Effect Of Congenital Heart Disease On Respiratory Diseases And The Study Of Tissue Engineered Trachea

Backgroundcongenital heart disease(CHD)is a common pediatric disease,which is closely related to respiratory diseases.Previous studies have shown that CHD can affect respiratory function,and some patients have airway high reactivity.On the other hand,CHD can change the normal anatomical structure of airway,and even cause tracheal stenosis.For patients with tracheal stenosis caused by CHD,it is recommended to treat both tracheal stenosis and cardiac malformation,and some patients even need tracheal replacement.While tissue engineered trachea provides the possibility for excellent tracheal substitutes.Therefore,the first part of this topic mainly studies the effect of CHD on cough variant asthma(CVA),and the second part discusses the treatment of tracheal stenosis caused by CHD by tissue engineered trachea.Part one:Effect of congenital heart disease on the recurrence of cough variant asthmaObjertiveTo explore the influence of CHD on CVA recurrence.MethodsThe study was involved in 489 CVA children range from 1 to 14 years old.Ultimately,67 CHD children with CVA and 134 non-CHD children with CVA were studied.The family history and clinical data were collected and patients were followed up for 12 months after the symptoms were controlled.The recurrence of CVA was evaluated by cough visual analogue scale(VAS),children asthma control test(C-TAC)and children Test for Respiratory and Asthma Control in Kids(TRACK).The adjusted risk ratio of CVA recurrence in CHD cohort and non-CHD cohort was determined by multivariate Cox proportional hazards regression model.ResultsAfter adjusting CHD classification,mycoplasma pneumoniae infection and IgE sensitization,the recurrence risk of CVA in complex congenital heart disease group was significantly higher than that in simple congenital heart disease group(aHR,3.281 VS 2.555).In addition,the risk of recurrence of CVA children sensitized by IgE was higher than that of non-IgE sensitized children(aHR=2.172,95%CI,1.482-3.184).The recurrence risk of CVA with mycoplasma pneumoniae infection was greater than that of CVA without mycoplasma pneumoniae infection(aHR=1.777,95%CI,1.188-2.657).ConclusionChildren with CHD increase the risk of recurrence of CVA,especially complex congenital heart disease.In addition,IgE sensitization or mycoplasma pneumoniae infection in CVA children increased the risk of CVA recurrence.Part two:To explore the treatment of tracheal stenosis caused by congenital heart disease with tissue engineered tracheaObjertive(1)To explore the bone marrow mesenchymal stem sheet and chondrocyte sheet in vitro and to provide seed cells for tissue engineered trachea.(2)To explore the performance of silk fibroin(SF)combined with polycaprolactone(PCL)tracheal stent and to provide stent for tissue engineered trachea.Methods(1)Bone marrow mesenchymal stem cells were isolated and cultured,and the mesenchyma cell sheet was produced by adding ascorbic aci to culture medium,and adding ascorbic acid to produce the bone marrow mesenchymal stem sheet.And Chondrocyte sheet was induced by adding induction medium containing ascorbic acid and TGF-β3 into mesenchymal cell sheet.(2)The tracheal model designed according to the size of rabbit trachea was made by silk fibroin trachea(SF)and polycaprolactone(PCL)tracheal rings.And the performance of porous tracheal stent was tested in vitro.Results(1)The sheet formed by bone marrow mesenchymal stem cells was further induced to chondrocyte sheet.The chondrocyte sheet was positive for Alisin blue staining and the chondrogenesis related genes COL-Ⅱ and GAG were highly expressed.(2)SF trachea showed multilayer three-dimensional porous structure under electron microscope.The pore size of 20%SF trachea is 90±12um and the porosity is 89.9±1.0%.The pressure-strain curves showed that PCL tracheal ring obviously enhanced the compressive performance of SF-PCL trachea.The compressive strength of SF trachea combined with PCL trachea ring with different concentrations is stronger than that of common trachea.SF trachea could be degraded completely by enzyme within 4 weeks,but PCL tracheal ring failed.Conclusion(1)The bone marrow mesenchymal stem sheet and chondrocyte sheet were produced effectively and quickly,which provided suitable seed cells for tissue engineered trachea.(2)The trachea made of SF-PCL porous material had porosity,good mechanical strength and degradation rate,which provided a growth place for cell membrane and prevented the trachea from collapsing during its growth.Therefore,SF trachea combined with PCL tracheal ring is expected to be a substitute in the treatment of tracheal stenosis.