| Antibiotic Loaded Bone Cement used as antibiotic locally chargeed from carrier system in the treatment of orthopaedic infection, can not only provide local high concentration of antibiotics, it will not bring about side effects by a big dose systemic administration, has been gradually accepted as treatment of orthopedic infection in clinic. Staphylococcus aureus, basically Staphylococcus aureus and coagulase-negative staphylococci (CNS)is the most common bacteria in orthopaedics infection, and methicillin-resistant Staphylococcus aureus or gentamicin resistant Staphylococcus aureus has been a popular trend. CNS have also some variant. Aminoglycoside has gradually been failure for killing these past sensitive bacteria, glycopeptide vancomycin become the treatment of choice for this type of bacterial infection. But local orthopedic administration is not yet largely reported. To achieve better efficacy in the treatment of orthopedic infection and avoid re-emergence of drug-resistant bacteria as a result, we have comprehensively research characteristics delivery of VCM-PMMA in vivo and in vitro, so that we can make normalization of use of VCM-PMMA. While bone cement used as carrier system was modified so that the new materials will better play the role of sustained-release carrier. In this paper, properties of VCM eluted from PMMA in vitro, effect of different mixing way of VCM and PMMA in vitro and in vivo environment on mechanical and eluted properties of PMMA, the efficacy of VCM-PMMA on prevention and treatment of osteomyelitis in animal experiments, the releaseed laws and safety of VCM in vivo, the efficacy of VCM-PMMA on treatment of hip prosthesis infection in animal experiments, the efficacy and safety of VCM-PMMA on prevention and treatment of osteomyelitis in clicic, the structural characteristics and elution in vitro of PCL-PMMA, and so on will be research. Research results are as follows:1 properties of VCM eluted from PMMA in vitroThe velocity of VCM eluted from PMMA descend increasingly with the time past. The descending extent is significantly within the first three days, and then become less in the lower level. Along with the dose of VCM in PMMA gradually increasing, the velocity and the cumulative amount of VCM eluted from PMMA has gradually increased. 3:40 Group> 2:40 group> 1:40 group. The velocities at least within 7 days and cumulative amount in 35 days of VCM eluted from PMMA among the three groups have significant differences. The total amount of VCM eluted from PMMA mostly comes from the cumulative amount within the initial 14 days. The cumulative amount in 35 days of VCM eluted from PMMA accounting for the proportion of total VCM content within specimens between groups do not have significant differences, 8-11% respectedly.Conclusion: The elution of VCM from PMMA is the release phenomena on the surface. The release of VCM mostly concentrated in the first 14 days. The increasing additives amount of VCM in PMMA will be significantly increased the velocity (7 days) and the cumulative amount(14 days) of VCM eluted from PMMA. 2 Impact of stir way on mechanical and eluted properties of VCM-PMMACompression strength in vitro testing: the maximum load and stress is biggest in the 3rd experimental groups, lest in the 2nd experimental group, there are significantly differences between them, the maximum load and stress of the 1st group and control group are in the middle of the upper groups. The velocities, the cumulative amounts of VCM eluted from PMMA and which accounting for the proportions of total VCM content within specimens do not have significant differences between Manual and vacuum mixing and stirring groups. In the strength testing of femoral prosthesis pulled-out, the maximum load were: experimental group 2> control group> experimental group 1, there were significantly different between experimental group 2 and control group, experimental group 1, there was not significant differences between the control group and experimental group 1. With scanning electron microscope we found there were some broken bone cement cracks and debris on the section of the manual stirring PMMA specimen, the morphologies and distributions of chambers, channels, VCM particles were uneven. There were not any broken bone cement cracks and debris on the section of the vacuum mixing PMMA specimen, the morphologies and distributions of chambers, channels, VCM particles were more homogeneous.Conclusion: With increasing of the ratio of quality between VCM and PMMA, the mechanical strength of VCM-PMMA has a downward trend. In the ratio of≤240 there were not significant difference between groups. The vacuum mixing way will improve the mechanical strength of VCM-PMMA better than the manual way, but both does not affect the velocity and the cumulative amount of VCM eluted from PMMA. The vacuum mixing way can make the morphologies and distributions of the chambers, channels, VCM particles more uniform. 3 prevention and treatment of rabbit femur osteomyelitis with VCM-PMMAIn the experiment of preventing osteomyelitis in rabbit femur, the incidence of osteomyelitis in experimental group 4 was significantly higher than that in experimental group 1, 2, 3, and there was a statistically significant difference; the incidence of osteomyelitis in the control group was significantly higher than that in experimental group 1,2,3, there is a statistically significant difference between the experimental group 1,2,3and control group. There is no significant difference between the experimental group 1, 2 and 3. In the experiments of treatment for osteomyelitis in rabbit femur, the cure rate were: experimental group 3> experimental group 2> experimental group 1> control group; there were significant differences between the control group and experimental group1, 2, 3 respectively; there were no significant differences among experimental group 1,2,3. The concentration of VCM in the blood is always floating at 0.15μg / ml irregularly, the floating interval is 0.11-0.23μg / ml, respectively. With time past, the concentrations of VCM in drainage fluid have a declining trend, the declining extent is less in the entire process. Along with the dose of VCM mixed in PMMA increased, the concentration of VCM in the drainage fluid increase gradually, followed by: group 3:40 > group 2:40 > group 1:40. There was significant difference between group 1:40 and grou2:40 p, group 3:40 respectively. The concentration of VCM within drainage fluid in group 2:40 and group 3:40 was still greater than 2.0μg/ml at the 42th day, and there was not significant difference between them in the course of disease.Conclusion: VCM-PMMA has affirmative effect in the prevention and treatment for osteomyelitis caused by methicillin and gentamicin-resistant doublely Staphylococcus aureus. The bigger ratio of quality between VCM and PMMA is, the better the clinical effect is. The clinical effect of VCM-PMMA in group 2:40 and group 3:40 do not have significant difference. The strict and thorough debridement is irreplaceable role in the prevention and treatment for osteomyelitis using VCM-PMMA. The amount of VCM in the blood was less and constant when VCM-PMMA used as local administrations , 1/20 to 1/10 of the minimum inhibitory concentration, 1/700 to 1/300 of poisoning dose, so it is safe. The concentration of VCM in vivo droped slower than its elution In vitro.4 effect of treatment for infection in rabbit hip prosthesis with VCM-PMMAThe healing rate of infection in group 2-stage replacement was significantly higher than that in group 1-stage replacement, but there was no significant difference between groups.Conclusion: Implantation of VCM-PMMA spacer in the 1st stage, and then the spacer drawn out, at the same time implantation of prosthesis and fixation with VCM-PMMA for the treatment of infection after total hip arthroplasty caused by methicillin and gentamicin -resistant doublely Staphylococcus aureus has good effect, and it is superior to 1-stage prosthesis implantation with fixation using VCM-PMMA. But there is not significantly different between groups. 1-stage replacement for treatment of infection after hip arthroplasty on the basis of entirely debridement can be considered when the infection is not heavy, and then using of ALBC to fix prosthesis.5 prevention and treatment for osteomyelitis in patients using VCM-PMMAThe incidence of osteomyelitis in two-stage allograft group was less than it in one-stage allograft group in the prevention from osteomyelitis in open fractures with bone defect, and there is a significant difference between groups. The healing rate of osteomyelitis induced by internal fixation of fractures in patients in intramedullary nail group was higher than it in external fixator group, but there was no significant differences between groups. Conclusion: Implantation of VCM-PMMA spacer into bone defect, and then the spacer drawn out, at the same time allograft for the prevention osteomyelitis has good effect in open fractures with bone defect, and it is superior to 1-stage allograft. The merger of fixation fracture with intramedullary nail and VCM-PMMA spacer filled into marrow cavity to treat osteomyelitis induced by internal fixation has reliable clinical effect than external fixator. Local application of VCM-PMMA is safe.6 composite carrier new materials of PCL nanofibers - PMMA microspheresThe velocity of VCM eluted from PCL-PMMA (2:40) was significantly higher than it from ordinary PMMA (2:40). The former velocity in the first three days were about 2,4,3-fold to the latter respectively. There were significant difference between groups. The cumulative amount of VCM eluted from PCL-PMMA (2:40) in 35 days was higher than it eluted from ordinary PMMA (2:40) in 35 days, the former was close to two-fold of latter, and there was significant difference between them. The former accounting for the proportion of total VCM content within specimens was higher than the latter, about 2 double of the latter. There was significant difference betweem them.Conclusion: PCL-PMMA composite materials has better property of elution than ordinary PMMA bone cement.The elution liquid in this study was simulate fluid, closer to the body fluid environment than the phosphate buffer saline or physiologic saline ever before used. Then result of VCM elution in vitro was closer to property of elution in vivo environment. The domestic and abroad research on the effects of stir way on mechanical properties of ALBC was few, and only mechanical experiments in vitro. On the basis of the above-mentioned study, we work the impact of mixing their ways on the mechanical properties of ALBC used to fix prothesis in vivo, at the same time we made elution experiment of ALBC in vitro, as well as with electron microscopy researched the impact of mixing methods on internal structure of ALBC. The establishment of animal model of osteomyelitis and infection after artificial joint replacement using of double drug resistant strains is not yet reported. We established animal model of osteomyelitis and infection after artificial joint replacement using methicillin and gentamicin-resistant doublely Staphylococcus aureus in order to meet clinical needs. We study effect of prevention and treatment of orthopaedic infection using VCM-PMMA, concentration of VCM in blood and drainage fluid, effective timing on local administration and security issues which has been always speculated in clinical. Clinically we originally filled VCM-PMMA into bone defects of the open fracture, it can effectively prevent from osteomyelitis at the same time create a good local soft tissue for allograft at 2-stage. The merger of fixation fracture with intramedullary nail and VCM-PMMA spacer filled into marrow cavity to treat osteomyelitis induced by internal fixation has reliable clinical effect. Finally, we use high-voltage electrostatic spinning technology, the PMMA bone cement combined with PCL, was modified to enhance the release of antibiotics. |
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