| Because of trauma,infection and tumor of the bone defect causing orthopedic clinical work were often encountered in question,usually on the current clinical repair material through the implantation treatment,implant repair material should play a major role in the following:(1)The role of bone conduction:the main graft stent assist the role of bone formation,that was,for the stent graft to the host blood vessels and cells into the implants,the formation of new bone,graft necrosis was absorbed and gradually by the new bone substitute.(2) Except from stent graft that was the role of role of bone conduction should also have a bone-inducing effect,the only way to play a quick good role to repair bone defects.Long-term implants often choose fresh autogenous bone and bone,fresh autogenous bone graft,although the ideal material,both its own and possesses osteoinductive bone conduction function, but its sources were limited,and will cause for the bone area of chronic pain, hematoma formation,infection and other complication;Although the source of bone is relatively abundant and can avoid the post-operative pain to the patients,because of infection,such as autologous bone complications brought about,but the rejection of its existence and the spread of HIV,hepatitis and other diseases possible.Can be seen that the above-mentioned two methods are the drawbacks of their own existence. Therefore,people have been looking for both good at the role of bone conduction as well with bone-inducing effect of artificial bone substitute material to repair,thus avoiding the application of autogenous bone and allograft bone material caused by chronic pain,infection and rejection,the spread of dangerous diseases.Research background:The 19th century,the end of the 70s,as a new type of hydroxyapatite(HA) since biological material,disciplines and material aroused wide interest in the medical profession.HA because of its chemical composition and crystal structure of human bone tissue and the main inorganic mineral composition was basically the same,the introduction of the human body did not produce rejection, so as a substitute for bone repair materials widely used at home and abroad.It had been animal experiments and clinical research had shown that with non-toxic, non-irritating,good bioactivity,biocompatibility and bone conductivity,high mechanical strength and chemical properties of stable.HA particles but also larger and brittle,the lack of plasticity,in vivo degradation of the slow and anti-fatigue damage to the lower intensity and difficult to be a perfect substitute for the body to use its clinical application is limited.With the development of nanotechnology,biological properties of nanocomposit -es better become a research hot spot.Study found that the basic components of natural bone was nanoscale HA and the collagen type I fibers,nano-hydroxyapatite (Nano-HA) of the composition and structure of human hard tissue,bone,teeth of the inorganic constituents similar,and the Nano-HA was able to self-curing molding, easy-to-use,non-toxic side effects,could absorb and degradation,with a smaller diameter of the nano-particles,and make it more conducive to functional well-differentiated osteoblast secretion of bone matrix,was more conducive to new bone formation,in the process of cell growth was more conducive to its function with better metabolic biology performance can be firmly integrated in the life of bone tissue the provision of adapting to the new bone matrix deposition physiological and guide bone tissue regeneration with bone lead and pro-bone,and have excellent biological activity,was considered to be a very ideal replacement organize material. Although its strength,toughness and bone-induced still not perfect,but so far it was still recognized by many scholars as a substitute for bone defect implants good scaffold material.Based on this,our experiments at the Nano-HA was chosen as an alternative to repair bone defects implanted matrix material. Polyhydroxybutyrate-hydroxyvalerate(PHBV) were polyhydroxybutyrate(PHB) and hydroxyvalerate(HV) copolymer,light weight,corrosion resistance,porosity, aperture could be controlled,and it had a good plasticity material,mechanical strength,biocompatibility,biodegradability,etc.,and there was piezoelectricity,could stimulate new bone growth.PHBV studies had shown there was a very good guided bone regeneration function,was a very good performance and biocompatibility of biodegradable polymer material and better guided bone regeneration of natural material.Polyethylene glycol(PEG) because of its molecular chain of supple line, withoutstanding physical and chemical and biological properties,with a hydrophilic, in water and soluble in organic solvent,non-toxic,non-antigenicity and immunity.At the application of biomedical material,PEG or its high molecular weight polymers are often used for modification of material,the study showed that surfactant addition of PEG could effectively reduce the particle surface tension and improve the products of the reunion,were present in the block copolymer material most widely used hydrophilic side chain,in the hydrophilic PEG segment length under certain conditions,you could by changing the hydrophobic segment to adjust the length of PLA polymer micelles of physical and chemical properties.To PHBV based on selection of high hydrophilic PEG material mixture could be improved with common PHBV,HA in the application of the limitations of bad hydrophilic,thus improving biodegradable composite material performance.Could be seen that these two substances the introduction of Nano-HA matrix material was expected to improve the plasticity of composite material,the degradation rate,biocompatibility,mechanical strength and bone biology,such as leading performance.Bone morphogenetic protein (BMP) could induce undifferentiated mesenchymal cells differentiate into osteogenic ability of cartilage.BMP activity in bone in growth material could induce mesenchymal cells to bone cell differentiation,secretion of type of bone matrix and then the ability of osteoblast mineralization.We added in the composite material of recombinant human bone morphogenetic protein-2(rhBMP -2) active material to increase the composite material-induced bone.To sum up,our Nano-HA in the matrix material by adding PHBV,PEG,and rhBMP-2 and other auxiliary components made of Nano-HA / PHBV-PEG-rhBMP-2 composite bone,the composite material to explore the possibility of repair the process of bone defect can be demonstrated more simply Nano-HA more excellent biological properties.Purpose and significance:Through the repair of radial bone defects in New Zealand white rabbits to explore Nano-HA / PHBV-PEG-rhBMP-2 composite artificial bone for repairing bone defects,in order to provide a theoretical basis for clinical application.Experimental Methods:①Through the synthetic methods separately into Nano-HA / PHBV-PEG-rhBMP-2 composite bone and the purely artificial Nano-HA materials.②Select 50 healthy male New Zealand white rabbits,weighing 1.5～2.0 kg,and were randomly divided into A,B two groups:each group 25,respectively, after its weighing,using 20g/L pentobarbital 30mg/kg satisfied rabbit ear fate intravenous anesthesia,conventional disinfection shop towel,take the rabbit with bilateral forelimb mid-lateral incision approximately 3cm longitudinal incision, exposing the radial shaft in the previous paragraph,At 2.5cm from the distal radius fracture department together with the periosteum using wire saw with radial saw,the same way in the first osteotomy line 1.5cm proximal radial saw again,together with periosteal resection between the two ends of the radial bone,resulting in double lateral radial segmental bone defect model,gentamicin after repeated washing,the left side of one of A group Nano-HA/PHBV-PEG-rhBMP-2 composite artificial bone implants,as the experimental group;B group of the left implant Nano-HA artificial bone material,as a control group;A,B were not implanted into the right side of any material,as the blank control group,the wound sutured layer by layer.Immediately after intramuscular injection of penicillin 400,000U each,only row 3d,no external fixation,sub-cage feeding.③Outcome Measures:Gross observation:Postoperative observation of the mental state of animals in each group,catering,toilet,activities and whether the wound swelling,secretions occur.Based on observation of the various components after the bone and material degradation.X-ray radiography examination: Materials were implanted after the first 2 weeks,4 weeks,8 weeks,12 weeks and 16 weeks were randomly selected based on two rabbit executed,the X-ray radiography examination,observation of each group of animal bone defect area the callus growth, material degradation and bone connections.Bone mineral density measurements: Materials were implanted after the first 4 weeks,8 weeks,12 weeks and 16 weeks from each group were randomly selected based on six killed rabbit,the experimental group and control group specimens home dual-energy X-ray absorptiometry,to measure bone mineral density into a bone defect area,application of statistical software to analyze the results on the determination.Biomechanical test:Materials were implanted after the first 4 weeks,8 weeks,12 weeks and 16 weeks bone mineral density test tick the net after the periosteum and soft tissue,at MTS-858 material testing machine up three points bending test specimens measured in each group of anti-bending strength,the results on the determination of the application of statistical software for analysis.Experimental results:The results of gross observation:None of the experimental animals after the death of animals after the normal eating and activity, incision-free swelling,exudate,such as inflammatory response,wound healing on schedule.Material implanted the first 4 to 8 weeks,experimental group and control group gradually material degradation,and bone interface vague,there was obvious new bone formation,combined with the host bone tissue close to the experimental group significantly.12～16 weeks,two groups of material degradation had been basically complete,the gradual integration with the host bone,new bone to further increase access to basic repair of bone defects is still experimental group.With the blank control group after the extension of time at the radial bone defect had no obvious new bone formation,no obvious bony connection formation,the medullary cavity closed end of the gradual hardening of bone absorption,bone defect without repair.The results of radial X-ray examination:The first 2 to 4 weeks after material implanted:Experimental group and control group than the host material density of bone mineral density in high and clear boundaries with the host bone,the department of material and osseointegration had a small amount of bone callus formation,and its low density to the experimental group significantly.8 weeks after implanted of material:Experimental group materials fuzzy boundaries with the host bone volume significantly reduced,implant materials had been with the receptor fragments of bone healing,better continuity of cortical bone,bone marrow cavity through the part;the control group implanted materials with the receptor fragments of bone healing,but poor continuity of cortical bone,bone marrow cavity has not yet been through.12 16 weeks after implantation of material:The experimental group implanted with the receptor gradually material bone healing into one,density gradually near,the basic cortical connections completed basic fully degradable material,bone marrow cavity had endorsed,completely remodeling,bone completion of defect repair;control group implanted with the receptor gradually materials bone healing into one,density gradually near,poor continuity of cortical bone,most of materials degradation,bone defect filled with bone,bone marrow cavity recanalization basic,plastic the basic shape completely,bone defect basic repair.Blank control group,bone defects can be seen there was a certain degree ofperiosteal reaction,no obvious new bone formation, no obvious connection of the formation of bone,bone-side gradually hardening absorption,medullary cavity closed without repair of bone defects.The results of new bone mineral density measurement:After implantation of material,the new bone mineral density between the two groups was significant difference(F =78.748,P = 0.000),the experimental group(mean 0.128 g/cm2) was significantly higher than the control group(mean 0.093g/cm2),respectively after 4 weeks,8 weeks,12 weeks,16 weeks compared between the two groups there was significant difference(t4w= 14.894,t8w=5.187,t12w= 3.173,t16w = 4.222,P4w = 0.000,P8w = 0.000,P12w = 0.010,P16w = 0.002),and the experimental group were all higher than the control group.Material at different time point after implantation,the new bone mineral density in the overall comparison between the two groups there was significant difference(F=115.337,P=0.000),the experimental group at different time point was significantly different(F=126.060,P=0.000),the control group at different time point was significantly different(F=135.585,P=0.000),and the results were all 16 weeks＞12 weeks＞8 weeks＞4 weeks.As the time extension after implantation of material,the new bone mineral density differences between the two groups had no significant changes(F=0.271,P=0.846).The results of biomechanical measurement:After implantation of material,the anti-bending strength of radial between the two groups was significant difference (F=125.543,P=0.000),the experimental group(mean 66.131Mpa) was significantly higher than the control group(mean 41.982Mpa ),respectively after 4 weeks,8 weeks, 12 weeks,16 weeks compared between the two groups there was significant difference(t4w=3.245,t8w=5.530,t12w=7.303,t16w=5.806,P4w=0.009,P8w=0.000,P12w=0.000,P16w=0.000),and the experimental group were all higher than the control group.Material at different time point after implantation,the anti-bending strength of radial in the overall comparison between the two groups there was significant difference(F=284.006,P=0.000),the experimental group at different time point was significantly different(F=142.682,P=0.000 ),the control group at different time point was significantly different(F=153.064,P=0.000 ),and the results were all 16 weeks＞12 weeks＞8 weeks＞4 weeks.As the time extension after implantation of material,the anti-bending strength of radial difference between the two groups of anti-radius bending strength gradually showed significant differences in trends(F=7.043, P=0.001).Major conclusions:①The formation of large bone defect after implantation is not any substitute material or deal with any intervention,bone defect will be no obvious connection of the formation of bone,bone-side will gradually hardening,gradually closed chamber,it is difficult to repair bone defect healing.②Nano-HA as the repairing bone defect after implantation of alternative material shows good biocompatibility,degradability and bone conduction,as to repair bone defect for a good alternative to implanted matrix material.③Material at Nano-HA by adding PHBV,PEG,and rhBMP-2 and other auxiliary components and synthetic Nano-HA/PHBV-PEG-rhBMP-2 composite bone in repairing bone defect demonstrated in the course of a more Nano-HA better biological performance,is a relatively good substitute for repairing bone defect implanted in composite material.④In this study,in order to further look for performance more excellent alternative to repair bone defect implanted reference material.
|
PDF Full Text Request