A number of short peptide amphiphiles consisting of dipeptides linked to fluorenylmethoxycarbonyl spontaneously form fibrous hydrogels under physiological conditions (see figure). The structural and physical properties of these gels are dictated by the amino acid sequence of the peptide building blocks, and the gels support the three‐dimensional cell culture of chondrocytes.
We highlight recent developments in hydrogel materials with biological responsiveness built in. These 'smart' biomaterials change properties in response to selective biological recognition events. When exposed to a biological target (nutrient, growth factor, receptor, antibody, enzyme, or whole cell), molecular recognition events trigger changes in molecular interactions that translate into macroscopic responses, such as swelling/collapse or solution-to-gel transitions. The hydrogel transitions may be used directly as optical readouts for biosensing, linked to the release of actives for drug delivery, or instigate biochemical signaling events that control or direct cellular behavior. Accordingly, bioresponsive hydrogels have gained significant interest for application in diagnostics, drug delivery, and tissue regeneration/wound healing
Abstract.
Stem cells are known to differentiate in response toHowever, identification of these stem cell inducing molecules is non-trivial and rational approaches to discover drugs for achieving reproducible, targeted stem cell control remain elusive. Here, we demonstrate the design of supramolecular hydrogels that allow targeting of a range of stem cell phenotypes, providing a useful platform for discovery of differentiation inducing metabolites. These gels are simple in composition, containing a fibre forming aromatic peptide amphiphile, which is coassembled with a surfactant-like amphiphile that provides hydrophilic surface functionality to the fibres. The stiffness of the gels can be precisely tuned over the entire range that is typically associated with stem cell differentiation (0.1-40 kPa).
3We demonstrate that the gels can be used to direct stem cell differentiation without the need for induction media and they are therefore ideally suited to study stem cell behaviour -including as drug discovery platforms. To achieve this, we study the cell's usage of biological small molecules, metabolites, during differentiation and select bioactive metabolites that can target bone and cartilage formation specifically. This new use of designed supramolecular biomaterials can be envisaged to remove serendipity from discovery of metabolites associated with biological processes as drug candidates. Introduction.
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