Iodine-doped TiO2 nanotube coatings: a technique for enhancing the antimicrobial properties of titanium surfaces against Staphylococcus aureus.

BACKGROUND: Implant-related infections are a challenging complication of orthopedic surgery, primarily due to the formation of bacterial biofilms on the implant surface. An antibacterial coating for titanium implants was developed to provide novel insights into the prevention and treatment of implant-related infections. METHODS: Titanium plates were coated with TiO2 nanotubes by anodization, and iodine was doped onto the coating via electrophoretic deposition. The obtained plates were characterized using a range of analytical techniques. Subsequently, Staphylococcus aureus was inoculated onto the surfaces of untreated titanium plates (control group), TiO2-nanocoated titanium plates (TiO2 group), and iodine-doped TiO2-nanocoated titanium plates (I-TiO2 group) to compare their antibacterial properties. RESULTS: Twenty-four hour in vitro antimicrobial activity test of the I-TiO2 group against Staphylococcus aureus was superior to those of the other groups, and this difference was statistically significant (P < 0.05). CONCLUSIONS: This coating technology provides a new theoretical basis for the development of anti-infective implants against Staphylococcus aureus in orthopedics.

Danggui sini decoction ameliorates myelosuppression in animal model by upregulating Thrombopoietin expression.

Danggui Sini decoction (DSD), a famous Chinese medicine, has been used therapeutically in various diseases. In this study, we tried to investigate whether and how DSD could ameliorate myelosuppression in an animal model, in which myelosuppression is induced by cyclophosphamide treatment. The myelosuppression model was established by intraperitoneal injection of 100 mg/kg cyclophosphamide in mice. Flow cytometry was used to assess cell numbers and evaluate the bone marrow cell cycle distribution. Spleen samples were collected, and the mRNA expression levels of thrombopoietin (TPO) and c-Mpl were analyzed by RT-PCR. Our results demonstrated that DSD could significantly elevate the level of bone marrow hematopoietic stem progenitor cells in myelosuppression mice model. DSD also accelerated cell proliferation by switching cell cycles from G0/G1 phase to S and G2/M phase. Moreover, DSD significantly elevated the mRNA expression level of TPO, but not c-Mpl in spleen. Overall, the present results indicated that DSD is a promising Chinese medicine that is highly potent to ameliorate myelosuppression induced by chemotherapy by upregulating TPO expression.

Gemcitabine for the treatment of patients with osteosarcoma.

BACKGROUND: Patients with recurrent or refractory osteosarcoma are considered to have a very poor prognosis, and new regimens are needed to improve the prognosis in this setting. Gemcitabine, a nucleoside antimetabolite, is an analog of deoxycytidine which mainly inhibits DNA synthesis through interfering with DNA chain elongation and depleting deoxynucleotide stores, resulting in gemcitabine-induced cell death. Here we performed a systemic analysis to evaluate gemcitabine based chemotherapy as salvage treatment for patients with recurrent or refractory osteosarcoma. METHODS: Clinical studies evaluating the impact of gemcitabine based regimens on response and safety for patients with osteosarcoma were identified by using a predefined search strategy. Pooled response rates (RRs) of treatment were calculated. RESULTS: In gemcitabine based regimens, 4 clinical studies which included 66 patients with recurrent or refractory osteosarcoma were considered eligible for inclusion. Systemic analysis suggested that, in all patients, pooled RR was 12.1% (8/66) in gemcitabine based regimens. Major adverse effects were hematologic toxicity, including grade 3 or 4 anemia, leucopenia and thrombocytopenia in gemcitabine based treatment. No treatment related death occurred in gemcitabine based treatment. CONCLUSION: This systemic analysis suggests that gemcitabine based regimens are associated with mild activity with good tolerability in treating patients with recurrent or refractory osteosarcoma.

Expression of FGF-2 and IGF-1 in diabetic rats with fracture.

OBJECTIVE: To observe the change of fibroblast growth factor-2 (FGF-2), insulin-like growth factor-1 (IGF-1) in serum and bone callus after fracture in diabetic rats, and to explore molecular biological mechanism of healing of diabetic fracture. METHODS: Thirty male SD rats were designed into normal (n=15) and control (n=15) groups randomly. Venous blood was extracted on the lst, 2nd, 4th, 6th, 8th week after surgery. It was certificated and the serum was obtained. Left lower extremity was observed by X- ray. Bone callus at broken ends was observed under light microscope. Expressions of FGF-2 and IGF-1 in tissue were detected by immunohistochemistry method, and ELISA was used to detect expression of FGF-2 and IGF-1 in serum. RESULTS: The results showed a significant increase in the density and area of newly formed bone in the distraction gaps of normal rats compared to control rats. Increased cell proliferation was also found in the distraction gaps of normal rats versus control rats. There was significant difference in serum levels of FGF-2 and IGF-1 between two groups. CONCLUSIONS: The decrease of FGF-2 and IGF-1 both in the serum and in the fracture region is one of the reasons for bad bone healing or delayed union in rats' fracture with diabetes. There are some synergistic effects possibly between FGF-2 and IGF-1.

Repair of the radial defect of rabbit with polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology.

OBJECTIVE: To evaluate the effects of repairing rabbit radial defects with polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology loaded with bovine bone morphogenetic protein (bBMP), and find new carriers for growth factors. METHODS: Polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology loaded with and without bovine BMP were used to repair the 15 mm radial defect in rabbit. Then the results of radiography, histology, scaffolds degrade rates and bone mineral density (BMD) were appraised to examine the effects at the 12th week. RESULTS: At the 12th week postoperatively, all defects treated with bBMP were radiographically repaired. No radius implanted polyester/tricalcium phosphate scaffolds without bBMP showed radiographic and histological union. At experimental groups, longitudinal alignment of lamellar structure was observed histologically at the 12th week, indicating that remodeling of regenerated bone was complete in different degree. Of the three experimental groups, the bony regeneration and remodeling of callus in poly lactide-co-glycolide/tricalcium phosphate (PLGA/TCP) group was the best. The BMD values were beyond 70% of normal value at the 12th week while the PLGA/TCP scaffolds group was the highest, and no abnormalities were observed in the surrounding soft tissue in all groups. CONCLUSIONS: Polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology loaded with bovine BMP can repair a 15 mm radial defect of rabbit. As for the results, the PLGA/TCP scaffold is ideal and better than poly L-lactide-co-D, L-lactide (PDLLA/TCP) scaffold, but the ploy L-lactic acid (PLLA/TCP) is not so good for its low degradation rates.

[Repair of the radial defect of rabbit by polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology].

OBJECTIVE: To evaluate the repairing effect of the rabbits radial defects of by polyester/tricalcium phosphate scaffolds prepared by rapid forming technology loaded with bovine BMP, and find a new carrier for growth factor. METHODS: Polyester/Tricalcium phosphate scaffolds prepared by rapid prototyping (RP) technology loaded with and without bovine BMP were used to repair the 15 mm radial defect of rabbit. Then results of radiography, histology, scaffolds degrade rates and bone density were appraised to examine the repairing effects of the scaffolds at 12 weeks. RESULTS: At 12 weeks, all defects treated with bBMP were radiographically repaired. No radii implanted polyester/tricalcium phosphate scaffolds alone showed radiographic and historical union. At experimental groups, longitudinal alignment of lamellar structure was observed histologically at 12 weeks, indicating that remodeling of regenerated bone almost completed, the scaffolds degradation rates were different by 12 weeks, and no abnormalities were observed in the surrounding soft tissue in all groups. CONCLUSION: Polyester/tricalcium phosphate scaffolds prepared by rapid prototyping technology loaded with bovine BMP can repair the rabbits radical defects. As for the effects, the poly (L-lactic-co-glycolide)/tricalcium phosphate (PLGA/TCP) scaffold are ideal and better than poly (L-lacide-co-D, L-lactide)/tricalcium phosphate (PDLLA/TCP) scaffold, but the poly (L-lactic acid)/tricalcium phosphate (PLLA/TCP) is not so good for its low degradation rates.

[Efficacy of double-door laminoplasty combined with hydroxyapatite artificial bone grafting for cervical spinal stenotic myelopathy].

OBJECTIVE: To evaluate the effects of double-door laminoplasty and hydroxyapatite artificial bone grafting in the treatment of cervical spinal stenotic myelopathy. METHODS: Twelve cases of cervical spinal stenotic myelopathy underwent expansive double-door laminoplasty of the cervical spine and hydroxyapatite artificial bone grafting. The clinical outcome of the patients and the operative procedures were assessed. RESULTS: The 5-year follow-up showed significantly alleviated clinical symptoms and improved physical signs in all the patients except for 1 patient who responded poorly to the surgery. CONCLUSIONS: Expansive double-door laminoplasty of the cervical spine in combination with hydroxyapatite artificial bone grafting is safe and effective for treating cervical spinal stenotic myelopathy. Hydroxyapatite artificial bone possesses good biological compatibility and osteoconduction, and is applicable in the laminoplasty procedures as an ideal bone graft material.

[Suppression of neutrophil immune function in rabbit models of hemorrhagic shock complicated by intra-abdominal hypertension].

OBJECTIVE: To investigate the effects of hemorrhagic shock and intra-abdominal hypertension (IAH) on inflammatory responses of peripheral circulating neutrophils such as intracellular cytokine production, phagocytic capacity and expression of nuclear factor (NF)- kappaB. METHODS: Twenty-four rabbits were divided equally into 4 groups including a hemorrhagic shock (HS) group complicated by abdominal compartment syndrome (ACS) (Group A), a HS group (Group B), a ACS group (Group C) and a normal control group (Group D). Intracellular interleukin (IL)-8 production in the peripheral neutrophils were measured in the rabbits by flow cytometry, phagocytic function of the neutrophils evaluated by a chemiluminescence method and the NF-kappaB expression detected by immunocytochemistry before, immediately and 4 h after the traumatization. RESULTS: Four hours after the trauma, decreased intracellular IL-8 production and impaired phagocytic function of the peripheral neutrophils were observed in Group A along with suppressed NF-kappaB expression. But in Group B and Group C, the intracellular IL-8 production, phagocytic function and expression of NF-kappaB returned to the normal levels 4 hours after the trauma following the early-stage changes. In Group D, no significant changes occurred during the observation. CONCLUSIONS: Responsiveness and function of the neutrophils to the stimuli by endotoxin are suppressed by the sequential second-hit of IAH after hemorrhagic shock, which may contribute to the occurrence of sepsis in ACS.

[Effect of marrow stromal cells derived chondrocytes on repair of full-thickness defects of rabbit articular cartilage].

OBJECTIVE: To investigate the feasibility of cartilaginous implants containing bone marrow stromal cells (MSCs) derived from chondrocytes in biological resurfacing procedures for repairing articular cartilage defect. METHODS: MSCs derived from chondrocytes were obtained with high initial cell density subculture. An implant was constructed by dispersing the chondrocytes in a acid soluble type I collagen gel(5 x 10(6) cells/ml, final cell concentration). A full-thickness defect 3 mm x 5 mm was created in the trochlear groove of femur in 36 rabbits. A piece of cotton soaked in 0.5% trypsin was laid into the defect for 5 minutes, then the defect was filled with MSC/collagen gel implant on one side (n = 36), filled with a plain collagen gel on the other side (n = 18), and left empty as controls on the other side (n = 18). The animals were sacrificed at 4, 8, 12, 24, 32, and 48 weeks. The repaired tissue was examined and evaluated with Pineda grading scale. RESULTS: In MSCs group, the implanted cells resembled well differentiated chondrocytes and were surrounded by metachromatic matrix and the reparative tissue resembled hyaline cartilage after 4 weeks; bone was formed at the base of the defects, the thickness of new cartilage was larger than tht of normal one after 8 weeks; the thickness was reduced proximally, approximating to that of normal cartilage, and chondrocyte columns was formed and subchondral bone and tidemark reappeared after 12 weeks; the thickness of the new tissue was about 55% of the normal tissue, with smooth surface and there were hypertrophic chondrocytes near the tidemark after 24 weeks; no hypertrophic chondrocytes were observed, indicating cessation of endochondral ossification after 32 weeks; the tissue architecture was the same as that at 32 weeks, hyaline-like cartilage persisting, with subchondral bone and tidemark in continuity after 48 weeks. The four layer cell orientation was not as clear as that of normal cartilage. The defects were partially filled with fibrous tissue in controls. At 32 weeks, erosive cartilage, naked subchondral bone and proliferative synovial membrane indicated the presence of osteoarthrosis. There were no statistical difference according to Pineda tissue scales in the specimens from the MSCs group between 24, 32, and 48 weeks, but there was significant difference between 4 weeks and 24, 32 and 48 weeks (P < 0.05). The joint function recovered after 2 weeks in MSCs group, while it deteriorated progressively in controls. CONCLUSION: MSCs derived from chondrocytes improve repair of large full-thickness defect in articular cartilage. The reparative hyaline-like cartilage is stable differentiation after 24 weeks, maintains good joint function after 48 weeks.

[Application of prosthesis replacement in limb salvage treatment of mild-malignant tumors at the articular ends of femurs].

OBJECTIVE: To investigate the clinical outcome of application of joint prosthesis in limb salvage treatment of mild-malignant tumor at the articular ends of femurs, with severe osteolysis. METHODS: The treatment of 15 cases of mild-malignant tumor at the articular ends of femurs with severe bone destruction, from 1978 to 1999, was reviewed. There were 10 cases of giant-cell bone tumor and 5 cases of chondrosarcoma, among which there were 5 cases at the stage of I A, 9 cases at I B, and 1 case at II A, with 4 cases at the proximal end and 11 cases at the distal end. The tumor was totally removed, with a massive bone defect left at the foci, and then the prosthesis replacement was performed to reconstruct the articular joint. All of the 15 patients were followed up for 9 months to 20 years, 4 years and 3 months on average, before clinical evaluation. RESULTS: All of the wound healed well, with primary healing. Local relapse occurred in one case and the patient died of lung metastasis; the amputation of the replaced knee joint was performed in one case due to severe infection after trauma; radiograph showed there was slight sunk of the prosthesis in 2 cases after replacement. The other 11 cases recovered well with satisfactory function. CONCLUSION: The limb salvage treatment of mild-malignant tumor at the articular ends of femurs would be available, especially for those with massive bone destruction, when the tumor is removed by whole and rationally marginal resection, followed by properly utilization of prosthesis and general post-operative exercise.