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Biomedical subjects

Christine Wandrey

Publications and source records attributed to Christine Wandrey.

7 recordsLinked to original sources
PubMed2005

Nonspherical assemblies generated from polystyrene-b-poly(L-lysine) polyelectrolyte block copolymers.

This report describes the aqueous solution self-assembly of a series of polystyrene(m)-b-poly(L-lysine)n block copolymers (m = 8-10; n = 10-70). The polymers are prepared by ring-opening polymerization of epsilon-benzyloxycarbonyl-L-lysine N-carboxyanhydride using amine terminated polystyrene macroinitiators, followed by removal of the benzyloxycarbonyl side chain protecting groups. The critical micelle concentration of the block copolymers determined using the pyrene probe technique shows a parabolic dependence on peptide block length exhibiting a maximum at n = approximately 20 (m = 8) or n = approximately 60 (m = 10). The shape and size of the aggregates has been studied by dynamic and static light scattering, small-angle neutron scattering (SANS), and analytical ultracentrifugation (AUC). Surprisingly, Holtzer and Kratky analysis of the static light scattering results indicates the presence of nonspherical, presumably cylindrical objects independent of the poly(L-lysine)n block length. This is supported by SANS data, which can be fitted well by assuming cylindrical scattering objects. AUC analysis allows the molecular weight of the aggregates to be estimated as several million g/mol, corresponding to aggregation numbers of several 10s to 100s. These aggregation numbers agree with those that can be estimated from the length and diameter of the cylinders obtained from the scattering results.

Journal Article↗
PubMed2005

Effect of microcapsule composition and short-term immunosuppression on intraportal biocompatibility.

With higher nutrient and oxygen supply and close contact to blood, the portal vein is a possible alternative to the peritoneal cavity for transplantation of encapsulated cells. Data regarding intraportal biocompatibility of microcapsules are lacking. Microcapsules were built from five alginate types differing in their molar mass and mannuronic/guluronic acid ratios by complex formation with divalent cations (barium or calcium) or mixtures of divalent cations and polycations. They were injected in the portal vein of rats, and cellular and fibrotic pericapsular infiltration thickness was measured 3 and 7 days after implantation. Overgrowth was characterized using various stainings or immunohistochemistry (hematoxylin and eosin, Giemsa, ED-1 for monocyte/macrophage, alpha-actin for myofibroblasts, CD31 for endothelial cells). The impact of short-term immunosuppression (gadolinium-chloride IV 20 mg/kg/day on days--1 and 4 as well as 10 days of rapamycin PO 1 mg/kg/day, tacrolimus PO 3 mg/kg/day, or combinations of rapamycin/tacrolimus or gadolinium/tacrolimus) was further assessed 3, 7, and 42 days after implantation. Overall, overgrowth increased from day 3 to day 7 (p < 0.05). Three and 7 days after implantation, polycation-containing microcapsules induced more reaction than microbeads (p < 0.0001 and p < 0.01). Considering polycation-free beads, barium-alginate induced the weakest reaction. Biocompatibility of microbeads was independent of mannuronic/guluronic acid ratio and molar mass of the alginate. Infiltration was mainly a monocyte/macrophage-rich foreign body reaction, but an eosinophil-containing immunoallergic reaction was also observed. Short-term immunosuppression significantly reduced infiltration in all conditions and up to 42 days after implantation. Biocompatibility after intraportal infusion was best for barium-alginate microbeads and poorest for polycation-containing microcapsules. Short- and long-term overgrowth could be significantly reduced by short-term immunosuppression.

Alginates↗
PubMed2004

Hydrogel microspheres: influence of chemical composition on surface morphology, local elastic properties, and bulk mechanical characteristics.

Hydrogel microspheres, beads, and capsules of uniform size, differing in their chemical composition, have been prepared by electrostatic complex formation of sodium alginate with divalent cations and polycations. These have served as model spheres to study the influence of the chemical composition on both surface characteristics and bulk mechanical properties. Resistance to compression experiments yielding the compression work clearly identified differences as a function of the composition, with forces at maximal compression in the range of 34-455 mN. The suitability and informative value of atomic force microscopy have been confirmed for the case where surface characterization is performed in a liquid environment equivalent to physiological conditions. Surface imaging and mechanical response to indentation revealed different average surface roughness and Young's moduli for all hydrogel types ranging from 0.9 to 14.4 nm and from 0.4 to 440 kPa, respectively. The hydrogels exhibited pure elastic behavior. Despite a relatively high standard deviation, resulting from both surface and batch heterogeneity, nonoverlapping ranges of Young's moduli were reproducibly identified for the selected model spheres. The findings indicate the reliability of contact mode atomic force microscopy to quantify local surface properties, which may have an impact on the biocompatibility of alginate-based hydrogel materials of different composition and conditions of preparation. Moreover, it seems that local elastic properties and bulk mechanical characteristics are subject to analogous composition influences.

Journal Article↗
PubMed2004

Adsorption of charged macromolecules on oppositely charged porous column materials.

A family of cationic polyelectrolytes possessing defined chain lengths, narrow chain length distributions, uniform charge density, but substituents of different hydrophilicity at the quaternary ammonium group served as model compounds for adsorption studies. These studies quantitatively revealed that polymer characteristics and electrostatic parameters affect the adsorption behavior on oppositely charged porous column materials. The presence of electrostatic exclusion, in addition to size exclusion, was proved comparing molecular, electrostatic and geometrical parameters. The dominance of electrostatic effects could be concluded evaluating the relation between molecular and electrostatic dimensions. The results provide a contribution how to estimate the threshold for electrostatic exclusion from pores as a function of dimensions and experimental conditions.

Adsorption↗
PubMed2003

Investigation of particle-based and monolithic columns for cation exchange protein displacement chromatography using poly(diallyl-dimethylammonium chloride) as displacer.

The overall topic of the investigation was the separation of basic proteins by cation exchange displacement chromatography. For this purpose two principal column morphologies were compared for the separation of ribonuclease A and alpha-chymotrypsinogen, two proteins found in the bovine pancreas. These were a column packed with porous particles (Macro-Prep S, 10 microm, 1000 A) and a monolithic column (UNO S1). Both columns are strong cation exchangers, carrying -SO3(-)-groups linked to a hydrophilic polymer support. Poly(diallyl-dimethylammonium chloride) (PDADMAC), a linear cationic polyelectrolyte composed of 100-200 quaternary pyrrolidinium rings, was used as displacer. The steric mass action (SMA) model and, in particular, the operating regime and dynamic affinity plots were used to aid method development. To date the SMA model has been applied primarily to simulate non-linear displacement chromatography of proteins using low molar mass displacers. Here, the model is applied to polyelectrolytes with a molar mass below 20000 g mol(-1), which corresponds to a degree of polymerization below 125 and an average contour length of less than 60 nm. The columns were characterized in terms of the adsorption isotherms (affinity, capacity) of the investigated proteins and the displacer.

Cation Exchange Resins↗
PubMed2003

Intra-portal injection of 400- microm microcapsules in a large-animal model.

To date, encapsulated grafts have usually been implanted in the peritoneal cavity. This site is, however, not ideal, mainly because of its low blood supply. We have investigated the feasibility of intra-portal injection of (400 microm) microcapsules in the pig. Ten-thousand microcapsules per kilogram body weight were injected into six Large White pigs. Portal pressure, various biological tests, portographies and liver histology were recorded before and at various time points after injection. As a result, portal pressure increased after injection (15+/-2.3 vs 8.7+/-1.7 mmHg) but remained within an acceptable range (<20 mmHg) and returned to normal values at 3 months (8.5+/-3.7 mmHg). During the 3-month follow up, liver function and liver tests remained stable. Portographies showed a homogenous implantation of the capsule, with the portal flow always directed to the liver. At histological examination after 3 months the capsules demonstrated various degrees of fibrosis. We can thus conclude that these results demonstrate that intra-portal injection of microcapsules is feasible in a large-animal model. Hemodynamic, biological and radiological results are similar to those observed in clinical free-islet transplantation.

Animals↗