SUPRAforORGANS has delivered two significant results that pave the way for the application of 1,3,5-benzene-tricarboxamides (BTAs) based supramolecular polymers for the design of artificial extracellular matrix:
• One of the most significant parameters of the extracellular matrix is its stiffness, which has a central role in guiding the differentiation of cells. Therefore, it is of paramount importance to design strategies that enable to regulate the stiffens of hydrogels. BTA monomers give rise to weak hydrogels due to fibre entanglement with a storage modulus of ca. 20 Pa at 2 wt%. In SUPRAforORGANS, we have developed a method to prepare BTA hydrogels with tuneable stiffness by using an analogue of the natural polymer hyaluronic acid (HA). HA is a polysaccharide that is present in the extracellular matrix of all tissues because it takes part in the regulation of cellular migration and proliferation. By using our HA analogue, the storage modulus of BTA hydrogels can be increased up to 50 times, thereby allowing a wide range of stiffens that are required to direct the stem cell differentiation towards different types of specialized cells.
• In general, the only method currently available to incorporate chemical functionalities into supramolecular polymers is by covalently binding them to the supramolecular monomers. Therefore, the affinity of such molecules for the polymer fibres depends on the interaction strength between the supramolecular monomers. This strategy usually yields to functionalities strongly bonded to the polymer fibres. In SUPRAforORGANS, we aimed to find a strategy that allows attaching chemical moieties to BTA supramolecular polymers with the desired interaction strength between a molecule having the selected chemical functionality and the polymer. Importantly, BTA water-soluble supramolecular polymers require hydrophobic chains in the vicinity of the core to protect their hydrogen-bonded networks from water, thereby giving rise to hydrophobic pockets in the polymer. We found that hydrophobic molecules can interact with these pockets. This strategy could be applied to decorate BTA fibres with different chemical functionalities in a straightforward way. Furthermore, the interaction strength of such interaction could be control by the chemical nature of the hydrophobic part of the guest molecule. This approach will be ideal for attaching different biological to the polymers fibres since it has been shown that some biomolecules required to be more strongly bound to the fibres than others.
