Recent advances in medicine and biotechnology have prompted the need to develop nanoengineered delivery systems that can encapsulate a wide variety of novel therapeutics such as proteins, chemotherapeutics, and nucleic acids. Moreover, these delivery systems should be "intelligent", such that they can deliver their payload at a well-defined time, place, or after a specific stimulus. Polymeric multilayer capsules, made by layer-by-layer (LbL) coating of a sacrificial template followed by dissolution of the template, allow the design of microcapsules in aqueous conditions by using simple building blocks and assembly procedures, and provide a previously unmet control over the functionality of the microcapsules. Polymeric multilayer capsules have recently received increased interest from the life science community, and many interesting systems have appeared in the literature with biodegradable components and biospecific functionalities. In this Review we give an overview of the recent breakthroughs in their application for drug delivery.

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Polyelectrolyte microcapsules were prepared by the layer-by-layer assembly of hyaluronic acid (HA) and a polycationic polymer, poly(allylamine) (PAH) or poly(lysine) (PLL). The influence of the polycationic partner on the morphology, stability, permeability properties, and enzymatic degradation of microcapsules was thoroughly analyzed. It was found that these properties could be tuned by shell cross-linking. Confocal microscopy studies of cellular uptake of the capsules showed that the polyelectrolyte shells remain stable outside the cells but readily break open once internalized by cells, suggesting their potential as carrier for intracellular drug delivery.

A Michael addition strategy involving the reaction between a maleimide double bond and amine group has been investigated for the synthesis of cryogels at subzero temperature (-8 o C).Low molecular weight PEG-based building blocks with amine end groups on one hand and disulfide containing building blocks with maleimide end groups on the other hand are combined to synthesize redox-responsive PEG cryogels. The cryogels exhibit an interconnected macroporous morphology, a high compressive modulus (> 100 kPa) and gelation yields of around 95%. While the cryogels are stable under physiological conditions, complete dissolution of the cryogels into water soluble products is obtained in the presence of a reducing agent (glutathione) in the medium. Cell seeding experiments and toxicologic analysis demonstrate their potential as scaffolds in tissue engineering.-2 -

Die Fortschritte der letzten Jahre in Medizin und Biotechnologie haben die Entwicklung von Transportsystemen im Nanomaßstab dringlich gemacht, die eine Vielzahl an neuartigen Therapeutika wie Proteine, Chemotherapeutika und Nucleinsäuren einschließen können. Zudem sollten diese Transportsysteme “intelligent” sein, d. h., sie sollten ihre Ladung zu einer festgelegten Zeit, an einem bestimmten Ort oder nach einer spezifischen Stimulierung abladen können. Seit polymere Mehrschichtkapseln verfügbar sind, die durch mehrstufiges Beschichten eines Opfertemplats und anschließendes Auflösen dieses Templats hergestellt werden, ist es möglich, Mikrokapseln unter rein wässrigen Bedingungen mithilfe einfacher Baustein‐ und Assoziationsverfahren gezielt herzustellen, was eine bislang unerreichte Steuerung der Mikrokapselfunktionalität erlaubt. Inzwischen sind polymere Mehrschichtkapseln auf zunehmendes Interesse in den Biowissenschaften gestoßen, und viele interessante Systeme mit bioabbaubaren Bestandteilen und biospezifischen Funktionen wurden beschrieben. In dieser Übersicht werden die neuesten Durchbrüche beim Einsatz für die Wirkstoffverabreichung vorgestellt.

Aortic heart valve disease is a growing health problem and a tissue-engineered aortic heart valve could be a promising therapy. In this paper, decellularized porcine aortic heart valve leaflets are used as scaffolds and loaded with growth factor and heparin via layer-by-layer electrostatic deposition (LbL technique) with the final purpose to stimulate and control cellular processes. Binding and subsequent release of heparin and basic fibroblast growth factor (bFGF) from aortic valve leaflets were assessed qualitatively by immunohistochemistry and quantitatively by radioactive labeling methods. It was observed that the amount of heparin and bFGF bound to aortic heart valve leaflets was directly proportional to the concentration of heparin and bFGF in the incubation medium. Release of heparin and bFGF from the decellularized heart valve leaflets at physiological conditions was sustained over 4 days while preserving the biological activity of the released growth factor.

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Here we present a facile method to fabricate microporous hydrogel scaffolds that can be functionalized with a chemokine gradient. These scaffolds allow studying cellular responses in a 3D environment.