Construction And Correction Of A Large Animal Model Of Early-onset Scoliosis With Thoracic Insufficiency Syndrome

Objectives: To establish an experimental large animal model of early-onset scoliosis with thoracic insufficiency syndrome(EOS+TIS)by modified posterior unilateral spinal fixation tethers and ipsilateral rib tethers,and explore the related corrective treatment methods.The aim of this study is to provide a scientific,effective and reproducible large animal model and related experimental basis for the further study of the clinical characteristics and treatment of EOS+TIS.Methods: Fourteen female piglets aged about 6 weeks were randomly divided into three groups: model group(n = 6),treatment group(n = 5)and control group(n =3).Model group: At the age of 6 weeks,polyaxial pedicle screws were inserted into the left pedicle of T6-T8 and T15-L1,and the spinal internal fixation tethered system(designed by research group)was inserted.The spine was precurved by manipulation and the tether was tightening to make it have a certain initial prebending degree.The left 6-10 ribs were stripped,the intercostal soft tissue was removed,and the bone cortex was fully ground and destroyed and grafted to cause periosteal reaction.The ipsilateral ribs are then tethered so that they come together and overlap and fuse together.Tethering of the spine and ribs was relieved at 14 weeks of age.Treatment group: the same operation was performed at the age of 6 weeks,and the specific operation was the same as the model group.At the age of 14 weeks,the spine and ribs were untethered and corrected,and the fisheye sliding screws were placed in the bilateral pedicle at T4-T5 and L2-L3,and binear compression screws were placed in the bilateral pedicle at T11-T12.After the spinal deformity was corrected by manipulation,the appropriate titanium rod was inserted,the binear compression screws and titanium rod connectors were locked,and the fisheye sliding screws could slide on the titanium rod rails.The left fused and proliferated ribs were removed,and the restriction and compression of the diseased chest on the lung tissue were relieved.In the control group,only tissue dissection was performed at the same incision site to expose the articular process at 6 and 14 weeks of age,and no pedicle screws or other devices were inserted.Anteroposterior and lateral X-ray films and CT scans of the spine were performed before modeling,8 weeks after modeling,2 weeks after treatment,and 4weeks after treatment.The coronal and sagittal Cobb angles of the spine,axial rotation of the vertebral body,thoracic area of bilateral T7-T10 cross section,bilateral lung volume,T7-T10 lung volume,bilateral lung mass,body length and weight were measured and recorded at each time point in each group.SPSS 25.0 software was used to analyze the data.Results: Eleven out of 14 experimental animals completed the study,including4 in the model group,4 in the treatment group and 3 in the control group.Two piglets in the model group had a deep infection after modeling,and the spinal internal fixation tethering failed completely.One pig in the treatment group died during the surgical anesthesia,and they were excluded.During the whole study,none of the pigs who completed the experiment developed obvious neurological complications such as muscle weakness,muscle atrophy,lameness,or even paralysis.There were no significant differences in body length,body weight,coronal and sagittal Cobb angles of the spine,axial rotation of the apical vertebral body,thoracic area of bilateral T7-T10 cross section,bilateral lung volume,T7-T10 lung volume,and lung mass among the three groups before modeling.There were no significant differences in coronal and sagittal Cobb angles of the spine,axial rotation of the apical vertebra,thoracic area of bilateral T7-T10 cross section,bilateral lung volume,T7-T10 lung volume,and lung mass between the model group and the treatment group before the correction surgery.After modeling and correction surgery,the body length and weight of the model group and the treatment group were lower than those of the control group,and the difference was statistically significant.At the age of 14 weeks after modeling,significant thoracic scoliosis(model group 28.00±7.16°,treatment group 26.00±6.38°)was induced,thoracic kyphosis disappeared and thoracic lordosis appeared(model group 37.5±8.66°,treatment group 31.00±8.72°).A certain degree of apical vertebral axial rotation(model group 10.00±1.83°,treatment group 10.25±3.30°),compared with the control group,the difference was statistically significant.The model group and the treatment group induced obvious asymmetry of bilateral thorax,lung volume and lung mass,that is,the T7-TI0 thoracic cross-sectional area,lung volume,T7-TI0 lung volume and lung mass on the left side were lower than those on the right side(P< 0.05),and were significantly lower than those in the control group,and the difference was statistically significant.Two weeks after surgery(16 weeks old),thoracic scoliosis(11.00±2.16°)and thoracic lordosis(12.00±3.16)in the treatment group were significantly lower than those before surgery(P < 0.05),and were lower than those in the model group(18.25±2.75°,39.5±8.18°),the difference was statistically significant.The vertebral rotation of the treatment group was lower than that of the model group,but the difference was not statistically significant.In the treatment group,only the left thoracic cross-sectional area was increased at TI0,which was higher than that in the model group(P < 0.05).The left lung volume and lung mass in the treatment group were increased than those in the model group,but the differences were not statistically significant.At 4 weeks after surgery(18 weeks old),the thoracic scoliosis(9.50±2.38°)and thoracic lordosis(10.25±3.20)in the treatment group were significantly lower than those before surgery(P < 0.05),and were lower than those in the model group(17.00±1.41°,36.00±7.87°),the difference was statistically significant.The vertebral rotation of the treatment group was lower than that of the model group,but the difference was not statistically significant.Compared with the model group,the treatment group had a significantly larger left thoracic cross-sectional area at each level of T7-TI0(P < 0.05),and the treatment group had a significantly larger left lung volume,lung mass,and left lung volume at T7,T9,TI0 than the model group,but there was no statistically significant difference.Only at the T8 level,the left lung volume of the treatment group increased significantly more than that of the model group,and the difference was statistically significant.Conclusions: A large animal model of EOS+TIS was successfully established by modified spine and ipsilateral rib tethers technique.The main deformity was coronal scoliosis,loss of sagittal kyphosis,significant lordosis,vertebral rotation,thoracic bulges on the convex side,thoracic fusion and thoracic cage coarctation on the concave side,and bronchopulmonary dysplasia on thr left lung was detected.This study is a preliminary exploration of the treatment of EOS+TIS in large animal model.The correct surgical technique can effectively control the deformity of spine and thorax,and allow the normal growth and development of spine,thorax and lung.