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PubMed1999

Diffusion characteristics of calcium alginate gels.

The diffusivity of a protein solute (bovine serum albumin) within calcium alginate gels made from sodium alginate of different guluronic acid content was determined. It was found that protein diffusion within alginate gels, prepared to be isotropic in structure, was greatest for gels prepared from sodium alginate of low guluronic acid content as opposed to those prepared from sodium alginate of high guluronic acid content. This finding was explained in terms of the difference in flexibility of the polymer backbone of the two alginates. The greater the polymer backbone flexibility, the greater the solute diffusivity within the gel.

Alginates↗

PubMed1997

Non-decay type fast-setting calcium phosphate cement: hydroxyapatite putty containing an increased amount of sodium alginate.

A hydroxyapatite [(HAP) Ca10(PO4)6(OH)2] putty that behaves like a putty or self-curing resin was made by increasing the amount of sodium alginate in non-decay type fast-setting calcium phosphate cement (nd-FSCPC). nd-FSCPC became viscous as the sodium alginate concentration was increased. The best handling properties were obtained when nd-FSCPC contained 8% sodium alginate in its liquid phase. When a 2-kg glass plate was placed on the paste, HAP putty spread to form an area three times that of FSCPC paste. Thus, HAP putty is expected to be easier to use than FSCPC in the filling of bone defects. HAP putty did not decay; in fact, it set within approximately 20 min when immersed in distilled water immediately after mixing. The wet diametral tensile strength value of HAP putty was approximately 12 MPa after 24 h, the same as that for nd-FSCPC containing 0.5% sodium alginate in its liquid phase, or FSCPC that is free from sodium alginate. The elements constituting set HAP putty were examined using powder X-ray diffraction and found to be predominantly apatitic minerals after 24 h. Since the handling properties of a putty or self-curing resin-like cement are very useful in certain surgical procedures, HAP putty made by increasing the sodium alginate concentration in nd-FSCPC is potentially a valuable new biomaterial for use in plastic and reconstructive surgery, as well as oral and maxillofacial surgery.

Alginates↗

PubMed1998

Evaluation of a novel alginate gel dressing: cytotoxicity to fibroblasts in vitro and foreign-body reaction in pig skin in vivo.

Calcium alginate dressings have beneficial effects on wound healing by providing a moist wound environment. However, cytotoxicity and the nonbiodegradable nature of calcium alginate dressings induce unresolved chronic foreign-body reaction. In this study, a novel freeze-dried alginate gel dressing (AGA-100) low in calcium ions was evaluated for cytotoxicity to L929 cells in vitro and in full-thickness pig wounds in vivo. Cytotoxicity testing on L929 cells showed the cytocompatibility of AGA-100 extracts, while extracts from Kaltostat, a well-established alginate dressing, induced cytopathic effects. In an in vivo study using pigskin, AGA-100, Kaltostat, and gauze were applied on 1-in-diameter circular full-thickness wounds on the back of pigs and the time course of wound closure was evaluated. Kaltostat and gauze dressings were used as controls. For histologic evaluation, wound tissue was harvested on day 18. AGA-100-treated wounds showed rapid wound closure compared to control wounds on day 15. Foreign-body reaction was marked in Kaltostat- and gauze-treated wounds, and differed significantly from AGA-100-treated wounds. Based on these data, AGA-100 could reduce the cytotoxicity to fibroblasts and foreign-body reaction that have been observed with currently available calcium alginate dressings; it was also found to be useful as an alginate dressing.

Alginates↗

PubMed1999

Pseudomonas aeruginosa alginate is a potent secretagogue in the isolated ferret trachea.

Airway mucus hypersecretion is in part a response to infection and inflammation. Pseudomonas aeruginosa infection is nearly universal in advanced cystic fibrosis (CF) lung disease. Mucoid strains of P. aeruginosa produce an exopolysaccharide product called alginate. The purpose of this study was to determine whether P. aeruginosa alginate stimulates secretion from mucous or serous cells in the ferret trachea exposed to alginate at concentrations reported to be present in the CF airway. We used a sandwich enzyme-linked lectin assay (ELLA) to measure mucin secretion and spectrophotometry to measure lysozyme secretion from isolated ferret tracheal segments. Purified Pseudomonas aeruginosa alginate stimulated mucin and lysozyme secretion in a dose-dependent fashion (mucin = +111%: P = 0.003; lysozyme = +20%: P = 0.024 at 200 microg/mL). This stimulated secretion was not due to proteolytic activity, and alginate exposure did not produce ultrastructural damage to the trachea. We conclude that alginate may contribute to mucus hypersecretion and respiratory morbidity associated with P. aeruginosa infection in patients with CF.

Alginates↗

PubMed2000

High interaction alginate-hyaluronate associations by hyaluronate deacetylation for the preparation of efficient biomaterials.

The paper presents fundamental investigations of alginate-hyaluronate association with significant polymer interactions for preparation of efficient biomaterials. For this purpose, acetamide functions of hyaluronate were partly cleaved by hydrazine at high temperature, yielding amino groups accessible to carboxylic functions of the alginate chain. Alginate-hyaluronate association was studied both in dissolved state by rheological measurements and CD, and in the form of gel slabs prepared after calcium diffusion. Appreciable interaction between carboxylic groups of alginate and the released amino groups of hyaluronate was put into evidence by enhanced values of the viscosity of mixed solutions, and by assessment of the properties of the gel formed: moderate deacetylation allowed gels of improved hardness and viscosity. Nevertheless, high deacetylation was observed to hinder the gel formation by Ca(2+) complexation of alginate, by the significant competition of COOH-NH(2) association. Interaction between alginate and modified hyaluronate results in regular gel structure, with small cavities.

Acetylation↗

PubMed2003

Properties of a novel magnetized alginate for magnetic resonance imaging.

Implanting recombinant cells encapsulated in alginate microcapsules to secrete therapeutic proteins has been proven clinically effective in treating several murine models of human diseases. However, once implanted, these microcapsules cannot be assessed without invasive surgery. We now report the preparation and characterization of a novel ferrofluid to render these microcapsules visible with magnetic resonance imaging (MRI). The ferrofluid was prepared as a colloidal iron oxide stabilized in water by alginate. The presence of iron particles in the ferrofluid was verified with chemical titration, dynamic light scattering, and magnetization measurement. The microcapsules fabricated with various concentrations of the ferrofluid in the core, or on the surface of alginate microcapsules, or both, all produced microcapsules with smooth surfaces as shown with light and scanning electron microscopy. However, at the nanoscale level, as revealed with atomic force microscopy, the ferrofluid-fabricated microcapsules demonstrated increased granularity, particularly when the ferrofluid was used to laminate the surface. From the force spectroscopy measurements, these modified microcapsules showed increasing surface rigidity in the following order: traditional alginate < ferrofluid in the core < ferrofluid on the surface. Although the mechanical stability of low-concentration ferrofluid (0.1%) microcapsules was reduced, increasing concentrations, up to 20%, were able to improve stability. When these ferrofluid microcapsules were examined with MRI, their T(2) relaxation time was reduced, thereby producing increased contrast readily detectable with MRI, whereas the traditional alginate microcapsules showed no difference when compared with water. In conclusion, such ferrofluid-enhanced alginate is suitable for fabricating microcapsules that offer the potential for in vivo tracking of implanted microcapsules without invasive surgery.

Alginates↗

PubMed2006

Alginate hydrogel and matrigel as potential cell carriers for neurotransplantation.

Development of biosynthetic conduits carrying extracellular matrix molecules and cell lines expressing neurotrophic growth factors represents a novel and promising strategy for spinal cord and peripheral nerve repair. In the present in vitro study, the compatibility and growth-promoting effects of (i) alginate hydrogel, (ii) alginate hydrogel complemented with fibronectin, and (iii) matrigel were compared between olfactory ensheathing cells (OECs), Schwann cells (SCs), and bone marrow stromal cells (BMSCs). Neurite outgrowth from embryonic dorsal root ganglia (DRG) neurons was used to assess the efficacy of the hydrogels alone or in combination with cultured cells to promote axonal regeneration. The result showed that alginate hydrogel transformed OECs, SCs, and BMSCs into atypical cells with spherical shape and inhibited their metabolic activity. Combination of alginate hydrogel with fibronectin promoted only OECs proliferation. Alginate hydrogel also inhibited outgrowth of DRG neurites, although this effect was attenuated by addition of fibronectin, SCs, or BMSCs. In contrast, matrigel stimulated cell proliferation, preserved the typical morphological features of the cultured cells and induced massive sprouting of DRG neurites. Addition of cultured cells to matrigel did not further improve DRG neurite outgrowth. The present findings suggest that addition of extracellular matrix should be considered when engineering biosynthetic scaffolds on the basis of alginate hydrogels.

Alginates↗

PubMed2007

Zeta-potentials of alginate-PLL capsules: a predictive measure for biocompatibility?

Alginate-poly-L-lysine (PLL) microencapsulation of cells is a promising approach to prevent rejection in the absence of immunosuppression. Clinical application, however, is hampered by insufficient insight in factors influencing biocompatibility of the capsules. By now, it has been accepted that not only the chemical composition of the materials applied but also other factors contribute to bioincompatibility. The zeta-potential serves as a measure for the electrical charge of the surface and has been shown to be a predictive value for the interfacial reactions between the biomaterial and the surrounding tissue in other applications. In the present study, we have assessed the streaming potential of alginate-PLL capsules composed of either low-, intermediate-, or high-guluronic (G) alginate to calculate the zeta-potential. The zeta-potentials of the capsules were compared to the biological response against the capsules at 4 weeks after implantation in the rat. We show that high-G and low-G alginates provoke a more severe response in the rat than capsules prepared of intermediate-G alginate. This correlates with a higher zeta-potential of the high-G and low-G alginates and by a change in zeta-potential at lower pH. These lower pH-levels are common directly after implantation as the consequence of a host-response associated with mandatory surgery. Our results suggest that we should not only consider the capsule properties under physiological circumstances to explain bioincompatibility but also the capsule features during common pathophysiological situations.

Alginates↗

PubMed2006

Design and delivery of silver sulfadiazine from alginate microspheres-impregnated collagen scaffold.

A reconstituted collagen scaffold impregnated with silver sulfadiazine (SSD) loaded alginate microspheres, capable of delivering the drug in a controlled manner has been developed. SSD-loaded alginate microspheres were prepared by modified water-in-oil emulsion technique through interfacial ionic gelation of alginate using CaCl2. The SSD-loaded microspheres were impregnated in pepsin-solubilized collagen, in situ, while inducing fibrillation and cast as thin scaffold. Morphological features of microspheres and microsphere-impregnated collagen were analyzed through SEM. Distribution homogeneity of impregnated microspheres, their in vitro behavior in (Dulbecco's modified minimal essential media) DMEM, and antibacterial efficiency against ATCC pathogens were determined. Initial drug load of 20% (w/w) with respect to alginate and 40% (v/v) of 2% alginate with respect to oil phase were found to produce microspheres of optimum drug entrapment (3%) and required size range (300-370 microm). In vitro drug release studies from the scaffold showed an initial burst release of 47.5% and a controlled release for 72 h with equilibrium concentration of 68.8%. SSD-loaded microspheres exhibited minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) levels of 32 and 40.2 microg/mL to both K. pneumoniae and E. coli respectively. P. aeruginosa showed MIC and MBC levels of 44.8 and 51.2 microg/mL respectively, while Staphylococcus aureus exhibited MIC and MBC at the same concentration range (57.6 microg/mL). The collagen-based scaffold impregnated with SSD-loaded alginate microspheres can deliver SSD in a controlled fashion, can control infection for extended time period with lesser dressing frequencies, and will enable easier assessment of wound.

Alginates↗

PubMed1994

Controlled release of albumin from chitosan-alginate microcapsules.

A polymeric delayed-release protein delivery system was investigated with albumin as a model drug. The polysaccharide chitosan was reacted with sodium alginate in the presence of calcium chloride to form microcapsules with a polyelectrolyte complex membrane. Variables believed to be important for membrane formation were examined; these included reaction time, chitosan molecular weight, alginate concentration, chitosan concentration, and solution pH. An alginate-chitosan reaction time, in the range of 10 to 45 min, had no effect on the release of albumin. Increasing the alginate concentration, however, resulted in a decreased rate of release of albumin (from 37% release at 4 h with 1.5% alginate to 20% release with 2.5% alginate). Another key variable was the chitosan molecular weight. The molecular weight of chitosan was varied from 1.25 x 10(6) to 0.25 x 10(6) through a nitrite oxidation reaction with sodium nitrite. Decreasing the molecular weight increased the release of albumin (from 37% release at 4 h with high molecular weight chitosan to 77% release with low molecular weight chitosan). The pH of the extracapsular environment was found to affect the release of albumin significantly (15% release over 24 h at a pH 3.0 and 73% release at pH 8.0). Capsules produced with high molecular weight chitosan and a combination of high and low molecular weight chitosan gave the best results for reducing elution of albumin in the first 4 h and increasing elution in the following 20 h.

Albumins↗

PubMed1994

Reexpression of cartilage-specific genes by dedifferentiated human articular chondrocytes cultured in alginate beads.

We have used the three-dimensional culture system in alginate beads to redifferentiate human articular chondrocytes which were first expanded on a plastic support. After 15 days in alginate beads, electron microscopy showed that cells had synthesized an extracellular matrix containing collagen fibrils. Electrophoretic analysis of proline-labeled cells demonstrated that redifferentiated chondrocytes synthesized mainly type II collagen and its precursors (pro alpha 1II, pc alpha 1II, and pn alpha 1II). After pepsin digestion a small amount of collagen type XI was also detected. These results were confirmed by Northern blot analysis of total RNAs. Hybridization with collagen cDNA probes coding for the alpha 1(II) and alpha 1(I) chains of collagen types II and I showed that chondrocytes cultured in alginate expressed mainly alpha 1(II) mRNA, whereas alpha 1(I) mRNA transcripts were almost undetectable. Such a result was observed even after several passages on plastic flasks, suggesting that dedifferentiated cells were able to revert to a chondrocytic phenotype in this three-dimensional system. However, SV40-transformed chondrocytes were not able to redifferentiate in alginate as no alpha 1(II) mRNAs were detected. Total RNA was converted into cDNA by reverse transcription and amplified by polymerase chain reaction. This technique was employed to amplify mRNAs specific for collagen type II and type X and the large aggregating proteoglycan aggrecan. Two transcripts resulting from an alternative splicing of the complement regulatory protein (CRP)-like domain of aggrecan were originally identified in chondrocytes in monolayers. Like intact cartilage, chondrocytes in alginate expressed only the larger transcript with the CRP domain, whereas the two transcripts were equally expressed in SV40-transformed chondrocytes. Thus, the alginate system appears to represent a relevant model for the redifferentiation of human chondrocytes, especially when only a small cartilage biopsy is available, and could prove useful for pulse-chase studies of patients with skeletal chondrodysplasias. However it was unable to restore the chondrocytic phenotype in virally transformed cells.

Alginates↗

PubMed1992

Fatty acid impurities in alginate influence the phenol tolerance of immobilized Escherichia coli.

A short time after the immobilization of Escherichia coli in calcium alginate substantial modifications of the fatty acid patterns of the cells were observed. This effect could be related to lipid impurities in the commercial alginate product used, which could be taken up, at least in part by the microorganisms. The impurities were mainly free fatty acids but sterols were also detected. Immobilization of the cells in alginate material extracted by chloroform or ethanol decreased the tolerance of the cells to phenol as compared with cells immobilized in raw alginate. This effect was diminished if the immobilized cells were exogenously supplied with palmitic acid, which is the main constituent of the fatty acids extracted from alginate. These results indicate that not only fatty acids but also other ingredients of commercial alginate have physiological effects on cells entrapped in this gel material.

Alginates↗

PubMed1996

Improved delivery of biocontrol Pseudomonas and their antifungal metabolites using alginate polymers.

Alginate polymer was evaluated as a carrier for seed inoculation with a genetically modified strain Pseudomonas fluorescens F113LacZY, which protects sugar-beet against Pythium-mediated damping-off. F113LacZY survived in alginate beads at 5 log10 CFU/bead or higher counts for 8 weeks of storage, regardless of the conditions of incubation. In plant inoculation experiments, colonisation of the growing area of the root by F113LacZY, derived from alginate beads placed in the soil next to the seed or from an alginate coating around the seeds, was improved compared with application of just free cells of the strain. F113LacZY trapped in alginate beads was an effective producer of antifungal phloroglucinols as indicated by direct HPLC quantification of phloroglucinols and in vitro inhibition of both the indicator bacterium Bacillus subtilis A1 and the pathogenic fungus Pythium ultimum. Alginate polymer represents a promising carrier for the delivery of biocontrol inoculants for root colonisation and production of antifungal metabolites.

Alginates↗

PubMed1986

Alginate biosynthesis by Pseudomonas aeruginosa: effect of arsenite and other metabolic inhibitors.

Biosynthesis of alginic acid in presence of metabolic inhibitors by resting cells of mucoid Pseudomonas aeruginosa was studied. Among the inhibitors tested, arsenite exhibited very interesting results, while the others showed no remarkable effect. Firstly, arsenite stopped alginate production from all the substrates during initial hours of incubation; secondly, degradation of newly synthesized alginates to smaller molecular weight fragments took place if it was added after a few hours of incubation with the substrate; and thirdly, uncontrolled synthesis of alginate started after several hours of inhibition. Presence of arsenite was needed for the initial inhibitory phase of alginate synthesis; but once the cells were capable of synthesizing alginate after initial hours of inhibition, arsenite may be omitted from the medium.

Alginates↗

PubMed1992

Alginic acid decreases postprandial upright gastroesophageal reflux. Comparison with equal-strength antacid.

This study tested the hypothesis that (alginic) acid may have a preferential effect on reflux in the upright position. We evaluated the effect of a compound containing alginic acid plus antacid (extra-strength Gaviscon) versus active control antacid with equal acid-neutralizing capacity on intraesophageal acid exposure following a high-fat meal (61% fat: sausage, egg, and biscuit). In random sequence, each of the 10 volunteers received either alginic acid-antacid or control antacid immediately following and 1, 2, and 3 hr after the meal. The sequence was repeated for both test drugs in the supine and upright positions with constant pH monitoring. Alginic acid-antacid significantly decreased postprandial reflux in the upright position compared to an equal amount of antacid. This effect did not occur in the supine position. These findings support the hypothesis that alginic acid is primarily effective in the upright position and the clinical observations of the effectiveness of alginic acid on daytime reflux symptoms.

Alginates↗

PubMed1999

Alginate oligosaccharides stimulate VEGF-mediated growth and migration of human endothelial cells.

Alginate oligosaccharides cleaved from alginic acid polysaccharides of seaweed were tested to determine their ability to enhance proliferation and migration of human umbilical vein endothelial cells. A mixture of alginate oligosaccharides (5 microg/ml in culture broth) stimulated endothelial cell growth, [(3)H]thymidine uptake and migration in the presence of recombinant vascular endothelial growth factor 165 (VEGF(165)). In contrast, a high concentration mixture of the oligosaccharides ( approximately 100 microg/ml) suppressed cell growth. The stimulatory activity was comparable to that of heparin, with affinity to VEGF(165), and decreased on heparin-induced stimulation. Each effective oligosaccharide had guluronic acid at the reducing end. A mixture of alginate oligosaccharides (5 microg/ml) and the most paragraph signeffective fraction (1 microg/ml) stimulated endothelial cell migration. In the presence of VEGF and heparin, some alginate oligosaccharides with the peripheral guluronic acid demonstrated marked stimulatory effects, and one fraction also showed a migratory effect. These findings indicate novel activities of alginate oligosaccharide(s) in endothelial cell growth and migration and suggest synergistic and/or stabilizing effects on VEGF(165)-dependent stimulation of endothelial cells.

Alginates↗

PubMed2006

A comparison between sodium alginate and magaldrate anhydrous in the treatment of patients with gastroesophageal reflux symptoms.

The aims of the present study were to compare effects of sodium alginate and the antacid magaldrate anhydrous in adults with gastroesophageal reflux (GOR) symptoms. Patients with heartburn and/or acid regurgitation for at least 3 days in the week before the study started (n=203) were randomized to receive a single dose of sodium alginate or magaldrate anhydrous at the onset of symptoms during a 3-day run-in period. Patients with symptoms during the run-in (n=191) were rerandomized to receive a 14-day treatment with either drug given as four daily doses. A speed of action < or =30 min was significantly more frequent among patients in the alginate group (49.4% vs. 40.4%; P=0.0074). A trend toward a more prolonged duration of action (median: 16.5 vs. 12.7 hr) and a greater sum of the symptom intensity difference (median: 40.0 vs. 31.0) was observed in the sodium alginate group. Total disappearance of symptoms was reported in 81.6% and 73.9% of patients in the sodium alginate group and magaldrate group, respectively. We conclude that sodium alginate was faster than magaldrate in relieving GRO symptoms and showed a tendency toward a more prolonged duration of action and a higher level of efficacy.

Adolescent↗

PubMed2005

Influence of alginate on type II collagen fibrillogenesis.

Collagen II is the majority of extracellular matrix components in articular cartilage, which with the major functions of preventing expansion of the tissue and distributing the load of body weight. To obtain man-made ECM, the reconstitution of collagen could be conducted in the presence of negatively charged polysaccharide, such as alginate. Alginate is an anionic polysaccharide capable of eversible gelated in calcium ion solution to prepare different shapes of biomaterials. Its well-known biocompatibility makes it an ideal material in biomedical applications. Thus, the aim of this study was to evaluate the effects of alginate on the fibrillogenesis of type II collagen. The preliminary results revealed that inclusion of alginate into soluble type II collagen solution could inhibit the development of turbidity of collagen solution, and the apparent rate constants in lag and growth phases decreased during collagen formation period, both rate constants decreased to about one-third of the original constants, respectively. From TEM observations, the collagen fibrils were significantly thicker in 0.05% and 0.1% alginate as compared with pure collagen solution. Furthermore, the D-periods of collagen fibers kept unchanged significantly under all reconstituted conditions, which meant the packing of collagen monomer was probably not affected by adding these amounts of alginate.

Alginates↗