Targeted drug delivery and controlled drug release can be obtained using specifically designed polymers as carriers. Due to their biocompatibility and biodegradability and especially the lack of an immune response, materials made of spider silk proteins are promising candidates for use in such applications. Particles made of recombinant spider silk proteins have previously been shown to be suitable drug and gene carriers as they could readily be loaded with various drug substances or biologicals, and subsequent release was observed over a defined period of time. However, the respective substances were bound non-covalently via hydrophobic or charge−charge interactions, and hence, the release of loaded substances could not be spatio-temporally controlled.Here, we present a setup of chemically modified recombinant spider silk protein eADF4 and variants thereof, combining their well-established biocompatible properties with covalent drug binding and triggered release upon changes in the pH or redox state, respectively. The usefulness of the spider silk platform technology was shown with model substances and cytostatic drugs bound to spider silk particles or films via a pH-labile hydrazine linker as one option, and the drugs could be released from the spider silk carriers upon acidification of the environment as seen, e.g., in tumorous tissues or endo/lysosomes. Sulfhydryl-bearing spider silk variants allowed model substance release if exposed to intracellular GSH (glutathione) levels as a second coupling option. The combination of non-immunogenic, nontoxic spider silk materials as drug carriers with precisely triggerable release chemistry presents a platform technology for a wide range of applications.
Hard tissues, e.g., bone, are mechanically stiff and, most typically, mineralized. To design scaffolds for hard tissue regeneration, mechanical, physico-chemical and biological cues must align with those found in the natural tissue. Combining these aspects poses challenges for material and construct design. Silk-based materials are promising for bone tissue regeneration as they fulfill several of such necessary requirements, and they are non-toxic and biodegradable. They can be processed into a variety of morphologies such as hydrogels, particles and fibers and can be mineralized. Therefore, silk-based materials are versatile candidates for biomedical applications in the field of hard tissue engineering. This review summarizes silk-based approaches for mineralized tissue replacements, and how to find the balance between sufficient material stiffness upon mineralization and cell survival upon attachment as well as nutrient supply.
Hydrogels are widely used in various biomedical applications, as they cannot only serve as materials for biofabrication but also as depots for the administration of drugs. However, the possibilities of formulation of water‐insoluble drugs in hydrogels are rather limited. Herein, we assembled recombinant spider silk gels using a new processing route with aqueous–organic co‐solvents, and the properties of these gels could be controlled by the choice of the co‐solvent. The presence of the organic co‐solvent further enabled the incorporation of hydrophobic drugs as exemplarily shown for 6‐mercaptopurine. The developed gels showed shear‐thinning behaviour and could be easily injected to serve, for example, as drug depots, and they could even be 3D printed to serve as scaffolds for biofabrication. With this new processing route, the formulation of water‐insoluble drugs in spider silk‐based depots is possible, circumventing common pharmaceutical solubility issues.
Hydrogele finden weitreichend Anwendung in der Biomedizin, wo sie nicht nur als Material in der Biofabrikation, sondern u. a. auch als Wirkstoffdepots verwendet werden. Die Möglichkeiten, wasserunlösliche Wirkstoffe in Hydrogelen zu formulieren, sind jedoch begrenzt. In dieser Studie konnten rekombinante Spinnenseidenproteine durch ein neuartiges Herstellungsverfahren in wässrig‐organischen Mischphasen zu Gelen selbstassemblieren. Deren Eigenschaften konnten dabei durch die Wahl der Lösungsmittel kontrolliert werden. Die Gegenwart einer organischen Phase erlaubte das Einbringen hydrophober Wirkstoffe, was exemplarisch anhand von 6‐Mercaptopurin gezeigt wurde. Die entwickelten Gele zeigten scherverdünnende Eigenschaften und konnten injiziert (zum Beispiel für Anwendungen als Wirkstoffdepot) und sogar 3D‐verdruckt werden, um Gerüste für die Geweberegeneration herzustellen. Mithilfe dieser neuen Herstellungsroute können nun wasserunlösliche Wirkstoffe in Spinnenseidendepots formuliert und damit gängige pharmazeutische Löslichkeitsgrenzen überwunden werden.
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