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Biomedical subjects

D Hunkeler

Publications and source records attributed to D Hunkeler.

29 records · Page 2Linked to original sources
PubMed1999

New multicomponent capsules for immunoisolation.

A new generation of microcapsules based on the use of oligomers which participate in polyelectrolyte complexation reactions has been developed. These freeze-thaw stable capsules have been applied as a bioartificial pancreas and have resulted in normoglycemia for periods of six months in concordant xenotransplantations. The new chemistry permits the control of permeability and mechanical properties over a wide range and can be adapted both to microcapsule and hollow fiber geometries rendering it a robust tool for encapsulation in general. Methods, and metrics, for the characterization of the mechanical properties and permeability of microcapsules are presented.

Artificial Organs↗
PubMed1999

Rationalizing the design of polymeric biomaterials.

Polymers are a promising class of biomaterials that can be engineered to meet specific end-use requirements. They can be selected according to key 'device' characteristics such as mechanical resistance, degradability, permeability, solubility and transparency, but the currently available polymers need to be improved by altering their surface and bulk properties. The design of macromolecules must therefore be carefully tailored in order to provide the combination of chemical, interfacial, mechanical and biological functions necessary for the manufacture of new and improved biomaterials.

Animals↗
PubMed1999

Intrinsic bioremediation of a petroleum hydrocarbon-contaminated aquifer and assessment of mineralization based on stable carbon isotopes.

This study presents a stepwise concept to assess the in situ microbial mineralization of petroleum hydrocarbons (PHC) in aquifers. A new graphical method based on stable carbon isotope ratios (delta 13C) was developed to verify the origin of dissolved inorganic carbon (DIC). The concept and the isotope method were applied to an aquifer in Student, Switzerland, in which more than 34,000 liters of heating oil were accidentally released. Chemical analyses of ground water revealed that in this aquifer locally, anaerobic conditions prevailed, and that PHC mineralization was linked to the consumption of oxidants such as O2, NO3-, and SO4(2-) and the production of reduced species such as Fe2+, Mn2+, H2S and CH4. However, alkalinity and DIC balances showed a quantitative disagreement in the link between oxidant consumption and DIC production, indicating that chemical data alone may not be a reliable assessment tool. delta 13C ratios in DIC have been used before for bioremediation assessment, but results were reported to be negatively influenced by methanogenesis. Using the new graphical method to display delta 13C data, it was possible to identify anomalies found in methanogenic monitoring wells. It could be shown that 88% of the DIC produced in the contaminated aquifer originated from microbial PHC mineralization. Thus, the new graphical method to display delta 13C ratios appears to be a useful tool for the assessment of microbial hydrocarbon mineralization in a complex environment.

Biodegradation, Environmental↗
PubMed1997

An encapsulation system for the immunoisolation of pancreatic islets.

Over a thousand combinations of polyanions and polycations were tested to search for new polymer candidates that would be suitable for encapsulation of living cells. The combination of sodium alginate, cellulose sulfate, poly (methylene-co-guanidine) hydrochloride, calcium chloride, and sodium chloride was most promising. In parallel, a novel multiloop chamber reactor was developed to control the time of complex formation and to negate gravitational effects such as pancreatic islet sedimentation and droplet deformation during the encapsulation process. Encapsulated rat islets demonstrated glucose-stimulated insulin secretion in vitro, and reversed diabetes in mice. This new capsule formulation and encapsulation system allows independent adjustments of capsule size, wall thickness, mechanical strength, and permeability, which may offer distinct advantages for immunoisolating cells.

Animals↗
PubMedDate not supplied

Polyvinylamine hydrochloride-based microcapsules: polymer synthesis, permeability and mechanical properties.

Mechanically stable microcapsules, with sizes of 0.4-1.5 mm, have been produced with permeabilities appropriate for applications involving living cells and controlled delivery. Polyvinylamine hydrochloride was employed alone, in miXtures with poly(methylene-co-guanidine) hydrochloride, or as a coating material for pre-formed capsules. The influence of polymer molar mass, the ratio between the two polycations, the coating time, and the capsule size on the properties of the capsules were analysed. The competitive displacement of one polycation with another in the polysaccharide matrix was also documented. The properties of the capsules vary remarkably, depending of the polyelectrolyte combinations used for their preparation. Specifically, capsules could withstand compressive loads of between 0.09-1.67 N, while the permeability varied from 10-120 kDa. Both are within the ranges required for clinical immunosuppressive therapies.

Capsules↗
PubMedDate not supplied

Characterization of microcapsules: recommended methods based on round-robin testing.

Alginate beads, as well as microcapsules based on alginate, cellulose sulphate and polymethylene-co-guanidine, were produced at diameters of 0.4, 1.0 and 1.5 mm. These standard materials were tested, by independent laboratories, in regards to water activity, bead or capsule size, mechanical resistance and transport behaviour. The water activity and mechanical resistance were observed to increase with bead and capsule size. Transport properties (ingress) were assessed using a variety of low molar mass and macromolecular probes. It was observed that the penetration of Vitamin B12 increased with bead diameter, as did dextran penetration. However, for the membrane-containing microcapsules, larger membrane thickness, observed for the larger capsules, retarded ingress. The authors, who are part of a European working group, recommend that permeability be assessed either using a large range of probes or a broad molar mass standard, with measurements at one or two molar masses insufficient to simulate the behaviour in application. Mechanical compression is seen as a good means to estimate elasticity and rupture of beads and capsules, with the sensitivity of the force transducer, which can vary from microN to tens of N, required to be tuned to the anticipated bead or capsule strength. Overall, with the exception of the mechanical properties, the precision in the inter-laboratory testing was good. Furthermore, the various methods of assessing transport properties agreed, in ranking, for the beads and capsules characterized, with gels having smaller radii being less permeable. For microcapsules, the permeation across the membrane dominates the ingress, and thicker membranes have lower permeability.

Alginates↗
PubMedDate not supplied

A new microencapsulation device for controlled membrane and capsule size distributions.

Microbeads and microcapsules, employed for the microencapsulation of bioactive material, should provide sufficient mechanical protection to the encapsulated material, insure an optimal diffusion of desired molecules and, for transplantation-related applications, block the ingress of the imunoagents. Microcapsules are also often required to be smooth, spherical, within narrow size and membrane thickness distributions. In addition, the bioactive material has to be centred within the capsule, whose size should be minimized in relation to the bioactive material in order to optimise the diffusion of active molecules. The production process of such microcapsules should respect the aforementioned constraints and, in addition, be sterile, repeatable, robust, and harmless to the bioactive material while showing a high output. Two prototypes, dedicated to the microencapsulation of bioactive materials are presented. A semi-manual device permits the control of microcapsule properties for small scale (< 10 000 microcapsules), sterile production. An 'automated reaction control' system has also been developed. The features of the former are demonstrated for the repeatable production of 400 microm-microcapsules using the alginate/cellulose sulphate/poly(methylene-co-guanidine) system. The production rate is 500 000 microcapsules/h, with a size distribution within +/-10% and membrane thickness distribution within +/-5 microm. The latter in particular is, to the authors' knowledge, better than can be achieved with currently disclosed technologies, and is due to the precise control of the reaction conditions and time.

Capsules↗
PubMedDate not supplied

Influence of alginate characteristics on the properties of multi-component microcapsules.

A variety of sodium alginates, differing in molar mass and structural composition, have been evaluated in the preparation of multi-component microbeads and microcapsules. Bead formation occurred by gelation with calcium chloride. Capsules were produced by reacting the pre-formed beads with the oligocation poly(methylene-co-guanidine). Despite the equiponderous (1:1) mixing with a second polyanion, sodium cellulose sulphate, the influence of the alginate properties remains evident. Specifically, the effect of the chemical composition was found to be more significant than that of the molar mass for both the mechanical and transport properties. Furthermore, for alginates of 73% alpha-l-guluronic acid content less shrinking was observed compared to the 38% guluronic materials. This results in the case of the same encapsulator settings in larger microsphere diameters and thicker membranes accompanied by enhanced mechanical resistance though, also, in a higher permeability for the high-G capsules. However, subsequent coating with lower molar mass alginate allows one to adjust the permeability over a broad range, suitable for cell encapsulation and immunoprotection, without compromising the durability.

Alginates↗