Tuning of Sol–Gel Transition in the Mixed Polymer Micelle Solutions of Copolymer Mixtures Consisting of Enantiomeric Diblock and Triblock Copolymers of Polylactide and Poly(ethylene glycol)

Poly(ethylene glycol) (PEG) is partially furanylated with different feed ratios of furfuryl isocyanate and used as the macro initiator of ring‐opening polymerization of l ‐ and d ‐lactides to synthesize copolymer mixtures of furan‐terminated AB diblock and ABA triblock copolymers (poly(oxyethylene)–poly(l ‐lactide)/poly(l ‐lactide)–poly(oxyethylene)–poly(l ‐lactide) and poly(oxyethylene–poly(d ‐lactide)/poly(d ‐lactide)–poly(oxyethylene)–poly‐(d ‐lactide)) having different diblock/triblock ratios. The mixed micelle solutions of these enantiomeric copolymer mixtures undergo sol‐to‐gel or gel‐to‐sol transition depending on the diblock/triblock ratio of the copolymer mixtures. The rheological properties of the mixed micelle solutions could also be controlled by changing the diblock/triblock ratios or the initial furanylation ratio of PEG.

     

聚乙二醇-柠檬酸共聚物(PEGCA)对聚乳酸的增韧及其机理

通过缩聚反应制备聚乙二醇-柠檬酸共聚物(PEGCA),通过密炼制备了PEGCA与聚乳酸(PLA)的共混物,研究了PEGCA对共混物的形貌结构、热性能和力学性能的影响。结果表明,PEGCA与PLA部分相容,PEGCA呈球状颗粒分散在PLA基体中。PEGCA对PLA有良好的增韧效果,当PEGCA质量分数为15%时,材料的断裂伸长率提高到327.9%,冲击强度提高到63.0 J/m。同时利用空穴化理论解释PEGCA增韧PLA的机理,用临界韧带厚度理论和J积分定量描述增韧的效果。     

In vitro biocompatibility evaluation of bioresorbable copolymers prepared from l-lactide, 1, 3-trimethylene carbonate,and glycolide for cardiovascular applications

PLLA-TMC-GA terpolymer was prepared by ring-opening polymerization of l-lactide, 1, 3-trimethylene carbonate (TMC), and glycolide (GA). The biocompatibility of terpolymer was evaluated in comparison with PLLA and PLLA-TMC with the aim of assessing their potential in the development of bioresorbable cardiovascular stents. Various aspects of in vitro biocompatibility were considered, including MTT assay, hemolytic test, dynamic clotting time, platelet adhesion, platelet activation, protein adsorption, plasma recalcification time and release of cytokines. The results revealed that the terpolymer presents good cytocompatibility and hemocompatibility. Moreover, no significant increase in the release of cytokines was detected. It is thus concluded that these polymers, in particular PLLA-TMC-GA terpolymer present good biocompatibility for cardiovascular applications.     

Surface characteristics and biocompatibility of lactide-based poly(ethylene glycol) scaffolds for tissue engineering

Novel lactide-based poly(ethylene glycol) (PEG) polymer networks (GL9-PEGs) were prepared by UV copolymerization of a glycerol-lactide triacrylate (GL9-Ac) with PEG monoacrylate (PEG-Ac) to use as scaffolds in tissue engineering, and the surface properties and biocompatibility of these networks were investigated as a function of PEG molecular weight and content. Analysis by ATR-FTIR and ESCA reveled that PEG was incorporated well within the GL9-PEG polymer networks and was enriched at the surfaces. From the results of SEM, AFM, and contact angle analyses, GL9-PEG networks showed relatively rough and irregular surfaces compared to GL9 network, but the mobile PEG chains coupled at their termini were readily exposed toward the aqueous environment when contacting water such that the surfaces became smoother and more hydrophilic. This reorientation and increase in hydrophilicity were more extensive with increasing PEG molecular weight and content. As compared to GL9 network lacking PEG, protein adsorption as well as platelet and S. epidermidis adhesion to GL9-PEG networks were significantly reduced as the molecular weight and content of PEG was increased, indicating that GL9-PEG networks are more biocompatible than the GL9 network due to PEG's passivity. Based on the physical and biological characterization reported, the GL9-PEG materials would appear to be interesting candidates as matrices for tissue engineering.     

In Situ Aggregates of Enantiomeric Poly(styrene)‐block‐Poly(lactide) Diblock Copolymers via Stereocomplexation in a Non‐selective Solvent

A comprehensive investigation of in situ aggregation of structurally well‐defined enantiomeric poly(styrene)‐block‐poly(lactide) (PS‐b‐PLLA and PS‐b‐PDLA) in a non‐selective solvent, tetrahydrofuran (THF), is presented. The isolated aggregates are found to form poly(L ‐lactide) (PLLA)/poly(D ‐lactide) (PDLA) racemic crystals by differential scanning calorimetry (DSC), wide‐angle X‐ray diffraction (WAXD), and Fourier transform infrared (FTIR) spectroscopy. The kinetic study reveals that the growth rate of the aggregates depends on the molecular weight of the enantiomeric PLA blocks, as well as the preparation conditions. The proposed mechanism demonstrates a new PS (shell)–PLA (core) structural hierarchy solely driven by stereocomplexation between enantiomeric PLLA and PDLA blocks.

     

Effects of chitosan and bioactive glass modifications of knitted and rolled polylactide‐based 96/4 L/D scaffolds on chondrogenic differentiation of adipose stem cells

The performance of biodegradable knitted and rolled 3‐dimensional (3D) polylactide‐based 96/4 scaffolds modified with bioactive glass (BaG) 13‐93, chitosan and both was compared with regard to the viability, proliferation and chondrogenic differentiation of rabbit adipose stem cells (ASCs). Scaffold porosities were determined by micro‐computed tomography (μCT). Water absorption and degradation of scaffolds were studied during 28‐day hydrolysis in Tris‐buffer. Viability, number and differentiation of ASCs in PLA96/4 scaffolds were examined in vitro. The dimensions of the scaffolds were maintained during hydrolysis and mass loss was detected only in the BaG13‐93 containing scaffolds. ASCs adhered and proliferated on each scaffold type. Cell aggregation and expression of chondral matrix components improved in all scaffold types in chondrogenic medium. Signs of hypertrophy were detected in the modified scaffolds but not in the plain PLA96/4 scaffold. Chondrogenic differentiation was most enhanced in the presence of chitosan. These findings indicate that the plain P scaffold provided a good 3D‐matrix for ASC proliferation whereas the addition of chitosan to the PLA96/4 scaffold induced chondrogenic differentiation independent of the medium. Accordingly, a PLA96/4 scaffold modified by chitosan could provide a functional and bioactive basis for tissue‐engineered chondral implants. Copyright © 2012 John Wiley & Sons, Ltd.     

Influence of polymer molecular weight in osteoinductive composites for bone tissue regeneration

In bone tissue regeneration, certain polymer and calcium-phosphate-based composites have been reported to enhance some biological surface phenomena, facilitating osteoinduction. Although the crucial role of inorganic fillers in heterotopic bone formation by such materials has been shown, no reports have been published on the potential effects the polymer phase may have. The present work starts from the assumption that the polymer molecular weight regulates the fluid uptake, which determines the hydrolysis rate and the occurrence of biological surface processes. Here, two composites were prepared by extruding two different molecular weight l/d,l-lactide copolymers with calcium phosphate apatite. The lower molecular weight copolymer allowed larger fluid uptake in the composite thereof, which was correlated with a higher capacity to adsorb proteins in vitro. Further, the large fluid absorption led to a quicker composite degradation that generated rougher surfaces and enhanced ion release. Following intramuscular implantation in sheep, only the composite with the lower molecular weight polymer could induce heterotopic bone formation. Besides influencing the biological potential of composites, the molecular weight also regulated their viscoelastic behaviour under cyclic stresses. The results lead to the conclusion that designing biomaterials with appropriate physico-chemical characteristics is crucial for bone tissue regeneration in mechanical load-bearing sites.     

人源抗VEGFR-2／As2O3-PEG-PLA隐形纳米粒的构建及质量控制研究

目的：探讨三氧化二砷（As2O3）纳米新剂型的制备和质量控制。方法以聚乙醇化聚乳酸（PEG‐PLA）为载体材料,W／O／W型超声乳化制备As2O3纳米粒,同时偶联具有肝癌靶向作用的VEGFR‐2,最终得到人源抗VEGFR‐2／As2O3‐PEG‐PLA纳米粒。对其粒径分布、Zata电位、载药量和包封率进行测定,通过透射电镜（TEM）观察其表观形态,同时考察其体外释药和稳定性。选择24只肝癌裸鼠,随机分为VEGFR‐2／As2O3‐PEG‐PLA组及As2O3‐PEG‐PLA组,通过尾静脉注射纳米粒,高效液相色谱法测定As2O3在两组裸鼠体内的分布;免疫组化及蛋白质印迹法（Westernblot）检测血管内皮细胞生长因子（VEGF）表达量。结果本实验制得的As2O3纳米制剂VEGFR‐2／As2O3‐PEG‐PLA粒径为（141．9±13．2）nm,Zata电位为（10．2±1．1）mV;经TEM观察呈圆形或椭圆形颗,粒状、大小较一致,分散性较好;载药量为（5．51±1．83）％,包封率为（62．12±5．98）％。体外释放发现其具有缓释效果,半数释放时间t1／2分别为10h;初步稳定性考察结果发现该制剂稳定性良好。与As2O3‐PEG‐PLA组比较,VEGFR‐2／As2O3‐PEG‐PLA组中肿瘤、肝组织的As2O3浓度较高,心、血液、肾组织的As2O3浓度较低（P＜0．05）,且肿瘤组织中VEGFR‐2阳性率及蛋白表达较低。结论以PEG‐PLA为载体材料制备得到As2O3纳米制剂,且偶联具有肝癌靶向作用的VEGFR‐2,最终得到粒径分布均匀,包封率和载药量高,稳定性良好的纳米制剂,且初步证实在肝癌裸鼠体内具有良好的靶向作用。     

均聚物PS共混对PI-PS-PLA薄膜中微纳米结构的影响

将均聚物聚苯乙烯（PS）与三嵌段共聚物聚异戊二烯聚苯乙烯聚乳酸（PIPSPLA）以一定摩尔比共混,采用原子力显微镜（AFM）研究了均聚物浓度对其薄膜样品中微纳米结构的影响。结果表明：当n(PS)∶n(PIPSPLA)为1∶2和1∶1时,薄膜呈现出规则排列的柱状微结构,且柱状微区的尺寸较混合前的样品有所改变;当n(PS)∶n(PIPSPLA)为2∶1时,PS与嵌段共聚物PIPSPLA的分子链发生了相分离,其中均聚物PS相形成了较大尺寸的岛状微区。