| Bone defect refers to the bone loss caused by fractures,nonunion,congenital anomalies,allogenic bone absorption or other pathogenic injury,and may cause pathological changes in the bones,joints and even surrounding soft tissues,and then the formation of somatic Organic or functional disorders of a class of diseases.In modern society,with the increasing pace of people's activities,the expansion of living space,the increasing speed of traffic,the increasing construction speed and the frequent occurrence of various accidents,the bone defect caused by high-performance injury has become a serious social problem.In addition,Due to infection,tumor resection and other reasons make more and more patients with bone defects,if not timely and effective treatment of bone defects,can easily lead to nonunion or bone nonunion,left over for life disabilities.This shows that the treatment of bone defects has become a difficult problem facing orthopedic surgeons.One of the important causes of nonunion of bone defects is local ischemia and hypoxia after bone injury.Studies have shown that: fractures of blood flow interrupted,the central part of the injury oxygen even reduced to 0%-2%,and the process of bone regeneration is a need a lot of oxygen and nutrients in the process,bone marrow hypoxia can lead to environment changes,abnormal bone metabolism,chronic hypoxia can also lead to "repair cells" of death.Therefore,to maintain the oxygen homeostasis after injury of bone tissue,and to localize the oxygen concentration in the damaged area to a certain extent is very important for promoting bone regeneration and healing.The timely and effective reoxygenation has been considered as a crucial step.The application of bone tissue engineering technology to build an oxygen-rich material to fill the bone defect may improve the local early hypoxia environment,improve the surviving rate of residual cells and the activity of "repairing cells",thereby promoting the healing of bone defects.In this experiment,a new type of oxygen-enriched temperature-sensitive hydrogel was constructed by using the temperature-sensitive chitosan hydrogel as carrier oxygen enrichment agent-Perflubron.The physical-chemical and biological properties of the hydrogel was tested through experiments to promote the healing of bone defects effect,and explore its mechanism.Part 1 The oxygen-enriched temperature-sensitive hydrogel construction and evaluationObjective:The physical and chemical properties,oxygen release ability and biological properties of oxygen-rich temperature-sensitive hydrogel was detected and explored.The optimum oxygenate concentration was screened.Methods:Two kinds of oxygen-rich hypersensitive hydrogels with 5% and 10% of perflubron were prepared and their gelling time,p H value and oxygen releasing capacity were measured at 37?,and the optimal concentration of perflubron was screened compared to the protocol,further examination of infrastructural,toxicity,bio compatibility and affordability of the optimally proportioned gel material was performed.Results:The two kinds of oxygen-rich temperature-sensitive hydrogels with two different concentrations of perflubron are all about 4.5 minutes at 37 ?,with no significant difference(P>0.05),and the p H values were all close to neutral,and there was no significant difference between the two groups(P>0.05).Oxygen-enriched hydrogel with a concentration of 10% of perflubron had a higher oxygen release rate and a faster oxygen release rate than the 5% oxygen-enriched hydrogel(P<0.01).However,the duration of oxygen release was the same for about 7 days.Therefore,in combination with the above experimental results,the follow-up experiments were conducted with perflubron 10% concentration of oxygen-enriched hydrogel;Oxygen-enriched hydrogel with a concentration of 10% of perflubron has a three-dimensional porous network structure(pore size of about 100-200?m),the fiber crisscrossing,dense pore;And the extract was not hematologic toxic and did not cause rupture of erythrocytes;muscle embedding experiments showed that oxygen-enriched temperature-sensitive hydrogel at a perflubron concentration of 10% did not cause tissue necrosis and almost completely degrade at 6 weeks.Conclusion:The new oxygen-enriched temperature-sensitive hydrogel screened and prepared in this section have good micro structure and physical-chemical properties,and oxygen-enriched hydrogel with 10% perflubron concentration have better oxygen releasing properties and good compatibility with the tissues,No stimulation to the tissue and toxic side effects,which can gradually degrade and absorb in vivo.This new type of oxygen-rich Temperature-sensitive hydrogel can be used as a scaffold for bone tissue engineering for further study.Part 2 The oxygen-rich temperature-sensitive hydrogel repair rabbit femoral condylar bone defects in experimental studyObjective:To detect and investigate the effect and cause of oxygen-rich temperature-sensitive hydrogel with 10% perflubron concentration on repair of rabbit femoral condylar bone defect model.Methods:The model of rabbit femoral condylar bone defect was constructed,and the oxygen-rich agent perflubron with oxygenation oxygen-rich temperature-sensitive hydrogel were filled in the bone defect as the experimental group;The oxygen-rich agent perflubron without oxygenation temperature-sensitive hydrogel filled in the bone defect as a control group;the bone defect model is not filled with any material group as a blank group.At the 4th,6th,8th and 12 th week after operation,the specimens were collected and the general repair of the bone defect was observed.X-ray,Micro-CT and histologic pathology examination were performed.Results:The general repair of bone defects and the results of X-ray,Micro-CT and histologic pathology examination showed that the repair effect of the experimental group was the best at each sampling time point,followed by the control group and the worst is blank group.At the 12 th week,the experimental group of bone defects completely healed;While the control group,although the cortex healed,but the bone is not mature;There are still significant bone defects in the blank group.Micro-CT count data showed that there was significant difference between the three groups at the 4 th,6 th,8 th,12 th weeks in the TMD,BVF,Tb.Th,and Tb.N(P<0.05),and the experimental group> control group> blank group.There was no significant difference between the three groups at the 4th week and the 6th week in the structural model index(SMI)(P>0.05).There was a significant difference between the three groups at the 4th week and the 12 th week(P<0.05),and the neoformative bone trabeculae in the blank group was still juvenile.However,the neoformative bone trabeculae in the control group and the experimental group was more mature plate,But the experimental group is better than the control group.Quantitative examination of microvessel density showed that there was significant difference between the three groups at the 4 th,6 th,8 th,12 th weeks(P<0.05),and the neovascularization in the experimental group is early and in quantity,the control group was second,the blank group was the least.Conclusion:The novel oxygen-enriched temperature-sensitive hydrogel screened and prepared in this experiment can promote the repair of the femoral condylar bone defect model in rabbits,which is a bone tissue engineering scaffold material with further research value. |
PDF Full Text Request