Trimethylamine N-Oxide (TMAO)-Derived Zwitterionic Hydrogels for Implantable Materials to Combat Biological Contamination

Hydrogels exhibiting excellent biocompatibility and resistance to foreign body response (FBR) hold significant promise in the biomedical field. In this study, we developed a photopolymerized hydrogel named poly(3,3′-((2-(2-((3-methacrylamidopropyl)amino)-2-oxoethyl)-4-((3-methacrylamidopropyl)carbamoyl)-2,4-dimethylhexanedioyl)bis(azanediyl))bis(N,N-dimethylpropan-1-amine oxide))(PIAPMANO_X), whose prepolymer is based on poly(itaconic acid)(PIA) and is grafted with varying ratios of zwitterionic trimethylamine N-oxide (TMAO) derivatives and N-(3-aminopropyl)methacrylamide hydrochloride (APMA). The TMAO derivatives possess the ability to form a compact hydration layer due to their distinctive properties─namely, the minimal spacing between zwitterionic groups, the robust hydrogen bonding interactions, the smallest net charge, and the lowest dipole moment. These characteristics collectively promote the establishment of a tightly packed hydration shell that effectively inhibits nonspecific adsorption of substances such as proteins and cells. Meanwhile, APMA contributes a carbon–carbon double bond that promotes photoinitiated radical polymerization for constructing a three-dimensional hydrogel network. Among the various materials studied, the hydrogel PIAPMANO_X, which incorporates the zwitterionic TMAO, demonstrates exceptional performance in terms of protein and cell rejection. The hydrogel was implanted into the peritoneal cavity of mice. Experimental results demonstrated that this hydrogel significantly reduced FBR, with no notable inflammatory reaction observed and a decrease in fibrosis. Therefore, the PIAPMANO_X series introduces innovative nontoxic zwitterionic materials to the field of biomaterials.