Synthesis And Properties Of Degradable Copolymers As Atrial Septal Defect And Patent Foramen Ovale Occluder Material

Heart occluder constitutes are widely used in the treatment of congenital heart disease. The conventional NiTi alloy occluder is non-degradable, and could induce a series of complications such as block of conduction, Arrhythmia, erosion, thrombosis, residual shunt, hemolysis, nickel allergy, etc. The development of biodegradable occluder with good mechanical properties and appropriate degradation rate has gradually become a hot research area for intervention therapy of congenital heart disease. It is also the topic of this work.(1) Various reaction conditions were used to synthesize high molecular weight poly(trilethylene carbonate-co-L-lactide-co-glycolide) (PTLGA) terpolymers. Data show that the optimal conditions are as follows:mole ratio of monomers to catalyst 8000/1, temperature 140℃, and monomers feed ratio TMC/LLA/GA= 25/60/15. Under these conditions, the molecular weight of PTLGA reached 135900.(2) A series of high molecular weight PTLGA terpolymers with different compositions were prepared using stannous octoate (Sn(Oct)2) as the catalyst. Polymers were characterized by gel permeation chromatography (GPC), infrared spectroscopy (FTIR),1H nuclear magnetic resonance (1H NMR), differential scanning calorimeter (DSC) and thermo-gravimetric analysis (TGA). Film samples were prepared by solution casting method. Tensile tests, in vitro degradation, biocompatibility studies were carried out.(3) The PTLGA terpolymers exhibit lower tensile strength as compared to poly(L-lactide) (PLLA) due to incorporation of the a contents of TMC and GA. In contrast, the toughness of the terpolymers is greatly improved. Thus they can be used as potential material for heart occluder fabrication.(4) In vitro degradation of terpolymer PTLGA25/60/15 was studied in comparison with a copolymer PTLA25/60. The terpolymer degrades faster than with PTLA25/60 due to the presence of fast degrding GA component. Morphological changes with crystallization of degradation by-products are observed in the case of PTLA25/60 due to Mn decrease during degradation and the stronger impact of plasticization of water during the degradation. PTLGA25/60/15 remains amorphous during degradation due to its highly random chain structure.(5) The hemocompatibility of PTLGA25/60/15 was evaluated using the blood clotting and dynamic blood clotting tests. Data show that this material didn’t cause clotting, indicating that PTLGA25/60/15 presents a good hemocompatibility. The effect of the terpolymer on the growth, metabolism and proliferation of histiocytes was analyzed with the extracting liquid. The results show that cells grew normally and the material has a good cytocompatibility.(6) A totally biodegradable heart occluder was designed and fabricated. A mini-bar is first fabricated using PTLGA25/60/15 using melt indexer. Short fibers were then attached to the bar with a dissolving process, followed by heat-treatment. The mechanical properties of the occluder were characterized.In conclusion, PTLGA25/60/15 terpolymer exhibits higher resilience, appropriate degradation rate, good biocompatibility and excellent processing performance, and thus is promising for the fabrication of bioresorbable heart occluder.