|
Hydrogels are key element of different TERM approaches because of their similarity with the extracellular matrix (ECM) and the possibility to adjust their properties (both mechanical and chemical) thus, tailoring cellular and tissue response. Nowadays, the main challenge in the design of biofunctional hydrogels is to understand and mimic the dynamics and complex chemical composition of the in vivo environment in which these gels are applied. Existing bioinspired supramolecular gels are typically based on peptides or polysaccharides, while natural ECM combines both. Herein, we report on a set of minimalistic biologically inspired supramolecular hydrogels that were obtained by co-assembly of simple carbohydrate and peptide amphiphiles as structural analogues of proteins and glycosaminoglycans – the main components of the ECM. We demonstrate that the co-assembly of these amphiphiles occurs under mild physiological conditions compatible with cell encapsulation process. Moreover, the assembled gels are highly hydrated and present branched nanofibril structure, which is of a similar scale to the native ECM. Finally, the obtained hydrogels have the inherent ability to respond to external stimuli, such as pH and the presence of certain protein(s), as they are assembled via weak and reversible non-covalent interactions.
We demonstrate that different functionalities (sulfate and phosphate) can be introduced in the carbohydrate amphiphiles giving rise to different bioactivities. We show that these subtle differences in the structure of the amphiphile impact tremendously on the properties of the assembled nanofibers such as branching, size and mechanical properties. The biofunctionality of the developed supramolecular gels was further tested. ECM serves as a structural support for cell adhesion which also provides biochemical information, e.g. the ECM stores, protects and activates soluble factors such as cytokines and growth factors (GFs), which involves selective binding of these GFs to ECM components. Among different families of GFs, fibroblast growth factors (FGFs) are major players in numerous physiological processes such as embryonic development, tissue repair, self-renewing proliferation and inhibition cellular senescence in nearly all tissues tested to date. FGFs are stored in the ECM by specific interaction with heparins – highly sulfated carbohydrates. We, therefore, tested the ability of the obtained gels to store and protect FGF-2 that was either encapsulated or uptaken from a solution. Our results demonstrated that the FGF-2 enhances the stability of the gels and increase their elastic moduli regardless of the used (sulphated or phosphorylated) amphiphiles. However, FGF-2 interacts specifically only with the gels assembled from the peptide and sulfated carbohydrate amphiphiles for which we observed formation of clusters from this GF. The loaded FGF-2 is stored and protected for up to 7 days in the absence of any external stimuli. We also show that the assembled gels can be used as functional supports for different cell culture, e.g. mesenchimal stem cells
|
