IDEA #9IGHJG Synthetic Mucins: A Versatile New Responsive Material

Key Words: glycopeptide-based hydrogels, synthetic mucins, biomimetic materials. C. What is the purpose and utility of the invention in general terms? We invented a synthetic material that mimics animal-derived mucus. It represents the first, scalable chemical synthesis of mucin-mimetic hydrogels that recapitulate all the salient structural features of mucins, including the peptidic backbone and high-grafting density pendant glycans. Mucus-inspired hydrogels could be used to address a wide range of materials needs, including as wound healing agents, tissue adhesives, articular lubrication, surgical materials, additives in cosmetics and dermatology, antiviral and antimicrobial barriers, drug delivery vehicles, and antifouling nanomaterials. Our invention provides mucus-inspired hydrogels that lead to an entirely new class of biomimetic materials that can serve needs related to adhesives that operate underwater or on tissue, wound healing agents, cell culture scaffolds, biocompatible inks for 3D printing, and lubricants. To expand the applicability of natural secreted mucuses, we present our work on scalable synthetic mucins. A glycosylated NCA monomer, Galactose-Threonine (Gal-Thr) NCA, was synthesized in gram scale. The Gal-Thr NCA monomer was subjected to ring-opening polymerization for the formation of glycopolymers with native peptide backbones. Subsequently, the Gal-Thr glycopolymers created mucus-inspired hydrogels that were analyzed for morphology and mechanical properties via Atomic Force microscopy (AFM) studies. We successfully obtained gels with lubricative and adhesive properties, with the main attribute that they are scalable and composed of synthetic polypeptides that replicate the molecular structures and properties of natural mucus. D. What un-met needs does this invention fulfill in the relevant field? Secreted mucus hydrogels have diverse functions in nature, including as adhesives, lubricants, barriers, and mineralizing and hydrating agents. Yet, there are several challenges precluding their wider adoption in materials, biotechnology, and medical applications. For example, the collection of natural mucus, such as porcine gastric mucins, can exhibit high levels of batch-to-batch variability because of pH-induced1-2 and bacterial degradation3. Additionally, natural mucus can be impractical or potentially dangerous to collect. Furthermore, the study of natural mucins requires challenging purification because mucus is a heterogeneous material containing proteins, salts, and carbohydrates4-5; adequately characterizing even a single natural mucin requires isolating a single protein from the bulk, crosslinked hydrogels, and independently determining the polypeptide and glycan structures, and the Mws of the polydisperse, stochastically structured glycoproteins6. To circumvent the challenges of understanding and implementing natural mucins for material applications, we designed mucin-inspired hydrogels that replicate the functions of their counterparts in nature. Applications include cosmetics, lubricants, joint replacements, implants, coatings, surgical adhesives.