| Maxillofacial fractures are a common disease in maxillofacial surgery field.Clinically,fracture healing often requires internal fixation to ensure anatomical reduction,support,and stability of the fracture.The success of fracture fixation is inextricably linked to the internal fixation system used for fractures.According to the degradation characteristics of the internal fixation system,it can be divided into a non-degradable internal fixation system and a degradable internal fixation system.Non-degradable internal fixation systems,such as stainless steel,titanium and titanium alloy internal fixation systems,have sufficient strength and good biosafety,but may cause allergies,stress shielding effects,resulting in poor fracture healing and osteoporosis.It is often necessary to take out a second operation,which increases the patient's pain and financial burden and consumes valuable medical resources.For the degradable internal fixation system,the polylactic acid internal fixation system is relatively mature and has been put into clinical use.However,due to its poor strength,the local environment is acidic,which may cause internal fixation failure,foreign body reaction and aseptic inflammation.The magnesium alloy has good strength and bio-safety,but it has the disadvantage that the degradation rate is too fast,hydrogen is generated,and the local degradation environment is alkaline,which cannot meet the requirements of the service period.Degradable iron alloys have good strength and biosafety,but the degradation rate is too slow,and the degradation products of iron oxide are difficult to be removed and metabolized by the body.Degradable zinc alloy material is a new type of degradable metal material with good mechanical properties,good biocompatibility and degradability.It is expected to become a new degradable internal fixation material.In previous study,we conducted a study on the internal fixation of the Beagle mandible fracture.It was found that the degradable zinc alloy internal fixation system has good fracture fixation effectiveness,the material can be degraded after implantation,and the blood zinc concentration fluctuates within the normal range.No abnormalities were found in heart,liver and kidney tissues.Purpose:The former experiments have only made a preliminary exploration on the degradability and biosafety of the degradable zinc alloy.For the degradability of zinc alloy internal fixation materials,such as degradation surface morphology,in vivo degradation forms,degradation products,the former experiments have not been thoroughly explored.In the previous experiment,only the zinc alloy internal fixation system was applied to the mandibular part of the dog.In addition to the mandible,the upper and middle part of the craniomaxillofacial region and the extremities were also potential sites to implant degradable zinc alloy,and the degradation of the degradable material depends on the environment.It is necessary to study whether the zinc alloy internal fixation material has degradability in different implant sites in the body.For the biosafety of zinc alloy internal fixation materials,the preliminary experiments did not study whether the damage caused to the body's circulation,metabolism,immunity,and other important organs after implanting zinc alloy internal fixation materials.In the previous experiment,two sets of small zinc alloy internal fixation system were used in the mandibular fracture of the dog.In the clinic,multiple fractures always occur.Many sets of internal fixation systems were often need to implanted in the body to ensure fracture healing.More degradable internal fixation materials increase the possibility of toxicity to the body.In summary,it is necessary to further study the biosafety and degradability of zinc alloy internal fixation materials,and to explore the safest use amount of zinc alloy internal fixation materials embedded in the body,to develop zinc alloy with better comprehensive performance,and to provide experimental data for zinc alloy internal fixation systems enter clinical trials.In the first and second parts of the experiment,four parts of the beagle dog were selected to implant zinc alloy internal fixation materials:the frontal bone,the bilateral mandible,and the right femur.It is necessary to observe the surface morphology of the sample degradation,to understand the degradation form of the sample,to analyze the degradation products,to observe the degradation of different potential application sites,and to understand its degradability.Blood routine,blood biochemistry,blood zinc,and visceral pathology were observed to explore the biosafety.In the third and fourth parts of this experiment,4,6,and 8 amount of zinc alloy internal fixation plates and nails were implanted in New Zealand rabbits.It was equivalent to 20~360 plates and 20~360 screws embedded in the human body.To observed whether a large number of zinc alloy internal fixation materials implanted in vivo may be harmful,blood routine,blood trace elements,peripheral blood T lymphocytes CD4/CD8,visceral zinc content,visceral pathology were observed.It is aimed to evaluate whether the degradation of the body caused damage to the body's circulation,metabolism,immunity,important organs,etc.,and explore the maximum safe use of zinc alloy internal fixation materials.Method:1.Beagle implant experiment:The materials were four-hole zinc alloy plate:thickness is 1.0mm,and nail:diameter is 2.0 mm,length is 7mm.Nine Beagle dogs were randomly divided into 3 groups with 3 dogs in each group.A zinc alloy plate and nail were implanted into the frontal bone,the bilateral mandible,and the right femur of the dog,and four sets of zinc alloy plates and nails were implanted in each dog.Gross observation,blood routine,blood biochemistry,blood zinc examination,heart,liver,spleen,lung,kidney,gonad,and prostate histological examination were performed at 3,6 and 9 months after surgery to observe the biosafety of the material.Scanning electron microscopy,micro-CT to observe the degradability of the material.2.New Zealand rabbit subcutaneous implant experiments:materials are the same as above.Eighteen New Zealand white rabbits were divided into three groups.The zinc alloy internal fixation plates and nails were implanted 4,6 and 8 respectively.The observation was performed in 3,6 months after surgery.Blood routine,blood biochemistry,blood trace element examination,peripheral blood T lymphocyte CD4/CD8,heart,liver,spleen,lung,kidney,gonad,prostate histological examination,visceral zinc ion content measurement,material weighing were performed comprehensively to evaluation the biosafety and degradability of a large amount of zinc alloy internal fixation materials implanted in vivo and to explore the maximum safe use of zinc alloy.Results:1.Beagle dog implant experiment results:1.1 Biosafety results:The white powdery substance adhering to the surface of the degradable zinc alloy material gradually increased after 3,6,and 9 months after surgery.After the corrosion surface was removed,the surface of the material became rougher with time.Red blood cells,platelets,hemoglobin,aspartate aminotransferase,alanine aminotransferase,albumin,total protein,urea nitrogen,creatinine,and blood zinc were not significantly different from those before surgery.The animals'visceral organs were stained with HE at 3,6 and 9 months after operation and no abnormalities were detected in the heart,liver,spleen,lung,kidney and gonads.1.2 Degradability results:Micro-CT results showed the volume of zinc alloy in frontal bone was 72.37±0.2263 mm~3 after 3 months.The average degradation was15.47±0.3348%;the volume of zinc alloy was 71.42±2.666 mm~3 6m post operation,and the average degradation was 16.59±2.708%;the volume of zinc alloy 9m post operation was 70.74±0.8627 mm~3,and the average degradation was 17.38±0.4207%.The degradation of the zinc alloy in the mandibular was 80.81±2.771 mm~3 at 3m post operation,and the average degradation was 12.97±1.269%;the volume of the zinc alloy 6m post operation was 78.25±1.667 mm~3 and the average degradation was15.64±1.513%.The degraded volume of zinc alloy was 77.65±5.031 mm~3 and the average degradation was 16.65±4.590%.The degradation of the alloy in the femoral part was as follows:the volume of the zinc alloy was 81.04±1.387 mm~3,and the average degradation was 12.68±1.770%.The volume of the zinc alloy was79.88±2.170 mm~3 6m post operation,and the average degradation was 13.96±0.8965%;the volume of zinc alloy 9m post operation was 76.84±2.350 mm~3,and the average degradation was 17.21±2.458%.Micro-CT measurement of zinc alloy internal fixation volume found that the volume of zinc alloy internal fixation in each implant site decreased significantly(P<0.05).There was no significant difference in the degradation of zinc alloy implanted in the frontal bone,mandible and femur at 3,6 and9 months after operation(P>0.05).Scanning electron microscopy observed various forms of degradation products at different microscopic locations on the surface of the material,but there was no specific association with the implanted sites and implants.The degradation of the material is uniformly and slowly.There is no damage,fragmentation and disintegration of the material with degradation process,and a relatively uniform degradation form is maintained during the degradation process.The EDS results showed that zinc decreases as it enters the bone tissue,and the zinc element released by the material does not accumulate in the bone tissue.2.New Zealand rabbit subcutaneous implant experiments:2.1 Biosafety results:The white powdery substance adhering to the surface of the degradable zinc alloy material gradually increased in 3,6 months after the operation.After the surface corrosion product was removed,the surface of the material became rougher with time.There was no significant difference in blood leukocytes,red blood cells,platelets,hemoglobin,aspartate aminotransferase,alanine aminotransferase,albumin,total protein,urea nitrogen,creatinine,blood zinc,blood magnesium,blood calcium,blood iron,blood copper,peripheral,blood T lymphocyte CD4/CD8 between preoperative and 3 and 6 months after surgery.No abnormalities were detected in the heart,liver,spleen,lung,kidney and gonads of the experimental animals at 3 and 6months after operation.There was no significant difference in liver and kidney zinc ion content between the 3 and 6 months after surgery.2.2 Degradability results:The degradation rates of the degradable zinc alloy internal fixation plates in 3,6 months post operation were 9.77±1.64%and11.82±1.91%,respectively,and the screw degradation rates were 0.79±0.66%and2.09±1.00%,respectively.Conclusion:This study is the first to explore the degradability of degradable zinc alloy as an internal fixation material,and for the first time to explored the maximum safe use of zinc alloy internal fixation materials.Based on the previous research,the biosafety of degradable zinc alloy was further studied.Through this study,we can draw the following conclusions:1.The degradable zinc alloy internal fixation material has similar degradability during the 9-month observation period of the frontal bone,mandible,and femur.There was no significant difference in the degradation rate of each part,and it degraded by about 17%9 month post operation.The degradation rate of the material in the first 3months of implantation is faster,and then the degradation rate is slower and more stable over time.The degradation products mainly contain Zn,O,C,P,Ca,Cl,N,Na,and K elements.The zinc element released by the material is not deposited in the bone tissue.Degradable zinc alloy internal fixation materials have various degradation products in the body,uniform degradation forms,good degradation behavior and safe degradation process.2.After a large amount of degradable zinc alloy internal fixation material was implanted in the body,the different amount of degradable zinc alloy internal fixation material had no toxic effect on the body during the observation period,and did not cause damage to cells,tissues,organs,blood and immune function.A large number of degradable zinc alloy internal fixation materials have good biosafety after being implanted into the body.3.Degradable zinc alloy internal fixation system materials have potential for application to the whole body. |
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