62 yr; range, 51 to 72 yr) with a history of conservative prosthodontic treatment failures were included this study. Using a transcutaneous submental approach, 4 endosseous dental implants were placed in the anterior mandible of each patient and covered with autogenous bone grafts harvested from the posterior iliac crest without the addition of platelet-rich plasma. Follow-up ranged from 3 to 9 years. RESULTS: The postoperative course of the patients was uneventful, without any surgical infections. At 3 months postoperatively, the density of the grafted bone appeared to closely resemble that of the surrounding alveolar bone on panoramic radiographs. The average alveolar augmentation was 6.3 mm (standard deviation, 1.59 mm; range, 4 to 10 mm) and long-term follow-up showed no bone resorption around the endosseous implants. CONCLUSIONS: The modified tent pole technique without the addition of platelet-rich plasma is a safe and effective method to reconstruct the severely resorbed mandible.

Ear canal and middle-ear tumors: a single-institution series of 87 patients.

BACKGROUND: Ear canal and middle ear tumors are rare and exhibit variability in histology and clinical manifestation. Surgical resection remains the treatment of choice, but individualized approach is needed to preserve function when possible. AIMS/OBJECTIVES: To review the management and outcome of ear canal and middle ear tumors at an academic referral center. MATERIALS AND METHODS: Helsinki University Hospital (HUS) patient files were searched for clinically and histologically confirmed ear canal and middle ear tumors over a 14-year period. The minimum follow-up time was 2 years. RESULTS: Eighty-seven patients with 88 tumors were identified. There were 20 (23%) benign external auditory canal (EAC), 36 (41%) benign middle ear space (MES), 29 (33%) malignant EAC, and 3 (3%) malignant MES tumors. Most (92%) tumors were managed with primary resection. Thirty-five percent of the operatively managed patients had a residual or a recurrent tumor. CONCLUSIONS AND SIGNIFICANCE: EAC and MES tumors show great diagnostic and histologic heterogeneity with need for individualized investigative and treatment approaches. In benign tumors, we advocate aggressive local surgical control without sacrificing vital structures. In malignant tumors, we recommend local surgical control with or without adjunct RT.

Posterior cranial vault distraction osteogenesis in craniosynostosis: estimated increases in intracranial volume.

PURPOSE: To study distraction osteogenesis of the posterior cranial vault in children requiring increased intracranial volume. MATERIALS AND METHODS: Ten patients were treated with cranial distractors. Five children had previously been operated for scaphocephaly and one child for Saether-Chotzen syndrome. Two patients had bilateral coronal suture synostosis with Muenke syndrome and two patients had Apert syndrome. At surgery, the cranial bones were mobilized, the head was widened during surgery, and the segments fixed to each other with distractors. Further expansion at a rate of 1 mm/day was performed over 2-4 weeks. The cranium was distracted posteriorly from 20 to 30 mm. RESULTS: The patients all tolerated surgery and distraction well. In all cases, the parents were able to perform the distraction at home. There were no technical problems with the distraction devices. Two cases had minor cutaneous problems, where the distractor penetrated the skin. These cases responded to gentle local wound care measures. At the time of distractor removal, ossification had occurred sufficiently in one of these two cases. In the other case, the device was removed and replaced with a resorbable plate, without any harmful effect on the result. In all cases, sufficient expansion was achieved without causing more cosmetic deformity. Ossification occurred in all cases. This method seems effective, as the calculated increase in intracranial volume was a mean of 20.2% (range 10.2-28.5%). CONCLUSIONS: This preliminary series shows that cranial bone distraction is a useful method for cranial expansion with low morbidity in children with craniosynostosis.

Tracheobronchial stents in patients with malignant airway disease: Finnish tertiary care experience.

OBJECTIVES: Tracheobronchial stenting has an established role in the palliation of malignant central airway obstruction (CAO). The purpose of this study is to describe the experience with self-expanding metal airway stents in 2 tertiary referral centres, covering a third of the population of Finland. METHODS: Patients referred to and treated with airway stenting for malignant CAO using self-expanding metal-stents were identified from electronic patient records, and data were collected using a structured Endoscopic Lower Airway Management instrument. Statistical analysis to reveal factors affecting patient benefit and survival was carried out. RESULTS: A total of 101 patients (mean age 65.8) and 116 procedures were identified. Procedure-related mortality was rare (3/101 patients) and complications infrequent. The median survival was 2.3 months [95% confidence interval (CI): 1.4-3.1). Stent benefit was not significantly affected by clinical characteristics. Survival was impacted by the use of adjunct procedures [hazard ratio (HR) 0.36, 95% CI: 0.23-0.58, P < 0.001), procedural urgency (HR 0.40; 95% CI: 0.23-0.71, P = 0.002) and post-treatment chemoradiotherapy (HR 0.29, 95% CI: 0.15-0.56, P < 0.001). CONCLUSIONS: The beneficial impact observed supports the further use of tracheobronchial stenting in malignant CAO. The use of self-expanding metal stents is encouraged.

Severe acute otitis media and mastoiditis caused by group A beta-hemolytic streptococcus.

OBJECTIVE: To describe the characteristics, diagnostics, treatment, and outcome of severe acute otitis media (AOM) and acute mastoiditis (AM) caused by group A beta-hemolytic streptococcus (GAS). STUDY DESIGN: A retrospective cohort study. METHODS: The yearly incidence of inpatient care-needing GAS AOM/AM patients in our hospital catchment area between 2002 and 2018 was investigated. A detailed analysis was performed for cases treated during the last GAS epidemic in 2017-2018. Anamnesis, signs and symptoms, pure-tone audiometry results, treatment, complications, and outcome were collected from medical charts. Patients responded to an otology-specific health-related quality of life survey (EOS-16) 1.5 to 3 years after their treatment. RESULTS: The number of GAS infections peaks at approximately 7-year intervals. During 2017 and 2018, altogether 37 patients (29 adults and 8 children) were hospitalized due to GAS AOM/AM. AM was diagnosed in 14 (38%) patients. The disease progression was typically very rapid. At presentation, all patients had severe ear pain, 68% tympanic membrane perforation and discharge, 43% fever, and 43% vertigo. In pure-tone audiometry, there was usually a marked mixed hearing loss at presentation. There was a significant recovery in both air and bone conduction thresholds; the pure tone average improvement from presentation was 32.3 ± 14.8 dB. Rapid strep tests (RST) proved to be more sensitive than bacterial culture in identifying GAS as a cause of AOM/AM. CONCLUSION: GAS AOM/AM has a rapid onset. Hearing loss usually includes a sensorineural component, which is usually reversible with adequate treatment. RST seems to be useful in detecting GAS from middle ear discharge. LEVEL OF EVIDENCE: 4.

[Management of facial bone fractures]. / Epäilen kasvoluun murtumaa--mitä teen?

Although the number of patients suffering from facial bone fractures has decreased more resources due to complexity of the fractures are needed. The initial treatment and reconstruction phase require hospitalisation and close collaboration between several medical and dental specialists. Fractures cause alterations in occlusion and masticatory functions and are frequently associated with soft tissue injuries. The primary radiographic examination is panoramic radiography in mandibular and computed tomography in maxillary and mid face fractures. The treatment principles have changed during the last three decades. Long-term maxillomandibular immobilisation has given way to internal fixation and direct osteosynthesis. The greatest innovations of the treatment have taken place in materials. Steel has been replaced by Titanium or resorbable plates, screws and meshes.

Preoperative evaluation and treatment consideration of parotid gland tumors.

BACKGROUND: The nature of parotid tumors often remains unknown preoperatively and final histopathology may reveal unexpected malignancy. Still, the use of fine-needle aspiration cytology (FNAC) and imaging varies in the management of these tumors. METHODS: We evaluated the preoperative examinations and management of all 195 parotid gland tumors diagnosed within our catchment area of 1.6 million people during 2015. RESULTS: Altogether 171 (88%) tumors were classified as true salivary gland neoplasms. FNAC showed no false malignant findings, but it was false benign in 5 (2.6%) cases. Preoperative MRI was utilized in 48 patients (25%). Twenty (10%) malignancies included 16 salivary gland carcinomas. Pleomorphic adenomas accounted for 52% of all adenomas. For 24 (40%) Warthin tumors, surgery was omitted. CONCLUSION: The proportion of malignancies was lower than generally presented. Our proposed guidelines include ultrasound-guided FNAC with certain limitations. MRI is warranted in selected cases, but seems unnecessary routinely.

Healing of extraction sockets in collagenase-2 (matrix metalloproteinase-8)-deficient mice.

Matrix metalloproteinase-8 (MMP-8) participates in skin wound healing and inflammation. We hypothesized that MMP-8 plays a role in wound healing after tooth extraction and in periapical inflammation. Bone formation, collagen metabolism, and inflammation in tooth extraction socket and in periapical lesions were analyzed in wild-type mice and in MMP-8-deficient (MMP-8(-/-)) mice. New trabecular bone area in the extraction sockets and in periapical lesions were similar in both groups. In extraction sockets significantly more type III procollagen was synthesized, and the neutrophil and MMP-9 levels were lower in MMP-8(-/-) mice. The amount of Fas ligand, identified as a substrate for MMP-8, was lower in alveolar mucosa but higher in alveolar bone of MMP-8(-/-) mice. These results indicate that MMP-8 can modulate inflammation and collagen metabolism of alveolar bone and mucosa.

Competing risks analysis of cause-specific mortality in patients with oral squamous cell carcinoma.

BACKGROUND: Survival studies on head and neck cancers are frequently reported with inadequate account for competing causes of death. Realistic descriptions and predictions of postdiagnosis mortality should be based on proper competing risks methodology. METHODS: Prognosis of patients with oral squamous cell carcinoma (OSCC) in terms of mortality from OSCC and from other causes, respectively, was analyzed according to recent methodological recommendations using cumulative incidence functions and models for cause-specific hazards and subdistribution hazards in 306 patients treated in a tertiary care center in Northern Finland. RESULTS: More coherent and informative descriptions and predictions of mortality by cause were obtained with state-of-the-art statistical methods for competing risks than using the prevalent but questionable practice to graph "disease-specific survival." CONCLUSION: From the patients' perspective, proper competing risks analysis offers more relevant prognostic scenarios than naïve analyses of "disease-specific survival"; therefore, it should be used in prognostic studies of head and neck cancers. © 2016 Wiley Periodicals, Head Neck 39: 56-62, 2017.

Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct.

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation. PURPOSE: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model. MATERIAL AND METHODS: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology. RESULTS: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 89 ± 4% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI. CONCLUSION: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI.

Iron-labeled adipose stem cells and neovascularization in rabbit calvarial critical-sized defects.

OBJECTIVE: The aim of this study was to evaluate the presence of iron-labeled adipose stem cells at the 2-week time point and vascular changes at the 2-week and 6-week time points using two different types of scaffolds. STUDY DESIGN: This study included 22 White New Zealand adult male rabbits. In six rabbits, full-thickness calvarial critical-sized defects were filled with autogenous adipose stem cells labeled with iron oxide seeded onto two scaffolds, namely, solid bioactive glass (BAG) or porous tricalcium phosphate granules (TCP) used on reciprocal sides of the skull. Eleven rabbits were implanted with adipose stem cell-seeded scaffolds without iron labeling for analysis of vascular changes. Five defects were left empty as negative control defects. The specimens were analyzed histologically at the 2-week and 6-week time points. RESULTS: The TCP group showed significantly more vascularity compared with the BAG group. A greater number of labeled stem cells were identified in the TCP group compared with the BAG group, but the difference was not statistically significant. CONCLUSIONS: This study revealed the differences in stem cell distribution and revascularization of the calvarial defect, which may be biomaterial dependent.

Expression of matrix metalloproteinases-2, -8, -13, -26, and tissue inhibitors of metalloproteinase-1 in human osteosarcoma.

Osteosarcoma (OS) is among most common malignant tumour of bone. Matrix metalloproteinases (MMPs) are predominantly associated with poor prognosis of several cancers, although some of them, like MMP-8, seem to have a protective role in some cancers. We analyzed the distribution patterns of MMP-2, -8, -13, -26, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in 25 OS patients. MMP-2, -8, -13, -26 and TIMP-1 were mostly detected in sarcoma cells. Response to chemotherapy affected the amount of MMP-2, -8, and -13 in resection sections when compared to biopsies: patients with excellent or good response had less positivity to MMP-2 in chemotherapy samples than those with moderate or poor response. We conclude that MMP-2, -8, -13, -26, and TIMP-1 are expressed in OS tissue, and all, except protective MMP-8, were also found in metastases indicating that MMPs and TIMP-1 can participate in the OS progression.

Collagenase-2 (MMP-8) and matrilysin-2 (MMP-26) expression in human wounds of different etiologies.

Wound healing involves highly controlled events including reepithelialization, neoangiogenesis, and reformation of the stromal compartment. Matrix metalloproteinases (MMPs) are a family of neutral zinc-dependent endopeptidases known to be essential for the wound-healing process. MMP-8 (collagenase-2) is a neutrophil-derived highly effective type I collagenase, recently indicated to be important for acute wound healing. MMP-26 is a more recent and less well-studied member of the MMP family. Our aim was to study the expression of MMP-8 and MMP-26 in human cutaneous wound repair and chronic wounds using histological methods and cell culture. MMP-8 expression was associated with epithelial cells, neutrophils, and other inflammatory cells in chronic human wounds. MMP-26 was prominently expressed in the extracellular compartment of most chronic wounds in close vicinity to the basement membrane area. MMP-26 was also expressed in acute day 1 wounds with declining expression thereafter. In vitro wound experiments showed that both MMP-8 and MMP-26 were expressed by migrating human mucosal keratinocytes. Inhibiting MMP-26 resulted in aberrant keratinocyte migration and proliferation. We conclude that MMP-8 and MMP-26 are differentially expressed in acute and chronic wounds.