聚己二酸丁二酯纳米纤维构建的微球的制备

建立了采用异相成核和可控水解相结合的方法制备由纳米纤维构建的聚合物微球的新方法.根据多取代卞叉山梨醇(TM6)对聚己二酸丁二酯(PBA)的异相成核作用以及结晶形态的影响,采用两种乳液溶剂挥发法、并在聚合物溶液中加入成核剂TM6制备了PBA微球,研究了成核剂含量对PBA微球在酶促降解之后形态变化的影响.研究结果表明,二次乳液溶剂挥发法可以制备具有多孔结构的PBA微球,这种多孔结构有利于酶溶液进入到微球内部,促进PBA微球的均匀水解,最终获得由PBA纳米纤维构建的微球.当TM6的含量为3 wt%时,采用二次乳液溶剂挥发法制备的PBA微球,经过5 h酶促降解处理,可以得到表面和内部由PBA纳米纤维均匀组成的微球.进一步的细胞实验表明,微球的纳米纤维结构,有利于MG-63细胞在聚合物微球上的黏附、铺展和向内生长.     

Biodegradable microspheres with poly(<Emphasis Type="Italic">N</Emphasis>-isopropylacrylamide) Enriched surface: Thermo-responsibility,biodegradation and drug release

Microspheres with thermo-responsible surface were fabricated by PCL-b-PEO-b-PNIPAM triblock copolymers. Thermo-responsible morphological changes of PCL-b-PEO-b-PNIPAM microspheres immersed in aqueous solution at temperatures above the LCST (e.g. 37 °C) were observed from porous surface structure to compact surface layer. Enzymatic degradation and in vitro drug release results showed that the thermo-responsible surface layer greatly influenced the degradation of microspheres as well as the drug release behavior from microspheres. With the copolymerization of PNIPAM block into PCL-b-PEO copolymers, the drug release could be well regulated by changing temperatures and microspheres composition, which revealed the great potentials of microspheres with thermo-responsible surface for controlled drug release.     

Biodegradable amphiphilic block copolymers containing functionalized PEO blocks: Controlled synthesis and biomedical potentials

A series of controllable amphiphilic block copolymers composed of poly(ethylene oxide) (PEO) as the hydrophilic block and poly(?-caprolactone) (PCL) as the hydrophobic block with the amino terminal group at the end of the PEO chain (PCL-b-PEO-NH₂) were synthesized. Based on the further reaction of reactive amino groups, diblock copolymers with functional carboxyl groups (PCL-b-PEO-COOH) and functional compounds RGD (PCL-b-PEO-RGD) as well as the triblock copolymers with thermosensitive PNIPAAm blocks (PCL-b-PEO-b-PNIPAAM) were synthesized. The well-controlled structures of these copolymers with functional groups and blocks were characterized by gel permeation chromatography (GPC) and ¹H NMR spectroscopy. These copolymers with functionalized hydrophilic blocks were fabricated into microspheres for the examination of biofunctions via cell culture experiments and in vitro drug release. The results indicated the significance of introducing functional groups (e.g., NH₂, COOH and RGD) into the end of the hydrophilic block of amphiphilic block copolymers for biomedical potentials in tissue engineering and controlled drug release.     

Controlled enzymatic degradation of poly(?-caprolactone)-based copolymers in the presence of porcine pancreatic lipase

Poly(?-caprolactone) (PCL) has been extensively studied for biomedical use due to its outstanding biocompatibility. Well-defined random and block copolymers based on PCL such as poly(?-caprolactone-r-2,2-dimethyltrimethylene carbonate) (PCD), poly[(?-caprolactone-r-2,2-dimethyltrimethylene carbonate)-b-PEG-b-(?-caprolactone-r-2,2-dimethyltrimethylene carbonate)] (PECD) and poly[MPEG-b-(?-caprolactone-r-2,2-dimethyltrimethylene carbonate)] (MPECD) containing 5.0-8.5 mol% 2,2-dimethyltrimethylene carbonate (DTC) and 15.9-18.3 mol% polyethylene glycol (PEG) or polyethylene glycol monomethyl ether (MPEG) have been synthesized by using lanthanum tris(2,6-di-tert-butyl-4-methylphenolate) as catalyst. Their crystallization properties, thermal behaviors, hydrophilicities and degradation properties depend on the tunable microstructures and morphologies. It is found for the first time that porcine pancreatic lipase (PP lipase) can effectively catalyze the degradation of PCD electrospun mats (EMs) with 92.0% weight loss within 7 days while it shows no detectable effect on PCL EMs. Surface erosion mechanism is proposed in the enzymatic degradation systems, and the high proportion of amorphous domain of PCD contributes to its fast degradation rate according to the degradation product analyses. The enzymatic degradation rates of PCD EMs with porous structures and huge surface areas are higher than those of compression molding films (CMFs). Introducing PEG segment improves the hydrophilicity of PCD but decreases the degradation rate. A PEG segment enrichment process on the surface is addressed, which prevents the contact of PP lipase with PCD segments in the PEG-involved electrospun fiber. PECD and MPECD exhibit different mechanical strengths and contact angles, but similar degradation profiles. This study provides a practical example for tunable biodegradation of polyesters by designing the materials' bulk structures and/or surface morphologies.     

Biodegradable microspheres containing poly(epsilon-caprolactone)-Pluronic block copolymers for temperature-responsive release of proteins

Temperature-responsive microspheres were fabricated for the purpose of releasing protein in responsive to surrounding temperature changes. Temperature-responsive polymer, Pluronic was synthesized into block copolymers of poly(epsilon-caprolactone)-Pluronic with two different chain lengths of poly(epsilon-caprolactone). Microspheres loaded with proteins were prepared by a W/O/W emulsion method. The surface morphology was examined by scanning electron microscopy, showing that microspheres with diblock copolymers had porous structures due to hydrophilicity of Pluronic blocks. After incubating the microsphere at 37 degrees C for 7 days, temperature-responsive protein release was monitored with alternating temperature changes between 20 and 37 degrees C. The protein release was attenuated when the microsphere was incubated at 20 degrees C but the release rate was recovered at 37 degrees C, confirming variable release rate according to the temperature changes. The variable release rate of protein was dependent on the length of poly(epsilon-caprolactone) blocks attached to Pluronic.     

Hydrolysis and biomineralization of porous PLA microspheres and their influence on cell growth

Poly(lactic acid) (PLA) microspheres have great potential in bone tissue engineering. However, their applications have been limited by surface and bulk properties such as hydrophobicity, lack of cell recognition sites and acidic degradation products. Apatite is a mineral which can effectively promote the adhesion and growth of bone cells. In this study, the bonelike mineral, carbonate apatite, was successfully used to functionalize porous PLA microspheres by a biomimetic mineralization method. To improve apatite formation, porous PLA microspheres were first selectively hydrolyzed in NaOH solution to increase the density of polar anionic groups on the surface, and then immersed in simulated body fluid for biomineralization. The morphology, composition, and phase structure of bioactive mineral grown on the original and hydrolyzed PLA microspheres were analyzed and compared quantitatively. The results showed that the hydrolysis which took place on the PLA microspheres enhanced the nucleation and growth of apatite. MG-63 cells attached well and spread actively on the mineralized PLA microspheres, indicating their strong potential in bone tissue engineering.     

Interactions between temperature-sensitive hydrogel microspheres and granulocytes

Poly(N-isopropylacrylamide) (PNIPAM) has a low critical solution temperature (LCST) at 32°C in water and the hydrophilicity changes through the LCST. The microspheres whose surface was composed of PNIPAM exhibited phase transition behavior around 32°C. Therefore, the interactions between PNIPAM micropheres and granulocytes depended on the temperature. That is, the oxygen consumption and active oxygen production by cells in contact with PNIPAM-containing microspheres and adhesion of the microspheres to the cell surface were more enhanced above the LCST of PNIPAM than below it, whereas no significant temperature dependence of cell–microspheres interaction was observed in nonthermosensitive microsphere systems. It was suggested that the function of cells could be controlled with temperature using the temperature-sensitive microspheres.     

SYNTHESIS OF POLY(DIVINYLBENZENE-co-ACRYLIC ACID) HOLLOW MICROSPHERES WITH GOLD NANOPARTICLES ON THE INTERIOR SURFACE

Poly(divinylbenzene-co-acrylic acid) (poly(DVB-co-AA)) hollow microspheres with gold nanoparticles on the interior surfaces were prepared from the gold nanoparticles-coated poly(methacrylic acid) (PMAA@Au@poly(DVB-co-AA)) core-shell microspheres by removal of the PMAA core in water.Au nanoparticles-coated PMAA microspheres were afforded by the in-situ reduction of gold trichloride with PMAA microsphere as stabilizer via the interaction between carboxylic acid groups and Au nanoparticles.Gold nanoparticle...     

Study on the fabrication and photovoltaic property of TiO2 mesoporous microspheres

Titanium dioxide mesoporous microspheres with high surface area was successfully prepared by a facile one-step hydrothermal approach using polyethylene glycol (PEG, MW 200) as the soft template. Study shows that ∼15 nm TiO₂ nanoparticles was assembled into ∼1.1 μm mesoporous microspheres. The Brunauer-Emmett-Teller surface area of TiO₂ microsphere is up to 137 m²/g. TiO₂ mesoporous microspheres were fabricated onto the surface of fluorine-doped tin oxide glass and used as the photoanode of dye-sensitized solar cells, which exhibits an open circuit photovoltage of 0.80 V and an overall conversion efficiency of 6.6%. Owing to the enhanced dye loading and light-harvesting efficiency, a 26% improvement in the overall conversion efficiency was achieved when compared with the commercial Degussa P₂₅ nanoparticles.     

Biodegradable Microspheres with Poly(N-isopropylacrylamide) Enriched Surface: Thermo-responsibility,Biodegradation and Drug Release

Microspheres with thermo-responsible surface were fabricated by PCL-b-PEO-b-PNIPAM triblock copolymers. Thermo-responsible morphological changes of PCL-b-PEO-b-PNIPAM microspheres immersed in aqueous solution at temperatures above the LCST(e.g. 37 ?C) were observed from porous surface structure to compact surface layer. Enzymatic degradation and in vitro drug release results showed that the thermo-responsible surface layer greatly influenced the degradation of microspheres as well as the drug release behavior from microspheres. With the copolymerization of PNIPAM block into PCL-b-PEO copolymers, the drug release could be well regulated by changing temperatures and microspheres composition, which revealed the great potentials of microspheres with thermo-responsible surface for controlled drug release.     

Preparation of DNA-loaded polysulfone microspheres by liquid-liquid phase separation and its functional utilization

DNA-loaded polysulfone (PSf) microspheres were fabricated by means of a liquid-liquid phase separation technique. The porous microspheres were then used to remove DNA-binding intercalating materials--ethidium bromide, acridine orange, and endocrine disruptors. The DNA-loaded PSf microspheres are stable in water. The stability of the DNA-loaded microspheres and/or the release rate of DNA from the microspheres can be controlled by manipulating the microsphere structure. Increasing the polymer concentration, which causes lower porosity and smaller pores on the outer surface of the microspheres, led to increased stability of the microspheres and decreased release rate of DNA. Additionally, the drying temperature also affected the stability of the microspheres. The DNA-loaded PSf microspheres could effectively accumulate harmful DNA-intercalating pollutants and endocrine disruptors, such as ethidium bromide, acridine orange, biphenyl, dibenzofuran, and dibenzo-p-dioxin. The amount of pollutants removed by the microspheres is dependent on the amount of incorporated DNA and on the microsphere structure. The DNA-loaded microspheres have the potential to be used in environmental applications.     

Investigation of the degradation behaviour of poly(ethylene glycol-co-d,l-lactide) copolymer

The aim was to investigate the degradation behaviour of poly(ethylene glycol-co-d,l-lactide) (PEG-d,l-PLA) multiblock copolymer, in bulk and as microspheres, in aqueous medium. The degradation behaviour of PLA homopolymers in bulk and microspheres was evaluated as comparison.Microsphere preparation was performed by the double emulsion solvent evaporation method. Physical-chemical characterization of the raw polymers and the microspheres was performed by nuclear magnetic resonance (NMR) and modulated differential scanning calorimetry (MDSC). Polymer molecular weight, before and after incubation in aqueous environment, was evaluated by GPC; water uptake and mass loss were determined gravimetrically.The presence of PEG segments inside PLA chains gave a characteristic spongy structure to the microspheres. A significant increase in polymer T_g values was found for the microsphere formulations compared to polymer in bulk. After 63 days of incubation in the aqueous environment, the PEG-d,l-PLA microspheres achieved an average M_w reduction of 47% compared to 20% for PLA microspheres. The corresponding M_w decrease of the polymers in bulk was significantly higher: 72% and 41% for PEG-d,l-PLA and PLA, respectively.The data show how the degradation behaviour of polymer in bulk in an aqueous environment is significantly different from the behaviour of the corresponding microspheres. These results highlight the importance of performing a thorough physical-chemical characterization on microsphere formulations.     

Graft copolymers having hydrophobic backbone and hydrophilic branches. X. Preparation and properties of water-dispersible polyanionic microspheres having poly(methacrylic acid) branches on their surfaces

The free radical copolymerization of poly(t-butyl methacrylate) (PBMA) macromonomer with styrene in ethanol give monodispersed microspheres with 0.8-1.6 μm diameter. The resulting microspheres were treated with HCl solution to convert into anionic microspheres having poly(methacrylic acid) chains. ESCA analysis of the microsphere surface suggested that PBMA chains were favorably located on the surface of the microspheres. The particle size of the microspheres decreased with increasing molecular weight and concentration of the macromonomer. Water dispersibilities of the microspheres were evaluated by measuring the relative turbidity of the suspension of microspheres as a function of pH. The results show that they were strongly dependent on pH. © 1995 John Wiley & Sons, Inc.     

Biodegradation of polyurethanes and nanocomposites to non-cytotoxic degradation products

Polyurethanes with controllable biodegradable properties have been considered for biomedical applications. However, the potential toxicity of their biodegraded by-products is still a concern. In this study, biodegradable polyurethanes based on poly(?-caprolactone) (PCL) and/or poly(ethylene glycol) as soft segments and biodegradable polyurethanes containing montmorillonite nanoparticles were synthesized and were subjected to in vitro biodegradation for 4 months. The post-degraded polyurethanes and nanocomposites were characterized by infrared spectroscopy (FTIR), X-ray diffraction (XRD) and small angle X-ray scattering (SAXS). The toxicity of the biodegradation by-products was evaluated by measuring their effect on the viability of retinal cells. FTIR results indicated that hard segments of the biomaterials were preserved during biodegradation, and suggested that the ester bonds of the PCL incorporated into the soft segments were hydrolytic broken. XRD data indicated also that the soft segments crystallized as a result of the hydrolysis of PCL ester bonds and re-organization of the amorphous phase during annealing at 37 °C. As the biodegradation of the biomaterials induced the formation of soft segment lamella crystals, a complex nanostructure was formed, resulting in the enhancement of the small angle X-ray scattering. The by-products were non-cytotoxic to the retinal cells. These results suggest that the hydrolytic unstable polyurethanes and nanocomposites can be possible candidates for ophthalmological applications.     

Synthesis of polymeric microspheres from a Merrifield resin by surface‐initiated nitroxide‐mediated radical polymerization

Polymeric microspheres were prepared from a Merrifield resin via nitroxide‐mediated radical polymerization. Polystyrene, poly(acetoxystyrene), and poly[styrene‐b‐(methyl methacrylate‐co‐styrene)], poly(acetoxystyrene‐b‐styrene), and poly(styrene‐co‐2‐hydroxyethyl methacrylate) copolymers were demonstrated to graft onto 2,2,6,6‐tetramethyl‐1‐piperidinyloxy nitroxide bound Merrifield resins. The polymerization control was enhanced both on the surface and in solution by the addition of sacrificial nitroxide. The significant increase in the particle diameter (more than a fivefold volume increase for polystyrene brushes) showed that polymer growth was not only on the surface but also within the particles, and this diameter increase could be adjusted through changes in the molecular weight of the polymers. The microspheres were characterized by elemental analysis, IR spectroscopy, particle size analysis, and optical microscopy. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 2145–2154, 2005     

Polyester scaffolds with bimodal pore size distribution for tissue engineering

This paper presents a method for the preparation of porous poly(L-lactide)/poly[(L-lactide)-co-glycolide] scaffolds for tissue engineering. Scaffolds were prepared by a mold pressing-salt leaching technique from structured microparticles. The total porosity was in the range 70-85%. The pore size distribution was bimodal. Large pores, susceptible for osteoblasts growth and proliferation had the dimensions 50-400 microm. Small pores, dedicated to the diffusion of nutrients or/and metabolites of bone forming cells, as well as the products of hydrolysis of polyesters from the walls of the scaffold, had sizes in the range 2 nm-5 microm. The scaffolds had good mechanical strength (compressive modulus equal to 41 MPa and a strength of 1.64 MPa for 74% porosity). Scaffolds were tested in vitro with human osteoblast-like cells (MG-63). It was found that the viability of cells seeded within the scaffolds obtained using the mold pressing-salt leaching technique from structured microparticles was better when compared to cells cultured in scaffolds obtained by traditional methods. After 34 d of culture, cells within the tested scaffolds were organized in a tissue-like structure. Photos of section of macro- and mesoporous PLLA/PLGA scaffold containing 50 wt.-% of PLGA microspheres after 34 d of culture. Dark spots mark MG-63 cells, white areas belong to the scaffold. The specimen was stained with haematoxylin/eosin. Bar = 100 microm.     

Poly(vinylphosphonate)s functionalized polymer microspheres via rare earth metal‐mediated group transfer polymerization

We demonstrate a facile, yet efficient method for the functionalization of crosslinked polystyrene (PS) microspheres with biocompatible poly(vinylphosphonate)s via the combination of a UV grafting polymerization and a surface‐initiated group transfer polymerization. Self‐initiated photografting and photopolymerization of ethylene glycol dimethacrylate results in direct photografting of poly(ethylene glycol dimethacrylate) on the PS microspheres with dangling methacrylate functionalities, which are used to immobilize ytterbocene complexes to form the surface‐bound rare‐earth metal catalyst system. The surface‐initiated GTP of dialkyl vinylphosphonates from the initiator system leads to the functionalization of PS microspheres with poly(vinylphosphonate) brushes. Polymerization kinetic investigation indicates that surface‐initiated GTP leads to a constant and remarkably rapid weight gain of the microsphere (a microsphere weight increase of 600% within 3 min), owing to the highly living and efficient character of GTP. The surface‐initiated GTP occurring inside the microsphere causes an accumulation of the tension between the polymer chains in the microsphere, which eventually induces fracture of the microsphere for longer polymerization time. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 2919–2925     

Encapsulation and release of biomolecules from Ca-P/PHBV nanocomposite microspheres and three-dimensional scaffolds fabricated by selective laser sintering

This study focused on the fabrication of calcium phosphate (Ca-P)/poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanocomposite scaffolds loaded with biomolecules using the selective laser sintering (SLS) technique and their evaluation. Ca-P/PHBV nanocomposite microspheres loaded with bovine serum albumin (BSA) as the model protein were fabricated using the double emulsion solvent evaporation method. The encapsulation efficiency of BSA in PHBV polymer microspheres and Ca-P/PHBV nanocomposite microspheres were 18.06 ± 0.86% and 24.51 ± 0.60%, respectively. The BSA loaded Ca-P/PHBV nanocomposite microspheres were successfully produced into three-dimensional porous scaffolds with good dimensional accuracy using the SLS technique. The nanocomposite microspheres served as protective carriers and maintained the bioactivity of BSA during SLS. The effects of SLS parameters such as laser power and scan spacing on the encapsulation efficiency of BSA in the scaffolds and in vitro BSA release were studied. An initial burst release was observed, which was followed by a slow release of BSA. After 28-day release, The PHBV matrix was slightly degraded after 28-day in vitro release study. It was shown that nanocomposite scaffolds with controlled architecture obtained via SLS could be incorporated with biomolecules, enhancing them with more functions for bone tissue engineering application or making them suitable for localized delivery of therapeutics.     

Surface modification of microspheres with steric stabilizing and cationic polymers for gene delivery

In this paper, we describe surface modification of poly( D,L-lactide- co-glycolide) (PLG) microspheres, intended for DNA vaccine application, with two functionalities: a steric stabilizing component, provided by poly(vinyl alcohol) (PVA) and a cationic component, aimed at subsequent DNA surface loading. The cationic functionality arises from polycations, such as PEI, poly( L-lysine), trimethyl chitosan, and (dimethylamino)ethyl methacrylate, introduced into the water phase of classical oil-in-water (o/w) solvent evaporation method of PLG microsphere fabrication. By systematic evaluation of production variables, a system was produced with balanced properties in terms of microsphere size appropriate for uptake by antigen presenting (e.g., dendritic) cells, colloidal stability, and relatively high DNA loading. The polycation (PEI) molecular weight and preparation concentration were both found to increase the surface polycation content and DNA binding capacity; however, they lead to an increased tendency for aggregation, particularly when the microsphere size was decreased. DNA loading of almost 100% efficiency was achieved under optimized conditions in physiologically acceptable buffers, resulting in a surface DNA loading appropriate for vaccine purposes. A further increase in surface DNA loading was however associated with an increase in the particles negative potential, indicating the surface presence of DNA charges not neutralized by the polycation and hence potentially not protected from in vivo enzymatic degradation. The internalization of surface-loaded DNA into the target cells was confirmed by monitoring fluorescent DNA after the microspheres were endocytosed by the cells in culture.     

Hierarchical structure microspheres of PCL block copolymers via electrospraying as coatings for fabric with mechanical durability and self‐cleaning ability

The various morphology and structure microspheres were fabricated via one‐step single‐solvent electrospraying of hydrophilic and hydrophobic block modified copolymer of polycaprolactone (PCL). A honeycomb‐like hierarchical structure microspheres of PCL‐b‐PTFOA(4h) and abundant nanometer pores of PCL‐b‐PEG400 microspheres were obtained due to the solvent evaporation, thermally and polymer diffusion‐induced phase separation effect. Furthermore, a superhydrophobic coatings and robust superhydrophobic‐coated cotton woven fabric surfaces were prepared by using PCL‐b‐PTFOA(4h) microspheres with hierarchical structure and low surface energy. The contact angle (CA) and sliding angle (SA) of PCL‐b‐PTFOA(4h) microspheres‐coated cotton woven fabric surfaces reached 164.4 ± 5.5° and 6.8 ± 0.5°, respectively, which allows for self‐cleaning. The self‐cleaning test demonstrated that the coated superhydrophobic surface could shed aqueous dyes and dust without any trace. The superhydrophobic‐coated fabric shows good soaping fastness against mechanical abrasion without significant reduction of CA. This electrospraying coating of block copolymers can provide a simple, facile, and promising technique for producing multifunctional textiles.