Heparan sulfate chains contribute to the anticoagulant milieu in malignant pleural effusion.

BACKGROUND: While malignant pleural effusion (MPE) is a common and significant cause of morbidity in patients with cancer, current treatment options are limited. Human heparanase, involved in angiogenesis and metastasis, cleaves heparan sulfate (HS) side chains on the cell surface. AIMS: To explore the coagulation milieu in MPE and infectious pleural effusion (IPE) focusing on the involvement of heparanase. METHODS: Samples of 30 patients with MPE and 44 patients with IPE were evaluated in comparison to those of 33 patients with transudate pleural effusions, using heparanase ELISA, heparanase procoagulant activity assay, thrombin and factor Xa chromogenic assays and thromboelastography. A cell proliferation assay was performed. EMT-6 breast cancer cells were injected to the pleural cavity of mice. A peptide inhibiting heparanase activity was administered subcutaneously. RESULTS: Levels of heparanase, factor Xa and thrombin were significantly higher in exudate than transudate. Thromboelastography detected almost no thrombus formation in the whole blood, mainly on MPE addition. This effect was completely reversed by bacterial heparinase. Direct measurement revealed high levels of HS chains in pleural effusions. Higher proliferation was observed in tumour cell lines incubated with exudate than with transudate and it was reduced when bacterial heparinase was added. The tumour size in the pleural cavity of mice treated with the heparanase inhibitor were significantly smaller compared with control (p=0.005). CONCLUSIONS: HS chains released by heparanase form an anticoagulant milieu in MPE, preventing local thrombosis and enabling tumour cell proliferation. Inhibition of heparanase might provide a therapeutic option for patients with recurrent MPE.

Heparanase level and procoagulant activity are reduced in severe sepsis.

BACKGROUND: During severe sepsis, levels and activity of all coagulation proteins are reduced. Heparanase is implicated in angiogenesis and tumor progression. We previously demonstrated that heparanase also affected the hemostatic system. It forms a complex and increases the activity of the blood coagulation initiator tissue factor. AIM: To evaluate heparanase levels and procoagulant activity as predictors of sepsis severity. MATERIALS AND METHODS: Twenty-one patients with non-trauma, non-surgical sepsis admitted to the intensive care unit and 35 controls were recruited. Plasma samples were drawn from the study participants on days 1 and 7 following admission. RESULTS: Heparanase levels and procoagulant activity on day 1 were significantly reduced in patients compared to controls (P < .0001, P < .0001, respectively). Day 1 heparanase procoagulant activity ≥350 ng/mL yielded a negative predictive value for severe sepsis of 89%. Additionally, heparanase procoagulant activity on day 7 correlated with the change in the APACHE score between days 1 and 7 (r = .66, P = .007). CONCLUSIONS: Heparanase procoagulant activity decreases during sepsis and returns to normal levels as soon as the patient recovers. Hence, it can be potentially used to predict the risk of severe sepsis. These findings need to be further explored in large-scale studies.

Recurrent episodes of micturition with expulsion of symphyseal plate screws following pelvic ring fixation: case report.

BACKGROUND: Based on a computer-assisted literature search, this case is the first description of repeated loosening of metallic internal fixation implants after pelvic ring stabilization, associated with intravesical metal migration and micturition with expulsion of two bone screws. CASE PRESENTATION: A 62-year old woman was seen after the urinary expulsion of a 6.5 mm diameter cancellous screw. About seven years earlier, she had been hit by a motorcyclist while crossing the street. On admission at the time of the initial injury, thoraco-abdominal computerized tomography with intravenous contrast material revealed a bladder injury and pelvic ring fractures. An anterior-posterior type injury to the pelvic ring was diagnosed with symphyseal pubis disruption, and widening of the left sacroiliac joint with an associated sacral fracture. Explorative laparotomy revealed two bladder lacerations of both the posterior and the anterior bladder wall, which were repaired primarily. Orthopedic surgeons reduced the pelvis and stabilized it with two plates and screws. Seven years after the original injury, the patient presented with recurrent abdominal pain after expelling a screw into the toilet while urinating. Planar radiographs showed only five of the original screws remaining in the two symphyseal plates, and all screws appeared to have loosened when compared to the original fixation radiograph. CONCLUSION: This clinical report emphasizes the importance of symphyseal plate positioning and the sequelae of imprecise positioning, especially postero-superiorly adjacent to the Retzius space. The presence of protruding metal prominences, even smooth ones like a plate corner or screw head, might endanger the bladder. When using superior plates, imprecise contouring may lead to plate edge protrusion which could damage the bladder even long after application.

Effect of seasonality, weather and holidays on the incidence of proximal hip fracture.

BACKGROUND: Proximal hip fractures in the elderly are common and place a heavy burden on health resources. Researching the timing of these fractures could contribute to diverting resources towards peaks in incidence and investing in prevention at certain times. OBJECTIVES: To examine the effect of seasonality, weather and Jewish holidays on hip fracture incidence in older adults. The study population comprised 2050 patients aged 65 years or more who sustained a proximal hip fracture. METHODS: The computerized files of the patients were reviewed for trends in incidence by season, precipitation, minimum and maximum temperatures, day of the week, and certain Jewish festivals. RESULTS: Hip fractures were more likely to occur in the winter than in the summer (P < 0.0001). Factors that significantly correlated with hip fracture were the maximum daily temperature (r = -0.746, P = 0.005) followed by the minimum daily temperature (r = -0.740, P = 0.006) and precipitation (r = 0.329, P = 0.02). There were fewer fractures on Saturdays (the Sabbath) as compared to other days of the week (P = 0.045). Researching the incidence on Jewish holidays, we found an elevated incidence on Passover (P < 0.0001) and a reduced incidence on the Day of Atonement (Yom Kippui) (P = 0.013). CONCLUSIONS: In older people there is an elevated incidence of proximal hip fractures during the winter and on the Jewish festivals. On weekends and on the Day of Atonement the incidence of proximal hip fractures was reduced.

Development of a local controlled release system for therapeutic proteins in the treatment of skeletal muscle injuries and diseases.

The present study aims to develop and characterize a controlled-release delivery system for protein therapeutics in skeletal muscle regeneration following an acute injury. The therapeutic protein, a membrane-GPI anchored protein called Cripto, was immobilized in an injectable hydrogel delivery vehicle for local administration and sustained release. The hydrogel was made of poly(ethylene glycol)-fibrinogen (PEG-Fibrinogen, PF), in the form of injectable microspheres. The PF microspheres exhibited a spherical morphology with an average diameter of approximately 100 micrometers, and the Cripto protein was uniformly entrapped within them. The release rate of Cripto from the PF microspheres was controlled by tuning the crosslinking density of the hydrogel, which was varied by changing the concentration of poly(ethylene glycol) diacrylate (PEG-DA) crosslinker. In vitro experiments confirmed a sustained-release profile of Cripto from the PF microspheres for up to 27 days. The released Cripto was biologically active and promoted the in vitro proliferation of mouse myoblasts. The therapeutic effect of PF-mediated delivery of Cripto in vivo was tested in a cardiotoxin (CTX)-induced muscle injury model in mice. The Cripto caused an increase in the in vivo expression of the myogenic markers Pax7, the differentiation makers eMHC and Desmin, higher numbers of centro-nucleated myofibers and greater areas of regenerated muscle tissue. Collectively, these results establish the PF microspheres as a potential delivery system for the localized, sustained release of therapeutic proteins toward the accelerated repair of damaged muscle tissue following acute injuries.

Core decompression and alendronate treatment of the osteonecrotic rat femoral head: computer-assisted analysis.

Femoral head avascular necrosis is a process leading to femoral head deformity and osteoarthritic changes in the hip joint. Alendronate slows down bone resorption and remodelling in rats, while core decompression hastens the healing processes. We evaluated the influence of daily alendronate treatment on the rat femoral head shape after surgical osteonecrosis with core decompression, compared with controls. No differences were found in shape factor and femoral head height/length ratios. It was concluded that alendronate treatment slows down the process of replacing osteonecrotic bone by new bone and prevents early immature new bone collapse resulting from early revascularization because of core decompression.

Surgical stabilisation in equivocal pelvic ring injuries - Into the grey zone.

Pelvic ring injuries comprise a spectrum of bony, ligamentous and muscular injuries, described by several common classification systems. However, the majority of injuries lie in areas of intermediate severity, where complexity and variable nature make it extremely hard to define in detail. This fact and associated injuries make it extremely difficult to conduct randomised control trials, with purpose to direct treatment guidelines. Thus, special interest and expertise are required by pelvic trauma surgeons, while surgical indications and fixation methods rely on their experience, at least in part. Namely, a significant grey zone of indication exists. As fixation methods evolve, specifically percutaneous fixation using osseous fixation pathways, some injuries in which morbidity bound with surgical fixation was considered too high relative to its benefits, may be considered eligible for surgical treatment nowadays. Moreover, due to significant progress in the treatment of the acute polytrauma casualties, the survival rate increased over the years, emphasizing the effect of long-term morbidity and functional outcome of pelvic ring injuries. The purpose of this manuscript is to describe the equivocal areas of controversies, hence "the grey zone", and to provide the readership with up-to-date published data. We aimed to collect and detail clinical and radiological clues in the diagnosis of intermediate unstable anterior-posterior compression and lateral compression injuries, and for the selection of treatment methods and sequence. Recent publications have provided some insights into specific injury features that are correlated with increased chance of instability, pain and delay in ambulation. Specific focus is given to the utility of examination under anaesthesia in selected cases. Other publications surveyed the shared experience of pelvic trauma surgeons as for the classification, indication and treatment sequence of pelvic ring injuries. Although the data hasn't matured yet to a comprehensive treatment algorithm, it may serve clinicians well when making treatment decisions in the grey zone of pelvic ring injuries, and serve as a basis for future prospective studies.

Antibiotic impregnated cement spacer for salvage of diabetic osteomyelitis.

BACKGROUND: Florid infection and osteomyelitis of the forefoot in patients with diabetic neuropathy often requires minor amputation, with risk of subsequent reulceration, reamputation, and patient dissatisfaction. We investigated use of an antibiotic-impregnated cement spacer (ACS) to release antibiotic locally to resolve residual infection and to fill the cavity created by debridement. METHODS: We report 23 cases of osteomyelitis and associated severe infection of forefoot joints in 20 consecutive patients, age 60.3 +/- 13.4 years. Antibiotic-impregnated cement, extensive meticulous debridement, and ACS placement to fill the gap were employed in all cases. Deep cultures were taken routinely. Fixation with Kirschner wires was used as necessary. Mean followup was 21.2 +/- 10.2 months. A successful result was resolution of infection and wound healing to full skin closure without amputation. RESULTS: Of 23 cases, 21 (91.3%) healed and two required toe amputation. ACS was left permanently in 10 patients, removed with arthrodesis in six, and removed without arthrodesis in five. One patient recovered but subsequently underwent transtibial amputation due to infection of a different site. CONCLUSION: Severe infection associated with osteomyelitis of the foot in diabetic patients was successfully treated with extensive debridement and use of ACS, which filled the void created by debridement. Amputation was avoided in most patients. This procedure allowed extensive debridement through filling large voids with ACS, with prolonged antibiotic release.

A combined cell and growth factor delivery for the repair of a critical size tibia defect using biodegradable hydrogel implants.

The ability to repair critical-sized long-bone injuries using growth factor and cell delivery was investigated using hydrogel biomaterials. Physiological doses of the recombinant human bone morphogenic protein-2 (rhBMP2) were delivered in a sustained manner from a biodegradable hydrogel containing peripheral human blood-derived endothelial progenitor cells (hEPCs). The biodegradable implants made from polyethylene glycol (PEG) and denatured fibrinogen (PEG-fibrinogen, PF) were loaded with 7.7 µg/ml of rhBMP2 and 2.5 × 106 cells/ml hEPCs. The safety and efficacy of the implant were tested in a rodent model of a critical-size long-bone defect. The hydrogel implants were formed ex-situ and placed into defects in the tibia of athymic nude rats and analyzed for bone repair after 13 weeks following surgery. The hydrogels containing a combination of 7.7 µg/ml of rhBMP2 and 2.5 × 106 cells/ml hEPCs were compared to control hydrogels containing 7.7 µg/ml of rhBMP2 only, 2.5 × 106 cells/ml hEPCs only, or bare hydrogels. Assessments of bone repair include histological analysis, bone formation at the site of implantation using quantitative microCT, and assessment of implant degradation. New bone formation was detected in all treated animals, with the highest amounts found in the treatments that included animals that combined the PF implant with rhBMP2. Moreover, statistically significant increases in the tissue mineral density (TMD), trabecular number and trabecular thickness were observed in defects treated with rhBMP2 compared to non-rhBMP2 defects. New bone formation was significantly higher in the hEPC-treated defects compared to bare hydrogel defects, but there were no significant differences in new bone formation, trabecular number, trabecular thickness or TMD at 13 weeks when comparing the rhBMP2 + hEPCs-treated defects to rhBMP2-treated defects. The study concludes that the bone regeneration using hydrogel implants containing hEPCs are overshadowed by enhanced osteogenesis associated with sustained delivery of rhBMP2.

[Plantar fasciitis and extracorporeal shock wave therapy--essence, diagnosis and treatment methods].

Heel pain is a very common foot complaint, usually caused by inflammation at the origin of the plantar fascia in the heel, termed plantar fasciitis (PF). The diagnosis is based on patient history and physical examination. Treatment of PF is mainly conservative. In recent years, extracorporeal shock wave therapy (ESWT) for a variety of orthopedic pathologies has become more acceptable and is increasing in popularity. Treating PF with ESWT is effective and should be considered before steroid injections and definitely prior to surgical intervention.

[A new non-invasive biomechanical therapy for knee osteoarthritis improves clinical symptoms and gait patterns].

BACKGROUND: The management of knee osteoarthritis (OA) focuses on reducing the levels of pain and disability. Recently, a novel biomechanical device and treatment methodology (AposTherapy) was shown to reduce the knee adduction moment while simultaneously challenging the neuromuscular control system through perturbation. AIM: The purpose of the study was to investigate the changes in gait patterns and clinical measurements following treatment with a novel biomechanical device on patients with knee OA. METHODS: A total of 745 patients with bilateral knee OA were analyzed. Patients completed a gait test, Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire and SF-36 Health Survey at baseline and after 12 weeks. The biomechanical device was individually calibrated to each patient. Shifting the center of pressure, through changes in the location of the biomechanical elements causes realignment and reduction in the knee adduction moment. Furthermore the configuration of the biomechanical element allows training under controlled perturbation. RESULTS: A significant decrease was found in WOMAC pain (28.6%) and WOMAC function (25.2%) following three months of therapy (p<0.001). A significant increase was found in the patients' physical quality of life (17.8%) and mental quality of life (11.0%) (p<0.001). Gait velocity, cadence step length, stance phase and single limb support phase improved significantly following three months of therapy (7.6%, 4%, 3.7% and 1.6%, respectively). CONCLUSIONS: Our results suggest an overall improvement in the gait patterns, level of pain, function and quality of life of patients with knee OA following three months of AposTherapy.

Interobserver and intraobserver agreement for Letournel acetabular fracture classification system using 3-dimensional printed solid models.

BACKGROUND: Acetabular fractures pose diagnostic and surgical challenges. They are classified using the Judet-Letournel system, which is based solely on X-ray. However, computed tomography (CT) imaging is now more widely utilized in diagnosing these injuries. The emergence of 3-dimensional (3-D) printing technology in varying orthopedic fields has provided surgeons a solid model that improves their spatial understanding of complex fractures and ability to plan pre-operatively. AIM: To evaluate the reliability of the Judet-Letournel classification system of acetabular fractures, when using either CT imaging or 3-D printed models. METHODS: Seven patients with acetabular fractures underwent pelvic CT imaging, which was then used to create solid, 3-D printed models. Eighteen orthopaedic trauma surgeons responded to questionnaires regarding fracture classification and preferred surgical approach. The same questionnaire was completed using only CT imaging, and two weeks later, using only 3-D printed models. The inter- and intra-observer agreement rates were then analyzed. RESULTS: Inter-observer agreement rates based on CT imaging or 3-D printed models were moderate for fracture classification: κ = 0.44, κ = 0.55, respectively (P < 0.001) and fair for preferred surgical approach: κ = 0.34, κ = 0.29, respectively (P < 0.005). Intra-observer agreement rates for fracture classification and preferred surgical approach comparing CT imaging or 3-D printed models were moderate: κ = 0.48, κ = 0.41, respectively. No significant difference in intra-observer agreement was detected when comparing orthopedic pelvic specialists to general orthopedic traumatologists. CONCLUSION: The Judet-Letournel classification demonstrated only moderate rates of agreement. The use of 3-D printed models increased the inter-observer agreement rates with respect to fracture classification, but decreased it with respect to the preferred surgical approach. This study highlights the role of 3-D printed models in acetabular fractures by improving spatial understanding of these complex injuries, thus providing more reliable fracture diagnoses and alternative viewpoints for pre-operative planning.

Growth Factor Delivery for the Repair of a Critical Size Tibia Defect Using an Acellular, Biodegradable Polyethylene Glycol-Albumin Hydrogel Implant.

Growth factor delivery using acellular matrices presents a promising alternative to current treatment options for bone repair in critical-size injuries. However, supra-physiological doses of the factors can introduce safety concerns that must be alleviated, mainly by sustaining delivery of smaller doses using the matrix as a depot. We developed an acellular, biodegradable hydrogel implant composed of poly(ethylene glycol) (PEG) and denatured albumin to be used for sustained delivery of bone morphogenic protein-2 (BMP2). In this study, poly(ethylene glycol)-albumin (PEG-Alb) hydrogels were produced and loaded with 7.7 µg/mL of recombinant human BMP2 (rhBMP2) to be tested for safety and performance in a critical-size long-bone defect, using a rodent model. The hydrogels were formed ex situ in a 5 mm long cylindrical mold of 3 mm diameter, implanted into defects made in the tibia of Sprague-Dawley rats and compared to non-rhBMP2 control hydrogels at 13 weeks following surgery. The hydrogels were also compared to the more established PEG-fibrinogen (PEG-Fib) hydrogels we have tested previously. Comprehensive in vitro characterization as well as in vivo assessments that include: histological analyses, including safety parameters (i.e., local tolerance and toxicity), assessment of implant degradation, bone formation, as well as repair tissue density using quantitative microCT analysis were performed. The in vitro assessments demonstrated similarities between the mechanical and release properties of the PEG-Alb hydrogels to those of the PEG-Fib hydrogels. Safety analysis presented good local tolerance in the bone defects and no signs of toxicity. A significantly larger amount of bone was detected at 13 weeks in the rhBMP2-treated defects as compared to non-rhBMP2 defects. However, no significant differences were noted in bone formation at 13 weeks when comparing the PEG-Alb-treated defects to PEG-Fib-treated defects (with or without BMP2). The study concludes that hydrogel scaffolds made from PEG-Alb containing 7.7 µg/mL of rhBMP2 are effective in accelerating the bridging of boney defects in the tibia.

Patients aged 80 and older undergoing orthopedic or urologic surgery: a prospective study focusing on perioperative morbidity and mortality.

BACKGROUND: The population is progressively aging and an increasing number of elderly patients face surgical treatment. OBJECTIVE: The current study was designed to examine the perioperative morbidity and mortality of elderly patients undergoing orthopedic or urologic surgery and look for predictors for adverse outcome. METHODS: This is a prospective study of elderly patients, 80 years of age and older, who underwent elective or emergent orthopedic or urologic surgery in our institution during a 5-month period. Data were collected on age, gender, chronic diseases, number of regular medications, whether or not the patient was bedridden before surgery, American Society of Anesthesiologists (ASA) class, type of surgery and anesthesia, duration of hospitalization, and 30-day postoperative morbidity and mortality. We studied correlations between pre- and intraoperative parameters and postoperative complications. RESULTS: During the study period, 39 patients underwent urologic surgery and 147 patients underwent orthopedic surgery. Age ranged from 80 to 98 years (85 +/- 4.2 years, mean +/- SD). One patient had an intraoperative complication, 5 patients had postoperative complications within 1 day of surgery, and 23 had complications within 1 month of surgery. Five (2.7%) patients, all of whom were operated urgently, died after surgery. Postoperative complications correlated significantly to poor ASA class (p = 0.01), urgency of the procedure (p = 0.03), and extent (p = 0.02) and duration (p = 0.01) of surgery. No significant correlation was found between outcome and any other pre- or intraoperative factors. CONCLUSIONS: Elderly surgical patients with poor ASA class or following urgent, extensive or long surgery are at a higher risk for postoperative morbidity and mortality, mandating special perioperative care.

Prevention of distortion of vascular deprivation-induced osteonecrosis of the rat femoral head by treatment with alendronate.

INTRODUCTION: In animals with a disrupted blood supply and drainage of the femoral head, the dead epiphyseal bone undergoes osteoclastic osteolysis and is replaced by newly synthesized, immature, and weak bone, which cannot withstand the daily loads and, therefore, the articular surface caves in. METHODS: Female Sprague-Dawley rats with interrupted blood circulation of the femoral head were treated with alendronate and compared to controls. RESULTS: There was no distortion of the femoral heads in the alendronate-treated animals. INTERPRETATION: Alendronate medication interferes with osteoclastic activities, slowing down bone turnover. These observations verify our hypothesis that osteoclastic activity is detrimental to the conservation of a hemispherical femoral head because of the rapidly occurring replacement of the dead by living tissues. Hence, halting the activities of the osteoclasts by alendronate stops the hasty new bone formation which is responsible for early femoral capital disfigurement.

Depletion of B cells rejuvenates the peripheral B-cell compartment but is insufficient to restore immune competence in aging.

Aging is associated with increasing prevalence and severity of infections caused by a decline in bone marrow (BM) lymphopoiesis and reduced B-cell repertoire diversity. The current study proposes a strategy to enhance immune responsiveness in aged mice and humans, through rejuvenation of the B lineage upon B-cell depletion. We used hCD20Tg mice to deplete peripheral B cells in old and young mice, analyzing B-cell subsets, repertoire and cellular functions in vitro, and immune responsiveness in vivo. Additionally, elderly patients, previously treated with rituximab healthy elderly and young individuals, were vaccinated against hepatitis B (HBV) after undergoing a detailed analysis for B-cell compartments. B-cell depletion in old mice resulted in rejuvenated B-cell population that was derived from de novo synthesis in the bone marrow. The rejuvenated B cells exhibited a "young"-like repertoire and cellular responsiveness to immune stimuli in vitro. Yet, mice treated with B-cell depletion did not mount enhanced antibody responses to immunization in vivo, nor did they survive longer than control mice in "dirty" environment. Consistent with these results, peripheral B cells from elderly depleted patients showed a "young"-like repertoire, population dynamics, and cellular responsiveness to stimulus. Nevertheless, the response rate to HBV vaccination was similar between elderly depleted and nondepleted subjects, although antibody titers were higher in depleted patients. This study proposes a proof of principle to rejuvenate the peripheral B-cell compartment in aging, through B-cell depletion. Further studies are warranted in order to apply this approach for enhancing humoral immune responsiveness among the elderly population.

Hydrogel composition and laser micropatterning to regulate sciatic nerve regeneration.

Treatment of peripheral nerve injuries has evolved over the past several decades to include the use of sophisticated new materials endowed with trophic and topographical cues that are essential for in vivo nerve fibre regeneration. In this research, we explored the use of an advanced design strategy for peripheral nerve repair, using biological and semi-synthetic hydrogels that enable controlled environmental stimuli to regenerate neurons and glial cells in a rat sciatic nerve resection model. The provisional nerve growth conduits were composed of either natural fibrin or adducts of synthetic polyethylene glycol and fibrinogen or gelatin. A photo-patterning technique was further applied to these 3D hydrogel biomaterials, in the form of laser-ablated microchannels, to provide contact guidance for unidirectional growth following sciatic nerve injury. We tested the regeneration capacity of subcritical nerve gap injuries in rats treated with photo-patterned materials and compared these with injuries treated with unpatterned hydrogels, either stiff or compliant. Among the factors tested were shear modulus, biological composition, and micropatterning of the materials. The microchannel guidance patterns, combined with appropriately matched degradation and stiffness properties of the material, proved most essential for the uniform tissue propagation during the nerve regeneration process.

A novel poly(ethylene glycol)-fibrinogen hydrogel for tibial segmental defect repair in a rat model.

The aim of this study is to investigate regeneration in a segmental bone defect using a novel fibrinogen-based hydrogel material. The use of hydrogels made from poly(ethylene glycol) (PEG) conjugated to fibrinogen for this purpose may be better to conventional fibrin-based materials as it offers an additional degree of control over the structural characteristics and biodegradation of the material. At the same time, it maintains some of the inherent biofunctionality of the fibrinogen molecule. PEGylated fibrinogen hydrogels with various degrees of proteolytic resistance based on PEG and fibrinogen composition were designed for slow, intermediate, and fast biodegradation. The hydrogels were implanted into 7-mm segmental rat tibial defects without additional osteoinductive factors with the rationale that the ingrowth matrix will displace the normal fibrin clot while sustaining a similar healing effect for a longer duration. Histological and X-ray results confirmed that the extent and distribution of newly formed bone in the defect after 5 weeks strongly parallels the biodegradation pattern of the implanted material. When compared to nonunions in animals treated with the fast-degrading implants and untreated control animals, the rats implanted with the intermediate-degrading material exhibited osteoneogenesis. This data supports the hypothesis that the perseverance of the PEGylated fibrinogen material can be synchronized with the optimal healing characteristics of a segmental osseous defect and that the consequent sustained release of fibrinogen fragments facilitates the osteogenic response at the injury site. The PEGylated fibrinogen material may, therefore, be a highly efficacious material for promoting the healing of bone defects and especially nonunion fractures.

Alveolar Bone Fracture: Pathognomonic Sign for Clinical Diagnosis.

AIM: Dental injuries, especially luxation and avulsion, are common. Dental trauma can cause alveolar bone fracture that can lead to tooth loss and malocclusion. Single tooth alveolar bone fractures are difficult to identify unless it protrudes through the overlying mucosa and can be visualized. Pain, malocclusion, and tooth mobility provide signs of suspected alveolar bone fractures. Integrity of the proximate alveolar bone should be examined for fractures where avulsion, luxation, or other tooth trauma is detected. Any suggestion of alveolar fractures should be further investigated with an appropriate radiograph. SUMMARY: This case report shows a pathognomonic sign that detects and diagnosis single tooth alveolar bone fractures, i.e., a localized hematoma crossing the attached gingiva from the free gingival margin to the vestibular mucosa. This should serve as a warning for localized alveolar bone fracture. A visualized hematoma and gentle, careful palpation may help detect covered fractures when the overlying mucosa is not perforated.