Designing a Nitro-Induced Sutured Biomacromolecule to Engineer Electroconductive Adhesive Hydrogels

Nitro-functionality, with a large deficit of negative charge, embraces biological importance and has proven its therapeutic essence even in chemotherapy. Functionally, with its strong electron-withdrawing capability, nitro can manipulate the electron density of organic moieties and regulates cellular-biochemical reactions. However, the chemistry of nitro-functionality to introduce physiologically relevant macroscopic properties from the molecular skeleton is unknown. Therefore, herein, a neurotransmitter moiety, dopamine, was chemically modified with a nitro-group to explore its influence on synthesizing a multifunctional biomaterial for therapeutic applications. Chemically, while the nitro-group perturbed the aromatic electron density of nitrocatecholic domain, it facilitated the suturing of nitrocatechol moieties to regain its aromaticity through a radical transfer mechanism, forming a novel macromolecular structure. Incorporation of the sutured-nitrocatecholic strand (S-nCAT) in a gelatin-based hydrogel introduced an electroconductive microenvironment through the delocalization of π-electrons in S-nCAT, while maintaining its catechol-mediated adhesive property for tissue repairing/sealing. Meanwhile, the engineered hydrogel enriched with noncovalent interactions, demonstrated excellent mechano-physical properties to support tissue functions. Cytocompatibility of the bioadhesive was assessed with in vitro and in vivo studies, confirming its potential usage for biomedical applications. In conclusion, this novel chemical approach enabled designing a multifunctional biomaterial by manipulating the electronic properties of small bioactive molecules for various biomedical applications.