Christian Lindqvist

Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells

Microvascular reconstruction is the state-of-the-art in many fields of defect surgery today. Currently, reconstruction of large bony defects involves harvesting of autologous bone causing donor site morbidity and risk of infection. Specifically, utilizing autologous adipose stem cells (autoASCs), large quantities of cells can be retrieved for cell therapy applications and the risk of tissue rejection is diminished. The authors describe the first case report of a microvascular custom-made ectopic bone flap employing good manufacturing practice (GMP) level ASCs. The patient underwent a hemimaxillectomy due to a large keratocyst. After 36 months of follow-up, the defect was reconstructed with a microvascular flap using autoASCs, beta-tricalcium phosphate and bone morphogenetic protein-2. ASCs were isolated and expanded in clean room facilities according to GMP standards and were characterized in vitro. After 8 months of follow-up, the flap had developed mature bone structures and vasculature and was transplanted into the defect area. Postoperative healing has been uneventful, and further rehabilitation with dental implants has been started. The in vitro characterization demonstrated multipotentiality and mesenchymal stem cell characteristics in ASCs. This is the first clinical case where ectopic bone was produced using autoASCs in microvascular reconstruction surgery and it will pave way for new clinical trials in the field.

A 5-year in vitro and in vivo study of the biodegradation of polylactide plates

PURPOSE The purpose of this study was to investigate the long-term tissue response and duration of degradation of self-reinforced poly-L-lactide (SR-PLLA) multilayer plates in vivo. MATERIALS AND METHODS Mandibular osteotomies in sheep were fixed with SR-PLLA multilayer plates. The animals were followed for 1, 2, 3, 4, and 5 years, after which histologic studies were performed. RESULTS The foreign-body reaction was mainly mild, and the osteotomies were well united. After 5 years in vivo, the material was almost completely resorbed, but small particles of polymer could still be detected at the implantation site. SR-PLLA plates were also incubated in vitro for 5 years. The material degraded considerably faster in vivo than in vitro. Molecular weight, melting temperature, and crystallinity of the plates remained at a constant level after 2 years in vitro, indicating very slow degradation of the oligomeric (molecular weight [Mw], 3500 daltons), highly crystalline (heat of fusion, 70 J/g), PLLA residue solely as a result of hydrolysis. Although the plates became increasingly fragile as they degraded, they retained their macroscopic form until the end of the 5-year follow-up. Loss of mass of the plates was 52%+/-8% after 5 years of incubation in vitro. CONCLUSIONS Although the long degradation period may seem to be a minor drawback to the use of such plates, it does not appear to affect the healing process.

Prevalence and physical status of human papillomavirus in squamous cell carcinomas of the head and neck

Fresh‐frozen biopsies were obtained from 61 patients at diagnosis of squamous cell carcinoma of the head and neck (HNSCC) for study of the prevalence and physical status of human papillomavirus (HPV) DNA. The frequency of HPV DNA and genotypes were determined by SPF10 PCR screening with a general probe hybridization and INNO‐LiPA HPV genotyping assay. In addition, a single‐phase PCR with primers FAP 59/64 and a nested PCR with primers CP 65/70 and CP 66/69 served to detect particularly cutaneous HPV types. By the sensitive SPF10 PCR and INNO‐LiPA assay, 37 of 61 (61%) samples were positive for HPV. HPV‐16 was the most frequently detected type (31 of 37, 84%). Multiple infections were found in 8 of 37 (22%) of the HPV‐positive samples, and co‐infection by HPV‐16 and HPV‐33 was predominant. No cutaneous HPV types were detected. Patients with HPV‐positive tumors had similar prognosis as those with HPV‐negative ones. Real‐time PCR analysis of the HPV‐16 positive samples indicated the presence of integrated (11 of 23, 48%), episomal (8 of 23, 35%) and mixed forms (4 of 23, 17%) of HPV DNA. The viral load of HPV DNA exhibited large variation. The median copy numbers of E6 DNA in tonsillar specimens were approximately 80,000 times higher than that in nontonsillar HNSCC ones. Patients with episomal viral DNA were more frequently found to have large (T3–T4) tumors at diagnosis than were those with integrated or mixed forms.

Poor dental status increases acetaldehyde production from ethanol in saliva: a possible link to increased oral cancer risk among heavy drinkers

Epidemiological data support evidence that poor dental status increases oral cavity cancer risk especially among heavy alcohol consumers, but the causality of this finding is unclear. The enzymatic conversion of ethanol by the physiological oral microflora may lead to an accumulation of the highly carcinogenic intermediate acetaldehyde. This study was conducted to evaluate the role of dental status on the microbial production of acetaldehyde from ethanol in saliva. The microbial acetaldehyde production from ethanol was related to the dental score in 132 volunteers. After adjustment for smoking, alcohol consumption, age and gender, poor dental status was shown to lead to an approximately twofold increase in salivary acetaldehyde production from ethanol (P=0.02). Our results could be an important factor underlying the role of poor dental hygiene and status in oral cancer risk associated with ethanol drinking.

Infection after rigid internal fixation of mandibular fractures : a clinical and radiologic study

Of 214 patients with mandibular fractures treated following the AO/ASIF principle of rigid fixation, 13 patients (6.1%) developed postoperative infection. The yearly percentage decreased remarkably during the study period. When rigid fixation became a routine method, the infection rate was as low as the corresponding figure for cases treated with nonstable techniques and maxillomandibular fixation (MMF). All but one of the infected fractures were in the angular region of the mandible. Teeth had been extracted from the fracture line in 9 of the 10 dentulous patients. It was concluded that erroneous techniques had been used in almost all infected cases, because compression could not be achieved when there was an irregular fracture line, an atrophic edentulous mandible, or inadequate stability due to removal of a tooth in the line of fracture. In five patients, successful reoperation was performed using a reconstruction plate. Detailed radiologic examination was useful in assessment of infection and in follow-up.

Rigid internal fixation of mandibular fractures: An analysis of 270 fractures treated using the AO/ASIF method

The results are reported on 214 patients treated for 270 mandibular fractures, using rigid internal fixation. Of these, 172 fractures (63.7%) in 131 patients had been re-evaluated at final follow-up in connection with plate and screw removal, on average 15.2 months, postoperatively. Although one-third of the patients had a history of alcohol abuse, and 86% were treated with a delay of more than 24 h (mean 3.2 days), good primary bone healing was observed in 93.9% of the patients. Infections, seen in 6.1% of the patients, were related exclusively to inadequate stability of the fracture. Malocclusion, observed in 18.2% of 159 dentate patients, was caused by incorrect plate bending and insufficient fracture reduction. Immediate postoperative dysfunction of the inferior alveolar nerve in 58.1% of the cases, and of the mandibular branch of the facial nerve in 12.7%, was followed by almost total recovery 1 year after operation. It is concluded that rigid internal fixation is a reliable method of treatment, especially indicated for patients with reduced healing capacity and poor co-operation.

Different patterns of condylar fractures: an analysis of 382 patients in a 3-year period

Three hundred eighty-two patients with 443 condylar fractures, accounting for 52.4% of all mandibular fractures, were given diagnoses and treated in our department between 1987 and 1989. A high proportion of the fractures (44%) were caused by interpersonal violence, followed in incidence by falls (29%) and road traffic accidents (21%). The type of condylar fracture seems to be influenced directly by its cause. Severe fractures in which the condyle was dislocated out of the glenoid fossa resulted more often from falls (22%) and road traffic accidents (26%) than from violence (8%). Fractures caused by violence showed a uniform type characterized by a subcondylar location and nondisplacement or deviation at the fracture line. A relatively large number of patients (56, 15%) were considered to have an indication for open reduction of the fracture.

Autogenous costochondral grafts in temporomandibular joint arthroplasty. A survey of 66 arthroplasties in 60 patients

Summary A clinical study of 60 patients who underwent 66 costochondral arthroplasties during the period 1969–1984 is presented. In nearly half of the cases ankylosis was the main indication for operation, followed by dysplasia, tumours and osteomyelitis. The results showed that all cases in which the rib was decorticated to fit into the mandible as an inlay healed well. The mean time of IMF was 3.5 weeks. In the majority of the patients (67%) the postoperative function of the mandible was considered to be good or excellent, and nearly all patients were pain free. There were no postoperative chest infections and only one case of pneumothorax. Motor and sensory disturbances in the lower lip were each diagnosed in ten per cent of the patients.

Severe bone resorption and osteoarthrosis after miniplate fixation of high condylar fractures: A clinical and radiologic study of thirteen patients

Thirteen cases of high condylar fracture treated by open reduction and fixation with miniplates were monitored for an average of 18 months postoperatively. Satisfactory functional results were achieved clinically in all but one patient. Radiologically, however, signs of condylar resorption and osteoarthrosis were diagnosed in all patients. In four patients with associated multiple fractures of the facial bones, rapid complete resorption of the condyle was observed. These changes were markedly more severe than those observed in our previous study, in which osteosynthesis was performed by transosseous wiring and subsequent intermaxillary fixation for 3 to 7 weeks. Indications for rigid and nonrigid fixation in the surgical treatment of condylar fractures are discussed.

Human Neutrophil Collagenase MMP-8 in Peri-implant Sulcus Fluid and its Inhibition by Clodronate

The exact molecular mechanisms of the loosening of a dental implant are not well-known. The characteristics of implant sulci are similar to those of periodontal sulci regarding gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF). Proteolytic enzymes, matrix metalloproteinases (MMPs), participate in peri-implant tissue remodeling. Clodronate is a well-tolerated bisphosphonate-group drug currently used in bone-resorption-related diseases in humans. The mechanisms of bisphosphonate action are not clarified. Collagenase activity in diseased PISF was significantly higher than in the clinically healthy group. Immunoblotting disclosed that diseased PISF contained increased immunoreactives MMP-8 compared with the healthy PISF. The residual latent collagenase activity in the diseased PISF was activated by gold thioglucose and inhibited completely by 100 pM of doxycycline closely resembling pure neutrophil collagenase (MMP-8). The presence of MMP-8 in diseased but not in clinically healthy PISF may prove to be a useful biochemical indicator to monitor peri-implant health and disease. Pure human neutrophil collagenase (MMP-8) and the MMP-8 present in PISF and in the GCF of both loosening implants and periodontitis-affected teeth were efficiently inhibited in vitro by clodronate (50% inhibition [IC50] was achieved by 150 uM of clodronate), an osteoactive, antiresorptive bisphosphonate. Furthermore, the new finding suggests an extended and hitherto-undescribed potential for clodronate in preventing the loosening of both implants and teeth, based on a dual beneficial effect: prevention of both bone resorption/osteolysis and of soft tissue/dental ligament destruction. Potential new therapeutic indications based on the collagenase-inhibiting effect of clodronate provide potential new therapeutic indications for a variety of diseases involving connective tissue breakdown, such as periodontal disease, arthritides, and tumor invasion.