| Background:Fracture is the most common clinical disease in traumatic orthopedics,which is usually caused by trauma.Except for some fractures that can be treated conservatively,most fractures still need surgery.For the surgical treatment of fractures,orthopedic doctors have been extremely confident in internal fixation instruments such as steel plates and nails for nearly a hundred years.However,with the development of technology,internal fixation equipment for treating fracture has gradually developed to the bottleneck.The most important thing is that orthopedic doctors gradually find that traditional internal fixation has some shortcomings,so scientific research pioneers have been thinking of developing a material similar to "bone glue" to deal with the situation that these traditional internal fixation devices can not cope with.However,biodegradability and biosafety seriously restrict the further clinical application of bone adhesive.Therefore,improving the bioactivity of bone adhesive is still a difficult problem in clinic.Recently,biomimetic multi-component bone adhesive with osteoconductivity and excellent structural design has attracted great interest of scientific researchers in orthopedics and material engineering,and is considered as a feasible scheme for bone adhesive treatment of fractures.The working principle of bone adhesive,which can continuously exert its biological activity after curing,is similar to that of scaffold,which is named "liquid scaffold".In addition,the design idea of many studies is to use bone adhesive as a patch and fix it on the bone cortex on both sides of the broken end of the fracture.This fixation method is somewhat similar to the steel plate,but the difference is that the bone adhesive is liquid or colloid when applied and becomes solid after curing.This bone adhesive can be named "liquid plate".The further research on bone adhesive mainly focuses on the development of osteoconductivity and osteoinductivity for "liquid scaffold",while for "liquid plate",it is necessary to develop its mechanical properties,including its adhesion strength and mechanical strength after curing.In addition,there is no unified model verification standard in the animal model verification of bone adhesive.Skull defect model in vivo animal experiments of bone adhesive is used,which can not truly reflect the effect of bone adhesive in treating fractures in vivo.Therefore,a standardized animal fracture model with good repeatability is also needed to verify the effect of donor in vivo repair.Purpose:To explore the ability of functional composite bone adhesive as "liquid scaffold" and double ester bone adhesive as "liquid plate" to repair fractures,and develop and make animal fracture models with good parallelism to verify the in vivo repair effect of bone adhesive,so as to provide preliminary experimental basis for the development of bone adhesive suitable for clinical application of fracture fixation and repair.Methods:In view of the main challenges,we designed and manufactured double ester bone adhesives and functional composite bone adhesives,characterized their physical and chemical properties,and studied the therapeutic effects of a variety of bone adhesives on fracture fixation in different ways.The specific research plan includes the following three aspects:(1)Double ester bone adhesive and functional composite bone adhesive were designed and prepared.Firstly,PGS(Poly(glycerol sebacate))was synthesized by polycondensation reaction,and then PGS and IPDI(Isophorone diisocyanate)were premixed to prepare PGS + IPDI double ester bone adhesive.We also prepared dopamine modified inorganic nanoparticles(n HA(Nano hydroxyapatite)and n BG(Nano bioglass)).After blending double ester bone adhesive with inorganic nanoparticles,we prepared functional composite bone adhesives PGS + IPDI + n HA and PGS + IPDI + n BG.Next,the physical and chemical properties of various bone adhesives were characterized in vitro,including in vitro bonding tensile strength,NMR,IR,hydrophilicity and so on.(2)Before in vivo experiments,we verified the biodegradability and cytotoxicity of different formulations of bone adhesives.Moreover,because we want to fix PGS + IPDI double ester bone adhesive on the bone cortex on both sides of the broken end of the fracture in the form of "liquid plate",we pretreated the surface of the bone cortex with phosphoric acid etchant in a pre experimental way,which proved that phosphoric acid etching can make the surface of the bone cortex rough and enhance the bonding strength between the bone adhesive and the bone cortex.(3)SD rats were selected to successfully construct the rat unilateral tibial 45°oblique fracture model with 3D printed osteotomy guide.After surgical modeling,various bone adhesives were used to fix the fracture,including two fixation methods of "liquid scaffold" and "liquid plate".The fracture healing was observed at different time.The fracture treatment effect between different groups was verified by X-ray,limb length measurement,micro-CT,H&E staining,Masson staining,three-point stress experiment of bone tissue and immunoprotein electrophoresis.Results and Conclusion:In this study,we obtained a variety of bone adhesives through the blending of PGS,IPDI,n HA or n BG,including double ester bone adhesives and functional composite bone adhesives.Various types of bone adhesives have excellent bonding strength,hydrophilicity and biodegradability.The biosafety of various types of bone adhesives is also verified by cell experiments.Nano particles of dopamine can enrich bone adhesive osteoconductivity,and the dopamine can be used to enrich bone adhesieve osteoinductiviity.These good biological activities ensure that the bone adhesive implanted into the fracture space will not act as a barrier to inhibit fracture healing,but promote fracture healing while fixing the fracture and maintaining the length.In addition,the double ester bone adhesive can firmly fix the bone cortex on both sides of the broken end of the fracture like a steel plate.The bone cortex is pretreated with phosphoric acid etchant,which not only increases the roughness,but also increases the bonding strength of the bone adhesive,improves the stability of fracture fixation,and also plays a role in promoting fracture healing.In addition,in the animal experiment part of this study,the SD rat unilateral tibial 45 ° oblique fracture model was successfully made by 3D printing osteotomy guide.The fracture model has good repeatability and can be used to verify the repair effect of bone adhesive in vivo fracture model.Under theoretical conditions,the fracture model made by this preparation method can be used to verify the therapeutic effect of any internal fixation method on simple fractures(transverse fractures and oblique fractures).To sum up,functional composite bone adhesive can act on the fracture gap like "liquid scaffold",while diester bone adhesive can act on both ends of the fracture like "liquid plate".These two fixation and repair methods are conducive to fracture healing and have been reliably verified in animal models. |
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