Anna Bergstrand

Nanocomposites of polyacrylic acid nanogels and biodegradable polyhydroxybutyrate for bone regeneration and drug delivery

Biodegradable cell scaffolds and local drug delivery to stimulate cell response are currently receiving much scientific attention. Here we present a nanocomposite that combines biodegradation with controlled release of lithium, which is known to enhance bone growth. Nanogels of lithium neutralized polyacrylic acid were synthesized by microemulsion-templated polymerization and were incorporated into a biodegradable polyhydroxybutyrate (PHB) matrix. Nanogel size was characterized using dynamic light scattering, and the nanocomposites were characterized with regard to structure using scanning electron microscopy, mechanical properties using tensile testing, permeability using tritiated water, and lithium release in PBS using a lithium specific electrode. The nanogels were well dispersed in the composites and the mechanical properties were good, with a decrease in elastic modulus being compensated by increased tolerance to strain in the wet state. Approximately half of the lithium was released over about three hours, with the remaining fraction being trapped in the PHB for subsequent slow release during biodegradation. The prepared nanocomposites seem promising for use as dual functional scaffolds for bone regeneration. Here lithium ions were chosen as model drug, but the nanogels could potentially act as carriers for larger and more complex drugs, possibly while still carrying lithium.

Comparison of PEI-PEG and PLL-PEG copolymer coatings on the prevention of protein fouling

The effect of surface charge on the protein resistance of adsorbed layers of poly(ethylene imine)-[g]-poly(ethylene glycol), PEI-PEG, and poly(L-lysine)-[g]-poly(ethylene glycol), PLL-PEG, was studied. Mixed and monofunctional self-assembled monolayers, SAMs, on gold were obtained by adsorption of 16-mercapto-1-hexadecanoic acid and 16-mercapto-1-hexadecanol. The surface charge was systematically varied by changing the ratio of the two alkanethiols. The graft copolymers PEI-PEG and PLL-PEG were adsorbed at the SAMs and tested for resistance towards human serum albumin and fibrinogen. The adsorbed amount of copolymers increased with increasing negative surface charge. However, the best protein resistance was found at an intermediate surface charge. The PLL-PEG covered surfaces showed better protein resistance than the PEI-PEG covered surfaces. Thus, this work demonstrates that an adsorbed layer of PEG-grafted PEI and, in particular, PEG-grafted PLL is efficient in preventing protein adsorption when there is charge neutralization between the copolymer and the underlying surface.

Osmotic-driven mass transport of water: Impact on the adhesiveness of hydrophilic polymers

Adhesion is an important property for the functionality of many medical devices. One reason for the development of adhesive forces is dehydration caused by mass transport of water. Osmotic pressure is one main driving force for mass transport and the correlation between osmotic pressure and adhesive force has not been studied yet, which was the aim of the present study. A model system was used where a Carbopol tablet was lowered onto a 1% (w/w) agarose gel. The force required to detach the tablet (adhesive force) and the weight gain of the tablet (as a measure of transported water) were determined. Sodium chloride and mannitol were added to the agarose gel to decrease the osmotic pressure difference between the agarose gel and the partially hydrated Carbopol tablet. This resulted in a decrease of both mass transport and adhesive force. In addition, experiments with restricted water transport within the agarose gel were performed by preparing gels with different agarose concentrations. An increase of the agarose concentration resulted in decreased water transport and higher adhesive forces. Hence, the results confirmed our hypothesis that osmotic-driven mass transport and restricted mass transport of water correlate very well with the adhesive force.

Permeability of Porous Poly(3-hydroxybutyrate) Barriers of Single and Bilayer Type for Implant Applications

Poly(3-hydroxybutyrate) (PHB) is a polyester which shows excellent biocompatibility and a PHB material is therefore considered suitable for many biomedical applications. A highly porous PHB material may be designed to facilitate the transport of small molecules and body fluids or serve as a biocompatible temporary barrier. In this study, PHB films with varying degree of porosity and pore interconnectivity were made by solvent casting using water-in-oil emulsion templates of varying composition. The morphology was characterized by SEM and the water permeability of the films was determined. The results show that an increased water content of the template emulsion resulted in a film with increased porosity. A fine tuning of the film morphology of the casted films was achieved by varying the salt content of the water phase of the template emulsion. It was concluded that the major determinant of the water permeability through these films is the pore interconnectivity. Furthermore, we report on the formation and water permeability of bilayer PHB films consisting of a porous layer combined with a dense backing layer.

Towards a biosensor immunoassay of protein-bound isopeptides in human plasma.

This study demonstrates that synthetic isopeptides formed on BSA can be quantitatively analyzed by a surface plasmon resonance-based biosensor method. A monoclonal IgM antibody 81D4, that reacts with the synthetic isopeptide and also with the natural isopeptide cross-link in D-dimer (but not with its non-cross-linked fibrin monomer), was covalently immobilized to a carboxymethylated dextran surface, a CM5 surface. Its immunocapturing efficiency was found to be good. The affinity of the interaction between the monoclonal 81D4 and the synthetic isopeptide was estimated to approximately 4x10(-7)M. Good reactivity was also observed when human plasma spiked with this isopeptide was used as test solution. Cross-linked D-dimer in the plasma of patients is a marker of disseminated intravascular coagulation (DIC) which occurs late in sepsis. This biosensor method has the potential to be developed into a rapid sensitive assay for measuring the level of natural isopeptide cross-links in proteins in the plasma of patients with a suspected diagnosis of sepsis.