Amyloidoses include a large variety of local and systemic diseases that share the common feature of protein unfolding or refolding into amyloid fibrils. The most studied amyloids are those directly involved in neurodegenerative diseases, while others, such as those formed by insulin, are surprisingly far less studied. Insulin is a very important polypeptide that plays a variety of biological roles and, first and foremost, is at the basis of the therapy of diabetic patients. It is well-known that it can form fibrils at the site of injection, leading to inflammation and immune response, in addition to other side effects. In this concise review, we analyze the current knowledge on insulin fibrillation, with a focus on the development of peptide-based inhibitors, which are promising candidates for their biocompatibility but still pose challenges to their effective use in therapy.

There is an increasing interest towards the development of new antimicrobial coatings, especially in light of the emergence of antimicrobial resistance (AMR) towards common antibiotics. Cyclodipeptides (CDPs) or diketopiperazines (DKPs) are attractive candidates for their ability to self-assemble into supramolecular polymers and yield gel coatings that do not persist in the environment. In this work, we compare the antimicrobial cyclo(Leu-Phe) with its heterochiral analogs cyclo(D-Leu-L-Phe) and cyclo(L-Leu-D-Phe), as well as cyclo(L-Phe-D-Phe), for their ability to gel. The compounds were synthesized, purified by HPLC, and characterized by ¹H-NMR, ¹³C-NMR, and ESI-MS. Single-crystal X-ray diffraction (XRD) revealed details of the intermolecular interactions within the supramolecular polymers. The DKPs were then tested for their cytocompatibility on fibroblast cells and for their antimicrobial activity on S. aureus. Overall, DKPs displayed good cytocompatibility and very mild antimicrobial activity, which requires improvement towards applications.

Cyclodipeptides (CDPs) or diketopiperazines (DKPs) are often found in nature and in foodstuff and beverages and have attracted great interest for their bioactivities, biocompatibility, and biodegradability. In the laboratory, they can be prepared by green procedures, such as microwave-assisted cyclization of linear dipeptides in water, as performed in this study. In particular, five CDPs were prepared and characterized by a variety of methods, including NMR and ESI-MS spectroscopies and single-crystal X-ray diffraction (XRD), and their cytocompatibility and anti-aging activity was tested in vitro, as well as their ability to penetrate the different layers of the skin. Although their mechanism of action remains to be elucidated, this proof-of-concept study lays the basis for their future use in anti-age cosmetic applications.

Despite recent significant advances in the controlled assembly of protocell units into complex 3D architectures, the development of prototissues capable of mimicking the sophisticated energy transduction processes fundamental to living tissues remains a critical unmet challenge in bottom‐up synthetic biology. Here a synthetic approach is described to start addressing this challenge and report the bottom‐up chemical construction of a photonastic prototissue endowed with photo‐mechano‐chemical transduction capabilities. For this, novel protocells enclosing photothermal transducing proto‐organelles based on gold nanoparticles and a thermoresponsive polymeric proto‐cortex are developed. These advanced protocell units are assembled into prototissues capable of light‐induced reversible contractions and complex motions, which can be exploited to reversibly switch off a coordinated internalized enzyme metabolism by blocking the access of small substrate molecules. Overall, the work provides a synthetic pathway to constructing prototissues with sophisticated energy transduction mechanisms, enabling the rational design of emergent behaviors in synthetic materials and addressing critical challenges in bottom‐up synthetic biology and bioinspired materials engineering.

Nanocomposite hydrogels have attracted researchers’ attention in recent years to achieve superior performances in a variety of materials applications. In this work, we describe the outcome of three different strategies to combine a self-assembling tripeptide and carbon nano-onions (CNOs), through covalent and non-covalent approaches, into supramolecular and nanostructured hydrogels. Importantly, the tripeptide coated the nano-onions and extended their aqueous dispersions’ stability by several hours. Furthermore, CNOs could be loaded in the tripeptide hydrogels at the highest level ever reported for nanocarbons, indicating high compatibility between the components. The materials were formed in phosphate-buffered solutions, thus paving the way for biological applications, and were characterized by several spectroscopic, microscopic, thermogravimetric, and rheological techniques. In vitro experiments demonstrated excellent cytocompatibility.

Bio‐inspired approaches in materials science and systems chemistry are yielding a variety of stimuli‐responsive and dynamic materials that are gradually changing our everyday life. However, the ability to chemically program these materials to exhibit macroscopic higher‐order behaviours such as self‐assembly, contractility, swarming, taxis, chemical communication, or predator‐prey dynamics remains an ongoing challenge. While still in its infancy, the successful fabrication of bio‐inspired materials displaying higher‐order behaviours not only will help bridging the gap between living and non‐living matter, but it will also contribute to the development of advanced materials for potential applications ranging from tissue engineering and biotechnology, to soft robotics and regenerative medicine. Our Mini‐Review will systematically discuss the higher‐order behaviours developed thus far in bio‐inspired systems, namely (i) polymer networks (ii) microbots, (iii) protocells, and (iv) prototissues. For each system it will provide key examples and highlight how the emergent behaviour could be chemically programmed.