Biodegradable polymers for use in surgery — poly(glycolic)/poly(Iactic acid) homo and copolymers: 2. In vitro degradation

The degradation mechanism of a series of polyglycolic/polylactic acid, (PGA/PLA), homo and copolymers synthesized as in Part 1¹, has been studied _vitro. An in vitro test model similar to that described in a previous study⁹, was used. The effects of time, temperature and pH on the rate and mechanism of degradation were elucidated. The degree of degradation was monitored molecularly by gel permeation chromatography (g.p.c.), tensile strength determination and mass loss measurements. The mechanism of degradation is shown to be by hydrolysis. The copolymers of PGA and PLA are shown to have a wide range of degradation rates governed by the hydrophilic/hydrophobic balance and crystallinity of the respective copolymer. The effect of the glass transition temperature (T_g) of PGA on its sensitivity to degradation is also demonstrated.     

Montmorillonite with unique interlayer space imparted polymer scaffolds with sustained release of Ag+

Polyglycolic acid (PGA) has been a potential scaffold material due to its good biocompatibility and processibility, but its poor mechanical properties and over fast degradation restricted its application in bone repair. Meanwhile, it is worth noticing that bacterial infection is a common problem in bone repair. In this study, montmorillonite (MMT), with unique interlayer space, was introduced to PGA scaffolds prepared via additive manufacturing to address the problems. The results indicated MMT acted as rigid reinforcements dispersing well in the PGA matrix, which effectively transferred and absorbed the stresses in the matrix, thereby significantly increasing the compressive properties and hardness of the scaffolds. Moreover, MMT played the role of impermeable barriers in the matrix, hindering the diffusion of water and its attack on the matrix, which inhibited the hydrolysis and hence significantly decreased the degradable rate. More importantly, Ag⁺ was loaded into the interlayer space of MMT via ion exchange and was further chemically reduced to metallic Ag with higher stability. The impermeable layered structure of MMT presented dual barrier effects on the release of Ag⁺ via inhibiting the attack of water on Ag from outside and the diffusion of Ag⁺ from inside. Hence, the scaffolds exhibited a sustained Ag⁺ release and a long-lasting antibacterial property.     

The Degradation of Polyglycolide in Water and Deuterium Oxide. Part II: Nuclear Reaction Analysis and Magnetic Resonance Imaging of Water Distribution

Magnetic resonance imaging (MRI) and scanning microbeam nuclear reaction analysis (NRA) were used to monitor changes of water ingress into polyglycolide (PGA) disks with degradation time. MRI detects H₂O, whereas NRA is sensitive to D₂O. The acid-catalysed hydrolysis of the ester is significantly slower in D₂O than H₂O because of the kinetic isotope effect. This behaviour was investigated in Part I. In this paper, NRA was used to investigate PGA hydration in buffers made from D₂O, and NRA and MRI experiments were performed on samples degraded buffers made from a 50% mixture of D₂O and H₂O (D₂O/H₂O 50:50) to allow a comparison between the two techniques. The NRA and MRI results provide direct evidence in support of the four-stage reaction-erosion model reported in previous literature, and show that this model applies to polymer degradation in heavy water and in a buffer made from D₂O/H₂O 50:50. It is believed that this is the first time that NRA and MRI have been compared for the same hydrating system.     

Preparation of rigidity toughness balance and stable poly(glycolic acid) based on chain extension reaction

As a completely degradable material, poly(glycolic acid) (PGA) has excellent rigidity, barrier properties, degradability and biocompatibility. However, the inherent brittleness and easily hydrolysable characteristics limit its widespread application. Herein, we introduced chain extension ADR to modify PGA to ameliorate these defects. The results showed that ADR could react with PGA to form “comb-like” and “cross-linked” chain extension structures resulting in the improvement of complex viscosity and formation of gel. Because of the chain entanglement of chain extension structures, the toughness of modified PGA was improved (which was verified by the impact strength value of 4.3 kJ/m² that was about 126% of virgin PGA) without sacrificing its rigidity. Furthermore, the hydrolysis results indicated that the representative PGA/1.0ADR had better hydrolysis stability, it had more complete morphology and slower degradation rate than virgin PGA in the 17-day hydrolysis experiment. Apart from better toughness and hydrolysis stability, there was also improvements in crystallization performance, the sample PGA/1.0ADR endowed with higher crystallization peak temperature (2.3°C higher than virgin PGA) and lower crystallization activation energy. In short, this work prepared a kind of modified PGA with rigidity toughness balance and better hydrolysis stability, which could expand the application range of PGA-based materials.     

Thermally crosslinked anionic hydrogels composed of poly(vinyl alcohol) and poly(γ‐glutamic acid): Preparation,characterization, and drug permeation behavior

pH‐sensitive anionic hydrogels composed of poly(vinyl alcohol) (PVA) and poly(γ‐glutamic acid) (γ‐PGA) were prepared by the freeze drying method and thermally crosslinked to suppress hydrogel deformation in water. The physical properties, swelling, and drug‐diffusion behaviors were characterized for the hydrogels. In the equilibrium swelling study, PVA/γ‐PGA hydrogels shrunk in pH regions below the pK_a (2.27) of γ‐PGA, whereas they swelled above the pK_a. In the drug‐diffusion study, the drug permeation rates of the PVA/γ‐PGA hydrogels were directly proportional to their swelling behaviors. The cytocompatibility test showed no cytotoxicity of the PVA/γ‐PGA hydrogels for the 3T3 fibroblast cell lines. The results of these studies suggest that hydrogels prepared from PVA and γ‐PGA could be used as orally administrable drug‐delivery systems. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

助剂复配对聚乙醇酸性能的影响

通过熔融共混方法,采用环氧类扩链剂对聚乙醇酸(PGA)进行反应挤出改性,同时添加亚磷酸酯类抗氧剂来降低熔融加工过程中的热降解。研究了扩链剂与抗氧剂联用对PGA熔体质量流动速率、热稳定性、熔体流变性能以及抗水解性能的影响。结果表明,扩链剂与抗氧剂复配,PGA改性料的熔体质量流动速率由原料的44.2 g/10min下降至11.2 g/10min;起始分解温度T_-5%(质量剩余95%的温度点)提高22.1℃;熔体黏度提高6倍以上;在提高了熔体强度的同时,改性料热稳定性明显改善,同时抗水解稳定性也有一定程度提高。     

Synthesis and characterization of pH-sensitive and biodegradable hydrogels prepared by γ irradiation using microbial poly(γ-glutamic acid) and poly(ϵ-lysine)

Poly(γ-glutamic acid) (PGA) and poly(?-lysine) (PL) solutions were used as components to prepare mixed hydrogels by γ irradiation. A PGA and PL mixed solution was crosslinked to form a hydrogel with specific water content (weight of absorbed water/weight of dry gel) of 10–100 when the 5 wt % solution of mixed polymer was exposed to γ radiation of 87 kGy dosage under N₂ atmosphere. The specific water content increased with increasing PGA content of the PGA/PL mixed gel. The influence of pH and salt concentration on equilibrium swelling was studied. A characteristic pH-sensitive swelling behavior was obtained using compositional changes of PGA and PL in the gel. PGA/PL 50/50 wt % mixed gel swelling in acid (pH < 4.0) and alkaline (pH > 6.0) conditions and was deswelled between pH 4.0 and 6.0 due to the ionic composition changes of the gel network. With an increase in the ratio of PGA to PL, the hydrogels showed increasing sensitivity to salt solutions (NaCl, Na₂SO₄, and CaCl₂). In addition, degradation of PGA/PL gel by protease produced from Aspergillus oryzae was investigated at 40°C and pH 7.0. PL gel was degraded completely within 2 days. An increase in the ratio of PAG in the PGA/PL mixed gel led to a decrease in the degree of degradation as expected. Some subtle degradation changes were found in the 50/50 and 80/20 wt % (PGA/PL) gels that were degraded by only 3.5 and 3.8% by protease, respectively. © 1995 John Wiley & Sons, Inc.     

Fabrication of a Nanofibrous Scaffold for the In Vitro Culture of Cardiac Progenitor Cells for Myocardial Regeneration

In this study, random Poly (?-caprolactone) (PCL):Poly glycolic acid (PGA) nanofibrous scaffold with various PCL:PGA compositions were fabricated by electrospinning method. The nanofibrous scaffolds were characterized by SEM, contact angle measurement, ATR-FTIR, and tensile measurements. The results showed that with the increase of the concentration of PGA in spinning blend solution, the average diameter of nanofibers, hydrophilicity, and mechanical properties of the nanofibrous scaffolds increased. An in vitro degradation study of PCL:PGA nanofibers were conducted in phosphate-buffered saline, pH 7.2. The experiments confirm that increasing of PGA provides faster degradation rate in blended nanofibers. To assay the biocompatibility and cell behavior on the nanofibrous scaffolds, cell attachment and spreading of cardiac progenitor cells seeded on the scaffolds were studied. The results indicate that among electrospun nanofibrous scaffolds, the most appropriate candidate for myocardial tissue engineering scaffolds is PCL:PGA (65:35).     

Hydrolytic Degradation and Morphological Characterization of Electrospun Poly(glycolic acid) [PGA] Thin Films of Different Molecular Weights Containing TiO<Subscript>2</Subscript> Nanoparticles

Thin films of polyglycolic acid (PGA), a biodegradable and biocompatible polymer, were prepared by electrospinning and were studied according to their molecular weights. TiO₂ nanoparticles were also used as additives at concentrations of 2–8 wt%. The films were morphologically characterized and exhibited a homogeneous distribution of TiO₂ with only slight differences depending on the molecular weight. In particular, fibers with low-molecular-weight PGA were thinner and had an average diameter of 77 nm. Furthermore, they showed a higher resolution of the TiO₂ crystal planes regardless of the crystal habit involved. During the melting of the PGA fibers, one single and prominent melting endotherm was observed, which was independent of molecular weight, TiO₂ content, and crystal phase involved. This was in contrast to quiescent PGA crystallization and melting, during which the typical double melting behavior was present. After thermal measurements, TiO₂ did not show characteristics of a nucleating agent for the PGA fibers. However, it acted as a degradation retardant for low-molecular-weight PGA. Because of its hygroscopicity, anatase, a material with the ability to absorb water, was a more efficient hydrolytic degrader than rutile.     

Epoxy resins. I. The stability of the epoxy–trimethoxyboroxine system

The useful life of a material depends on its environmental exposure. The diglycidyl ether of bisphenol A (DGEBA) cured with trimethoxyboroxine (TMB) was evaluated under various aging conditions. For isothermal aging, the main factor controlling weight loss appeared to be related to the diffusion of the degradation products (E_act = 22.1 kcal/mole). Chemical decomposition kinetic parameters were obtained using vacuum thermogravimetric analysis (TGA) on powder samples. The thermal decomposition activation energy and the reaction order of cured DGEBA were 37.5 kcal/mole and 1.05, respectively. The hydrolytic aging of this material was also kinetically analyzed, and it was concluded that the weight change was controlled by both water diffusion into the sample and diffusion of hydrolysis products from the sample. During hydrolytic aging below the glass transition temperature, the specimens gained weight up to 0.05 g based on 1-g unaged cured resin and then leveled off. At higher temperatures, the specimens initially gained weight and then began to lose weight, reaching a constant weight gain. The activation energies for water diffusion into the cured resin are 19.5 kcal/mole at temperatures above T_g and 21.5 kcal/mole at temperatures below T_g. The main hydrolysis product was boric acid from reaction of the boroxine ring with water. The time-temperature superposition principle was used for the weight loss study on isothermal and isothermal hydrolytic aging. The scale factor in this approach was found to be the ratio of the diffusion coefficient at the temperature of interest to that at a reference temperature.     

In situ examination of water diffusion to the polypropylene-silane interface using FTIR-ATR

This study investigated the effect of moisture on a model silane coupling agent modified adhesive bond. Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy was used to characterize the transport of moisture to a polypropylene-silane interphase and monitor the resulting chemical changes. The FTIR-ATR method offers the advantage of in-situ examination of the diffusion process, as well as the ability to characterize chemical changes that occur due to the presence of moisture. Experiments were conducted at ambient and elevated temperatures. The results of the real-time measurements demonstrated that moisture will migrate through the polypropylene to the silane interphase. The diffusion behavior was described well by a Fickian model. The apparent diffusion coefficients for water in the polypropylene-silane bilayer were on the order of the diffusion coefficients for water in polypropylene at both test temperatures. Furthermore, changes in the spectra were observed during the diffusion experiments. These changes were indicative of hydrolysis of the siloxane backbone in the silane layer while buried beneath the polypropylene film. This finding is significant as it presents direct evidence of a degradation mechanism in silane-modified adhesive bonds. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 64: 1971–1985, 1997     

The effect of buffer concentration,pH and buffer ions on the degradation and drug release from polyglycolide

Samples of polyglycolide were degraded in various buffered solutions in order to investigate the effects of buffer concentration, pH and particular buffer ions on the hydrolysis reaction. The small‐angle X‐ray scattering profiles changed with degradation; long periods were calculated and their changes with degradation used as a measure of the degradation rate. The release of a model drug, theophylline, was also investigated under these different buffering conditions. In more concentrated buffer solutions theophylline was released slightly earlier and the samples began to swell sooner. Increasing the pH of the phosphate buffer also resulted in an earlier swelling and release of drug. These effects were attributed to the neutralisation and increased solubility of acidic degradation products in more concentrated or alkaline buffer solutions. When an imidazole–HCl rather than a phosphate or citrate–citric acid buffer system was used, swelling and drug release were accelerated, as imidazole catalysed the ester hydrolysis reaction. The results are interpreted within the context of a four‐stage model of PGA degradation. © 2003 Society of Chemical Industry     

Diffusion coefficient and equilibrium solubility of water molecules in biodegradable polymers

The diffusion coefficient and solubility of water molecules were measured in polyglycolide (PGA), poly(L ‐lactide) (PLLA), poly[(R)‐3‐hydroxybutyrate] (PHB), poly(ϵ‐caprolactone) (PCL), and Skygreen^R (SG). The diffusion coefficient and equilibrium solubility decreased in the order SG > PCL > PLLA > PHB > PGA and PGA > SG > PLLA > PHB > PCL, respectively. The diffusion coefficient and solubility of water at low sorption temperature in PHB varied according to the initial crystallinity of the matrix polymer even though crystallization of PHB molecules took place during the sorption experiment. In contrast, the amorphous PLLA and the crystalline PLLA showed an almost identical diffusion coefficient and solubility of water, in spite of the fact that the amorphous PLLA remained practically amorphous during the whole sorption procedure. A strong correlation existed between the water solubility and the surface tension or contact angle of the polymer matrix. The water diffusivity in PGA was almost 2 orders of magnitude lower while water was more soluble in PGA with a lower heat of sorption than that corresponding to the other more hydrophobic polymers, indicating that the transport of water molecules in PGA followed the solution–diffusion model. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 1716–1722, 2000     

In situ injectable poly(γ‐glutamic acid) based biohydrogel formed by enzymatic crosslinking

Enzymatic crosslinking was developed to prepare in situ forming poly(γ‐glutamic acid) (γ‐PGA) based hydrogel in this study. First, the precursor of poly(γ‐glutamic acid)–tyramine (γ‐PGA–Ty) was synthesized through the reaction of carboxyl groups from a γ‐PGA backbone with tyramine. The structure of the grafted precursor was confirmed by ¹H‐NMR and Fourier transform infrared spectroscopy. After that, the crosslinking of the phenol‐containing γ‐PGA–Ty precursor was triggered by horseradish peroxidase in the presence of H₂O₂; this resulted in the formation of the γ‐PGA–Ty hydrogels. The equilibrium water content, morphology, enzymatic degradation rate, and mechanical properties of the hydrogels were characterized in detail. The data revealed that the well‐interconnected hydrogels had tunable water contents, mechanical properties, and degradability through adjustments of the composition. Furthermore, cell experiments proved the biocompatibility of the hydrogels by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. These characteristics provide an opportunity for the in situ formation of injectable biohydrogels as potential candidates in cell encapsulation and drug delivery. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42301.     

Hydrolytic thermal degradation of poly(naphthoyleneimide benzimidazole) in concentrated sulfuric acid

Translational diffusion in 96% H₂SO₄ and intrinsic viscosity of poly(naphthoyleneimide benzimidazole) (PNIB) have been investigated in different stages of its degradation in solution in the temperature range from 65 to 120°C. The degradation rate constant k has been determined from the change in molecular weight M of degraded products with time at the fixed temperature of solution. The activation energy of the process E was calculated from the temperature dependence of k. The difference in E values at low and high temperatures was found. At degradation temperatures above 90°C, the activation energy of hydrolysis was obtained as E = 133 kJ/mol, which coincides with that of aromatic polyamides in sulfuric acid. The data obtained are compared with the results of the investigations of optical properties of products of PNIB degradation in solution and PNIB stability in the solid state. An explanation of anomalies observed during PNIB degradation at low temperatures is suggested. © 1995 John Wiley & Sons, Inc.     

Miscibility and hydrolytic degradation in alkaline solution of poly(l-lactide) and poly(methyl methacrylate) blends

Poly(l-lactide) (PLLA) was melt blended with poly(methyl methacrylate) (PMMA) using a two-roll mill. The miscibility and hydrolytic degradation of the blend films were characterized. It was found that PLLA/PMMA blend has high miscibility in the amorphous state because only single T_g was observed in the DSC and DMA measurements. In alkaline solution, the hydrolytic degradation rate of the blends whose PMMA content is higher than 30 wt% was decelerated while the rate of the blends whose PMMA content is lower than 30 wt% was accelerated. That is, the hydrolytic degradation rate of the blends could be widely controlled by PMMA content in the blend. It was also found that only PLLA was hydrolyzed and eluted into alkaline solution, while PMMA remained during alkaline hydrolysis.     

Formation of TiO2 hollow microparticles by spraying water droplets into an organic solution of titanium tetraisopropoxide (TTIP) — Effects of TTIP concentration and TTIP-protecting additives

Hollow, spherical TiO₂ microparticles of several tens of micrometers in diameter can be prepared by spraying water into an organic phase containing titanium tetraisopropoxide (TTIP) as a titanium source. The concentration of TTIP did not affect the shell thickness. On the contrary, the shell thickness was increased with the concentration of the additives such as acetic acid and acetylacetone, having effects to protect TTIP from hydrolysis and condensation. The formation of a hollow particle was described by a simple model involving the hydrolysis of TTIP at the water–oil interface, the inward diffusion of hydrolyzed titanium hydroxide through the passage in the shell and its incorporation into the TiO₂ shell by condensation. The reduction of porosity of shell inhibits the diffusion, resulting in the formation of hollow structure. The simulation based on this model predicted that the shell thickness increased as the diffusion rate increased or the reaction rate decreased, and was independent of the outer TTIP concentration. These predictions were in qualitative agreement with the experimental results.     

Relating laboratory and outdoor exposure of coatings: IV. Mode and mechanism for hydrolytic degradation of acrylic-melamine coatings exposed to water vapor in the absence of UV light

Acrylic-melamine coatings are known to be susceptible to hydrolysis when exposed to water or humid environments. The mode and specific pathways for hydrolytic degradation of acrylic-melamine coatings exposed to water vapor in the absence of ultraviolet light are presented. Samples of a partially methylated melamine-acrylic coating applied to CaF₂ substrates were subjected to five different relative humidity levels ranging from approximately 0 to 90% at 50°C. Coating degradation was measured with transmission Fourier transform infrared spectroscopy (FTIR) and tapping mode atomic force microscopy (AFM). In humid environments, partially methylated melamine-acrylic coatings undergo hydrolysis readily, causing considerable material loss and formation of mainly primary amines and carboxylic acids. The rate of hydrolysis increases with increasing RH. Hydrolytic degradation of acrylic-melamine coatings is an inhomogeneous process in which pits form, deepen, and enlarge with exposure. Such localized degradation mode suggests that hydrolysis of this material is an autocatalytic progression where acidic degradation products formed in the pits catalyze and accelerate the hydrolysis reactions. Presented at the 79th Annual Meeting of the Federation of Societies for Coatings Technology, November 5–7, 2001, in Atlanta, GA. 100 Bureau Dr., Mail Stop 8621, Gaithersburg, MD 20899.     

Preparation and properties of poly(benzyl glutamate)–poloxamer–poly(benzyl glutamate) and poly(glutamic acid)–poloxamer–poly(glutamic acid) triblock polymers

The novel block copolymer poly(benzyl glutamate) (PBLG)–polomamer–PBLG were synthesized from glutamic acid and poloxamer in six steps with three different molecular weights, and another new block copolymer, poly(glutamic acid) (PGA)–poloxamer–PGA, was obtained by the benzyl deprotection of PBLG–poloxamer–PBLG. The obtained compounds were characterized by IR spectroscopy, gel permeation chromatography, and ¹H‐NMR. The in vitro biological degradation and water absorption of PBLG showed that a greater proportion of PBLG in the copolymer led to a slower degradation and weaker water absorption, so the speed of degradation and water absorption could be adjusted through adjustment of the ratio of poloxamer. Both PBLG–poloxamer–PBLG and PGA–poloxamer–PGA exhibited lower cytotoxicity and good biocompatibility in the methyl thiazolyl tetrazolium (MTT) assay. The results show that both block polymers are promising as drug‐carrier materials. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Particle Coarsening Influence on Oxygen Reduction in LSM–YSZ Composite Materials

The microstructure influence on the oxygen reduction process for the LSM–YSZ composite materials has been studied in this paper. To localize the effect of particle coarsening influence, the oxygen isotope exchange measurements with the gas phase analysis have been performed for LSM–YSZ | YSZ | LSM–YSZ symmetric cells during 300 and 1000 hours at T = 850 °C and Po₂ = 10⁻² atm. In order to find quantitative relations the changes in the oxygen surface exchange and the diffusion coefficients and its microstructure parameters such as porosity and triple phase boundary (TPB) length have been compared. The rate determining stage of the LSM–YSZ degradation has been suggested to be the LSM‐phase surface diffusion and the LSM surface diffusion coefficient have been estimated.