Isothermal crystallization kinetics and morphology of biodegradable poly(3-hydroxybutyrate-co-4-hydroxybutyrate)

Isothermal crystallization kinetics and morphology of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) [P(3HB-co-4HB)] with different 4-hydroxybutyrate (4HB) molar fraction were investigated by differential scanning calorimetry (DSC), wide angle X-ray diffraction (WAXD), and polarized optical microscopy (POM). The results show that the crystallization mechanism and crystal structure of P(3HB-co-4HB) copolymers are the similar as those of poly(3-hydroxybutyrate) (PHB). While the equilibrium melting point and crystallization rate decrease with the increase of 4HB molar fraction. Banded spherulites are observed in neat PHB and P(3HB-co-4HB) copolymers, and morphology is influenced apparently by the crystallization temperature and 4HB unit.     

Novel Biodegradable and Biocompatible Poly(3‐hydroxyoctanoate)/Bacterial Cellulose Composites

Novel poly(3‐hydroxyoctanoate), P(3HO), and bacterial cellulose composites have been developed. P(3HO) is hydrophobic in nature whereas bacterial cellulose is extremely hydrophilic in nature. Therefore, homogenized bacterial cellulose has been chemically modified in order to achieve compatibility with the P(3HO) matrix. Modified bacterial cellulose microcrystals and P(3HO) have been physically blended and solvent casted into two‐dimensional composite films. Mechanical characterization shows that the Young's modulus of the P(3HO)/bacterial cellulose composites is significantly higher in comparison to the neat P(3HO) film. The melting temperature (T_m) of the composites is lower while the glass transition temperature (T_g) is higher than the neat P(3HO) film. Also, the composite film has a rougher surface topography as compared to the neat P(3HO) film. A month's in vitro degradation study has been carried out in Dulbeccos modified eagle medium and in phosphate buffer saline. The incorporation of modified bacterial cellulose microcrystal in the P(3HO) film has increased the degradability of the composite film. Finally, in vitro biocompatibility studies using human microvascular endothelial cells established the biocompatibility of the P(3HO)/bacterial cellulose microcrystal films. The cell proliferation was 50–110% higher on the P(3HO)/bacterial cellulose composites as compared to the neat P(3HO) film. Hence, in this study, for the first time, P(3HO)/bacterial cellulose composites have been developed. The addition of bacterial cellulose has resulted in properties that are highly desirable for medical applications including the development of biodegradable stents.     

The surface modification of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) copolymers to improve the attachment of urothelial cells

Biocompatible and biodegradable poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) [P(HB-co-HHx)] substrates were modified to improve the attachment of porcine urothelial cell culture. The pristine copolymer exhibits excellent mechanical properties to replace the bladder tissue, but its surface lacks chemical functionalities to interact with cells. Thus, wet chemical treatments based on NaOH and ethylenediamine in aqueous [ED(aq)] and isopropanol [ED(isoOH)] media to functionalize the P(HB-co-HHx) films surfaces were compared. Among these treatments, short ED(aq) treatment was able to decrease the hydrophobicity, rendering a surface with amino groups and without a significant alteration of the mechanical properties. Furthermore, to enhance the interaction with urothelial cells, laminin derived YIGSR sequence was covalently bound to these amino functionalized substrates. The focal attachment was clearly improved with this last treatment, comparing with those results found with the unmodified and first-step functionalized P(HB-co-HHx).     

A comparative investigation of biodegradable polyhydroxyalkanoate films as matrices for in vitro cell cultures

The paper describes the production and investigation of flexible films made of high-purity polyhydroxyalkanoates (PHAs)--polyhydroxybutyrate [poly-(3HB)] and poly-3-hydroxybutyrate-co-poly-3-hydroxyvalerate [poly(3HB-co-3HV)], containing 4-30 mol % hydroxyvalerate. Poly(3HB-co-3HV) films have a more porous structure than poly-(3HB) films, which are more compact, but their surface properties, such as wettability and surface and interface energies, are the same. Sterilisation of the PHA films by conventional methods (heat treatment and gamma-irradiation) did not impair their strength. Cells cultured on PHA films exhibited high levels of cell adhesion. Cell morphology, protein synthesis and DNA synthesis were estimated by extent of 3H-thymidine incorporation into the animal cell cultures of various origins (fibroblasts, endothelium cells, and isolated hepatocytes) in direct contact with PHAs. The investigation showed that this material can be used to make matrices for in vitro proliferous cells. The investigated properties of poly-(3HB) and poly(3HB-co-3HV) films proved to be fundamentally similar.     

Anti-fouling properties of polylactic acid film modified by pegylated phosphorylcholine derivatives

Anti-fouling properties are important for both pharmaceutical and biomedical applications of polylactic acid (PLA). In this study, highly hydrated hydrophilic bilayers containing phosphatidylcholine (PC) and polyethylene glycol (PEG) were applied to PLA films to prevent the protein adsorption and blood platelet adhesion. The PLA films were coated with three PLA copolymers of PC and PEG, namely, a PLA-b-PEG block copolymer with a PC group on the end of a PEG chain (PC-PEG-PLA), a poly[2-methacryloyloxyethyl phosphatidylcholine (MPC)]-PLA graft copolymer (PMPC-g-PLA), and a PMPC-PLA graft copolymer with PEG serving as a spacer (PMPC-g-(PEG-b-PLA)). The influence of the copolymer structure on the anti-fouling properties of PLA film was then investigated. The results showed that the introduction of PC and PEG polar copolymers decreased the water-contact angle (WCA) and increased the equilibrated degree of hydration (H_eq) of the PLA surface significantly. The PMPC-g-(PEG-b-PLA) copolymer achieved the lowest WCA value and the highest H_eq value as it provided a higher density of PC on the outer surface. In addition, the strong hydration of the PEG and PC groups efficiently suppressed the bovine serum albumin (BSA) and fibrinogen (Fg) adsorption and subsequently inhibited platelet adhesion. The above results demonstrated that a good “anti-fouling” surface layer on the PLA substrate could be achieved by a combination of PEG and PC in copolymers.     

Thermal degradation of poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) in nitrogen and oxygen studied by thermogravimetric-Fourier transform infrared spectroscopy

The thermal degradation behavior of poly(3-hydroxybutyrate) (PHB) and poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(HB-co-HHx), HHx=12 mol%) has been studied under different environmental conditions by thermogravimetric analysis (TGA) Fourier transform infrared (FT-IR) spectroscopy. It is reported that at higher temperature (>400 degrees C) carbon dioxide and propene are formed from the decomposition product crotonic acid in a nitrogen atmosphere, whereas in an oxygen atmosphere propene oxidizes in a further step to carbon dioxide, carbon monoxide and hydrogen. It was also found that PHB and P(HB-co-HHx) have a similar thermal degradation mechanism. The analysis of the FT-IR-spectroscopic data was performed with 2D and perturbation-correlation moving-window 2D (PCMW2D) correlation spectroscopy.     

Compositional study and cytotoxicity of biodegradable poly(ester urethane)s consisting of poly[(R)-3-hydroxybutyrate] and poly(ethylene glycol)

Biodegradable PHB–PEG multi-block polyurethane copolymers comprising PHB blocks (M_n: 1100, 1740 and 3240) and PEG blocks (M_n: 1960, 3250, 4150 or 7950) were synthesized followed by characterization by GPC, ¹H NMR, and FT-IR. The PHB contents ranged from 9 to 62% by weight. The copolymers displayed improved thermal stabilities compared with their respective precursors. The morphological structures of the copolymers were studied by FT-IR, DSC and XRD. FT-IR revealed the existence of amorphous and crystalline phases of PHB. Both DSC and XRD analyses showed that separate crystalline phases are formed by PEG and PHB blocks in the copolymers. Upon annealing, the melting transition temperature (T_m), melting enthalpy (ΔH_m) and the fractional crystallinity (X_c) of the PEG block increased when the length of PEG incorporated into the copolymer increased. These values were higher when the PHB block length is shorter as the shorter PHB chain does not disrupt the crystallization of PEG as much as the longer PHB chain. A similar disruptive effect on the crystallization of PHB segments was observed by varying PEG chain lengths but the effect is less pronounced compared with the PEG segments. A comparison of the swelling properties of the poly(ester urethane)s showed that the length and crystalline properties of the PHB block significantly affects the water uptake properties of the copolymers. The crystalline properties and the water uptake capacities of the copolymers could be fine-tuned by consideration of the length of the PHB and PEG block incorporated. The results of the cytotoxicity tests demonstrated that the poly(PHB/PEG) urethanes were non-cytotoxic and could potentially be used for biomedical purposes.     

聚氨基酸共聚物合成研究进展

聚氨基酸共聚物是一类新型生物降解高分子材料。文中简单综述了聚氨基酸-聚醚嵌段共聚物、聚氨基酸-甲壳素共聚物、聚氨基酸-硅氧烷共聚物和聚氨基酸-聚酯共聚物的合成方法。     

聚(3-羟基丁酸酯-co-4-羟基丁酸酯)@海藻酸钠复合纤维膜的制备及其对Pb2+和Cu2+的吸附性

采用三氯甲烷和N,N二甲基甲酰胺（DMF）为溶剂,制备聚（3-羟基丁酸酯-co-4-羟基丁酸酯）（P（3HB-co-4HB））纺丝溶液,并通过静电纺丝技术制备P（3HB-co-4HB）纳米纤维膜,用海藻酸钠（SA）对P（3HB-co-4HB）纳米纤维膜进行包覆,获得P（3HB-co-4HB）@SA复合纤维膜。利用SEM、比表面积仪、原子吸收光谱分别表征了P（3HB-co-4HB）@SA复合纤维膜的纤维形态、比表面积、溶液残留液离子浓度。结果表明:纺丝液浓度在12%时,P（3HB-co-4HB）纤维成纤性好;随着静电压增大,P（3HB-co-4HB）纤维直径先减小后增大。P（3HB-co-4HB）支架材料可以使SA的比表面积提高约3.9倍,P（3HB-co-4HB）@SA复合纤维膜对Cu2+离子、Pb2+离子最大吸附量分别为26.25 mg/g和36.25 mg/g,折算为SA的吸附量分别为364.58 mg/g和503.47 mg/g。      

GF/P(3HB-co-4HB)-PLA生物基复合材料的制备与性能

为了提高聚（3-羟基丁酸酯-co-4 羟基丁酸酯）-聚乳酸（P（3HB-co-4HB）-PLA）生物基共混材料的力学性能和尺寸稳定性,扩大应用领域,以P（3HB-co-4HB）和PLA共混物为基体,盐酸或偶联剂表面处理的玻璃纤维（GF）为增强材料,采用熔融共混法制备GF/P（3HB-co-4HB）-PLA复合材料。通过傅里叶变换红外光谱仪（FTIR）、扫描电子显微镜（SEM）、热失重分析仪（TGA）和万能电子拉力机等研究了GF表面处理方法对复合材料力学性能、热性能、尺寸稳定性及断面形态的影响。研究结果表明：表面改性GF的加入可显著提高P（3HB-co-4HB）-PLA共混材料的综合性能。经偶联剂表面接枝的GF可均匀分散在P（3HB-co-4HB）-PLA基体中并形成较强的界面结合。添加质量分数20%的偶联剂改性GF使复合材料的拉伸强度、弯曲强度、缺口冲击强度和硬度分别提高了29.38%、20.32%、41.38%和15.31%;初始热分解温度（IDT）和维卡软化温度（VST）分别提高了6.64 ℃和10.7 ℃;室温和60 ℃放置60 d后复合材料试样长度方向的尺寸稳定性分别提高了32.47%和33.70%。     

Preparation and characterization of poly(3-octylthiophene)/carbon fiber thermoelectric composite materials

Poly(3-alkylthiophene) (P3AT) with a high Seebeck coefficient has recently been reported. However, P3AT/inorganic conductive composites exhibit relatively poor thermoelectric performance because of their low electrical conductivity. In this work, carbon fiber sheets with a high electrical conductivity were chosen as the inorganic phase, and poly(3-octylthiophene)(P3OT)/carbon fiber composites were prepared by casting P3OT solution onto the carbon fiber sheets. The carbon fiber sheets incorporated into the composites can provide good electrical conductivity, and P3OT can provide a high Seebeck coefficient. The highest power factor of 7.05 μW m⁻¹ K⁻² was obtained for the composite with 50 wt% P3OT. This work suggests a promising method for preparing large-scale thermoelectric composites with excellent properties.     

成核剂对聚(3-羟基丁酸酯-co-4羟基丁酸酯)性能的影响

分别以氮化硼(BN)、BRUGGOLENP250、CaCO3和Tm-3为成核剂,用熔融模压法制备了聚(3-羟基丁酸酯-co-4羟基丁酸酯)[P(3HB-co-4HB)]样品,借用偏光显微镜(POM)、差示扫描量热(DSC)、热重分析(TGA)和扫描电镜(SEM)等考察了成核剂种类及用量对P(3HB-co-4HB)结晶形态、熔点、热分解温度、力学性能及断面形态的影响。结果表明,各种成核剂均能有效细化P(3HB-co-4HB)的球晶尺寸,提高其熔点及热分解温度;当成核剂BN的质量分数为5‰~8‰时,P(3HB-co-4HB)的综合性能最好。     

Dielectric behaviors of PHBHHx–BaTiO3 multifunctional composite films

Multifunctional polymeric composites were investigated for potential use in high energy storage capacitors and tissue engineering. The polymeric composites were fabricated by employing biodegradable polyester, poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx), as the matrix. Ferroelectric BaTiO₃ ceramic powders were added to the composites as fillers. The dielectric spectroscopy of the composites was measured over a wide frequency range (10⁰–10⁷ Hz) from −100 to 60 °C. The composition dependent dielectric behavior was modeled by a self-consistent effective medium theory. A percolation threshold of 0.367 was observed in the composites. The glass transition relaxation of the composite was also discussed by comparing the popular Vögel–Fulcher–Tammann law with a new glass model. The composites show attractive ferroelectricity and piezoelectricity for biomedical applications.     

Microbial synthesis and enzymatic degradation of renewable poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate]

This paper reports our recent progress on a microbial system for efficient production of biodegradable copolyester of poly[(R)-3-hydroxybutyrate-co-(R)-3-hydroxyhexanoate], P(3HB-co-3HHx), with desirable copolymer compositions using genetically engineered bacteria. We have developed a fermentation technique to achieve high cell density cultivation of a recombinant Ralstonia eutropha using inexpensive soybean oil as a sole carbon source. In addition, we demonstrate that the use of polyhydroxyalkanoate (PHA) synthase (PhaC) mutants having an amino acid substitutions is able to vary the copolymer composition of P(3HB-co-3HHx) synthesized from soybean oil by the recombinant bacteria. On the other hand, it is also important to understand the enzymatic degradation process of PHA materials for establishing a method to regulate the rate of biodegradation. The enzymatic degradation process of P(3HB-co-3HHx) thin film using an extracellular PHB depolymerase has been studied by in situ atomic force microscopy in buffer solution. We demonstrate that the PHA depolymerase predominantly degrades the less-ordered molecular chain-packing regions along the crystallographic a-axis.     

Synthesis and physicochemical characterization of copolymers of 3-octylthiophene and thiophene functionalized with azo chromophore

Polythiophene derivatives with azo chromophore were synthesized via copolymerization of 3-octylthiophene (3OT) and 2-[N-ethyl-N-[4-[(4-nitrophenyl)azo]phenyl]amino]ethyl 3-thienylacetate (3-DRT). This copolymer has interesting optoelectronic properties and a variety of applications such as electrochromic and electronic devices. The polymerization process of 3OT and the functionalized thiophene was carried out via FeCl₃ oxidative polymerization. Thin films of poly(3OT-co-3-DRT) copolymer were prepared by spin-coating technique from toluene. FTIR and ¹H NMR spectroscopy revealed the presence of chromophore groups in the copolymer chain. Molecular weight and polydispersity of the polymers were measured by size exclusion chromatography. Changes in the surface topography of copolymers were analyzed by atomic force microscopy; the results showed that the copolymers presented some protuberances of variable size unlike the homogeneous granular morphology of P3OT. It is believed that these changes appeared by the incorporation of 3-DRT in the polymer. P3ATs are electrochromic materials that show color change upon oxidation-reduction process. We report that electrochemical characterization of poly(3OT-co-3-DRT) copolymer films synthesized chemically on indium-tin oxide (ITO) glass substrates showed an additional color to the P3OT homopolymer. Optical absorption properties of the polymer films were analyzed in the undoped and doped states and as a function of 3-DRT concentration in the copolymer. The nonlinear optical properties of the copolymers in the undoped and doped states were analyzed by Z-scan technique. The copolymers showed a change of non-linearity sign when the film was doped and results showed that the copolymers have a positive (self-focusing) and negative (self-defocusing) nonlinear optical properties which make them interesting for application as optoelectronic devices. We determined that the nonlinearity of the polymer films was a Kerr type.     

Dependence of the contact angle on the molecular structure of poly(propene-alt-N-maleimide) and poly(styrene-alt-N-maleimide) copolymers

Dynamic contact angle measurements on poly(propene-alt-N-maleimide) and poly(styrene-alt-N-maleimide) copolymers are presented. The copolymers were altered by side chains of saturated hydrocarbons of increasing length. Films of these copolymers were formed on silica wafers by casting from polymer solutions. Axisymmetric Drop Shape Analysis for Profiles (ADSA-P) was used for low rate dynamic contact angle measurements. The solid surface tension _SV was calculated using an Equation of State. For poly(propene-alt-N-maleimide) copolymers increasing length of the side chains lead to an increasing contact angle. The solid surface tension _SV varied in the range from 22.6 to 41.5 mJ/m². For a side chain with 12 carbon atoms the surface tension _SV is at the value reported in the literature for surfaces consisting mainly of CH₃-groups. The wetting behavior for poly(styrene-alt-N-maleimide) copolymers, however, showed a very strange behavior for water and glycerol, respectively. No trend of the contact angle versus the length of the side chain could be found. Instead, two different ranges of the contact angle appeared. At three carbon atoms it is inconsistent. Molecular modeling suggested a conformation for poly(styrene-alt-N-maleimides) to explain the unexpected behavior. This model was supported by wide angle X-ray diffraction (WAXS). A similar conformation was also suggested by Natta. From this it can be concluded that contact angle measurements are very sensitive to structural changes and represent a simple, yet powerful technique to characterize solid surfaces.     

Synthesis,characterization and structure dependence of thermochromism of polythiophene derivatives

In order to investigate the effect of the bulky pendant group and the spacer length between the pendant group and polythiophene main chain on the optical property of polythiophene backbone, a series of polythiophene derivatives were synthesized via copolymerization of 3-hexylthiophene with four different types of 4-((4-(phenyl)azo)phenoxy)alkyl-3thienylacetate. The alkyl spacers with different lengths, i.e., butyl, hexyl, octyl and undecyl groups were used between the bulky azobenzene group and the thiophene ring. The compositions and structures of these polythiophene derivatives were characterized. The structural dependence of thermochromic behaviour of these copolymers were systematically studied and results compared with poly(3-hexylthiophene) (P3HeT). A thermochromic temperature coefficient (C_TC) was defined for the first time in an attempt to quantitatively compare the sensitivity of the thermochromism in the copolymers. The results have shown that these copolymers with a bulky azobenzene group in side chain have a higher (C_TC) value than P3HT and the C_TC value of the copolymers increase with increasing the spacer length.     

Block copolymers of L-lactide and poly(ethylene glycol) for biomedical applications

Poly (L-lactide)-poly (oxyethylene)-poly (L-lactide) block copolymers obtained in bulk, by a ring opening mechanism, from poly (ethylene glycol)s (PEG)s and L-lactide (LA), at 120–140°C, in the absence of added catalysts are described. By using PEGs with different molecular masses, 3000 and 35000, respectively, and varying the initial molar ratio LA to PEG, two series of copolymers with different molecular masses, relative length of blocks and hydrophilicity were obtained. Physico-chemical characterization of the copolymers had been previously performed. The morphological characteristics of the copolymers were investigated by means of X-ray diffractometry, optical and scanning electron microscopy. The biological properties of the materials were determined by evaluating their cytotoxicity, cytocompatibility, hemocompatibility and degradability using different standard tests. The results obtained indicate that the block copolymers synthesized may be useful for biomedical applications, in particular as resorbable drug vehicles. The materials are brittle and their mechanical properties are not appropriate for implant devices.     

In vitro bio-immunological and cytotoxicity studies of poly(2-oxazolines)

Poly(2-oxazolines) with varying alkyl chain lengths (e.g., methyl, ethyl, aryl) and molar masses have been tested for cell cytotoxicity in vitro. A standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used for the estimation of cell viability. Two monomers, 2-methyl-2-oxazoline and 2-ethyl-2-oxazoline, were found to provide polymers with non-cytotoxic properties. The dependence of cell viability on molar mass confirmed the expected trend; the viability increased with the higher molar mass of poly(2-ethyl-2-oxazoline) (PETOX), up to 15,000 g/mol. The results obtained for the polymers with aliphatic side chains were compared with the analogues that possessed an aromatic moiety. All results confirmed low cytotoxicity of the polymers prepared by cationic polymerization of 2-alkyl- and 2-aryl-2-oxazolines, which supports their utilization in biomedical applications. Fluorescence microscopy and steady-state fluorescence were used to observe pyrene-labeled polymer interactions with living cells. Polymer accumulated within the cells was found to be dependent on polymer concentration in media. The immunoefficiency of aromatic and aliphatic oxazoline polymers and copolymers was also studied. Phagocytic and metabolic activities of macrophages were used to assess the immunosuppressive effects of the selected copolymers for possible applications in drug delivery and immunobiology. Overall, the tested polymers demonstrated no significant influences on the cellular immunological parameters.     

Physical properties of high molecular weight 1,3-trimethylene carbonate and D,L-lactide copolymers

High molecular weight statistical copolymers of 1,3-trimethylene carbonate (TMC) and D,L-lactide (DLLA) were synthesized and characterized with the aim of assessing their potential in the development of degradable and flexible materials for application in the biomedical field. Under the applied polymerization conditions (130 °C, 3 days using stannous octoate as a catalyst) monomer conversion was high or almost complete, and high molecular weight polymers (_M _n above 170 000) were obtained. Significant improvement of the mechanical performance of these materials was observed in comparison to results previously reported for TMC and DLLA based copolymers of lower molecular weight. For the entire range of compositions the polymers are amorphous with a glass transition temperature ranging between –17 °C for poly(TMC) and 53 °C for poly(DLLA). The polymers vary from rubbers to stiff materials as the content of TMC decreases. All polymers are hydrophobic with very low equilibrium water absorption (<1.5 wt %). Thermal analyses and tensile tests were performed on polymer samples after water uptake. Due to a plasticizing effect of the water, the thermal properties, and consequently the mechanical performance, of the copolymers with higher content of DLLA were the most affected. After water absorption, the polymer mechanical behavior can change from glassy to rubbery, as observed for the copolymer with 80 mol % of DLLA. The obtained results suggest that these copolymers are promising candidates as biomaterials in the preparation of degradable medical devices and systems.