The most striking and general property of the biological fibrous architectures in the extracellular matrix (ECM) is the strong and directional interaction between biologically active protein subunits. These fibers display rich dynamic behavior without losing their architectural integrity. The complexity of the ECM taking care of many essential properties has inspired synthetic chemists to mimic these properties in artificial one-dimensional fibrous structures with the aim to arrive at multi-component biomaterials. Due to the dynamic character required for interaction with natural tissue, supramolecular biomaterials are promising candidates for regenerative medicine. Depending on the application area, and thereby the design criteria of these multi-component fibrous biomaterials, they are used as elastomeric materials or hydrogel systems. Elastomeric materials are designed to have load bearing properties whereas hydrogels are proposed to support in vitro cell culture. Although the chemical structures and systems designed and studied today are rather simple compared to the complexity of the ECM, the first examples of these functional supramolecular biomaterials reaching the clinic have been reported. The basic concept of many of these supramolecular biomaterials is based on their ability to adapt to cell behavior as a result of dynamic non-covalent interactions. In this review, we show the translation of one-dimensional supramolecular polymers into multi-component functional biomaterials for regenerative medicine applications.

Minimally invasive intervention strategies after myocardial infarction use state‐of‐the‐art catheter systems that are able to combine mapping of the infarcted area with precise, local injection of drugs. To this end, catheter delivery of drugs that are not immediately pumped out of the heart is still challenging, and requires a carrier matrix that in the solution state can be injected through a long catheter, and instantaneously gelates at the site of injection. To address this unmet need, a pH‐switchable supramolecular hydrogel is developed. The supramolecular hydrogel is switched into a liquid at pH > 8.5, with a viscosity low enough to enable passage through a 1‐m long catheter while rapidly forming a hydrogel in contact with tissue. The hydrogel has self‐healing properties taking care of adjustment to the injection site. Growth factors are delivered from the hydrogel thereby clearly showing a reduction of infarct scar in a pig myocardial infarction model.

Liquid–liquid phase separation (LLPS) of biopolymers has recently been shown to play a central role in the formation of membraneless organelles with a multitude of biological functions^1–3. The interplay between LLPS and macromolecular condensation is part of continuing studies^4,5. Synthetic supramolecular polymers are the non-covalent equivalent of macromolecules but they are not reported to undergo LLPS yet. Here we show that continuously growing fibrils, obtained from supramolecular polymerizations of synthetic components, are responsible for phase separation into highly anisotropic aqueous liquid droplets (tactoids) by means of an entropy-driven pathway. The crowding environment, regulated by dextran concentration, affects not only the kinetics of supramolecular polymerizations but also the properties of LLPS, including phase-separation kinetics, morphology, internal order, fluidity and mechanical properties of the final tactoids. In addition, substrate–liquid and liquid–liquid interfaces proved capable of accelerating LLPS of supramolecular polymers, allowing the generation of a myriad of three-dimensional-ordered structures, including highly ordered arrays of micrometre-long tactoids at surfaces. The generality and many possibilities of supramolecular polymerizations to control emerging morphologies are demonstrated with several supramolecular polymers, opening up a new field of matter ranging from highly structured aqueous solutions by means of stabilized LLPS to nanoscopic soft matter.

The extracellular matrix (ECM) forms through hierarchical assembly of small and larger polymeric molecules into a transient, hydrogel‐like fibrous network that provides mechanical support and biochemical cues to cells. Synthetic, fibrous supramolecular networks formed via non‐covalent assembly of various molecules are therefore potential candidates as synthetic mimics of the natural ECM, provided that functionalization with biochemical cues is effective. Here, combinations of slow and fast exchanging molecules that self‐assemble into supramolecular fibers are employed to form transient hydrogel networks with tunable dynamic behavior. Obtained results prove that modulating the ratio between these molecules dictates the extent of dynamic behavior of the hydrogels at both the molecular and the network level, which is proposed to enable effective incorporation of cell‐adhesive functionalities in these materials. Excitingly, the dynamic nature of the supramolecular components in this system can be conveniently employed to formulate multicomponent supramolecular hydrogels for easy culturing and encapsulation of single cells, spheroids, and organoids. Importantly, these findings highlight the significance of molecular design and exchange dynamics for the application of supramolecular hydrogels as synthetic ECM mimics.