Synthesis And Structure-properties Of Bioresorbable Copolyester-carbonates

Cyclic monomers such as lactide,glycolide and trimethylene carbonate were prepared by polycondensation followed by cyclization.A series of homopolymers such as poly(lactide)(PLLA or PDLLA),poly(glycolide)(PGA),poly(trimethylene carbonate)(PTMC),poly(ε-caprolactone)(PCL) and copolymers such as poly(trimethylene carbonate-co-lactide)(PTLLA and PTDLA),poly(trimethylene carbonate-co-glycolide)(PTGA),poly(trimethylene carbonate-co-caprolactone) (PTCA),poly(ethylene glycol)-b-poly(trimethylene carbonate-co-lactide)(PTDLA-b-PEG) were then synthesized by ring opening polymerization(ROP) of appropriate monomer feeds using zinc lactate or stannous octoate as catalyst.The thermal properties,hydrolytic degradation,enzymatic degradation,mechanical properties and shape memory behavior were investigated by using DSC,NMR,SEC,ESEM,DMA and Instron tensile instrument.The biocompatibility was evaluated from haemolysis experiments,platelet adhesion,MTT assay and cell culture.PTDLA copolymers are all amorphous.The glass transition temperature(Tg) increases with increasing LA content.PTDLA copolymers can be degraded not only by pure hydrolysis,but also by proteinase K.The mass loss reaches about 50%after 53 weeks' hydrolytic degradation,while during enzymatic degradation,the mass loss increases with increasing LA content.In particular,PTDLA copolymer containing 82mol.%LA units lost 91%of its initial mass after 264 h in the presence of proteinase K.The molecular weight of PTDLA copolymers rapidly decreases in the initial stage of hydrolytic degradation,followed by slower decrease.The LA content also decreases during hydrolytic degradation.In the case of enzymatic degradation,the molecular weight decreases at the initial stage,and then remains unchanged.The composition also remains unchanged during enzymatic degradation.Heterogeneous cavities are observed on the surface of PTDLA copolymers with high LA contents (＞50%),and gradually reach the polymer bulk.It can be concluded that the PTDLA copolymers are degraded through surface erosion during enzymatic degradation.The PTDLA copolymer composed of the same TMC and LA contents is highly elastic.The residual strain is approximately 4%after the first cycle at a strain of 50%, and ca.80%recovery even after 20 cycles.The shape recovery ratio is up to 83%. Moreover,the initial recovery temperature is close to the glass transition temperature (Tg).Tg acts as the switch temperature between temporary shape and permanent shape.The temporary shape of the copolymer is formed above the T_g,and fixed below the T_g.The permanent shape can be recovered above the Tg(near body temperature).PTMC homopolymer cannot be degraded by pure hydrolysis,or by proteinase K. The mass,molecular weight and surface morphology of PTMC remain pratically unchanged during degradation.In contrast,PTMC can be degraded by lipase CA and lipase HP.Lipase CA is most efficient.The mass loss of PTMC reaches 98%after 216h in lipase CA solution,and 22%lipase HP solution.During enzymatic degradation,the molecular weight significantly decreases and the molecular weight distribution becomes larger.Bimodal molecular weight distributions are observed. The enzymatic degradation of PTGA copolymer with 10%GA units is significantly different from that of PTMC homopolymer.PTGA cannot be degraded by lipase CA. Only 5.8%of mass loss is detetced after 216h,and the molecular weight and its distribution keep constant.In the lipase HP solution,however,the mass loss of PTGA reaches 58%after 216h.Meanwhile,the molecular weight decreases and its distribution becomes broader.Bimodal molecular weight distributions are also obtained.The composition of the PTGA copolymer remains constant.ESEM and contact angle measurements show that the polymers are homogeneously eroded from the surface during enzymatic degradation.PTDLA-b-PEG triblock copolymers were synthesized using stannous octoate as catalyst.The glass transition temperature of the copolymers decrease with increasing EG content,while copolymers with high EG contents are crystallizable.During degradation by proteinase K,copolymers with higher EG content or lower LA content degrade at slower rate.In fact,proteinae K can only degrade the PLA component.On the other hand,high EG content leads to increase of the hydrophilicity of the polymer surface as shown by contact angle measurements.During degradation,the molecular weight slightly decreases and the composition remains constant.Changes in surface morphology are observed,in agreement with surface erosion process.The haemolysis rate of the PLLA,PTMC,PCL,PTLLA,PTDLA and PTCA polymers is very small,especially that of PCL and PTCA,respectively 1.5%and 1.4%.Adhesion and activation of platelets are observed on the surface of PLLA,PCL, PTLLA,PTDLA films,while less platelets and lower activation are found on PTMC. The most interesting results were obtained with PTCA which exhibited the lowest degree of activation with few adhered platelets,in agreement with its outstanding anti-coagulant properties.Both indirect and direct cytocompatibility studies were performed on the polymers.The relative growth ratio data obtained from the liquid extracts during the 6-day cell culture period indicate that all the polymers present very low cytotoxicity.Microscopic observations demonstrate adhesion,spreading and proliferation of human umbilical vein endothelial cells ECV304 cells.Therefore,copolyester-carbonates,and especially PTDLA,are promising candidate for applications in minimally invasive surgery such as bioresorbable stents or stent coating.