Effect of gamma,ethylene oxide,electron beam,and plasma sterilization on the behaviour of SR-PLLA fibres in vitro

- The aim of this study was to evaluate the effect of various sterilization processes on the physical and mechanical properties of self-reinforced bioabsorbable fibres made out of polylactide (PLLA). The samples were sterilized using plasma, ethylene oxide (one and two cycles), gamma (25 kGy at room temperature, 25 kGy in dry ice, and 2 × 25 kGy at room temperature), and electron beam (15, 25, and 55 kGy) sterilization. The intrinsic viscosity, crystallinity, and mechanical properties (modulus of elasticity, yield strength, and ultimate tensile strength) were tested before and immediately after each sterilization treatment, as well as up to 30 weeks in vitro. Compared with unsterilized fibres, the intrinsic viscosity was markedly decreased after radiation sterilization (gamma and electron beam) and the loss in mechanical properties was accelerated during in vitro degradation. Plasma and ethylene oxide (one and two cycles) did not markedly alter the properties of the samples after sterilization or during in vitrodegradation. These data are important for determining the effect of various sterilization processes on the physical and mechanical properties of polylactidebased materials and can be used to predict how fast degradation of the mechanical properties of the self-reinforced PLLA will occur. They can also be used to tailor the degradation kinetics to optimize implant design.     

Mechanical properties and in vitro degradation of self-reinforced radiopaque bioresorbable polylactide fibres

The aim of this study was to evaluate the effect of the radiopaque filler, barium sulfate (BaSO4), on the mechanical properties of self-reinforced bioresorbable fibres. The bioresorbable polymer was a copolymer of L- and D-lactide with an L/D monomer ratio of 96:4 (96L/4D PLA). The fibres were manufactured using an extrusion and a drawing process. Three different methods of processing the composites were studied. The materials were blended prior to extrusion. In the first method, the BaSO4 powder was mixed with the polymer granulates by hand (manual blending). The blend was then processed using a twin-screw extruder. The second and third methods utilized a single-screw extruder. In the second method, the BaSO4 powder was manually mixed with the polymer prior to extrusion. In the third method, the BaSO4 powder was mechanically attached on the polymer granulates (mechanical blending) prior to extrusion. The mechanical and chemical properties of the radiopaque bioresorbable fibres were measured after processing and during in vitro degradation. The fibres were gamma, plasma or EtO sterilized. There was no statistical difference in the mechanical properties of the fibres when manufactured using the twin-screw extrusion with manual blending or the single-screw extrusion with mechanical blending. The gamma sterilization markedly decreased the initial intrinsic viscosity of all fibres, whereas the plasma and EtO sterilization methods had no effect on the initial intrinsic viscosity. During in vitro testing, the loss in the intrinsic viscosity occurred at the same rate whether the fibres were loaded with the barium sulfate or not.     

Mechanical properties and in vitro degradation of self-reinforced radiopaque bioresorbable polylactide fibres

The aim of this study was to evaluate the effect of the radiopaque filler, barium sulfate (BaSO₄), on the mechanical properties of self-reinforced bioresorbable fibres. The bioresorbable polymer was a copolymer of L- and D-lactide with an L/D monomer ratio of 96 :4 (96L/4D PLA). The fibres were manufactured using an extrusion and a drawing process. Three different methods of processing the composites were studied. The materials were blended prior to extrusion. In the first method, the BaSO₄ powder was mixed with the polymer granulates by hand (manual blending). The blend was then processed using a twin-screw extruder. The second and third methods utilized a single-screw extruder. In the second method, the BaSO₄ powder was manually mixed with the polymer prior to extrusion. In the third method, the BaSO₄ powder was mechanically attached on the polymer granulates (mechanical blending) prior to extrusion. The mechanical and chemical properties of the radiopaque bioresorbable fibres were measured after processing and during in vitro degradation. The fibres were gamma, plasma or EtO sterilized. There was no statistical difference in the mechanical properties of the fibres when manufactured using the twin-screw extrusion with manual blending or the single-screw extrusion with mechanical blending. The gamma sterilization markedly decreased the initial intrinsic viscosity of all fibres, whereas the plasma and EtO sterilization methods had no effect on the initial intrinsic viscosity. During in vitro testing, the loss in the intrinsic viscosity occurred at the same rate whether the fibres were loaded with the barium sulfate or not.     

Mechanical properties and in vitro degradation of bioresorbable knitted stents

The aim of this study was to characterize the mechanical properties and in vitro degradation of bioresorbable knitted stents. Each stent was knitted using a single self-reinforced fibre made out of either PLLA or 96L/4D PLA or 80L/20G PLGA. The mechanical and physical properties of the fibres and stents were measured before and after gamma sterilization, as well as during in vitro degradation. The mechanical properties of the knitted stents made out of bioresorbable fibres were similar to those of commercially available metallic stents. The knitting geometry (loop height) had a marked effect on the mechanical properties of the stents. The rate of in vitro degradation in mechanical and physical properties for the PLLA and 96L/4D PLA stents was similar and significantly lower than that of the 80L/20G PLGA stents. The 80L/20G PLGA stents lost about 35% of their initial weight at 11 weeks. At this time, they had lost all their compression resistance strength. These data can be used as a guideline in planning further studies in vivo.     

Mechanical properties and in vitro degradation of bioresorbable knitted stents

- The aim of this study was to characterize the mechanical properties and in vitro degradation of bioresorbable knitted stents. Each stent was knitted using a single self-reinforced fibre made out of either PLLA or 96L/4D PLA or 80L/20G PLGA. The mechanical and physical properties of the fibres and stents were measured before and after gamma sterilization, as well as during in vitro degradation. The mechanical properties of the knitted stents made out of bioresorbable fibres were similar to those of commercially available metallic stents. The knitting geometry (loop height) had a marked effect on the mechanical properties of the stents. The rate of in vitro degradation in mechanical and physical properties for the PLLA and 96L/4D PLA stents was similar and significantly lower than that of the 80L/20G PLGA stents. The 80L/20G PLGA stents lost about 35% of their initial weight at 11 weeks. At this time, they had lost all their compression resistance strength. These data can be used as a guideline in planning further studies in vivo.     

Crosslinking of poly(L-lactide) nanofibers with triallyl isocyanutrate by gamma-irradiation for tissue engineering application

The radiation crosslinked poly(L-lactide) (PLLA) electrospun nanofibers have been developed with improved thermal stability and mechanical properties. Trially isocyanurate (TAIC) were added into PLLA solution at different weight ratios (1, 3, and 5%) and electrospun into nanofibrous mats, the mats were then irradiated by gamma ray at different radiation doses (5, 10, and 25 kGy) to crosslink the PLLA chains. Their surface morphology, thermal properties, mechanical properties, and biodegradation properties were investigated and compared before and after gamma irradiation. Furthermore, the in vitro biocompatibilities were also evaluated by using mouse L929 fibroblasts. The results indicated that the efficient crosslinking networks can be generated when the TAIC content is higher than 3%. The thermal stability and tensile mechanical properties were significantly increased at higher irradiation dose of 10 and 25 kGy. However, radiation dose at 25 kGy have an adverse effect on the thermal stability of crosslinked samples due to thermal degradation induced by irradiation, the crosslinked samples irradiated at 10 kGy exhibited the best enzymatic degradation. The in vitro results also revealed that the crosslinked PLLA/TAIC composite nanofibers did not induce cytotoxic effects and are suitable for cell growth. Therefore, the crosslinked PLLA nanofibers are one of the promising materials for future tissue engineering applications.     

左旋聚乳酸可吸收骨钉两种灭菌法效果评价

目的评价左旋聚乳酸可吸收骨钉经环氧乙烷灭菌和^60Co-γ辐照灭菌的效果。方法将左旋聚乳酸可吸收骨钉放人环氧乙烷灭菌器中灭菌,灭菌后将材料置于空气中静置5d,以清除残留的环氧乙烷;另将左旋聚乳酸可吸收骨钉采用^60Co-γ辐照灭菌装置灭菌,吸收剂量15kGy。然后对2种方法灭菌的骨钉分别进行性能表征。结果与左旋聚乳酸可吸收骨钉初始弯曲强度相比,经2种方法灭菌的骨钉弯曲强度均无明显下降（P〉0．05）;与左旋聚乳酸可吸收骨钉初始分子量相比,经^60Co-γ辐照灭菌的骨钉分子量明显减小,下降约11％,表明材料发生降解;经环氧乙烷灭菌的骨钉分子量无明显变化,下降约3％,表明材料未发生明显降解。结论左旋聚乳酸可吸收骨钉以环氧乙烷灭菌为佳。     

Effect of electron beam irradiation on the structure and properties of electrospun PLLA and PLLA/PDLA blend nanofibers

Poly(l-lactide) (PLLA) and a PLLA/poly(d-lactide) (PDLA) blend (50/50 wt.%) were electrospun into nanofibers. Electron beam (e-beam) irradiation of the electrospun PLLA and blend nanofibers was used as a method to alter their structures and surface properties. The crystalline structures of the nanofibers before and after irradiation were investigated by differential scanning calorimetry. Tensile tests of the aligned nanofibers were also performed to determine the effects of irradiation on the mechanical properties of the nanofibers. The hydrophilicity of the nanofibers was determined by water contact angle measurements, while any degradation of the fibers caused by irradiation could be detected by intrinsic viscosity measurements. The e-beam irradiation method was able to improve the surface hydrophilicity of the PLLA and blend nanofibers, although bulk degradation was inevitable.     

Enhanced retention of polymer physical characteristics and mechanical strength of 70:30 poly(L-lactide-co-D,L-lactide) after ethylene oxide sterilization

This study examined the effect of ethylene oxide (EtO) and electron beam (e-beam) irradiation on the properties of 70:30 poly(L-lactide-co-D,L-lactide). The effects of sterilization upon the polymer physical characteristics and strength retention of the material were examined, both initially and after being subjected to real time ageing. Commercially available 70:30 poly(L-lactide-co-D,L-lactide) material was fabricated into rectangular, cylindrical, screw, and sheet designs, and tested in compression, shear, or tension. Sterilization of 70:30 poly(L-lactide-co-D,L-lactide) by ethylene oxide had a nearly negligible effect on the physical properties of the polymer, regardless of specimen size or manufacturing technique. The molecular weight and inherent viscosity of the specimens decreased by approximately 3% after sterilization by EtO. However, sterilization of 70:30 poly(L-lactide-co-D,L-lactide) by e-beam irradiation resulted in immediate changes to some of the physical properties of the polymer. Specimens sterilized by e-beam irradiation displayed an immediate decrease in inherent viscosity of approximately 67% as compared to the respective nonsterile samples. The immediate decrease in inherent viscosity and molecular weight with e-beam irradiation required approximately 39 weeks of real time ageing of the EtO sterilized parts. At all time points investigated in the present study, the strength retention of the EtO sterilized devices equaled or exceeded that of the e-beam irradiated samples.     

左旋聚乳酸的改性实验

背景：目前临床上大量使用的金属支架永久存留于人体,对人体存在潜在的风险。 目的：观察改性对左旋聚乳酸的作用以及改性材料用于可降解支架制备的可行性。 方法：以左旋聚乳酸/聚己内酯为95∶5的比例,用溶液法制备左旋聚乳酸、聚乳酸/聚己内酯共聚材料(PLCL-J 9505)和聚乳酸/聚己内酯共混材料(PLCL-H 9505)薄膜。 结果与结论：力学性能测试结果显示,3个月左旋聚乳酸材料的脆性明显升高,材料变得容易断裂,成为制备支架的一大缺陷;PLCL-J材料力学性能损失过快,第3周屈服完全消失,第4周拉伸强度开始急剧下降,到第10周已经完全丧失力学性能;PLCL-H材料不仅初始时断裂伸长率高,而且在降解过程中能始终保持较高的弹性。特性黏数测试和表面形态观测结果显示PLCL-J材料的降解速率过快,不适合在支架上应用,而左旋聚乳酸和PLCL-H基本是匀速的水解,且PLCL-H相对于左旋聚乳酸降解速率有一定程度的增加。提示左旋聚乳酸与聚己内酯共混改性比例为95∶5时不仅能保证材料具备支架所需的力学强度,还能显著提高材料的断裂伸长,达到了增塑目的的同时,也加快降解速率,有望成为制备可降解支架的新型材料。     

Poly(ethylene glycol)-poly(L-lactide) diblock copolymer prevents aggregation of poly(L-lactide) microspheres during ethylene oxide gas sterilization

Sterilization procedure is one of the most important obstacles in the clinical applications of biodegradable microspheres. The microspheres prepared with poly(alpha-hydroxy acid) were severely aggregated during ethylene oxide (EO) gas sterilization, and could not be used in clinical applications. In this study, the effects of EO gas sterilization on the poly(L-lactide) (PLLA) microspheres were analyzed by nuclear magnetic resonance spectroscopy (1H-NMR), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), scanning electron microscope (SEM) and size fractionation. The aggregation between the microspheres might be stimulated by high mobility of amorphous regions of PLLA on the microsphere surfaces since both water vapor and gas mixture can reduce glass transition temperature (Tg) of PLLA below the sterilization temperature. During EO gas sterilization, there were no changes in the molecular structure and the molecular weight of PLLA in microspheres, but there were changes in the crystallinity of PLLA in microspheres. In this study, poly(L-lactide)-poly(ethylene glycol) diblock copolymers (PLE) were blended with PLLA homopolymers in various ratios to design the microsphere suitable for EO gas sterilization. Aggregation of PLLA microspheres was markedly prevented when more than 4wt% of PLE was blended in the microspheres. This inhibition effect on aggregation may be due to the increased initial crystallinity of the microspheres, which help to maintain the microsphere morphology during EO gas sterilization.     

Enhanced wear performance of highly crosslinked UHMWPE for artificial joints

It is well known that osteolysis induced by polyethylene wear debris is the main cause of long-term failure of hip and knee prostheses. We developed a treatment of medical-grade ultra-high molecular-weight polyethylene (UHMWPE) in order to improve its tribologic properties and reduce its wear. Medical-grade UHMWPE was irradiated with a 200 kGy dose of radiation, thermally stabilized at a temperature close to the melting point, and then sterilized with ethylene oxide. The irradiation treatment was performed to crosslink the UHMWPE. The thermal stabilization treatment, contributing to the reaction between the free radicals generated by the irradiation process, was chosen to enhance crosslinking and to prevent oxidation and the shortening of chains. The non-invasive sterilization process with ethylene oxide was chosen to prevent the re-formation of free radicals. The wear performance of this material was compared to UHMWPE, untreated or treated with different sterilization techniques, using gamma and beta irradiation. Insoluble crosslinked constituents were measured with an extraction method. Wear was evaluated using a flat-on-ring wear test machine. While small differences were found among the different sterilization processes, 200 kGy-irradiated UHMWPE followed by thermal treatment and sterilization with ethylene oxide had the least wear and the greatest amount of crosslinking.     

Effect of sterilization on the physicochemical properties of molded poly(L-lactic acid)

In this study, the process of manufacturing and sterilizing an orthopedic implant constructed from poly(L-lactic acid) (PLLA) was closely simulated. The hydrogen peroxide gas plasma (HPGP) sterilization process was comparatively investigated against ethylene oxide (EtO). Characterization of the physical, thermal, mechanical, morphological, and chemical properties was monitored. The results indicate that the HPGP sterilization process did not have a significant influence on M(n) or M(w) initially or through 12 weeks of in vitro conditioning when compared with EtO. Only indications of physical aging were evident in the analysis of the thermal and mechanical properties by differential scanning calorimeter and tensile testing for each sterilization processes. Using wide angle X-ray diffraction to determine morphology characteristics, it was determined that no changes were observed between the as molded, HPGP, and EtO specimens initially or through the 12 week in vitro conditioning period. Contact angle measurements revealed a significant reduction in the surface energy following treatment by the HPGP process, suggesting the formation of polar groups. However, surface chemistry analysis by ATR-FTIR indicated no significant chemical modification from either sterilization method. PLLA showed intermediate levels of residual hydrogen peroxide absorption following processing by HPGP.     

Evaluation of hydroxylapatite/poly(L-lactide) composites: mechanical behavior.

By mixing hydroxylapatite (HA) into L(-)-dilactide monomer, prior to polymerization to poly(L-lactide) (PLLA), hydroxylapatite filled poly(L-lactide) composites were obtained. This study reports about the mechanical properties of these composites compared with unfilled PLLA. It was concluded that a 30 wt% HA/PLLA composite has better compressive and tensile strengths, higher stiffness and Vickers hardness number than unfilled PLLA (Mv: 125-150,000). Gas sterilization (ethylene oxide) affects molecular weight and flexural strength significantly. Implantation studies revealed loss of 50% of initial flexural strength within 3 weeks, and a faster decline of flexural strength was observed in phosphate buffered saline than in the subcutis of goats. From a mechanical point of view storage at -20 degrees C proved to be a safe method. In its current state HA/PLLA composites can not be used as implant materials that have to resist major forces. However, such composites might be useful in non-loadbearing applications in orthopedic or maxillofacial surgery.     

Uniaxial and biaxial properties of terminally sterilized porcine urinary bladder matrix scaffolds

Scaffolds composed of extracellular matrix have been successfully used to support the reconstruction of a variety of tissues in preclinical studies and in clinical applications. As an off-the-shelf product, extracellular matrix (ECM) scaffolds must be subjected to terminal sterilization before use. The choice of sterilization method may alter the integrity of the ECM's composition and structure such that the mechanical and material properties are adversely affected. The present study evaluated selected structural properties of an ECM scaffold derived from the urinary bladder termed urinary bladder matrix after being sterilized by three different methods: ethylene oxide (ETO) (750 mg/h for 16 h), gamma irradiation (2.0 Mrads), or electron beam irradiation (e-beam) (2.2 Mrads). The structural properties that were evaluated include maximum force, maximum elongation, maximum tangential stiffness, energy dissipation, and ball-burst strength. All sterilization methods affected at least two of the measured properties. ETO was shown to have the least detrimental effect upon the measured properties. Gamma and e-beam irradiation were shown to decrease the uniaxial and biaxial strength, maximum tangential stiffness, and the energy dissipation of the ECM scaffolds. The present study showed that the choice of terminal sterilization method affects the structural properties of scaffolds composed of extracellular matrix.     

Processing, annealing and sterilisation of poly-L-lactide

Poly-L-lactide (PLLA) is one of the most significant members of a group of polymers regarded as bioabsorbable. Degradation of PLLA proceeds through hydrolysis of the ester bonds in the polymer chains and is influenced significantly by the polymer's molecular weight and crystallinity. To evaluate the effects of processing and sterilisation on these properties, PLLA pellets were either compression moulded or extruded, subjected to annealing at 120 degrees C for 4h and sterilised by ethylene oxide (EtO) gas. Procedures were used to evaluate the mechanical properties, molecular weight and crystallinity. Upon processing, the crystallinity of the material fell from 61% for the PLLA pellets to 12% and 20% for the compressed and extruded components, respectively. After annealing, crystallinity increased to 43% for the compression-moulded material and 40% for the extruded material. Crystallinity further increased upon EtO sterilisation. A slight decrease in molecular weight was observed for the extruded material through processing, annealing and sterilisation. Young's modulus generally increased with increasing crystallinity, and extension at break and tensile strength decreased. The results from this investigation suggest that PLLA is sensitive to processing and sterilisation, altering properties critical to its degradation rate.     

Mechanical properties and in vitro degradation of bioabsorbable self-expanding braided stents

The aim of this study was to characterize the mechanical and self-expansion properties of braided bioabsorbable stents. In total four different stents were manufactured from PLLA fibres using a braiding technique. The changes in radial pressure stiffness and diameter recovery of the stents were determined initially, and after insertion and release from a delivery device. The braided stents were compared to three commercially available metallic braided stents. The changes in physical and mechanical properties of the PLLA fibres and stents during in vitro degradation were investigated. After release from the delivery device, the PLLA stents did not fully recover to their original diameter. The radial pressure stiffness of the bioabsorbable stents was similar to that of the metallic stents. The in vitro degradation study showed that the stents would keep at least half of their initial radial pressure stiffness for more than 22 weeks.     

In vitro flexural properties of hydroxyapatite and self-reinforced poly(L-lactic acid)

Poly(L-lactic acid) (PLLA) has been used for fracture fixation devices, but its use is limited because of its poor biocompatibility and mechanical properties. The effects of extrusion, incorporation of hydroxyapatite (HA) and self-reinforced composites (SRCs) on the resultant mechanical properties of PLLA were examined. Samples were conditioned for up to 52 weeks in PBS at 37 degrees C. Extrusion did not adversely affect the mechanical properties of PLLA. After in vitro conditioning, a slight but significant reduction in the strain to failure and modulus was seen. HA (10-40%) by weight was evenly distributed into PLLA using an intermeshing twin-screw extruder. As ceramic content increased, the initial modulus increased but flexural strength decreased. After immersion, the modulus of all HA-PLLA blends was lower than PLLA. HA particles did not form a strong bond with the PLLA, which promoted easier degradation of the HA-PLLA matrix. SRCs showed a higher modulus and strength when compared to all materials except the modulus of 30 and 40% HA-PLLA composites before immersion. Water preferentially attacked the matrix of the composite, leading to more fiber pullout, but the fiber orientation maintained the advantages in strength and modulus up to 24 weeks in vitro.     

Alterations of human acellular tissue matrix by gamma irradiation: histology, biomechanical property, stability, in vitro cell repopulation, and remodeling

AlloDerm, a processed acellular human tissue matrix, is used in a number of surgical applications for tissue repair and regeneration. In the present work, AlloDerm serves as a model system for studying gamma radiation-induced changes in tissue structure and stability as well as the effect of such changes on the cell-matrix interactions, including cell repopulation and matrix remodeling. AlloDerm tissue matrix was treated with 2-30 kGy gamma irradiation at room temperature. Gamma irradiation reduced the swelling of tissue matrix upon rehydration and caused significant structural modifications, including collagen condensation and hole formation in collagen fibres. The tensile strength of AlloDerm increased at low gamma dose but decreased with increasing gamma dosage. The elasticity of irradiated AlloDerm was reduced significantly. Calorimetric study showed that gamma irradiation destabilized the tissue matrix, resulting in greater susceptibility to proteolytic enzyme degradation. Although gamma irradiation did not affect in vitro proliferation of fibroblast cells, it promoted tissue degradation upon cell repopulation and influenced synthesis and deposition of new collagen.     

Mechanical properties and in vitro degradation of bioabsorbable self-expanding braided stents

The aim of this study was to characterize the mechanical and self-expansion properties of braided bioabsorbable stents. In total four different stents were manufactured from PLLA fibres using a braiding technique. The changes in radial pressure stiffness and diameter recovery of the stents were determined initially, and after insertion and release from a delivery device. The braided stents were compared to three commercially available metallic braided stents. The changes in physical and mechanical properties of the PLLA fibres and stents during in vitro degradation were investigated. After release from the delivery device, the PLLA stents did not fully recover to their original diameter. The radial pressure stiffness of the bioabsorbable stents was similar to that of the metallic stents. The in vitro degradation study showed that the stents would keep at least half of their initial radial pressure stiffness for more than 22 weeks.