Multifunctional use of casein as release system and blocking layer for implant coatings

In situ tissue engineering requires to functionalize the surfaces of implants, to achieve better biocompatibility or to release pharmaceuticals. Often a burst release of such pharmaceuticals takes place and the surface functionality is gone rapidly. Casein-micelles (M-Cas) offer unique release capabilities for hydrophobic and hydrophilic substances. In this work, M-Cas were reconstructed and used as release system for curcumin as a model drug. Modified electrospun polycaprolactone (PCL)-fiber mats were coated with chitosan / tripolyphosphate nanoparticles (CS/TPP-NP) and functionalized with the reconstructed M-Cas. [1] CS/TPP-NPs and Na-caseinate (Cas) were used as blocking layer to slow down the release of curcumin loaded micelles. The layers were investigated by surface zeta-potential (ZP). The release of the curcumin from surfaces was possible and the blocking layers had a significant influence on the kinetics

Electrospinning, photocrosslinking of Arylazide Chitosan Nanofibers and Application as Biocatalyst Support Matrix

A process yielding water stable chitosan nanofiber mats is described and their significance in the field of biocatalyst immobilization is proven. Electrospinning was adapted to produce nanofibers from chitosan derivatives bearing photoreactive arylazide groups. These photoreactive groups of chitosan were then crosslinked by irradiation with UV-light. This stabilizes the fiber morphology even upon incubation in water and provides an alternative to crosslinking with harmful chemicals. Applicability of the fiber mats as enzyme immobilization matrix was demonstrated, using β-D-galactosidase as model enzyme. Although an initial leaching of enzyme was observed, after 40 days of incubation a significant portion of active enzyme is still present on the fibers. Thus, the fiber mats are suitable matrices to support enzymes and can revolutionize future enzymatic production processes of e.g. active pharmaceutical ingredients

Optimization of Critical Parameters for Carbodiimide Mediated Production of Highly Modified Chitosan

An optimization of the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and hydroxy benzotriazole mediated conjugation of the polysaccharide chitosan with functional carboxylic acids was shown. Optimal parameters that enable resource-efficient synthesis of highly functionalized chitosan were identified. In particular, use of only catalytic instead of stoichiometric amounts of hydroxy benzotriazole and tight control of pH in reaction mixture resulted in highly efficient incorporation of the desired moieties as side chains in chitosan. As a result, the model reactant 4-azidobenzoic acid was incorporated resulting in a degree of substitution of over 30% with very high coupling efficacy of up to 90%. Similar results were obtained with other carboxylic acids such as methacrylic acid, 3-(2-furyl) propionic acid and 3-maleimido propionic acid, highlighting the broad applicability of our findings for the functionalization of chitosan

Temperature-triggered liquefication of hydrogels for intentional implant removal

The Diels-Alder (DA) reaction is one of the most studied thermoreversible reactions, suitable for the preparation of thermoreversible crosslinked materials. In this study, temperature- triggered liquefaction of DA hydrogels will be investigated. A DA model reaction is used to determine the retro- DA temperature of the two stereoisomers. A hydrogel based on furan-functionalized Poly-(N-(2-hydroxy-propyl) methacryl amide (PHPMA) and 4-arm-polyethylene glycol (PEG) with maleimide endgroups is rheologically investigated and liquefaction experiments are performed

Mechanical Adaptive Silicone Composites for UV-triggered Facilitated Cochlear-Implant Removal

The removal of the cochlear implant (CI), which in some cases is without alternative, is still an act of simple pulling, not only causing harm for the patient by damaging tissue but also making reimplantation more difficult. For that reason, it is necessary to develop mechanisms to make an explantation easier. To overcome this problem adaption of the mechanical properties by light-degradable periodic mesoporous organosilica (PMO) can be one solution. By introducing PMO nanoparticles into the CI's silicone matrix, the particles act as a stiffening agent, which can be degraded by irradiation with UV light. Using this mechanism, the silicone becomes softer, thus making explantation easier and safer for patients. Here first results, concerning the creation of a silicone composite material with light-sensitive adaptive mechanical properties are reported

Core-Shell-Nanoparticles with Superparamagnetic Properties for Novel Applications as Biomaterials

Due to the increasing average age of the population, the number of implants is also increasing and with it the number of explantations. Therefore, facilitated implant removal is of great interest. A nanocomposite consisting of superparamagnetic core-shell nanoparticles (CSNPs) and a synthetic polymer is supposed to be used as implant coating, aiming for a stimulus-inducible modification of the composite's rheological properties by hyperthermia. Here, the first steps following this concept, the synthesis and modification of the CSNP are reported. In this work magnetite nanoparticles build the core and are surrounded by a periodic mesoporous organisilica (PMO) shell. For this reason, the CSNP are referred to as magnetic PMO (mPMO) particles in the following

Enzyme-Responsive Nanoparticles and Coatings Made from Alginate/Peptide Ciprofloxacin Conjugates as Drug Release System

Infection-controlled release of antibacterial agents is of great importance, particularly for the control of peri-implant infections in the postoperative phase. Polymers containing antibiotics bound via enzymatically cleavable linkers could provide access to drug release systems that could accomplish this. Dispersions of nanogels were prepared by ionotropic gelation of alginate with poly-L-lysine, which was conjugated with ciprofloxacin as model drug via a copper-free 1,3-dipolar cy-cloaddition (click reaction). The nanogels are stable in dispersion and form films which are stable in aqueous environments. However, both the nanogels and the layers are degraded in the presence of an enzyme and the ciprofloxacin is released. The efficacy of the released drug against Staphylococcus aureus is negatively affected by the residues of the linker. Both the acyl modification of the amine nitrogen in ciprofloxacin and the sterically very demanding linker group with three annel-lated rings could be responsible for this. However the basic feasibility of the principle for enzyme-triggered release of drugs was successfully demonstrated

Nanoporous silica nanoparticles with spherical and anisotropic shape as fillers in dental composite materials

The objective of this study was to test whether nanoporous silica nanoparticles can be employed as fillers in dental composite materials to improve their mechanical properties. These nanoporous silica nanoparticles were synthesized using sol-gel methods, in part modified by silanization, and thoroughly characterized. The nanoporous nanoparticles were added to dental resins to form nanocomposites (resins impregnated with nanoparticles) and hybrid composites (containing in addition conventional microfillers). The incorporation of these nanoporous nanoparticles in dental resins or composites was characterized by investigation of the complex viscosity and double bond conversion as well as by determination of flexural strength and Young's modulus. The dispersion of the nanofillers was examined by SEM and EDX imaging of fracture surfaces. Incorporation of small contents (1-3 wt%) of unmodified nanoporous particles leads to improved mechanical properties. However, the incorporation of larger contents results in particle agglomeration and declining mechanical properties. This effect is less pronounced when the surface of the particles is modified with methacrylate residues, resulting in a lower agglomeration tendency and a more homogeneous filler dispersion. Surface properties and, concomitantly, dispersibility of the nanoparticles have a strong influence on mechanical properties. But the incorporation of nanoporous instead of solid nanoparticles into dental composite materials is indeed a possibility to improve the mechanical behavior. However, modification of the surface is necessary and the key to achieving uniform dispersion and, thereby, improving mechanical properties

ELISA- and Activity Assay-Based Quantification of BMP-2 Released In Vitro Can Be Biased by Solubility in “Physiological” Buffers and an Interfering Effect of Chitosan

Chitosan nanogel-coated polycaprolactone (PCL) fiber mat-based implant prototypes with tailored release of bone morphogenic protein 2 (BMP-2) are a promising approach to achieve implant-mediated bone regeneration. In order to ensure reliable in vitro release results, the robustness of a commercially available ELISA for E. coli-derived BMP-2 and the parallel determination of BMP-2 recovery using a quantitative biological activity assay were investigated within a common release setup, with special reference to solubility and matrix effects. Without bovine serum albumin and Tween 20 as solubilizing additives to release media buffed at physiological pH, BMP-2 recoveries after release were notably reduced. In contrast, the addition of chitosan to release samples caused an excessive recovery. A possible explanation for these effects is the reversible aggregation tendency of BMP-2, which might be influenced by an interaction with chitosan. The interfering effects highlighted in this study are of great importance for bio-assay-based BMP-2 quantification, especially in the context of pharmaceutical release experiments

Chitosan-Azide Nanoparticle Coating as a Degradation Barrier in Multilayered Polyelectrolyte Drug Delivery Systems

Therapeutics, proteins or drugs, can be encapsulated into multilayer systems prepared from chitosan (CS)/tripolyphosphat (TPP) nanogels and polyanions. Such multilayers can be built-up by Layer-by-Layer (LbL) deposition. For use as drug-releasing implant coating, these multilayers must meet high requirements in terms of stability. Therefore, photochemically crosslinkable chitosan arylazide (CS-Az) was synthesized and nanoparticles were generated by ionotropic gelation with TPP. The particles were characterized with regard to particle size and stability and were used to form the top-layer in multilayer films consisting of CS-TPP and three different polysaccharides as polyanions, namely alginate, chondroitin sulfate or hyaluronic acid, respectively. Subsequently, photo-crosslinking was performed by irradiation with UV light. The stability of these films was investigated under physiological conditions and the influence of the blocking layer on layer thickness was investigated by ellipsometry. Furthermore, the polyanion and the degree of acetylation (DA) of chitosan were identified as additional parameters that influence the film structure and stability. Multilayer systems blocked with the photo-crosslinked chitosan arylazide showed enhanced stability against degradation