Pluronic嵌段共聚物F127胶团对布洛芬的增溶(英文)

研究了PluronicF127胶团溶液对药物布洛芬(IBU)的增溶作用.通过芘探针荧光法测定了不同温度下F127在水溶液和0.01mo·lL-1pH7.4磷酸盐缓冲生理(PBS)溶液中的临界胶束浓度(cmc),采用高效液相色谱(HPLC)测定了F127溶液中布洛芬的溶解度,并依据公式计算了增溶参数(摩尔增溶量c和胶团-水分配系数K),考察了温度、溶剂和F68的加入对F127胶团化行为及其对布洛芬增溶作用的影响.结果表明:布洛芬的溶解度随F127质量分数的提高线性增加;随着温度升高,cmc急剧下降,胶团内核的疏水性增强,χ和K稍有增大;与水溶液相比,在PBS溶液中cmc减小,χ几乎不变,K显著降低;F68的加入对F127胶团的性质几乎无影响,对增溶的影响也不明显.对增溶参数的分析表明,K反映的是药物布洛芬的性质,χ则可反映嵌段共聚物F127的溶解效能,并证实了布洛芬是通过F127胶团的内核和栅栏层而实现增溶的.     

Synthesis and characterization of amphiphilic fluorinated pentablock copolymers based on Pluronic F127

The synthesis and self‐assembly behavior of pentablock copolymers consisting of Pluronic F127 (PEO₁₀₀‐PPO₆₅‐PEO₁₀₀) and poly(2, 2, 3, 3, 4, 4, 5, 5‐octafluoropentyl methacrylate) (POFPMA) is herein described. Using the difunctional potassium alcoholate of F127, K⁺O^–‐(PEO₁₀₀‐PPO₆₅‐PEO₁₀₀)‐O^–K⁺, as the macroinitiator, the POFPMA‐F127‐POFPMA pentablock copolymers were synthesized via oxyanion‐initiated polymerization. The chain length of POFPMA can be controlled by the original molar ratio of macroinitiator to OFPMA monomer, that is, F‐monomer. The composition and chemical structure of POFPMA‐F127‐POFPMA pentablock copolymers have been characterized by FTIR, ¹HNMR, and ¹⁹F NMR spectroscopy, and gel permeation chromatography techniques. The solution behavior of POFPMA‐F127‐POFPMA copolymers was investigated by the methods of surface tension, cloud point, transmission electron microscopy, and high performance particle sizer (HPPS). The results indicate that these Pluronic F127‐based block copolymers modified with fluorinated segments possess relatively high surface activity and low cloud points, depending on various factors, such as the length of fluorinated block, the concentration of the copolymers in aqueous solution, and the adscititious inorganic salt. TEM measurements showed that the pentablock copolymers can self‐assemble in aqueous solution to form various micellar morphologies. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 3029–3041, 2008     

Effect of poly(γ‐glutamic acid) on the gelation of Pluronic F127

The gelation of Pluronic F127 aqueous solution was investigated in the presence of sodium poly(γ‐glutamate) (PGA). The gelation temperature was determined based on the tube inversion technique. The gelation temperature increased greatly when the ratio of PGA to F127 was 0.2, and then decreased at higher ratios. The enthalpy of gelation (ΔH_gel) was calculated based on the model of Eldridge and Ferry. A splitting in the model was observed when the PGA/F127 ratio was 0.2 which yielded both a maximum and a minimum of ΔH_gel. These results indicate that PGA can significantly affect the gelation of F127. Copyright © 2008 John Wiley & Sons, Ltd.     

含叶酸功能端基Pluronic F127的合成及其在水中的形态

通过一系列反应将三嵌段共聚物Pluronic F127的端羟基转变为氨基。利用氨基化F127大单体,最终成功的将生物活性大分子叶酸接到了F127端基上(F127-Folate) 作为靶向配体。利用1H-NMR对嵌段共聚物的结构进行了表征。用透析法制备胶束溶液,利用TEM研究了F127-Folate在水溶液中的自组装形态,结果表明F127-Folate正在水溶液中自组装形成纳米胶束。     

Electroactive 3D Scaffolds Based on Silk Fibroin and Water‐Borne Polyaniline for Skeletal Muscle Tissue Engineering

Silk fibroin (SF) with good biocompatibility and degradability has great potential for tissue engineering. However, the SF based scaffolds lack the electroactivity to regulate the myogenic differentiation for the regeneration of muscle tissue, which is sensitive to electrical signal. Herein, a series of electroactive biodegradable scaffolds based on SF and water‐soluble conductive poly(aniline‐co‐N‐(4‐sulfophenyl) aniline) (PASA) via a green method for skeletal muscle tissue engineering are designed. SF/PASA scaffolds are prepared by vortex of aqueous solution of SF and PASA under physiological condition. Murine‐derived L929 fibroblast and C2C12 myoblast cells are used to evaluate cytotoxicity of SF/PASA scaffolds. Moreover, myogenic differentiation of C2C12 cells is investigated by analyzing the morphology of myotubes and related gene expression. These results suggest that electroactive SF/PASA scaffolds with a suitable microenvironment, which can enhance the myogenic differentiation of C2C12 cells, have a great potential for skeletal muscle regeneration.     

Effect of Pluronic F127 on the pore structure of macrocellular biodegradable polylactide foams

Thermally induced phase separation technique was utilized to fabricate biodegradable poly(l ‐lactic acid) (PLLA) macrocellular foams which were capable of being applied in tissue engineering. The block copolymer Pluronic F127 composed of (polyethyleneoxide)‐(polypropyleneoxide)‐(polyethyleneoxide) [(PEO)‐(PPO)‐(PEO)] was used as a porogen. Water/dioxane mixtures with different volume ratios were used as solvents. The addition of Pluronic F127 could induce an appearance of large pores (50–200 μm) besides small pores (10–20 μm) or a change from a solid–liquid phase separation to a liquid–liquid phase separation. The role of Pluronic F127 depends on the water/dioxane ratios in the PLLA/dioxane/water system. The X‐ray diffraction patterns and porosity measurement results showed that Pluronic F127 was crystallized and existed on the pore wall. The effect of Pluronic F127 on changing pore structure is attributed to the occurrence of the interaction of the lipophilic PPO blocks in Pluronic F127 with PLLA clews, consequently, this results in PLLA aggregation and early phase separation on cooling. Copyright © 2004 John Wiley & Sons, Ltd.     

Cell‐Laden Hydrogels for Multikingdom 3D Printing

Living materials are created through the embedding of live, whole cells into a matrix that can house and sustain the viability of the encapsulated cells. Through the immobilization of these cells, their bioactivity can be harnessed for applications such as bioreactors for the production of high‐value chemicals. While the interest in living materials is growing, many existing materials lack robust structure and are difficult to pattern. Furthermore, many living materials employ only one type of microorganism, or microbial consortia with little control over the arrangement of the various cell types. In this work, a Pluronic F127‐based hydrogel system is characterized for the encapsulation of algae, yeast, and bacteria to create living materials. This hydrogel system is also demonstrated to be an excellent material for additive manufacturing in the form of direct write 3D‐printing to spatially arrange the cells within a single printed construct. These living materials allow for the development of incredibly complex, immobilized consortia, and the results detailed herein further enhance the understanding of how cells behave within living material matrices. The utilization of these materials allows for interesting applications of multikingdom microbial cultures in immobilized bioreactor or biosensing technologies.     

All‐in‐One Cellulose Nanocrystals for 3D Printing of Nanocomposite Hydrogels

Cellulose nanocrystals (CNCs) with >2000 photoactive groups on each can act as highly efficient initiators for radical polymerizations, cross‐linkers, as well as covalently embedded nanofillers for nanocomposite hydrogels. This is achieved by a simple and reliable method for surface modification of CNCs with a photoactive bis(acyl)phosphane oxide derivative. Shape‐persistent and free‐standing 3D structured objects were printed with a mono‐functional methacrylate, showing a superior swelling capacity and improved mechanical properties.     

Evaluation of 3D Printed Gelatin‐Based Scaffolds with Varying Pore Size for MSC‐Based Adipose Tissue Engineering

Adipose tissue engineering aims to provide solutions to patients who require tissue reconstruction following mastectomies or other soft tissue trauma. Mesenchymal stromal cells (MSCs) robustly differentiate into the adipogenic lineage and are attractive candidates for adipose tissue engineering. This work investigates whether pore size modulates adipogenic differentiation of MSCs toward identifying optimal scaffold pore size and whether pore size modulates spatial infiltration of adipogenically differentiated cells. To assess this, extrusion‐based 3D printing is used to fabricate photo‐crosslinkable gelatin‐based scaffolds with pore sizes in the range of 200–600 µm. The adipogenic differentiation of MSCs seeded onto these scaffolds is evaluated and robust lipid droplet formation is observed across all scaffold groups as early as after day 6 of culture. Expression of adipogenic genes on scaffolds increases significantly over time, compared to TCP controls. Furthermore, it is found that the spatial distribution of cells is dependent on the scaffold pore size, with larger pores leading to a more uniform spatial distribution of adipogenically differentiated cells. Overall, these data provide first insights into the role of scaffold pore size on MSC‐based adipogenic differentiation and contribute toward the rational design of biomaterials for adipose tissue engineering in 3D volumetric spaces.     

Green Synthesis of Silver Nanoparticles Using Extract of Cilembu Sweet Potatoes (Ipomoea batatas L var. Rancing) as Potential Filler for 3D Printed Electroactive and Anti-Infection Scaffolds

Electroactive biomaterials are fascinating for tissue engineering applications because of their ability to deliver electrical stimulation directly to cells, tissue, and organs. One particularly attractive conductive filler for electroactive biomaterials is silver nanoparticles (AgNPs) because of their high conductivity, antibacterial activity, and ability to promote bone healing. However, production of AgNPs involves a toxic reducing agent which would inhibit biological scaffold performance. This work explores facile and green synthesis of AgNPs using extract of Cilembu sweet potato and studies the effect of baking and precursor concentrations (1, 10 and 100 mM) on AgNPs’ properties. Transmission electron microscope (TEM) results revealed that the smallest particle size of AgNPs (9.95 ± 3.69 nm) with nodular morphology was obtained by utilization of baked extract and ten mM AgNO₃. Polycaprolactone (PCL)/AgNPs scaffolds exhibited several enhancements compared to PCL scaffolds. Compressive strength was six times greater (3.88 ± 0.42 MPa), more hydrophilic (contact angle of 76.8 ± 1.7°), conductive (2.3 ± 0.5 × 10⁻³ S/cm) and exhibited anti-bacterial properties against Staphylococcus aureus ATCC3658 (99.5% reduction of surviving bacteria). Despite the promising results, further investigation on biological assessment is required to obtain comprehensive study of this scaffold. This green synthesis approach together with the use of 3D printing opens a new route to manufacture AgNPs-based electroactive with improved anti-bacterial properties without utilization of any toxic organic solvents.     

Facile Synthesis of Cellulose Acetate Ultrafiltration Membrane with Stimuli‐Responsiveness to pH and Temperature Using the Additive of F127‐b‐PDMAEMA

We fabricate a novel cellulose acetate (CA) ultrafiltration membrane modified by block copolymer F127‐b‐ PDMAEMA, which is synthesized using F127 and DMAEMA via the ARGET ATRP method. Compared to conventional ultrafiltration membranes, the incorporation of both F127 and PDMAEMA can not only readily increase the hydrophilicity of the membrane, but also exhibit stimuli‐responsiveness to temperature and pH. Fourier transform infrared spectroscopy (FT‐IR), nuclear magnetic resonance spectroscopy (NMR), and gel permeation chromatography (GPC) are employed to analyze the structure of the F127‐b‐PDMAEMA. The membrane properties are evaluated via scanning electron microscope (SEM) imaging, porosity test, automatic target recognition Fourier transform infrared spectroscopy (ATR‐FTIR), water contact angle test and permeation test. The results indicate that the F127‐b‐PDMAEMA is an excellent pore agent, which contributes to an enhancement of the membrane in sensitivity to temperature and pH. The modified membrane also exhibits lower water contact angle (64.5°), which is attributed to the good anti‐fouling performance and high water permeation.     

3D Printing of Silk Protein Structures by Aqueous Solvent‐Directed Molecular Assembly

Hierarchical molecular assembly is a fundamental strategy for manufacturing protein structures in nature. However, to translate this natural strategy into advanced digital manufacturing like three‐dimensional (3D) printing remains a technical challenge. This work presents a 3D printing technique with silk fibroin to address this challenge, by rationally designing an aqueous salt bath capable of directing the hierarchical assembly of the protein molecules. This technique, conducted under aqueous and ambient conditions, results in 3D proteinaceous architectures characterized by intrinsic biocompatibility/biodegradability and robust mechanical features. The versatility of this method is shown in a diversity of 3D shapes and a range of functional components integrated into the 3D prints. The manufacturing capability is exemplified by the single‐step construction of perfusable microfluidic chips which eliminates the use of supporting or sacrificial materials. The 3D shaping capability of the protein material can benefit a multitude of biomedical devices, from drug delivery to surgical implants to tissue scaffolds. This work also provides insights into the recapitulation of solvent‐directed hierarchical molecular assembly for artificial manufacturing.     

On‐Demand Production of Flow‐Reactor Cartridges by 3D Printing of Thermostable Enzymes

The compartmentalization of chemical reactions is an essential principle of life that provides a major source of innovation for the development of novel approaches in biocatalysis. To implement spatially controlled biotransformations, rapid manufacturing methods are needed for the production of biocatalysts that can be applied in flow systems. Whereas three‐dimensional (3D) printing techniques offer high‐throughput manufacturing capability, they are usually not compatible with the delicate nature of enzymes, which call for physiological processing parameters. We herein demonstrate the utility of thermostable enzymes in the generation of biocatalytic agarose‐based inks for a simple temperature‐controlled 3D printing process. As examples we utilized an esterase and an alcohol dehydrogenase from thermophilic organisms as well as a decarboxylase that was thermostabilized by directed protein evolution. We used the resulting 3D‐printed parts for a continuous, two‐step sequential biotransformation in a fluidic setup.     

3D X‐Ray Nanotomography of Cells Grown on Electrospun Scaffolds

Here, it is demonstrated that X‐ray nanotomography with Zernike phase contrast can be used for 3D imaging of cells grown on electrospun polymer scaffolds. The scaffold fibers and cells are simultaneously imaged, enabling the influence of scaffold architecture on cell location and morphology to be studied. The high resolution enables subcellular details to be revealed. The X‐ray imaging conditions were optimized to reduce scan times, making it feasible to scan multiple regions of interest in relatively large samples. An image processing procedure is presented which enables scaffold characteristics and cell location to be quantified. The procedure is demonstrated by comparing the ingrowth of cells after culture for 3 and 6 days.

     

Polypropylene Copolymers Designed for Fused Filament Fabrication 3D‐Printing

Several chemical properties which influence the printability for fused filament fabrication 3D‐printing are derived from analyses of commercially available filaments. In preliminary experiments, polymerization conditions are optimized and suitable monomers and selectivity control agents (donors) are selected. An experimental series in which propene is copolymerized with the comonomers 1‐butene and 1‐hexene with an industrial Ziegler–Natta catalyst will be discussed here. The experiments are planned using design of experiments. Based on a split‐plot design, the design is adapted for mixtures and the combination of homo‐ and copolymerization. The observed factors, besides the mixture composition, are hydrogen partial pressure and the amount of donor. The obtained polymers are analyzed by means of high‐temperature size exclusion chromatography, differential scanning calorimetry, and rheology. 1‐Butene copolymers show good printing results and promising properties almost matching the desired ones. The targeted polymer properties are achieved within certain limits. 1‐Hexene copolymers result in lower molecular masses while crystallinity remains slightly higher, which does not match with the desired profile. Beneficial properties are likely to be achieved within a wider factor range, for example, higher comonomer amount and lower hydrogen partial pressure.     

Chitosan and Whey Protein Bio-Inks for 3D and 4D Printing Applications with Particular Focus on Food Industry

The application of chitosan (CS) and whey protein (WP) alone or in combination in 3D/4D printing has been well considered in previous studies. Although several excellent reviews on additive manufacturing discussed the properties and biomedical applications of CS and WP, there is a lack of a systemic review about CS and WP bio-inks for 3D/4D printing applications. Easily modified bio-ink with optimal printability is a key for additive manufacturing. CS, WP, and WP–CS complex hydrogel possess great potential in making bio-ink that can be broadly used for future 3D/4D printing, because CS is a functional polysaccharide with good biodegradability, biocompatibility, non-immunogenicity, and non-carcinogenicity, while CS–WP complex hydrogel has better printability and drug-delivery effectivity than WP hydrogel. The review summarizes the current advances of bio-ink preparation employing CS and/or WP to satisfy the requirements of 3D/4D printing and post-treatment of materials. The applications of CS/WP bio-ink mainly focus on 3D food printing with a few applications in cosmetics. The review also highlights the trends of CS/WP bio-inks as potential candidates in 4D printing. Some promising strategies for developing novel bio-inks based on CS and/or WP are introduced, aiming to provide new insights into the value-added development and commercial CS and WP utilization.     

Wet 3‐D printing of epoxy cross‐linked chitosan/carbon microtube composite

Over the last decays, the use of conductive biopolymer composites has been growing in areas such as biosensors, soft robotics, and wound dressing applications. They are generally soft hydrophilic materials with good elastic recovery and compatible with biological environments. However, their application and removal from the host are still challenging mainly due to poor mechanical strength. This work displays a technique for the fabrication of complex‐shaped conductive structures with improved mechanical strength by wet three‐dimensional (3‐D) printing, which uses a coagulation bath to quickly solidify an epoxy cross‐linked chitosan/carbon microtube composite ink. The fabricated conductive structure demonstrated higher elongation strength and improved elastic stability upon the introducing of polypropylene glycol diglycidyl ether (PPGDGE) as the epoxy cross‐linker, which can be due to the formation of networks between oxiran groups of PPGDGE and chitosan amino groups.     

Direct Ink 3D Printing of Porous Carbon Monoliths for Gas Separations

Additive manufacturing or 3D printing is the advanced method of manufacturing monolithic adsorbent materials. Unlike beads or pellets, 3D monolithic adsorbents possess the advantages of widespread structural varieties, low heat and mass transfer resistance, and low channeling of fluids. Despite a large volume of research on 3D printing of adsorbents having been reported, such studies on porous carbons are highly limited. In this work, we have reported direct ink 3D printing of porous carbon; the ink consisted of commercial activated carbon, a gel of poly(4-vinylphenol) and Pluronic F127 as plasticizer, and bentonite as the binder. The 3D printing was performed in a commercial 3D printer that has been extensively modified in the lab. Upon 3D printing and carbonization, the resultant 3D printed porous carbon demonstrated a stable structure with a BET area of 400 m²/g and a total pore volume of 0.27 cm³/g. The isotherms of six pure-component gases, CO₂, CH₄, C₂H₆, N₂, CO, and H₂, were measured on this carbon monolith at 298 K and pressure up to 1 bar. The selectivity of four gas pairs, C₂H₆/CH₄, CH₄/N₂, CO/H₂, and CO₂/N₂, was calculated by Ideally Adsorbed Solution Theory (IAST) and reported. Ten continuous cycles of adsorption and desorption of CO₂ on this carbon confirmed no loss of working capacity of the adsorbent.     

A new Phosphorylated Polysaccharide for Biomedical Applications: Generation of 3D Scaffolds with Osteogenic Activity and Coating of Titanium Oxide Surfaces

Summary: A new phosphorylated derivative of carboxymethylcellulose and amidic carboxymethylcellulose containing one phosphate group for each disaccharide unit was synthesized using sodium trimetaphospahte (STMP) as the phosphating agent. The new polysaccharide was characterized by infrared spectroscopy (FT-IR) and the amount of phosphate groups was determined by elemental analysis. These modified polysaccharides were used both to prepare 3D scaffolds and functionalize titanium oxide surfaces with the aim to improve the osseointegration with the host tissue. The presence of phosphate groups modify the physical-chemical properties of the hydrogels with respect to the native ones. The evaluation of the bioactivity of the phosphorylated carboxymethylcellulose hydrogels towards osteoblast-like cells showed a significant increase in the osteocalcin production. The modified surfaces were chemically characterized by means of X-ray photoelectron spectroscopy (XPS) and FT-IR, whereas the surface topography was analysed by Atomic Force Measurements (AFM) measurements before and after the polysaccharide coating. In vitro biological tests using osteoblast-like cells demonstrated that phosphorylated carboxymethylcellulose functionalized TiO₂ surfaces promoted better cell adhesion and significantly enhanced their proliferation. These findings suggest that the phosphate polysaccharide both as a 3D scaffold and as a surface coating promotes osteoblast growth potentially improving the biomaterial osseointegration rate.     

Acrylic‐Acid‐Functionalized PolyHIPE Scaffolds for Use in 3D Cell Culture

This study describes the development of a functional porous polymer for use as a scaffold to support 3D hepatocyte culture. A high internal phase emulsion (HIPE) is prepared containing the monomers styrene (STY), divinylbenzene (DVB), and 2‐ethylhexyl acrylate (EHA) in the external oil phase and the monomer acrylic acid (Aa) in the internal aqueous phase. Upon thermal polymerization with azobisisobutyronitrile (AIBN), the resulting porous polymer (polyHIPE) is found to have an open‐cell morphology and a porosity of 89%, both suitable characteristics for 3D cell scaffold applications. X‐ray photo­electron spectroscopy reveals that the polyHIPE surface contained 7.5% carboxylic acid functionality, providing a useful substrate for subsequent surface modifications and bio‐conjugations. Initial bio‐compatibility assessments with human hepatocytes show that the acid functionality does not have any detrimental effect on cell adhesion. It is therefore believed that this material can be a useful precursor scaffold towards 3D substrates that offer tailored surface functionality for enhanced cell adhesion.