| Congenital heart diseases,such as atrial septal defect,ventricular septal defect,and patent ductus arteriosus,etc.,seriously affect the survival and quality of life of newborns.The clinical methods for treating such diseases include thoracotomy for defect repair or minimally invasive interventional closure.The latter involves the use of occluders.At present,occluders are mostly made of non-degradable metal materials,but such occluders will remain in the patient's body permanently,causing many serious consequences.Thus the development of novel degradable heart occluders has become a research hotspot in the medical field.In this work,poly(L-lactide-trimethylene carbonate)(PLT)copolymers were synthesized and used to fabricate occluders using 3D printing technology.The degradation behavior of the occluder material was studied in vitro and in vivo.The safety of the materials was assessed from cyto-compatibility,blood compatibility,zebrafish embryo toxicity,and histocompatibility experiences to comprehensively evaluate the potential of PLT copolymers as biodegradable cardiac occluder materials.The main research contents are as follows:1.Synthesis and characterization of copolymers: PLT copolymers were synthesized by ring-opening polymerization of L-lactide(LLA)and trimethylene carbonate(TMC)using stannous octoate as catalyst.The physico-chemical properties of the copolymers were characterized by various test methods.The composition of the synthesized copolymers was close to the feed ratio.The copolymers have a molecular weight of 80,000 to 110,000,a polydispersity index of 1.8 to 2.0,which fulfills the requirements of targeted applications.The glass transition temperature(Tg)of the copolymers is between 34.1°C and 42.8°C.The fact that the Tg of some copolymers is slightly higher than 37°C makes them have good elasticity at the human body temperature.The tensile strength of the copolymers varies from 16.5 to 31.5 MPa,and the elongation at break from 87 to 512%,thus showing a certain mechanical strength and good toughness as compared to PLLA and PTMC homopolymers.2.Design and processing of occluder: According to the design of clinically used alloy occluders,the shape and size of PLT degradable occluder was designed.Through 3D printing technology,a series of double disc heart occluder samples were fabricated with a diameter of 12 mm for left and right discs,a disc thickness of 2 mm,a waist height of 8 mm,and a waist diameter of 8 mm.The occluders were produced by using the same batch of copolymers,and have uniform weight and size without apparent imperfections.3.Degradation of occluder materials in vitro and in vivo: PLT copolymer materials and occluder samples were studied in vitro and in vivo,respectively.In the in vitro degradation,the LLA/TMC molar ratio,molecular weight,water absorption,weight loss,and Tg changes were followed.The ester bond in the PLLA component is easier to hydrolytically break than the carbonate bond in the PTMC component.Therefore,faster degradation was observed for copolymers with higher LLA contents.In vivo degradation rate of the occluder samples appears faster than that of in vitro degradation.This difference is assigned to the presence of various enzymes in the body which promote degradation,and the influence of blood circulation and pressure in the body.4.Biocompatibility evaluation of occluder materials: The safety of occluder materials was evaluated,including cytocompatibility test,hemocompatibility(hemolysis rate,dynamic clotting time,plasma recalcification time,and platelet adhesion test),zebrafish embryo toxicity test,and histocompatibility test.The results show that the PLT occluder materials have reached relevant safety indicators and have good biocompatibility.In summary,the PLT copolymer materials and occluder samples prepared in this work have good mechanical and thermal properties,suitable degradation behavior,and meet biological safety standards,showing that they have the potential for applications as a degradable cardiac occluder. |
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