The effect of peptide charge on the self-assembly and gelation behaviour of three octa-peptides: VEVKVEVK (VEK2), VKVKVEVK (VEK3) and VEVEVKVE (VEK1) has been investigated and characterised. The critical gelation concentration of each peptide was found to correlate with the charge modulus carried by the peptide and to be independent of the sign of the charge. Hydrogels formed were found to be transparent and stable when the peptide charge modulus is > 1. No differences in hydrogel structure or mechanical properties, as probed by TEM and SAXS and shear rheology, were found when the peptides were at the same concentration and carried the same charge modulus. These peptides were shown to form dense fibrillar network formed by β-sheet rich single fibre which lateral aggregation is controlled by the peptide charge modulus. The increase in fibre lateral aggregation with decreasing charge modulus was found to correlate with the increase in hydrogel mechanical properties, showing that fibre lateral aggregation pays a key role in controlling the mechanical properties of these hydrogels. The release profiles from VEK1 and VEK3 at pH 7 of two hydrophilic model drug molecules, namely napthol yellow (NY) and martius yellow (MY) was analysed using UV-Vis spectrophotometry. The incorporation of the guest molecules did not affect the self-assembly of the peptide at a molecular level but did affect the level of lateral fibre aggregation observed and therefore the mechanical properties of the hydrogels. The release of each of the model compounds was monitored over time and shown to be controlled by Fickian diffusion. The guest molecule diffusion rate D was dependent on the ratio between the overall effective charges carried by the peptide, i.e.: the fibrillar network, and the overall charges carried by the guest molecules but independent from the hydrogel concentration and mechanical properties, in the concentration and guest loading range investigated. This work shows that the rate of release of small drug molecules can be manipulated, not only by changing the charges on the guest molecules, but also by manipulating the charged state of the self-assembling peptide molecule and through it the charge state of the fribrillar network. Furthermore the VEK3 system was conjugated to a series of thermo-responsive synthetic polymers which imparted a significant change in mechanical properties, assembled structures and release profiles upon heating. Observed changes when above the polymers LCST include increased mechanical strength, fibre thickening and increased diffusion coeffcients. The synthesis, and subsequent characterisation, of these materials is the first time responsive hydrogels of OEGMA copolymers has been reported.

Inspiriert durch natürliche Grenzflächenproteine in Knochen wurden bifunktionale Biokonjugate für verschiedene Grenzflächenstabilisierungen genutzt. In einem kombinatorischen Ansatz wurden materialspezifische Peptid-block-Polyethylenglycol-Konjugate eingesetzt, um die Grenzflächen von Nanopartikeln in Lösung sowie in Polymerkompositen zu stabilisieren. Dazu wurden biokombinatorisch ausgewählte Peptid-Sequenzen mit einer Affinität für MgF2-Oberflächen in Form eines MgF2-bindenden Konjugats (MBC) synthetisiert, welches die materialaffine Bindung der monodispersen Peptid-Domäne mit der zusätzlichen Funktion des synthetischen Polymer-Blocks verbindet. Aus detaillierten Untersuchungen der Bindungseigenschaften von MBC und davon abgeleiteten Konjugaten mit variierten Peptidarchitekturen bzw. Polymer-Blocklängen bei verschiedenen Inkubationsbedingungen ging hervor, dass das sequenzspezifisch bindende MBC das Potenzial zur Stabilisierung von MgF2-Nanopartikeln hat. Das Konjugat verhinderte die Agglomeration der Partikel und ermöglichte im Gegensatz zu etablierten Stabilisatoren die vollständige Redispergierbarkeit sogar nach Eintrocknung. Die Stabilisierung in Lösung wurde auf die Kompatibilisierung von Partikeln in Polycaprolacton (PCL)-Kompositen übertragen, in denen das grenzflächenaktive MBC die Materialeigenschaften von bioabbaubaren PCL/MgF2-Kompositen optimierte. Die Grenzflächenstabilisierung führte zur gleichzeitigen Erhöhung der Steifigkeit und der Zähigkeit der Materialien bis in den Bereich natürlicher Knochen. Durch die gemeinsame Zugabe von MBC-kompatibilisiertem MgF2 und Hyxdroxylapatit zu PCL wurde ein bioaktives Material geschaffen, das nachweislich die osteogene Differenzierung von mesenchymalen Stammzellen und die Mineralisierung von neuem Knochengewebe unterstützte. Damit stellt es ein vielversprechendes Komposit für die Regeneration von Knochengewebe und weitere Anwendungen dar. / Inspired by natural interface proteins in bone, bifunctional bioconjugates were exploited for different interface stabilization applications. The interfaces of nanoparticles both in solution and in polymeric composites were stabilized by combinatorially selected, material specific peptide-polymer conjugates. Peptide sequences showing affinity to MgF2 particle surfaces were selected from a phage display library and translated into a MgF2-binding peptide-block-poly(ethylene glycol) conjugate (MBC). The MBC combined the material-affine binding of the monodisperse peptide domain with an additional function of a synthetic polymer block. Detailed studies of the binding properties of MBC and congeneric conjugates with other peptide architectures or different polymer block lengths, as well as varied incubation conditions revealed the potential of the sequence-specific MBC to stabilize MgF2 nanoparticles in solution. The conjugate inhibited the agglomeration of the particles. In contrast to established stabilizers, it enabled fully redispersable nanoparticles even after complete drying. The stabilization approach in solution was expanded to the compatibilization of the particles in polycaprolactone (PCL) composites. Inspired by the structure of highly specific interface proteins, MBC optimized the material properties of biodegradable PCL/MgF2 composites. Additionally, the interface stabilization simultaneously increased both the stiffness and the toughness of the composites up to the range of natural bone. The addition of hydroxyapatite alongside MBC-compatibilized MgF2 to PCL created a bioactive material that showed enhanced osteogenic differentiation of mesenchymal stem cells and the mineralization of new bone tissue. Therefore, a mechanically reinforced, osteoinductive material was prepared showing high potential in extensive in vitro studies for biomedical applications such as guided bone regeneration, yet not limited to that.