Lipase-catalyzed biodegradation of poly(epsilon-caprolactone) blended with various polylactide-based polymers

Poly(epsilon-caprolactone) was blended with various polylactide-based polymers and processed to films by the solution casting method. Blends of 25/75, 50/50, 75/25, 90/10, and 95/5 (w/w) poly(epsilon-caprolactone)/poly(l-lactide), a 95/5 (w/w) blend of poly(epsilon-caprolactone) with a poly(d-lactide), a 50/50 (w/w) poly(l-lactide)-poly(d-lactide) mixture, and a poly(l-lactide-co-epsilon-caprolactone) copolymer were considered comparatively. The various phase-separated films were allowed to degrade in the presence of Pseudomonas lipase, biodegradation being monitored by proton nuclear magnetic resonance, size exclusion chromatography, differential scanning calorimetry, X-ray diffraction, and environmental scanning electron microscopy. The formation of separated phases during solvent evaporation and their morphologies are discussed. The introduction of poly(l-lactide) dramatically decreased the degradation rate of poly(epsilon-caprolactone)/poly(l-lactide) blends. The higher the percentage of poly(l-lactide), the slower the degradation, while the presence of cracks and increasing the lipase concentration acted in favor of the enzymatic degradation. Long-term enzymatic degradation of the various 95/5 blends was investigated over 480 h. The poly(epsilon-caprolactone) phase was enzymatically degraded by the lipase regardless of the blend type, the degradation rate depending on the nature of the co-components.     

Grafting of cellulose fibers with poly(epsilon-caprolactone) and poly(L-lactic acid) via ring-opening polymerization

In this study, ring-opening polymerization (ROP) of epsilon-caprolactone (epsilon-CL) and L-lactide (L-LA) has been performed from cellulose fibers. The hydroxyl groups on cellulose act as initiators in the polymerization, and the polymers are covalently bonded to the cellulose fiber. As an attempt to introduce more available hydroxyl groups on the surface, and thereby obtain higher grafting efficiency in the ROP of epsilon-CL and L-LA, unmodified paper was modified with xyloglucan-bis(methylol)-2-methylpropanamide (XG-bis-MPA) and 2,2-bis(methylol)propionic acid (bis-MPA), respectively. The grafted substrates were characterized via Fourier transform infrared spectroscopy (FTIR), contact angle measurement, atomic force microscopy, and enzymatic degradation. The results showed a successful grafting of poly(epsilon-caprolactone) (PCL) and poly(L-lactic acid) (PLLA) from the cellulose fiber surfaces. Furthermore, the results showed an improved grafting efficiency after activation of the cellulose surface with bis-MPA, and showed that the amount of grafted polymer could be controlled by the ratio of added free initiator to monomer.     

Synthesis and modification of functional poly(lactide) copolymers: toward biofunctional materials

A polylactide copolymer with pendant benzyloxy groups has been synthesized by the copolymerization of a benzyl-ether substituted monomer with lactide. Debenzylation of the polymer to provide pendant hydroxyl groups followed by modification with succinic anhydride affords the corresponding carboxylic acid functionalized copolymer that is amenable to standard carbodiimide coupling conditions to attach amine-containing biological molecules. An amino-substituted biotin derivative was coupled to the carboxyl functional groups of copolymer films as proof-of-concept. In a demonstration of the function of these new materials, an RGD-containing peptide sequence was tethered to copolymer films at various densities and was shown to enhance the adhesion of epithelial cells. This strategy provides the opportunity for the attachment of a variety of ligands, allowing for the fabrication of a versatile class of biodegradable, biocompatible materials.     

Hydroxyapatite surface modified by L-lactic acid and its subsequent grafting polymerization of L-lactide

A new method of surface modification of hydroxyapatite nanoparticles (n-HA) by surface grafting reaction of l-lactic acid and ring-opening polymerization of l-lactide (LLA) was developed. Two modified HA nanoparticles were obtained: HA modified by l-lactic acid (l-HA) and HA grafting with poly(l-lactide) (PLLA; p-HA). The modified surface of n-HA was attested by Fourier transformation infrared, (31)P MAS NMR, and thermal gravimetric analysis. The results showed that l-lactic acid could be easily grafted onto the n-HA surface by forming a Ca carboxylate bond and initiated by the hydroxyl group of the grafted l-lactic acid and LLA could be graft-polymerized onto the n-HA surface in the presence of stannous octanoate. The highest grafting amounts of l-lactic acid and PLLA were about 33 and 22 wt %, respectively. The modified HA/PLLA composites showed good mechanical properties and uniform microstructure. The tensile strength and modulus of the p-HA/PLLA composite containing 15 wt % of p-HA were 67 MPa and 2.1 GPa, respectively, while those of the n-HA/PLLA composites were 45 MPa and 1.7 GPa, respectively. The elongation at the break of the l-HA/PLLA composite containing 15 wt % l-HA could reach 44%, in comparison with 6.5% of the n-HA/PLLA composites containing 15 wt % n-HA.     

Formation of and coalescence from the inclusion complex of a biodegradable block copolymer and alpha-cyclodextrin. 2: A novel way to regulate the biodegradation behavior of biodegradable block copolymers

A biodegradable block copolymer (PCL-b-PLLA, M(n) = 1.72 x 10(4), M(w)/M(n) = 1.37) of poly(epsilon-caprolactone) (PCL) and poly(L-lactide) (PLLA) with very low crystallinity was obtained by forming the inclusion complex between alpha-cyclodextrin molecules and PCL-b-PLLA followed by coalescence of the guest polymer chains. Films of the as-synthesized and coalesced copolymer samples, PCL and PLLA homopolymers of approximately the same chain lengths as the corresponding blocks of PCL-b-PLLA, and a physical blend of PCL/PLLA homopolymers with the same molar composition as PCL-b-PLLA were prepared by melt-compression molding between Teflon plates. Subsequently, the in vitro biodegradation behavior of these films was studied in phosphate buffer solution containing lipase from Rhizopus arrhizus, by means of ultraviolet spectra, attenuated total reflectance FTIR spectra, differential scanning calorimetry, wide-angle X-ray diffraction measurements, and weight loss analysis. PCL segments were found to degrade much faster than PLLA segments, both in the pure state and in copolymer or blend samples. Consistent with our expectation, suppression of the phase separation, as well as a decrease of crystallinity, in the coalesced copolymer sample led to a much faster enzymatic degradation than that of either as-synthesized copolymer or the PCL/PLLA physical blend sample, especially during the early stages of biodegradation. Thus the biodegradation behavior of biodegradable block copolymers, which is of decisive importance in drug delivery and controlled release systems, may be regulated by the novel and convenient means recently reported by us.(1)     

Phase structure and enzymatic degradation of poly(L-lactide)/atactic poly(3-hydroxybutyrate) blends: an atomic force microscopy study

Phase structures and enzymatic degradation of poly(l-lactide) (PLLA)/atactic poly(3-hydroxybutyrate) (ata-PHB) blends with different compositions were characterized by using atomic force microscopy (AFM). Differential scanning calorimetry (DSC) thermograms of PLLA/ata-PHB blends with different compositions showed two glass transition temperatures, indicating that the PLLA/ata-PHB blends are immiscible in the melt. Surface morphologies of the thin films for PLLA/ata-PHB blends were determined by AFM. Phase separated morphology was recognized from the AFM topography and phase images. The domain size of the components was dependent on the blend ratio. Enzymatic degradation of the PLLA/ata-PHB blends was performed by using both PHB depolymerase and proteinase K. Either PLLA or ata-PHB domains were eroded depending on the kinds of enzyme. Surface morphologies after enzymatic degradation have revealed the phase structure along the depth direction. Enzymatic adsorption of PHB depolymerase was examined on the surface of PLLA/ata-PHB blends. The enzyme molecules were found on both domains of the binary blends. The larger number of enzyme molecules was found on the PLLA domains relative to those on the ata-PHB domains, suggesting the higher affinity of the enzyme against PLLA domain.     

L-Phe end-capped poly(L-lactide) as macroinitiator for the synthesis of poly(L-lactide)-B-poly(L-lysine) block copolymer

A poly(L-lactide)-b-poly(Nepsilon-(Z)-L-lysine) (PLLA-b-PZLys) block copolymer was synthesized through the ring-opening polymerization of Nepsilon-(Z)-lysine-N-carboxyanhydride using L-Phe-terminated PLLA as a macroinitiator. The L-Phe-terminated PLLA was prepared through a novel three-step process. First, the hydroxyl-terminated PLLA was synthesized through the ring-opening polymerization of L-lactide initiated by n-butanol under the existence of tin(II) ethylhexanoate. Subsequently, the complete capping of the hydroxyl end group of PLLA with BOC-L-Phe was achieved by using a mixed anhydride of BOC-L-Phe under the catalysis of 4-(1-pyrrolidinyl) pyridine. Finally, the free amino end group was obtained by removal of the t-butoxycarbonyl group through trifluoroacetic acid treatment under anhydrous condition. All these treatments were conducted under mild conditions, thus avoiding the breakdown of the PLLA backbone. Poly(L-lactide)-b-poly(L-lysine) block copolymer was produced after deprotection treatment of PLLA-b-PZLys. The structure of the block copolymer was confirmed by 1H NMR, IR, and GPC. Adjustment of the ratio of the NCA monomer to the macroinitiator could control the chain length of the PLys block.     

Structural effects of terminal groups on nonenzymatic and enzymatic degradations of end-capped poly(L-lactide)

Poly(L-lactide) (PLLA) with various alkyl ester chain end groups were synthesized by ring-opening polymerization of L-lactide in the presence of zinc alkoxide as a catalyst. The structural effect of chain end groups on the rate of enzymatic and nonenzymatic degradations for amorphous films of PLLA were investigated at 37 degrees C in a Tris-HCl buffer solution (pH 8.6) with proteinase K and at 60 degrees C in a phosphate buffer solution (pH 7.4), respectively. The rate of enzymatic degradation for PLLA films was dependent on the carbon numbers of alkyl ester chain end groups, and the rates of PLLA samples with dodecyl (C12), tridecyl (C13), and tetracocyl (C14) ester end groups were much lower than those of the other samples. The surface morphologies of PLLA films after enzymatic degradation were characterized by scanning electron microscopy. After the enzymatic degradation, non-end-capped PLLA, PLLA with methyl (C1) and hexyl (C6) ester chain ends, were degraded homogeneously by proteinase K and the film surface was very smooth. In contrast, the PLLA with alkyl ester chain ends of carbon numbers over 12 were degraded heterogeneously by the enzyme, and the sponge-like network structure was formed on the film surface. These results indicated that the long alkyl ester groups at the chain ends of PLLA molecules aggregated in the amorphous films and the erosion rate was depressed due to the coverage of the aggregated terminal groups on the film surface. For the nonenzymatic degradation, the molecular weight of non-end-capped PLLA was remarkably decreased with progress of degradation. In contrast, the molecular weight of the end-capped PLLA gradually reduced at the initial stage of degradation and then the rate of degradation was accelerated. The decreases of molecular weight of PLLA by autocatalyzed degradation were retarded by the capping of carboxyl chain ends.     

Covalent grafting of poly(L-lactide) to tune the in vitro degradation rate

The in vitro rate of degradation was purposely affected by covalently grafting the surface of poly(l-lactide) (PLLA). PLLA films were surface modified by our vapor-phase nondestructive photografting technique. Films were grafted for 20 min with one of the following monomers: acryl amide (AAm), N-vinyl pyrrolidone (VP), or acrylic acid (AA) and thereafter incubated in vitro in a phosphate-buffered saline solution at 37 degrees C for 154 days. The films were studied with contact angle measurements, SEM, ATR-FTIR, SEC, and DSC. The analyses verified that the in vitro rate of degradation was enhanced and that the grafted surface layer did remain covalently attached to the surface during the initial stages of incubation.     

Macromolecular design of aliphatic polyesters with maintained mechanical properties and a rapid, customized degradation profile

An innovative type of triblock copolymer that maintains and even increases the mechanical properties of poly(l-lactide) (PLLA) and poly(ε-caprolactone) (PCL) with a controlled, predictable, and rapid degradation profile has been synthesized. Elastic triblock copolymers were formed from the hydrophobic and crystalline PLLA and PCL with an amorphous and hydrophilic middle block of poly(but-2-ene-1,4-diyl malonate) (PBM). The polymers were subjected to degradation in PBS at 37 °C for up to 91 days. Prior to degradation, ductility of the PLLA-PBM-PLLA was approximately 4 times greater than that of the homopolymer of PLLA, whereas the modulus and tensile stress at break were unchanged. A rapid initial hydrolysis in the amorphous PBM middle block changed the microstructure from triblock to diblock with a significant reduction in ductility and molecular weight. The macromolecular structure of the triblock copolymer of PLLA and PBM generates a more flexible and easier material to handle during implant, with the advantage of a customized degradation profile, demonstrating its potential use in future biomedical applications.     

Synthesis, characterization, and degradation behavior of amphiphilic poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide]-g-poly(epsilon-caprolactone)

A series of biodegradable amphiphilic graft polymers were successfully synthesized by grafting poly(epsilon-caprolactone) (PCL) sequences onto a water-soluble poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA) backbone. The graft copolymers were prepared through the ring-opening polymerization of epsilon-caprolactone (CL) initiated by the macroinitiator PHEA with pendant hydroxyl groups without adding any catalyst. By controlling the feed ratio of the macroinitiator to the monomer, the copolymers with different branch lengths and properties can be obtained. The successful grafting of PCL sequences onto the PHEA backbone was verified by FTIR, 1H NMR, and combined size-exclusion chromatography and multiangle laser light scattering (SEC-MALLS) analysis. The hydrolytic degradation and enzymatic degradation of these graft copolymers were investigated. The results show the hydrolytic degradation rate increases with increasing content of hydrophilic PHEA backbone. While the enzymatic degradation rate is affected by two competitive factors, the catalytic effect of Pseudomonas cepacia lipase on the degradation of PCL branches and the hydrophilicity which depends on the copolymer composition. In situ observation of the degradation under polarizing light microscope (PLM) demonstrates the different degradation rates of different regions in the polymer samples.     

Synthesis and characterization of RGD peptide grafted poly(ethylene glycol)-b-poly(L-lactide)-b-poly(L-glutamic acid) triblock copolymer

Advances in tissue engineering require biofunctional scaffolds that can provide not only physical support for cells but also chemical and biological cues needed in forming functional tissues. To achieve this goal, a novel RGD peptide grafted poly(ethylene glycol)-b-poly(L-lactide)-b-poly(L-glutamic acid) (PEG-PLA-PGL/RGD) was synthesized in four steps (1) to prepare diblock copolymer PEG-PLA-OH and to convert its -OH end group into -NH(2) (to obtain PEG-PLA-NH(2)), (2) to prepare triblock copolymer PEG-PLA-PBGL by ring-opening polymerization of NCA (N-carboxyanhydride) derived from benzyl glutamate with diblock copolymer PEG-PLA-NH(2) as macroinitiator, (3) to remove the protective benzyl groups by catalytic hydrogenation of PEG-PLA-PBGL to obtain PEG-PLA-PGL, and (4) to react RGD (arginine-glycine-(aspartic amide)) with the carboxyl groups of the PEG-PLA-PGL. The structures of PEG-PLA-PGL/RGD and its precursors were confirmed by (1)H NMR, FT-IR, amino acid analysis, and XPS analysis. Addition of 5 wt % PEG-PLA-PGL/RGD into a PLGA matrix significantly improved the surface wettability of the blend films and the adhesion and proliferation behavior of human chondrocytes and 3T3 cells on the blend films. Therefore, the novel RGD-grafted triblock copolymer is expected to find application in cell or tissue engineering.     

Synthesis of xylan-graft-poly(l-lactide) copolymers via click chemistry and their thermal properties

Di-O-(6-azidohexanoyl)-xylan-graft-poly(l-lactide)s (XylC6N₃-g-PLLAs) were prepared by grafting propargyl-terminated poly(l-lactide) onto di-O-(6-azidohexanoyl)-xylan (XylC6N₃) via click chemistry. Di-O-(6-azidohexanoyl)-xylan (XylC6N₃) was prepared via two steps from xylan extracted from eucalyptus kraft pulp with aqueous sodium hydroxide solution. Propargyl-terminated poly(l-lactide)s (PLLA) with three different molecular weights were synthesized via ring-opening polymerization of l-lactide using propargyl alcohol as initiator and tin (II) octanoate (Sn(Oct)₂) as catalyst. XylC6N₃ and propargyl-terminated PLLAs were treated with N,N,N′,N′,N″-pentamethyldiethylenetriamine (PMDETA) and copper(I) bromide, and the graft copolymers XylC6N₃-g-PLLAs were obtained. DSC measurements revealed that the glass transition temperatures (T_g) of the copolymers decreased compared to that of XylC6N₃, suggesting that the grafted PLLA side-chains act as an internal plasticizer for xylan. TGA measurements revealed that XylC6N₃-g-PLLAs had higher decomposition temperatures than those of XylC6N₃ or PLLA, and that the decomposition temperatures of the copolymers increased with decrease in the number of PLLA side-chains grafted to the xylan main-chain.     

Syntheses, characterization, and in vitro degradation of ethyl cellulose-graft-poly(epsilon-caprolactone)-block-poly(L-lactide) copolymers by sequential ring-opening polymerization

Well-defined ethyl cellulose-graft-poly(epsilon-caprolactone) (EC-g-PCL) graft copolymers were successfully synthesized via ring-opening polymerization (ROP) of epsilon-caprolactone (CL) with an ethyl cellulose (EC) initiator and a tin 2-ethylhexanoate (Sn(Oct)2) catalyst in xylene at 120 degrees C. Then, novel ethyl cellulose-graft-poly(epsilon-caprolactone)-block-poly(L-lactide) (EC-g-PCL-b-PLLA) graft-block copolymers were prepared by ROP of L-lactide (L-LA) with a hydroxyl-terminated EC-g-PCL macroinitiator and Sn(Oct)2 catalyst in bulk at 120 degrees C. Various graft and block lengths of EC-g-PCL and EC-g-PCL-b-PLLA copolymers were obtained by adjusting the molar ratios of CL monomer to EC and the L-LA monomer to CL. The thermal properties and crystalline morphologies of EC-g-PCL and EC-g-PCL-b-PLLA copolymers were different from those of linear PCL. The in vitro degradation rate of EC-g-PCL-b-PLLA was faster than those of linear PCL and EC-g-PCL due to the presence of PLLA blocks.     

Structural characterization of a lipase-catalyzed copolymerization of epsilon-caprolactone and D,L-lactide

The copolymerization of epsilon-caprolactone (epsilon-CL) and d,l-lactide catalyzed by Candida antarctica lipase B was studied. Copolymerizations with different epsilon-CL-to-lactide ratios were carried out, and the product was monitored and characterized by MALDI-TOF MS, GPC, and (1)H NMR. The polymerization of epsilon-CL, which is normally promoted by C. antarctica lipase B, is initially slowed by the presence of lactide. During this stage, lactide is consumed more rapidly than epsilon-CL, and the incorporation occurs dimer-wise with regard to the lactic acid (LA) units. As the reaction proceeds, the relative amount of CL units in the copolymer increases. The nonrandom copolymer structure disappears with time, probably due to a lipase-catalyzed transesterification reaction. In the copolymerizations with a low content of lactide, macrocycles of poly(epsilon-caprolactone) and copolymers having up to two LA units in the ring were detected.     

Investigation of the Drug Release and Surface Morphological Properties of Film-Coated Pellets, and Physical, Thermal and Mechanical Properties of Free Films as a Function of Various Curing Conditions

The purpose of the present investigation was to elucidate the influence of curing on different physical properties of Eudragit NE and RS coating systems. Increased curing times resulted in decreased drug release rates from Eudragit NE-coated beads. However, an increase in drug release rates was noticed at longer curing times and higher temperatures for the Eudragit RS coating system. The surface morphological changes of the film-coated beads revealed that there were no visible macroscopic changes as a result of curing. The absence of any ibuprofen melting peak in the DSC thermograms of cured NE and RS coated beads confirmed that there was no surface crystallization of ibuprofen. These results indicated that the increase in drug release rates from RS coated pellets, when subjected to long curing times, resulted from loss of plasticizer. Free films of Eudragit NE exhibited an increase in tensile strength with increased curing times, whereas Eudragit RS free films showed a decrease in tensile strength beyond 4 h of curing at 70 and 90 degrees C. The film thicknesses and weights of free films of Eudragit RS prepared with triethyl citrate plasticizer were found to change more dramatically with curing than did free films of Eudragit RS prepared with ibuprofen as the plasticizer. An increase in pore volume was also observed with increased curing times for Eudragit RS free films. Such changes with curing were shown to be due to the loss of plasticizer molecules, leading to the formation of molecular-scale voids and channels.     

Synthesis and characterization of biodegradable amphiphilic triblock copolymers containing L-glutamic acid units

A novel biodegradable amphiphilic triblock copolymer bearing pendant carboxyl groups PLGG-PEG-PLGG was successfully prepared by ring-opening copolymerization of l-lactide (LA) with (3s)-benzoxylcarbonylethyl-morpholine-2, 5-dione (BEMD) in the presence of dihydroxyl poly(ethylene glycol) (PEG) as a macroinitiator in bulk at 130 degrees C using SnOct(2) as catalyst and by subsequent catalytic hydrogenation. The copolymer could form micelles in aqueous solution with the cmc dependent on the composition of the copolymer. The micelles exhibited a homogeneous spherical morphology and a unimodal size distribution. Their degradation rate in the presence of proteinase K was faster than that of PLA, and they showed a low degree of cytotoxicity to the articular cartilage cells. This biodegradable amphiphilic block copolymer with pendant carboxyl groups is capable of further modification and is expected to facilitate a variety of potential biomedical applications, such as drug carriers, tissue engineering, etc.     

Novel preparation method for poly(L-lactide)-based block copolymers: extended chain crystallites as a solid-state macro-coinitiator

A novel synthetic method for poly(L-lactide) (PLLA)-based diblock copolymers was developed by the use of PLLA extended chain crystallites (or crystalline residues) as a solid-state macro-coinitiator. In this study, we showed one example, i.e., a synthesis of diblock copolymer composed of a crystalline PLLA chain and an amorphous poly(DL-lactide) chain by ring-opening polymerization of DL-lactide initiated with stannous octoate (i.e., tin(II) 2-ethylhexanoate) in the presence of PLLA extended chain crystallites. The PLLA extended chain crystallites were prepared by hydrolytic degradation of crystallized PLLA films at 97 degrees C for 70 h. The chains inside the extended chain crystallites are expected to be protected from transesterfication reaction. Gel permeation chromatography, polarimetry, 1H NMR spectroscopy, wide-angle X-ray scattering, and differential scanning calorimetry revealed that the diblock copolymer poly(L-lactide-block-DL-lactide) was successfully prepared without significant transesterification.     

Dynamic adsorption behavior of poly(3-hydroxybutyrate) depolymerase onto polyester surface investigated by QCM and AFM

Time-dependent adsorption behavior of poly(3-hydroxybutyrate) (PHB) depolymerase from Ralstonia pickettiiT1 on a polyester surface was studied by complementary techniques of quarts crystal microbalance (QCM) and atomic force microscopy (AFM). Amorphous poly(l-lactide) (PLLA) thin films were used as adsorption substrates. Effects of enzyme concentration on adsorption onto the PLLA surface were determined time-dependently by QCM. Adsorption of PHB depolymerase took place immediately after replacement of the buffer solutions with the enzyme solutions in the cell, followed by a gradual increase in the amount over 30 min. The amount of PHB depolymerase molecules adsorbed on the surface of amorphous PLLA thin films increased with an increase in the enzyme concentration. Time-dependent AFM observation of enzyme molecules was performed during the adsorption of PHB depolymerase. The phase response of the AFM signal revealed that the nature of the PLLA surface around the PHB depolymerase molecule was changed due to the adsorption function of the enzyme and that PHB depolymerase adsorbed onto the PLLA surface as a monolayer at a lower enzyme concentration. The number of PHB depolymerase molecules on the PLLA surface depended on the enzyme concentration and adsorption time. In addition, the height of the adsorbed enzyme was found to increase with time when the PLLA surface was crowded with the enzymes. In the case of higher enzyme concentrations, multilayered PHB depolymerases were observed on the PLLA thin film. These QCM and AFM results indicate that two-step adsorption of PHB depolymerase occurs on the amorphous PLLA thin film. First, adsorption of PHB depolymerase molecules takes place through the characteristic interaction between the binding domain of PHB depolymerase and the free surface of an amorphous PLLA thin film. As the adsorption proceeded, the surface region of the thin film was almost covered with the enzyme, which was accompanied by morphological changes. Second, the hydrophobic interactions among the enzymes in the adlayer and the solution become more dominant to stack as a second layer.     

Mechanical properties of laser cut poly(L-lactide) micro-specimens: implications for stent design, manufacture, and sterilization

BACKGROUND: The development of endoluminal stents from polymeric materials requires an understanding of the basic mechanical properties of the polymer and the effects of manufacturing and sterilization on those properties. METHODS: Pure poly(L-lactide) (PLLA) and PLLA containing varying amounts of triethylcitrate (TEC) as a plasticizer (5-10-15%) were studied. The specimens were solution-cast and CO2 laser-cut. Specimen dimensions were adapted to the strut size of polymeric vascular stents. The properties of the PLLA micro-specimens were assessed before and after sterilization (EtO cold gas, H2O2-plasma, beta- and gamma-irradiation). Tensile tests, and creep and recovery tests were carried out at 37 degrees C. Additionally the thermal and thermo-mechanical characteristics were investigated using dynamic-mechanical analysis (DMA) and differential scanning calorimetry (DSC). RESULTS: The results showed the dramatic influence of the plasticizer content and sterilization procedure on the mechanical properties of the material. Laser cutting had a lesser effect. Hence the effects of processing and sterilization must not be overlooked in the material selection and design phases of the development process leading to clinical use. Altogether, the results of these studies provide a clearer understanding of the complex interaction between the laser machining process and terminal sterilization on the primary mechanical properties of PLLA and PLLA plasticized with TEC.