Synthesis of biofunctional supramolecular hydrogels by co-assembly of simple carbohydrate and peptide amphiphiles

Hydrogels are widely used in different biomedical areas such as tissue engineering and regenerative medicine because their mechanical properties together with the chemical composition can be tailored to influence tremendously both cellular and tissue compatibility.[1] However, tailoring the hydrogel properties is not a straightforward task as changes in chemical composition often result in altered mechanical properties. Another challenge in the design of biofunctional hydrogels is the dynamic of the in vivo environment in which these gels are applied: synthesis of smart materials that are environmental responsive is in the focus of the contemporary biomaterial field.

Herein, we report on a strategy that uses short amphiphiles to obtain supramolecular hydrogels with tuned properties. In this strategy the chemistry of the gel is determined by the structure of the amphiphile(s), while its mechanical properties are tailored by adjusting the amphiphile(s) concentration.[2] We have used simple carbohydrate and peptide amphiphiles as structural analogues of proteins and glycosaminoglycans (GAGs) – the main components of the extracellular matrix (ECM). The co-assembly of these amphiphiles occurs under mild physiological conditions and have the inherent ability to respond to external stimuli, such as pH and temperature, as they are assembled via weak and reversible non-covalent interactions. Moreover, the assembled gels are highly hydrated and present nanofibril structure, which is of a similar scale to the native ECM.

One of the key roles of the ECM is to store and protect soluble factors such as cytokines and growth factors via specific interactions with ECM components such as glycosaminoglycans Fibroblast growth factors (FGFs) and their receptors 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. Therefore, we tested the FGF-2 uptake and release from the prepared gels. Our results demonstrated that in the presence of the growth factor more stable gels with a higher elastic moduli are formed regardless of the used amphiphiles. In the absence of any external stimuli, the gels did not release most of the encapsulated FGF and protected it. However, FGF-2 interact specifically only with the sulfated gels for which we have observed formation of clusters from the growth factor. Finally, we show that the assembled gels are compatible with different cells, e.g. adipose-derived stem cells and bone marrow stem cells.