Intramedullary Cavity Research Articles

Idiopathic Intrasyringal Hemorrhage: A Case Report and Review of the Literature

Abstract INTRODUCTION Intrasyringal hemorrhages, also known as Gower's hemorrhages, are exceedingly rare entities. There are sporadic case reports of intrasyringal hemorrhages arising from intramedullary tumors, trauma, anticoagulation, or syringomyelic cavities secondary to Chiari malformations. Management is typically tailored to the underlying pathology. Given the paucity of literature, the clinical course and management modalities remain poorly defined. METHODS We present the case of a 19-yr-old male with a complex pasat medical history significant for Pierre Robin sequence, cervicomeddulary dysfunction with posterior fossa decompression and occipital-cervical fusion, hydrocephalus with fourth ventricular outlet fenestration, ventriculoperitoneal shunt conversion to ventriculoatrial shunt, and complex syringomyelia with thoracic syringo-subarachnoid shunt. Our patient presented to us with 3 wk of acute decompensation with complete loss of lower extremity function and a mid-thoracic sensory level. An magnetic resonance imaging (MRI) demonstrated an extensive dilation of his known syrinx with associated accumulation of heterogeneous blood products within the cavity encapsulating the syringo-subarachnoid shunt. RESULTS We performed a prompt revision thoracic laminectomy to identify the patient's existing syringo-subarachnoid shunt. Once the shunt was identified we performed a myelotomy overlying the existing shunt, and immediately noted high pressure chronic hematoma exiting from the myelotomy site. We placed a new syringo-subrachnoid shunt and gently advanced the catheter superiorly while gently irrigating the syrinx cavity. We continued to irrigate the cavity until the blood products cleared and fluid resembling cerebrospinal fluid returned from the cavity. The postoperative MRI demonstrated overall decreased size of the syrinx with less intrasyringal hemorrhage. The patient had a slight improvement in his thoracic sensory level at short-term follow-up. CONCLUSION Intrasyringal hemorrhages are exceedingly rare pathologic entity which may cause significant dilation of an existing syrinx even in the presence of a syringo-subrachnoid shunt. Exam features are variable but may demonstrate an acute and drastic progression. Prompt surgical intervention may improve functional neurologic prognosis.

HISTOPATHOLOGICAL EVALUATION OF EFFECT OF LASER VERSUS FOSFOMYSINE IN TREATMENT OF OSTEOMYELITIS INDUCED BY METHICILLIN-RESISTANT

Introduction: Fosfomycin has been shown highly effective in the treatment of experimental MRSA osteomyelitis. Laser therapy appeared to be a promising alternative technique to pharmacological agents in the treatment of osteomyelitis. Consequently, this study aimed to determine the effects of fosomycin and laser in the treatment of induced osteomylitis by MRSA in rabbits.Material and methods: Localized osteomyelitis was induced in rabbits by percutaneous injection of 0.1 ml of 108 cfu of MRSA clinical isolate into the intramedullary cavity of tibia. After two weeks, tibial osteomyelitis was confirmed radiographically. Rabbits were divided into three groups (each group contained 10 rabbits): untreated controls group, group treated with fosfomycin 75 mg/kg subcutaneously every 24 h and group treated with Diode laser 940 nm, three times weekly. After 14 days of treatment, rabbits were left untreated for 24 hours then euthanized and the tibias harvested. evaluation of treatment was done by measurement of bone density radiologically, Histopathological examination and each tibia were cultured for bacterial counts determinationResults: Bacterial cultures from bones were positive for MRSA in 8 out of 10 (80%) rabbits in the control group, in 9 out of 10 (90%) rabbits in the fosfomycin and laser treated group . Laser group showed the highest bone density among the studied groups. No significant difference was found in the bone cultures and bone density between the three groups; P value 0.302 and 0.157 respectively

Veterinary Cuttable Plate in a Plate-Rod Construct for Repair of Diaphyseal Femoral Fractures in the Cat.

This study evaluated retrospectively the effectiveness of the veterinary cuttable plate (VCP) in a plate-rod construct, for the treatment of diaphyseal femoral fractures in cats. A total of 29 cats with diaphyseal femoral fracture underwent stabilization with a VCP-rod construct. Fractures were classified as type A (7/29), type B (11/29) and type C (11/29) following the AO classification. Biological osteosynthesis was elected in three type B and 10 type C fractures, and open approach in the other cases. Pin diameter was 2 mm (n = 16) or 2.5 mm (n = 13); this corresponded to a percentage of pin occupation of 39.9 and 53.0% of the intramedullary cavity respectively. The 2.0/2.7-mm VCP and 2-mm screws were used in all cases. The median length of the VCP was 12 holes, and the median number of screws placed in the plate was 6. The median number of cortices engaged per fragment was 6. Ninety-nine percent of the screws were bicortical. Quadriceps contracture was an unacceptable functional outcome in one cat. Follow-up was available in 20 cases. Complete bone healing was assessed in 16/20 cases with a functional outcome considered as full in 17/20, acceptable in 2/20, and unacceptable in 1/20. Telephonic owner outcome assessment was available for five more cats and was considered as full in all cases. The VCP-rod construct is effective to manage all configurations of diaphyseal femoral fracture in cats. The high amount of screw holes per unit length of a VCP allows bicortical screws placement without interfering with the intramedullary rod.

Durable engraftment of genetically modified FVIII-secreting autologous bone marrow stromal cells in the intramedullary microenvironment.

Genetically modified FVIII‐expressing autologous bone marrow‐derived mesenchymal stromal cells (BMSCs) could cure haemophilia A. However, culture‐expanded BMSCs engraft poorly in extramedullary sites. Here, we compared the intramedullary cavity, skeletal muscle, subcutaneous tissue and systemic circulation as tissue microenvironments that could support durable engraftment of FVIII‐secreting BMSC in vivo. A zinc finger nuclease integrated human FVIII transgene into PPP1R12C (intron 1) of culture‐expanded primary canine BMSCs. FVIII‐secretory capacity of implanted BMSCs in each dog was expressed as an individualized therapy index (number of viable BMSCs implanted × FVIII activity secreted/million BMSCs/24 hours). Plasma samples before and after implantation were assayed for transgenic FVIII protein using an anti‐human FVIII antibody having negligible cross‐reactivity with canine FVIII. Plasma transgenic FVIII persisted for at least 48 weeks after implantation in the intramedullary cavity. Transgenic FVIII protein levels were low after intramuscular implantation and undetectable after both intravenous infusion and subcutaneous implantation. All plasma samples were negative for anti‐human FVIII antibodies. Plasma concentrations and durability of transgenic FVIII secretion showed no correlation with the therapy index. Thus, the implantation site microenvironment is crucial. The intramedullary microenvironment, but not extramedullary tissues, supported durable engraftment of genetically modified autologous FVIII‐secreting BMSCs.

Technical Overview of Osseointegrated Transfemoral Prostheses: Orthopedic Surgery and Implant Design Centered

Bone-anchored prostheses represent a promising solution to numerous medical complications associated with conventional socket-suspended prostheses. The following technical overview was constructed for engineers and orthopedic surgeons interested in osseointegrated implants for transfemoral prosthesis-residuum interfacing. Existing osseointegrated implants comprise different biomaterial compositions (i.e., titanium alloy versus cobalt-chromium-molybdenum alloy) and mechanical designs (i.e., screw-fixated versus press-fixated devices). Perioperative systems of osseointegration surgery include preoperative assessments (i.e., alongside inclusion and exclusion criteria), intraoperative procedures, and postoperative rehabilitation (i.e., static loading and dynamic gait rehabilitation). The intraoperative procedures involve transecting and reorganizing the residual musculature, embedding the implant into the femoral intramedullary cavity, and coupling the osseointegrated implant to an external prosthesis. Postoperative clinical evaluations have demonstrated significant biomechanical, psychological, and physiological improvements in patients using bone-anchored prostheses compared to conventional socket-suspended prostheses. Nevertheless, bacterial infections surrounding the skin-implant bio-interface, often resulting from Staphylococcus aureus or other coagulase-negative staphylococci, remain a relatively frequent medical complication, which can culminate in periprosthetic osteomyelitis and/or implant extraction. The technical overview concludes with discussing the recent Food and Drug Administration humanitarian use device designations, financial analyses between bone-anchored prostheses and socket-suspended prostheses, and applications of vibrotactile osseoperception for augmenting walking and balance feedback control.

Enchondroma Protuberans of the Transverse Process of D8 Vertebra Extending to the 7th and 8th Ribs: A Rare Case Report.

Enchondroma protuberans (EP) is rare, benign cartilaginous bone tumor arising from the intramedullary cavity of long bones and usually protrudes beyond the cortex with an exophytic growth pattern resembling osteochondroma. This study reports on a rare case of EP arising from the transverse process of the D8 vertebra and extending to the adjacent 7th and 8th ribs and the paraspinal tissues. A 45-year-old female patient came in with complaints of upper back pain radiating up to the left costal margin for the past 6 months. There were no parasthesias, and there was no history of any sensory or motor symptoms. On physical examination there was midline and left paraspinal tenderness over the D6 to D8 region. Anteroposterior and lateral X-ray images revealed a well-defined oval ossific mass lesion over the lateral aspect of the D8 vertebra, extending to the 7th and 8th ribs on the left side, and multiple bridging osteophytes were noted. Computed tomography scan showed an ossific mass lesion arising from the D8 transverse process with extension to the adjacent 7th and 8th ribs; its margins were well defined, with no periosteal reaction. Magnetic resonance imaging showed a well-defined expansile mass lesion arising from the transverse process of the D8 vertebra matrix; it was was isointense with adjacent marrow and had no evidence of calcifications or vascular flow voids and no encroachment into the spinal canal. Complete resection of the mass lesion with the adjacent part of the 7th and 8th ribs and with intramedullary curettage was performed and sent for histopathologic examination. Histopathology showed bony trabeculae with normal mucosal elements, and a mild hypercellularity with binucleation. Chondrocytes in the myxoid matrix located in round lacunae were compatible with enchondroma, with no evidence of atypia. The postoperative period was uneventful, and after 12 months there were no signs of recurrence noted in computed tomography scan. EP is a rare presentation in the dorsal spine; it should be considered in the differential diagnosis of osteochondroma, enchondroma, chondrosarcoma, and periosteal chondroid tumors.

Valence State Manipulation of Cerium Oxide Nanoparticles on a Titanium Surface for Modulating Cell Fate and Bone Formation.

Understanding cell–biomaterial interactions is critical for the control of cell fate for tissue engineering and regenerative medicine. Here, cerium oxide nanoparticles (CeONPs) are applied at different Ce4+/Ce3+ ratios (i.e., 0.46, 1.23, and 3.23) to titanium substrate surfaces by magnetron sputtering and vacuum annealing. Evaluation of the cytotoxicity of the modified surface to cultured rat bone marrow mesenchymal stem cells (BMSCs) reveals that the cytocompatibility and cell proliferation are proportional to the increases in Ce4+/Ce3+ ratio on titanium surface. The bone formation capability induced by these surface modified titanium alloys is evaluated by implanting various CeONP samples into the intramedullary cavity of rat femur for 8 weeks. New bone formation adjacent to the implant shows a close relationship to the surface Ce4+/Ce3+ ratio; higher Ce4+/Ce3+ ratio achieves better osseointegration. The mechanism of this in vivo outcome is explored by culturing rat BMSCs and RAW264.7 murine macrophages on CeONP samples for different durations. The improvement in osteogenic differentiation capability of BMSCs is directly proportional to the increased Ce4+/Ce3+ ratio on the titanium surface. Increases in the Ce4+/Ce3+ ratio also elevate the polarization of the M2 phenotype of RAW264.7 murine macrophages, particularly with respect to the healing‐associated M2 percentage and anti‐inflammatory cytokine secretion. The manipulation of valence states of CeONPs appears to provide an effective modulation of the osteogenic capability of stem cells and the M2 polarization of macrophages, resulting in favorable outcomes of new bone formation and osseointegration.

Creation of an intramedullary cavity by hemorrhagic necrosis removal 24 h after spinal cord contusion in rats for eventual intralesional implantation of restorative materials.

Intramedullary hemorrhagic necrosis occurs early after spinal cord injury at the site of injury and adjacent segments. It is considered harmful because of its potential to aggravate secondary injury, and to interfere with axonal regeneration; it might also lead to an unfavorable environment for intralesional implants. Removal of hemorrhagic necrosis has been attempted before with variable results. The invasive nature of these procedures carries the risk of exacerbating damage to the injured cord. The overall objective for this study was to test several strategies for non-damaging removal of hemorrhagic necrosis and characterize the resulting cavity looking for a space for future intralesional therapeutic implants in rats with acute cord injury. Rats were subjected to graded cord contusion, and hemorrhagic necrosis was removed after 24h. Three grades of myelotomy (extensive, medium sized, and small) were tested. Using the small surgical approach to debridement, early and late effects of the intervention were determined by histology and by analytical and behavioral analysis. Appearance and capacity of the resulting cavity were characterized. Satisfactory removal of hemorrhagic necrosis was achieved with all three surgical approaches to debridement. However, bleeding in spared cord tissue was excessive after medium sized and extensive myelotomies but similar to control injured rats after small cord surgery. Small surgical approach to debridement produced no swelling nor acute inflammation changes, nor did it affect long-term spontaneous locomotor recovery, but resulted in modest improvement of myelination in rats subjected to both moderate and severe injuries. Cavity created after intervention was filled with 10 to 15 μL of hydrogel. In conclusion, by small surgical approach to debridement, removal of hemorrhagic necrosis was achieved after acute cord contusion thereby creating intramedullary spaces without further damaging the injured spinal cord. Resulting cavities appear suitable for future intralesional placement of pro-reparative cells or other regenerative biomaterials in a clinically relevant model of spinal cord injury.

Treatment of comminuted proximal humeral fractures using locking plate with strut allograft

This study compared the radiologic outcome of fixation using locking plate only with fixation using locking plate with an endosteal strut allograft in the treatment of comminuted proximal humeral fracture. Among 52 patients with comminuted proximal humeral fracture, 32 patients underwent fixation with locking plate only, and 20 patients underwent fixation using locking plate with an endosteal strut allograft. The strut allograft was inserted into the intramedullary cavity of the humerus to support the humeral head and fixed with the locking plate. Immediate postoperative radiologic findings were compared with those of 6 months or more after the surgery, and loss of anatomic fixation was defined if the varus malalignment of neck-shaft angle (NSA) was more than 5° or if the change of humeral head height (HHH) was more than 3 mm. In the locking plate-only group, 22 of 32 patients (69%) showed the change in NSA of more than 5°, with an average of 10.2°. The HHH change in 20 patients (62.5%) was more than 3 mm, with an average of 4 mm. Among 20 patients who underwent locking plate with the endosteal strut allograft, the average NSA and HHH change was 3° and 1 mm, respectively. Varus malalignment was evident in 2 patients (10%). The HHH change was more than 3 mm in 1 patient (5%). Fixation using a locking plate with an endosteal strut allograft can be considered a reasonable option to maintain the anatomic reduction in elderly patients with comminuted proximal humeral fracture.

An Intramedullary Locking Nail for Standardized Fixation of Femur Osteotomies to Analyze Normal and Defective Bone Healing in Mice.

Bone healing models are essential to the development of new therapeutic strategies for clinical fracture treatment. Furthermore, mouse models are becoming more commonly used in trauma research. They offer a large number of mutant strains and antibodies for the analysis of the molecular mechanisms behind the highly differentiated process of bone healing. To control the biomechanical environment, standardized and well-characterized osteosynthesis techniques are mandatory in mice. Here, we report on the design and use of an intramedullary nail to stabilize open femur osteotomies in mice. The nail, made of medical-grade stainless steel, provides high axial and rotational stiffness. The implant further allows the creation of defined, constant osteotomy gap sizes from 0.00 mm to 2.00 mm. Intramedullary locking nail stabilization of femur osteotomies with gap sizes of 0.00 mm and 0.25 mm result in adequate bone healing through endochondral and intramembranous ossification. Stabilization of femur osteotomies with a gap size of 2.00 mm results in atrophic non-union. Thus, the intramedullary locking nail can be used in healing and non-healing models. A further advantage of the use of the nail compared to other open bone healing models is the possibility to adequately fix bone substitutes and scaffolds in order to study the process of osseous integration. A disadvantage of the use of the intramedullary nail is the more invasive surgical procedure, inherent to all open procedures compared to closed models. A further disadvantage may be the induction of some damage to the intramedullary cavity, inherent to all intramedullary stabilization techniques compared to extramedullary stabilization procedures.

An Intramedullary Locking Nail for Standardized Fixation of Femur Osteotomies to Analyze Normal and Defective Bone Healing in Mice

Bone healing models are essential to the development of new therapeutic strategies for clinical fracture treatment. Furthermore, mouse models are becoming more commonly used in trauma research. They offer a large number of mutant strains and antibodies for the analysis of the molecular mechanisms behind the highly differentiated process of bone healing. To control the biomechanical environment, standardized and well-characterized osteosynthesis techniques are mandatory in mice. Here, we report on the design and use of an intramedullary nail to stabilize open femur osteotomies in mice. The nail, made of medical-grade stainless steel, provides high axial and rotational stiffness. The implant further allows the creation of defined, constant osteotomy gap sizes from 0.00 mm to 2.00 mm. Intramedullary locking nail stabilization of femur osteotomies with gap sizes of 0.00 mm and 0.25 mm result in adequate bone healing through endochondral and intramembranous ossification. Stabilization of femur osteotomies with a gap size of 2.00 mm results in atrophic non-union. Thus, the intramedullary locking nail can be used in healing and non-healing models. A further advantage of the use of the nail compared to other open bone healing models is the possibility to adequately fix bone substitutes and scaffolds in order to study the process of osseous integration. A disadvantage of the use of the intramedullary nail is the more invasive surgical procedure, inherent to all open procedures compared to closed models. A further disadvantage may be the induction of some damage to the intramedullary cavity, inherent to all intramedullary stabilization techniques compared to extramedullary stabilization procedures.

Gadolinium accumulation in organs of Sprague-Dawley® rats after implantation of a biodegradable magnesium-gadolinium alloy.

In the last years, biodegradable Mg alloys are under investigation due to their promising properties as orthopaedic devices used for bone fracture stabilization. Gadolinium as Rare Earth Element enhances the mechanical properties of Mg-Gd alloys but its toxicity in humans is still questionable. Up to now, there is no study investigating the elements' metabolism of a REE-containing Magnesium alloy in an animal model. In this study, we examined the gadolinium distribution and accumulation in rat organs during the degradation of Mg10Gd. Our findings showed that Gd is accumulating in the animal organs, especially in spleen, liver and kidney. This study is of crucial benefit regarding a safe application of REE-containing Magnesium alloys in humans.

Tanshinone IIA Exerts an Antinociceptive Effect in Rats with Cancer-induced Bone Pain

Background: Cancer-induced bone pain (CIBP) is a common chronic pain characterized by 2 components, ongoing pain and breakthrough pain. Tanshinone IIA (TSN IIA) is a bioactive constituent of the traditional Chinese medicine Danshen, which has been reported to have an antinociceptive effect on neuropathic and inflammatory pain through downregulation of the late proinflammatory cytokine high-mobility group protein B1 (HMGB1). Objective: To assess the antinociceptive effect of TSN IIA on CIBP. Study Design: A randomized, double-blind, controlled animal trial was performed. Setting: University lab in China. Methods: A rat CIBP model was established by injecting Walker 256 mammary gland carcinoma cells into the intramedullary cavity of the tibia. Both ongoing pain, e.g., flinching and guarding, and breakthrough pain, e.g., limb use and von Frey threshold, were evaluated. The effects of intraperitoneally administered TSN IIA on pain behavior and the expression levels of spinal HMGB1, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6 were determined. The effect of TSN IIA on the electrically evoked response of spinal wide-dynamic range (WDR) neurons was performed in vivo. Results: TSN IIA dose-dependently inhibited cancer-induced ongoing pain and breakthrough pain. The expression levels of spinal HMGB1 and other inflammatory factors (IL-1β, TNF-α, and IL-6) were increased in the rat model, but they were suppressed by TSN IIA in a dose-dependent manner. Moreover, TSN IIA significantly inhibited the neuronal responses of WDR neurons in spinal deep layers. Limitations: Further studies are warranted to ascertain how TSN IIA attenuates cancer-induced ongoing pain. Conclusions: Our results indicate that TSN IIA attenuates cancer-induced ongoing pain and breakthrough pain, possibly via suppression of central sensitization in CIBP rats. Therefore, we have provided strong evidence supporting TSN IIA as a potential and effective therapy for relieving CIBP. Key words: Cancer-induced bone pain, high-mobility group protein B1, Tanshinone IIA, ongoing pain, breakthrough pain

Planning the microsurgical myelotomy in intramedullary tumors or cysts by intraoperative neuromonitoring

Background: Surgical approach to the intramedullary tumors and cavities are microsurgical techniques of dorsal myelotomies, which entails the risk of damage to the dorsal columns and the central spinal cord gray matter. The aim of the study is to analyze the clinical sensory dysfunction before surgery and the changes of the intraoperative SEP (somatosensory potentials) before myelotomy. These data would be of help to neurosurgeons in planning the myelotomy – dorsomedial or dorsolateral. Methods: 16 patients were operated on for deafferentation pain syndromes, intramedullary tumors and syringomyelia of the cervical spinal cord. Preoperatively the patients sensory system of dorsal columns and central gray matter was examined for vibration and position sense dysfunction and pain and temperature damage. Before myelotomy the intraoperative SEP from the dorsal surface of the spinal cord after the stimulation of the median and tibial nerves were recorded. Results: After median nerve stimulation the N13 wave was partially or completely absent, and fast negative waves appeared instead. The presence and absence of N13 was in association with pain and temperature dysfunction or with dissociative sensory loss. The mean duration of the SEP potential was shorter than normal (p < 0.0005, n = 11). After tibial nerve stimulation the first negative waves were most stabile, fast negative waves as the most prominent element of the normal SEP were partially or completely absent. This change was in association with diminution or loss of vibration and posture senses. The duration of the conductive SEP was shorter than normal (p = 0.064, n = 5). Conclusions: Dissociative sensory loss is associated with absence of the N13 in median nerve SEP and connected to the central cord destruction. The loss of vibration and posture senses affects the fast negative waves of tibial SEP and points toward damage of the dorsal columns. The dorsolateral myelotomy is justified in cases of central cord destruction, and dorsomedial myelotomy in cases of dorsal columns damage.

Fluorescence-guided surgery of human prostate cancer experimental bone metastasis in nude mice using anti-CEA DyLight 650 for tumor illumination.

The present report demonstrates efficacy of fluorescence-guided surgery (FGS) to resect and prevent recurrence of experimental skeletal metastasis in a nude-mouse model of human prostate cancer. Green fluorescent protein (GFP)-expressing PC-3 human prostate cancer cells were injected into the intramedullary cavity of the tibia in 25 nude mice. One week after implantation, monoclonal antibodies, specific for carcinoembryonic antigen (CEA), labeled with DyLight 650, were injected into the tail vein of 13 mice. Thirteen mice underwent FGS and 12 mice underwent bright-light surgery (BLS). Weekly GFP fluorescence imaging of the mice was performed to observe tumor recurrence. The extent of residual tumor after BLS was 13-fold greater than after FGS (p < 0.001). Time-course imaging visualized rapid growth of the residual tumor in the BLS group, whereas the FGS group showed only slight tumor growth and significantly improved disease-free survival of the treated mice. Our study demonstrated that FGS significantly reduced residual tumor as well as the recurrence of experimental prostate-cancer bone metastasis. The present results suggest that FGS will be effective for resection of skeletal metastases in selected patients with prostate cancer.

Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model

Treatment of large bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials and strategies. Local deficiency in osteogenic connective tissue progenitors (CTP-Os) due to tissue loss is one of the central biological barriers to bone regeneration. Density separation (DS) and selective retention (SR) represent two promising methods that can be used intraoperatively to rapidly concentrate cells and potentially select CTP-Os. This project was designed to compare DS and SR using the canine femoral multidefect (CFMD) model. Mineralized cancellous allograft (MCA) was used as a standardized scaffold for cell transplantation. Two experiments were performed using a cohort of six animals in each comparison. In Cohort I, unprocessed bone marrow aspirate (BMA) clot was compared to DS processing. MCA combined with raw BMA or DS processed cells produced a robust and advanced stage of bone regeneration throughout the defect in 4 weeks with reconstitution of hematopoietic marrow. However, the retention of DS processed cells and CTP-Os in the MCA matrix was low compared to BMA clot. In Cohort II, MCA with DS-T cells (addition of calcium chloride thrombin to induce clotting and enhance cell and CTP-O retention) was compared to MCA with SR cells. A mean of 276 ± 86 million nucleated cells and 29,030 ± 10,510 CTP-Os were implanted per defect in the DS-T group. A mean of 76 ± 42 million nucleated cells and 30,266 ± 15,850 CTP-Os were implanted in the SR group. Bone formation was robust and not different between treatments. Histologically, both groups demonstrated regeneration of hematopoietic marrow tissue. However, SR sites contained more hematopoietic vascular tissues, less fibrosis, and less residual allograft, particularly in the intramedullary cavity, suggesting a more advanced stage of remodeling (p = 0.04). These data demonstrate excellent overall performance of DS and SR processing methods. Both methods achieve a bone regeneration response that approaches the limits of performance that can be achieved in the CFMD model. Further advancement and comparison of these intraoperative bone marrow cell processing methods will require use of a larger and more biologically compromised defect site to guide the next steps of preclinical development and optimization.

Analgesic effects of adenylyl cyclase inhibitor NB001 on bone cancer pain in a mouse model.

BackgroundCancer pain, especially the one caused by metastasis in bones, is a severe type of pain. Pain becomes chronic unless its causes and consequences are resolved. With improvements in cancer detection and survival among patients, pain has been considered as a great challenge because traditional therapies are partially effective in terms of providing relief. Cancer pain mechanisms are more poorly understood than neuropathic and inflammatory pain states. Chronic inflammatory pain and neuropathic pain are influenced by NB001, an adenylyl cyclase 1 (AC1)-specific inhibitor with analgesic effects. In this study, the analgesic effects of NB001 on cancer pain were evaluated.ResultsPain was induced by injecting osteolytic murine sarcoma cell NCTC 2472 into the intramedullary cavity of the femur of mice. The mice injected with sarcoma cells for four weeks exhibited significant spontaneous pain behavior and mechanical allodynia. The continuous systemic application of NB001 (30 mg/kg, intraperitoneally, twice daily for three days) markedly decreased the number of spontaneous lifting but increased the mechanical paw withdrawal threshold. NB001 decreased the concentrations of cAMP and the levels of GluN2A, GluN2B, p-GluA1 (831), and p-GluA1 (845) in the anterior cingulate cortex, and inhibited the frequency of presynaptic neurotransmitter release in the anterior cingulate cortex of the mouse models.ConclusionsNB001 may serve as a novel analgesic to treat bone cancer pain. Its analgesic effect is at least partially due to the inhibition of AC1 in anterior cingulate cortex.

Free intra-osseous muscle transfer for treatment of chronic osteomyelitis

Background: Chronic osteomyelitis is still a big reconstructive challenge. Even with standard care, therapeutic failures and recurrences are common. Multiple techniques of tissue transfer have increased the success rate. This study recommends free muscle transfers into the intramedullary bone cavities for treatment of chronic osteomyelitis. Patients and methods: The review included 29 patients that were treated for chronic osteomyelitis. Osteomyelitis was located at the femur in four patients, the tibia in 22 patients, and the foot in three patients. Dead bone and scar tissue were replaced with durable free muscle flap with special attention to fill the dead space. Results: The average age of these patients was 48.5 years old (range = 23–70 years old). The average duration of osteomyelitis was 8.2 years (range = 1–45 years). Gracilis was applied in 20 cases (69%), latissimus dorsi was used in five cases (17.2%), and rectus abdominis was performed in four cases (13.8%). There was one flap failure, one partial superficial flap necrosis, two arterial thrombosis, and one venous thrombosis. All the remaining 28 muscle flaps survived. From 1–10 years follow-up, there was one recurrence of the osteomyelitis in the distal end of the intra-medullary cavity of a femur after reconstructing using the gracilis flap. Conclusion: The present study demonstrated that free intramedullary muscle transfers are effective in providing a high rate of success in the treatment of chronic osteomyelitis. The secondary filling of the intramedullary cavity after extensive removal of all infected bony sequesters has proven to give a long-term arrest of chronic osteomyelitis.

Synergetic Use of Neural Precursor Cells and Self-assembling Peptides in Experimental Cervical Spinal Cord Injury

Spinal cord injuries (SCI) cause serious neurological impairment and psychological, economic, and social consequences for patients and their families. Clinically, more than 50% of SCI affect the cervical spine. As a consequence of the primary injury, a cascade of secondary mechanisms including inflammation, apoptosis, and demyelination occur finally leading to tissue scarring and development of intramedullary cavities. Both represent physical and chemical barriers to cell transplantation, integration, and regeneration. Therefore, shaping the inhibitory environment and bridging cavities to create a supportive milieu for cell transplantation and regeneration is a promising therapeutic target. Here, a contusion/compression model of cervical SCI using an aneurysm clip is described. This model is more clinically relevant than other experimental models, since complete transection or ruptures of the cord are rare. Also in comparison to the weight drop model, which in particular damage the dorsum columns, circumferential compression of the spinal cord appears advantageous. Clip closing force and duration can be adjusted to achieve different injury severity. A ring spring facilitates precise calibration and constancy of clip force. Under physiological conditions, synthetic self-assembling peptides (SAP) self-assemble into nanofibers and thus, are appealing for application in SCI. They can be injected directly into the lesion minimizing damage to the cord. SAPs are biocompatible structures erecting scaffolds to bridge intramedullary cavities and thus, equip the damaged cord for regenerative treatments. K2(QL)6K2 (QL6) is a novel SAP introduced by Dong et al. In comparison to other peptides, QL6 self-assembles into β-sheets at neutral pH. 14 days after SCI, after the acute stage, SAPs are injected into the center of the lesion and neural precursor cells (NPC) are injected into adjacent dorsal columns. In order to support cell survival, transplantation is combined with continuous subdural administration of growth factors by osmotic micro pumps for 7 days.

An Improved Technique for Removing Intramedullary Antibiotic Beads in Osteomyelitis of the Tibial Shaft

The intramedullary insertion of antibiotic-impregnated cement beads is used widely for the treatment of intramedullary infection. This report describes an improved technique for removing chains of antibiotic beads inserted into the intramedullary cavity. We examined four cases in three patients of the intramedullary insertion of chains of antibiotic-impregnated cement beads for the treatment of osteomyelitis of the diaphysis of the tibia after the fixation of fractures with interlocking nails. During bead removal, the tip of an intramedullary guidewire was bent into a hook shape and was then engaged with the chain of impacted beads. The guidewire was removed from the intramedullary cavity, permitting the extraction of any beads adhering to the wire. As beads came into contact with the tip of the intramedullary guidewire, they could be extracted easily. No additional incision or bone fenestration was required. The use of a hook-shaped intramedullary guidewire simplifies the removal of chains of antibiotic-impregnated cement beads without the need for an invasive procedure. This technique makes the use of chains of cement beads a favorable choice for treating intramedullary infection.