Exploration of TiO2 nanoparticle mediated microdynamic therapy on cancer treatment.

Radical therapy takes advantage of the reactive oxygen species produced in greater quantities within tumor cells than in normal cells. Here, for the first time, we explore a TiO2 nanoparticle mediated microwave induced radical therapy (termed as Microdynamic Therapy) as a new cancer treatment method. The experiments in vitro and in vivo demonstrate that colloidal TiO2 nanoparticles could significantly suppress the growth of osteosarcomas, even under low power (5 W) microwave (MW) irradiation for 5 min. The high photocatalytic activity of TiO2 nanoparticles efficiently utilizes the microwave-induced plasmonic effect for the formation of reactive oxygen species (ROS). Furthermore, TiO2 nanoparticles exhibit a higher cytotoxicity on cancer cells (osteosarcoma UMR-106 cells) than on normal cells (mouse fibroblast L929 cells). The effectiveness of TiO2 nanoparticles for microwave induced radical therapy demonstrates that this is a new landmark approach to treating cancers.

Zero-Dimensional Carbon Dots Enhance Bone Regeneration, Osteosarcoma Ablation, and Clinical Bacterial Eradication.

Zero-dimensional carbon dots (CD) and their effects on osteogenesis have been rarely studied in bone repair scaffolds. Here, we fabricate a novel CD doped chitosan/nanohydroxyapatite (CS/nHA/CD) scaffold with full potential to promote bone regeneration by a facile freeze-drying method. The CS/nHA/CD scaffolds enhanced cell adhesion and osteoinductivity in rat bone mesenchymal stem cells by up-regulating genes involved in focal adhesion and osteogenesis in vitro, which significantly improved the formation of vascularized new bone tissue at 4 weeks compared to pure CS/nHA scaffolds in vivo. Inspired by the excellent photothermal effect of CD, the scaffolds were applied in tumor photothermal therapy (PTT) under near-infrared (NIR) irradiation (808 nm, 1 W/cm2). The scaffolds significantly inhibited osteosarcoma cell proliferation in vitro and effectively suppressed tumor growth in vivo. Moreover, the CS/nHA/CD scaffolds possessed distinct antibacterial properties toward clinically collected S. aureus and E. coli, and their antibacterial activity was further enhanced under NIR irradiation. This work demonstrates that zero-dimensional CD can enhance the osteogenesis-inducing property of bone repair scaffolds and that CD doped scaffolds have potential for use in PTT for tumors and infections.

A unique procedure of joined transoral and retropharyngeal high cervical approach (JTRC) without mandibulectomy for treating upper cervical neoplasm involving both C2 and C3.

PURPOSE: To investigate a unique procedure of joined transoral and retropharyngeal high cervical approach (JTRC) without mandibulectomy for treating upper cervical neoplasm involving both C2 and C3. METHOD: A 23-year-old male patient had neoplasma involving C2 and C3 that caused pathologic fracture of C2 and bony destruction of C3. The neoplasm excision and cervical spine reconstruction were performed through JTRC approach without splitting up the mandible. In this approach, there were two surgery windows that could be applied in turns by closing or opening the mouth to gain an ideal exposure. By rotating the mandible, we could gain maximized exposure for either surgery windows. In addition, there was an overlay zone between transoral approach and high cervical retropharyngeal approach that could eliminate the blind area behind the mandible. RESULTS: All the procedures were successfully performed; the surgical incisions healed without infection. By operating alternatively between the two surgery windows, we have successfully performed neoplasm excision and cervical spine reconstruction involving both C2 and C3. Pathologic results showed metastatic renal cell cancer to the resected cervical tumor and confirmed the patient's diagnosis of tuberous sclerosis (Bourneville disease). A 3-month postoperative cervical spine radiography and CT scan demonstrated a favorable placement of the bone implant as well as a favorable instrumentation. CONCLUSION: The JTRC approach could provide good surgical exposure for treating disorders involving both upper and lower cervical spine without splitting up the mandible.

Biomechanical Effects of Masticatory Muscles on Human Mandible After Reconstructed Mandibulectomy Tumor.

BACKGROUND: This study aimed to analyze and compare the stress distribution on the condylar process. This study was also designed to determine the effect of closing and opening muscle groups of the jaw on mandibular stability after mandibular tumor osteotomy reconstruction by three-dimensional finite element analysis. MATERIALS AND METHODS: Three-dimensional reconstructed mandibles were used and divided into 2 groups: (1) 6 patients with normal mandible and (2) 6 mandibular tumor patients who underwent osteotomy reconstruction. Computed tomography scans of normal and reconstructed mandibular tumor osteotomy patients were obtained. Three-dimensional models were reconstructed using Simpleware 5.0 software. Boundary constraint and load conditions were applied. The solution process was run, and the actions of closing and opening muscle groups were simulated and calculated using finite element analysis software. Statistical software was used for analysis of the condylar stress distribution. RESULTS: A significant difference was observed in stress distributions on the anterior condyle of the healthy volunteers and the reconstructed mandibular tumor osteotomy patients, who were subjected to tumor osteotomy surgery in the opening muscle groups (P < 0.05). By contrast, no significant difference was observed in the posterior condyle of the opening muscle group and the closing muscle group (P > 0.05). CONCLUSIONS: Muscular imbalance in postoperative mandibular tumor reconstruction was changed in patients. We adjusted the force of the mandible closing muscle intraoperatively to achieve muscle balance. Therefore, poor swallowing, failure to retain saliva, speech impairment, and esthetic disfigurement were repaired and/or resolved.

Treatment of basilar invagination with atlantoaxial dislocation: atlantoaxial joint distraction and fixation with transoral atlantoaxial reduction plate (TARP) without odontoidectomy.

PURPOSE: Although direct transoral decompression and one-stage posterior instrumentation can obtain satisfactory cord decompression for the treatment of basilar invagination with atlantoaxial dislocation, surgical injuries run high as combinative anterior-posterior approaches were necessary. Furthermore, the complications will rise notably when involvement of dens and/or clivus in the decompression necessitates relatively complicated surgical techniques. First initiated in 2005, transoral atlantoaxial reduction plate (TARP) works as an internal fixation for the treatment of basilar invagination with irreducible atlantoaxial dislocation. Therefore, this article aimed to describe several operative experiences about this approach, which has delivered successful decompression, fixation and fusion. METHODS: 21 consecutive patients with basilar invagination underwent the TARP operation. The pre- and postoperative medulla-cervical angles were measured and compared. The JOA scores of spinal cord function were calculated pre- and post-operatively. 20 cases (20/21) were followed up to average 12.5 months. RESULTS: Symptoms of all the 20 cases were relieved in different degrees. The postoperative imaging showed the odontoid processes obtained ideal reduction and the internal fixators were all in good position. The medulla-cervical angle was correctd from an average (± standard deviation) 128.7° + 11.9° (n = 20) before surgery to 156.5° + 8.1° (n = 20) after surgery (P < 0.01). The average preoperative and postoperative Japaneses Orthopedic Association scores were 11.25 (n = 20) and 15.9 (n = 20), respectively, indicating 76 % improvement. Screw-loosening was observed in one patient due to severe osteoporosis. After a revised operation with a TARP in another size, the neurological symptoms showed no obvious improvements. Then the treatment was terminated. CONCLUSIONS: The TARP operation and intra-operative traction could reduce the odontoid process superiorly migrating into the foramen magnum, directly ease the ventral compression of spinal cord, and fix the reduced atlantoaxial joints through a single transoral approach without the need of a posterior operation. In this stury, 21 patients were evaluated and 20 did well with TARP operation. The preliminary clinical result was satisfactory.

Osteogenic activity of silver-loaded coral hydroxyapatite and its investigation in vivo.

In this study, the scaffolds based on mineralized silver-loaded coral hydroxyapatites (SLCHAs) were developed for bone regeneration in the radius of rabbit with a 15-mm infective segmental defect model for the first time. The SLCHAs were achieved by surface adsorption and ion-exchange reaction between Ca(2+) of coral hydroxyapatite (CHA) and Ag(+) of silver nitrate with different concentration at room temperature. Release experiment in vitro, X-ray diffraction and scanning electron microscopy equipped with energy-dispersive X-ray spectrometer were applied to exhibit that the scaffold showed some features of natural bone both in main component and hierarchical microstructure. The three-dimensional porous scaffold materials imitate the microstructure of cancellous bone. Mouse embryonic pre-osteoblast cells (MC3T3-E1) were used to investigate the cytocompatibility of SLCHAs, CHA and pure coral. Cell activity were studied with alkaline phosphataseenzyme assay after 2, 4, 6 days of incubation. It was no statistically significant differences in cell activity on the scaffolds of Ag(+)(13.6 µg/mL)/CHA, Ag(+)(1.7 µg/mL)/CHA, CHA and pure coral. The results indicated that the lower silver concentration has little effect on cell activity. In the implantation test, the infective segmental defect repaired with SLCHAs was healed up after 10 weeks after surgery, and the implanted composites were almost substituted by new bone tissue, which were very comparable with the scaffold based on mineralized CHA. It could be concluded that the SLCHAs contained with appropriate silver ionic content could act as biocidal agents and maintain the advantages of mineralized CHA or coral, while avoiding potential bacteria-dangers and toxical heavy-metal reaction. All the above results showed that the SLCHAs with anti-infective would be as a promising scaffold material, which whould be widely applied into the clinical for bone regeneration.

[An observation on risk of infection in treatment of craniovertebral junction disorders by transoral approach operation].

OBJECTIVE: To study the changes of bacterial flora after a series of preoperative oral disinfection and the postoperative recovery of patients with craniovertebral junction disorders who were treated with transoral approach operations. And to provide a theoretical basis for the prevention of postoperative complications such as infection. METHODS: The clinical data of 20 cases with craniovertebral junction disorders and treated with transoral approach operations between October 2009 and May 2010 were analyzed. There were 8 males and 12 females, aged 2-66 years (median, 34.5 years). According to the classification of American Spinal Injury Association (ASIA)，there were 4 cases of grade B, 8 of grade C, 6 of grade D, and 2 of grade E. The Japanese Orthopedic Association (JOA) score was 10.3±3.0. The mucosa samples of the posterior pharyngeal wall were sent for bacteria culture. These samples were collected by sterile cotton swabs at four crucial points including 3 days before operation/before gargling (T1), 3 days after continuous gargling by chlorhexidine acetate/after anesthesia intubation on the day of operation (T2), after intraoperative cleaning and washing of the mouth (T3), and after intraoperative iodophor immersion for 5-10 minutes (T4). The microflora was stained by means of smear and further counted after an investigation by microscope. The ASIA classification and the JOA scores were applied to evaluate the postoperative nerve function of the patients. A regular reexamination of cervical vertebra with X-ray film, CT, and MRI was conducted after operation to evaluate the reduction of atlantoaxial dislocation, internal fixation position, bone graft fusion, inflammatory lesion, and tumor resection in the craniovertebral junction. RESULTS: After a series of oral disinfection, the mucosa of the posterior pharyngeal wall of all the patients was in a sterile state, which was considered as type Ⅰ incision. All these 20 patients were treated with successful operations, without any intraoperative injury in vertebral artery and spinal cord, or any postoperative complications such as plate loosening, incision infection, or intracranial infection. All the patients were followed up 3-23 months, with an average of 5.15 months. The symptoms such as neck pain, limb numbness and weakness, neural symptoms, etc. were improved to different degrees after operation. The JOA score was improved to 13.4±1.9 at 3 months after operation, showing significant difference when compared with preoperative score ( t=8.677, P=0.000); and the atlantoaxial joints had been fused. At last follow-up, the ASIA grades were improved when compared with those before operation. CONCLUSION: It is safe and effective to cut the posterior pharyngeal muscle layer and implant internal fixation by means of transoral approach in the treatment of craniovertebral junction disorders.

Atlantoaxial Joint Distraction for the Treatment of Basilar Invagination: Clinical Outcomes and Radiographic Evaluation.

OBJECTIVE: To investigate the causes of partial remission in patients with basilar invagination (BI) and irreducible atlantoaxial dislocation (IAAD) treated with transoral atlantoaxial reduction plate (TARP) without odontoidectomy and quantify the distance of odontoid descent. METHODS: Between August 2010 and July 2012, 22 consecutive patients with BI with IAAD who underwent TARP surgery were reviewed. The preoperative and postoperative radiographic parameters were evaluated. Follow-up data and the symptom treatment interval (STI), defined as the interval between the onset of symptoms and surgical treatment, were assessed. Neurological function was evaluated as neurologic improvement, defined as ([Postoperative Japanese Orthopedic Association (JOA) score] - [Preoperative JOA score])/(17 - [Preoperative JOA score]). The patients were assigned to group A (<50%) or group B (≥50%) based on their level of neurologic improvement. RESULTS: All 22 patients improved clinically to varying degrees. The mean preoperative STI was 105.6 ± 67.6 months for group A and 45.3 ± 46.7 months for group B (P < 0.05). There were no significant between-group differences in follow-up (P > 0.05) or with respect to radiographic parameters (P > 0.05). Persistent brainstem compression was observed in 1 patient, whose symptoms were not adequately relieved after revision surgery (transoral odontoidectomy and posterior decompression and fusion). No fixation failure was observed. CONCLUSIONS: Descent of the odontoid process is useful for treating basilar invagination. TARP surgery without odontoidectomy may pull the dens caudally and ventrally to achieve sufficient decompression of the spinal cord. Neurologic improvement may be associated with STI.

High-activity chitosan/nano hydroxyapatite/zoledronic acid scaffolds for simultaneous tumor inhibition, bone repair and infection eradication.

Implanted biomaterials combined tumor inhibition and bone repair property are urgently needed to address the huge bone destruction and the high local recurrence following primary surgery in bone tumor therapy. In this work, a high-activity chitosan/nano hydroxyapatite (CS/nHA) scaffold containing zoledronic acid (CS/nHA/Zol) was prepared with a facile method. The prepared CS/nHA/Zol scaffolds exhibited excellent tumor inhibition property towards giant cell tumor of bone (GCT) in vitro through inducing cells apoptosis by up-regulating pro-apoptosis genes expression and reducing the osteoclastic activity of tumor cells by down-regulating osteoclastic genes. Meanwhile, the prepared scaffolds possessed well biocompatibility and osteoinductivity as compared to pure CS/nHA scaffolds. Furthermore, the prepared scaffolds also presented outstanding antibacterial activity against clinical pathogenic S. aureus and E. coli. These overall findings successfully demonstrated the prepared CS/nHA/Zol scaffolds had a multifunction of tumor therapy, bone repair, and antibacterium, which provides a new approach possessed promising advantages in bone tumor therapy.

The anatomical study of transoral atlantoaxial reduction plate internal fixation.

OBJECTIVE: To study relevant anatomical features of the structures involved in transoral atlanto-axial reduction plate (TARP) internal fixation through transoral approach for treating irreducible atlanto-axial dislocation and providing anatomical basis for the clinical application of TARP. METHODS: Ten fresh craniocervical specimens were microsurgically dissected layer by layer through transoral approach. The stratification of the posterior pharyngeal wall, the course of the vertebral artery, anatomical relationships of the adjacent structures of the atlas and axis, and the closely relevant anatomical parameters for TARP internal fixation were measured. RESULTS: The posterior pharyngeal wall consisted of two layers and two interspaces: the mucosa, prevertebral fascia, retropharyngeal space, and prevertebral space. The range from the anterior edge of the foramen magnum to C(3) could be exposed by this approach. The thickness of the posterior pharyngeal wall was (3.6+/-0.3) mm (ranging 2.9-4.3 mm) at the anterior tubercle of C1, (6.1+/-0.4) mm (ranging 5.2-7.1 mm) at the lateral mass of C(1) and (5.5+/-0.4) mm (ranging 4.3-6.5 mm) at the central part of C(2), respectively. The distance from the incisor tooth to the anterior tubercle of C(1), C(1) screw entry point, and C(2)screw entry point was (82.5+/-7.8) mm (ranging 71.4-96.2 mm), (90.1+/-3.8) mm (ranging 82.2-96.3 mm), and (89.0+/-4.1) mm (ranging 81.3-95.3 mm), respectively. The distance between the vertebral artery at the atlas and the midline was (25.2+/- 2.3) mm (ranging 20.4-29.7 mm) and that between the vertebral artery at the axis and the midline was (18.4+/- 2.6) mm (ranging 13.1-23.0 mm). The allowed width of the atlas and axis for exposure was (39.4+/-2.2) mm (ranging 36.2-42.7 mm) and (39.0+/-2.1) mm (ranging 35.8-42.3 mm), respectively. The distance (a) between the two atlas screw insertion points (center of anterior aspect of C(1) lateral mass) was (31.4+/-3.3) mm (ranging 25.4-36.6 mm). The vertical distance (b) between the line connecting the two C(1) screw entry points and that connecting the two C(2) screw entry points (at the central part of the vertebrae, namely 3-4 mm lateral to the midline of C(2) vertebrae) was (21.3+/-2.7) mm (ranging 19.4-24.3 mm), with an a/b ratio of 1.3-1.5. The screws of TARP had a lateral tilt of 12.2 degrees+/-0.4 degrees(ranging 10.2 degrees-14.6 degrees) at C(1) and a medial tilt of 7.3 degrees+/-0.3 degrees (ranging 5.1 degrees-9.4 degrees) at C(2) relative to the coronal plane. CONCLUSIONS: An atlanto-axial surgery through transoral approach is safe and feasible. This approach is suitable for an anterior TARP internal fixation, and the design of the internal fixation system should be based on the above anatomical data.

Surgical Outcome and Prognostic Analysis of Transoral Atlantoaxial Reduction Plate System for Basilar Invagination: A Voxel-Based Morphometry Study.

BACKGROUND: The use of a transoral atlantoaxial reduction plate (TARP) system is an effective surgical approach for the treatment of basilar invagination. With the aim of improving the therapeutic efficacy of the TARP operation, we conducted a voxel-based morphometric study to quantitatively investigate the descent of the odontoid process and craniocervical volume changes. METHODS: We enrolled 20 patients with basilar invagination who underwent a TARP procedure. Craniocervical computed tomography (CT) scanning and a 3-dimensional (3-D) reconstruction of the craniocervical junction were performed. Craniocervical volumes and odontoid process descent distances were measured preoperatively and postoperatively. Individual neurological function was evaluated according to the Japanese Orthopaedic Association (JOA) scoring system for cervical disorders. Pearson correlation analysis was applied for statistical testing. RESULTS: Surgical efficacy (the JOA-score improvement rate) was significantly associated with the craniocervical volume improvement rate, the odontoid descent distance, and the absolute craniocervical volume changes (p < 0.01 for all), with correlation coefficients (r) of 0.83, 0.80, and 0.61, respectively. No significant correlation was noted between surgical efficacy and age, symptom duration, preoperative neurological function, odontoid process displacement, or change in clivus-odontoid angle (p > 0.05). The craniocervical volume improvement rate was significantly associated with the odontoid descent distance (r = 0.8; p < 0.01), but it was not associated with the odontoid displacement or the change in the clivus-odontoid angle (p > 0.05). CONCLUSIONS: We found that the odontoid descent distance predicted the craniocervical volume improvement rate following TARP procedures in patients with basilar invagination, and we believe that both can serve as predictors of surgical efficacy. We believe that planning the odontoid descent distance preoperatively may help to improve the efficacy of TARP operations. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Unique antitumor property of the Mg-Ca-Sr alloys with addition of Zn.

In clinical practice, tumor recurrence and metastasis after orthopedic prosthesis implantation is an intensely troublesome matter. Therefore, to develop implant materials with antitumor property is extremely necessary and meaningful. Magnesium (Mg) alloys possess superb biocompatibility, mechanical property and biodegradability in orthopedic applications. However, whether they possess antitumor property had seldom been reported. In recent years, it showed that zinc (Zn) not only promote the osteogenic activity but also exhibit good antitumor property. In our present study, Zn was selected as an alloying element for the Mg-1Ca-0.5Sr alloy to develop a multifunctional material with antitumor property. We investigated the influence of the Mg-1Ca-0.5Sr-xZn (x = 0, 2, 4, 6 wt%) alloys extracts on the proliferation rate, cell apoptosis, migration and invasion of the U2OS cell line. Our results show that Zn containing Mg alloys extracts inhibit the cell proliferation by alteration the cell cycle and inducing cell apoptosis via the activation of the mitochondria pathway. The cell migration and invasion property were also suppressed by the activation of MAPK (mitogen-activated protein kinase) pathway. Our work suggests that the Mg-1Ca-0.5Sr-6Zn alloy is expected to be a promising orthopedic implant in osteosarcoma limb-salvage surgery for avoiding tumor recurrence and metastasis.

Treatment of Basilar Invagination With Klippel-Feil Syndrome: Atlantoaxial Joint Distraction and Fixation With Transoral Atlantoaxial Reduction Plate.

BACKGROUND: Klippel-Feil syndrome (KFS) is characterized by congenital vertebral fusion of the cervical spine and a wide spectrum of associated anomalies. In patients with KFS with basilar invagination (BI), compression of the brainstem and upper cervical cord results in neurological deficits, and decompression and occipitocervical reconstruction are required. The highly varied anatomy of KFS makes a posterior occipitocervical fixation strategy challenging. For these patients, the transoral atlantoaxial reduction plate (TARP) operation is an optimal option to perform a direct anterior fixation to achieve stabilization. OBJECTIVE: To evaluate the effectiveness of TARP internal fixation for the treatment of BI with KFS. METHODS: Ten consecutive patients with BI and KFS who underwent TARP reduction and fixation from 2010 to 2012 were reviewed. Clinical assessment and image measurements were performed preoperatively and at the most recent follow-up. Nine patients (9/10) were followed for an average of 31.44 months. RESULTS: Symptoms were alleviated in 9 of 9 patients (100.00%). The odontoid process was ideally corrected with the TARP system. The mean clivus canal angle improved from 124° preoperatively to 152° postoperatively. The average preoperative and postoperative Japanese Orthopedic Association scores were 10.56 (n = 9) and 14.67 (n = 9), respectively, indicating 63.82% improvement. There was bony bridge catenation on the computed tomography scans and no evidence of hardware failure at 6 months. CONCLUSION: The TARP operation is effective and safe for treating patients with BI with KFS. The midterm clinical results were satisfactory.

An antibacterial and absorbable silk-based fixation material with impressive mechanical properties and biocompatibility.

Implant-associated infections and non-absorbing materials are two important reasons for a second surgical procedure to remove internal fixation devices after an orthopedic internal fixation surgery. The objective of this study was to produce an antibacterial and absorbable fixation screw by adding gentamicin to silk-based materials. The antibacterial activity was assessed against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro by plate cultivation and scanning electron microscopy (SEM). We also investigated the properties, such as the mechanical features, swelling properties, biocompatibility and degradation, of gentamicin-loaded silk-based screws (GSS) in vitro. The GSS showed significant bactericidal effects against S. aureus and E. coli. The antibacterial activity remained high even after 4 weeks of immersion in protease solution. In addition, the GSS maintained the remarkable mechanical properties and excellent biocompatibility of pure silk-based screws (PSS). Interestingly, after gentamicin incorporation, the degradation rate and water-absorbing capacity increased and decreased, respectively. These GSS provide both impressive material properties and antibacterial activity and have great potential for use in orthopedic implants to reduce the incidence of second surgeries.

[Comparative clinical observation of the short-term bone fusion effect of composite biosynthetic bone and ilium auto-grafting].

OBJECTIVE: To evaluate the short-term bone fusion after implantation of composite biosynthetic bone made of coralline hydroxyapatite composite (CHC) as a substitute for autologous bone grafting. METHODS: A clinical sequential trial was designed and the biosynthetic bone and the patient's ilium were respectively used in the treatment of femoral nonunions and interbody fusion. X-ray examinations were performed 10 weeks after the operations and the bone fusion was graded according to Lane-Sandhu's method. RESULTS: The biosynthetic bone was capable of bone fusion as observed in this experiment. Sequential analysis found that the upper bound was reached when the X-ray examination scores of 15th pairs were transcribed in the chart with 2 pairs of cases dismissed for having the same grade. CONCLUSION: The bone fusion effect of CHC is better than auto-grafting judging from the present observation at 10 weeks after operation.

The development and evaluation of individualized templates to assist transoral C2 articular mass or transpedicular screw placement in TARP-IV procedures: adult cadaver specimen study.

OBJECTIVES: The transoral atlantoaxial reduction plate system treats irreducible atlantoaxial dislocation from transoral atlantoaxial reduction plate-I to transoral atlantoaxial reduction plate-III. However, this system has demonstrated problems associated with screw loosening, atlantoaxial fixation and concealed or manifest neurovascular injuries. This study sought to design a set of individualized templates to improve the accuracy of anterior C2 screw placement in the transoral atlantoaxial reduction plate-IV procedure. METHODS: A set of individualized templates was designed according to thin-slice computed tomography data obtained from 10 human cadavers. The templates contained cubic modules and drill guides to facilitate transoral atlantoaxial reduction plate positioning and anterior C2 screw placement. We performed 2 stages of cadaveric experiments with 2 cadavers in stage one and 8 in stage two. Finally, guided C2 screw placement was evaluated by reading postoperative computed tomography images and comparing the planned and inserted screw trajectories. RESULTS: There were two cortical breaching screws in stage one and three in stage two, but only the cortical breaching screws in stage one were ranked critical. In stage two, the planned entry points and the transverse angles of the anterior C2 screws could be simulated, whereas the declination angles could not be simulated due to intraoperative blockage of the drill bit and screwdriver by the upper teeth. CONCLUSIONS: It was feasible to use individualized templates to guide transoral C2 screw placement. Thus, these drill templates combined with transoral atlantoaxial reduction plate-IV, may improve the accuracy of transoral C2 screw placement and reduce related neurovascular complications.

[Biocompatibility of silicon containing micro-arc oxidation coated magnesium alloy ZK60 with osteoblasts cultured in vitro].

OBJECTIVE: To research in vitro biocompatibility of silicon containing micro-arc oxidation (MAO) coated magnesium alloy ZK60 with osteoblasts. METHODS: The surface microstructure of silicon containing MAO coated magnesium alloy ZK60 was observed by a scanning electron microscopy (SEM), and chemical composition of the coating surface was determined by energy dispersive spectrum analysis. The experiments were divided into 4 groups: silicon containing MAO coated magnesium alloy ZK60 group (group A), uncoated magnesium alloy ZK60 group (group B), titanium alloy group (group C), and negative control group (group D). Extracts were prepared respectively with the surface area to extraction medium ratio (1.25 cm(2)/mL) according to ISO 10993-12 standard in groups A, B, and C, and were used to culture osteoblasts MC3T3-E1. The a-MEM medium supplemented with 10% fetal bovine serum was used as negative control in group D. The cell morphology was observed by inverted phase contrast microscopy. MTT assay was used to determine the cell viability. The activity of alkaline phosphatase (ALP) was detected. Cell attachment morphology on the surface of different samples was observed by SEM. The capability of protein adsorption of the coating surface was assayed, then DAPI and calcein-AM/ethidium homodimer 1 (calcein-AM/EthD-1) staining were carried out to observe cell adhesion and growth status. RESULTS: The surface characterization showed a rough and porous layer with major composition of Mg, O, and Si on the surface of silicon containing MAO coated magnesium alloy ZK60 by SEM. After cultured with the extract, cells grew well and presented good shape in all groups by inverted phase contrast microscopy, group A was even better than the other groups. At 5 days, MTT assay showed that group A presented a higher cell proliferation than the other groups (P < 0.05). Osteoblasts in groups A and C presented a better cell extension than group B under SEM, and group A exhibited better cell adhesion and affinity. Protein adsorption in group A [ (152.7 +/- 6.3) microg/mL] was significantly higher than that of group B [(96.3 +/-3.9) microg/mL] and group C [ (96.1 +/-8.7) microg/mL] (P < 0.05). At each time point, the adherent cells on the sample surface of group A were significantly more than those of groups B and C (P < 0.05). The calcein-AM/EthD-1 staining showed that groups A and C presented better cell adhesion and growth status than group B. The ALP activities in groups A and B were 15.55 +/-0.29 and 13.75 +/-0.44 respectively, which were significantly higher than those in group C (10.43 +/-0.79) and group D (10.73 +/-0.47) (P < 0.05), and group A was significantly higher than group B (P < 0.05). CONCLUSION: The silicon containing MAO coated magnesium alloy ZK60 has obvious promoting effects on the proliferation, adhesion, and differentiation of osteoblasts, showing a good biocompatibility, so it might be an ideal surface modification method on magnesium alloys.

[Determination of silver content in silver-loaded coral hydroxyapatite in relation to the biocompatibility].

OBJECTIVE: To determine the amount of silver in silver-loaded coral hydroxyapatite (Ag(+)-CHA) bone substitute and its impact on the biocompatibility of this material with mouse embryonic osteoblast cells. METHODS: Ag(+)-CHA was prepared by immersing coral hydroxyapatite in a serial concentration of silver nitrate solutions. The amount of silver in the prepared Ag(+)-CHA was measured by inductively coupled plasma atomic emission spectrometry (ICP-AES). The viability of MC3T3-E1 cells incubated with Ag(+)-CHA was measured by MTT colorimetric assay, and the cell growth and morphological changes were observed by inverted phase-contrast microscope and confocal laser scanning microscope. RESULTS: The amount of silver loading in the bone substitutes prepared by immersion in 1×10(-2), 1×10(-3), 5×10(-4), 10(-4), 8×10(-5), and 5×10(-5) mol/L silver nitrate solutions were 4127.67∓47.35, 167.90∓11.00, 83.42∓4.51, 30.20∓2.32, 22.39∓4.09, and 15.11∓0.55 µg/g, respectively. A low silver content in the material (prepared with silver nitrate solution of less than 8×10(-5) mol/L) showed no significant inhibitory effect on the growth of MC3T3-E1 cells or produced noticeable cytotoxic effect. On the materials prepared with 8×10(-5) and 10(-5) mol/L silver nitrate solution, the osteoblasts displayed active proliferation similar to those incubated on materials without silver loading. The confluent cells showed a normal fusiform morphology with tight arrangement. CONCLUSION: Ag(+)-CHA with low silver content has a good biocompability and can promote the proliferation and growth of MC3T3-E1 cells in vitro, suggesting the clinical potential of this material as a anti-infection bone substitute.

The development and evaluation of individualized templates to assist transoral C2 articular mass or transpedicular screw placement in TARP-IV procedures: adult cadaver specimen study

OBJECTIVES: The transoral atlantoaxial reduction plate system treats irreducible atlantoaxial dislocation from transoral atlantoaxial reduction plate-I to transoral atlantoaxial reduction plate-III. However, this system has demonstrated problems associated with screw loosening, atlantoaxial fixation and concealed or manifest neurovascular injuries. This study sought to design a set of individualized templates to improve the accuracy of anterior C2 screw placement in the transoral atlantoaxial reduction plate-IV procedure. METHODS: A set of individualized templates was designed according to thin-slice computed tomography data obtained from 10 human cadavers. The templates contained cubic modules and drill guides to facilitate transoral atlantoaxial reduction plate positioning and anterior C2 screw placement. We performed 2 stages of cadaveric experiments with 2 cadavers in stage one and 8 in stage two. Finally, guided C2 screw placement was evaluated by reading postoperative computed tomography images and comparing the planned and inserted screw trajectories. RESULTS: There were two cortical breaching screws in stage one and three in stage two, but only the cortical breaching screws in stage one were ranked critical. In stage two, the planned entry points and the transverse angles of the anterior C2 screws could be simulated, whereas the declination angles could not be simulated due to intraoperative blockage of the drill bit and screwdriver by the upper teeth. CONCLUSIONS: It was feasible to use individualized templates to guide transoral C2 screw placement. Thus, these drill templates combined with transoral atlantoaxial reduction plate-IV, may improve the accuracy of transoral C2 screw placement and reduce related neurovascular complications. .

[In vitro drug release from a mitomycin C delivery system and its effect against scar tissue adhesion in vivo].

OBJECTIVE: To develop a chitosan (CH)/polyethylene glycols succinate acid (PEG-SA)-mediated mitomycin C (MMC) delivery system and investigate its drug release characteristics in vitro and its effect against scar tissue adhesion in vivo. METHODS: Mitomycin C loading in the composite CH/PEG-SA/MMC films was determined using ultraviolet. The freeze-dried films were dispersed in 1 ml PBS (pH7.4) and mitomycin C release in vitro was determined according to the mitomycin C concentration-UV value standard curve. The influence of the film structure on the drug release was evaluated. The drug delivery system was then implanted in SD rats, and 4 weeks later, immunohistochemical and histological examinations were carried out to assess the therapeutic effect on epidural scar tissue. RESULTS: The linear regression equation of the mitomycin C concentration-UV value standard curve was y=0.593x(3)-2.563x(2)+25.944x-0.236 (R(2)=1.000). The film demonstrated good drug delivery capability, and 20 mg of the samples in PBS showed a peak mitomycin C release after 12 days of 14.9616 microg/ml, which was higher than the ID(50) of mitomycin C (10.4713 microg/l) to the fibroblasts. On days 18 and 32, another two drug release peaks occurred (14.4824 microg/ml and 11.4092 microg/ml, respectively), followed by maintenance of slow release. Till day 60, the accumulative mitomycin release reached 0.1793 microg/ml, and the loaded drug was ultimately completely released. Significant differences were noted in the hydroxyproline content in the scar tissues of different groups (F=12.085, P=0.000), and the CH/PEG-SA/MMC DDS reduced the amount of scar tissue and promoted its orderly alignment to control potential scar hyperplasia that may compress the spinal cord and nerve roots. CONCLUSION: The composite film for drug delivery possesses good flexibility and mechanical properties and allows sustained drug release of mitomycin C to prevent epidural scar tissue adhesion following lumbar laminectomy.