Using Biomimetic Polymers in Place of Noncollagenous Proteins to Achieve Functional Remineralization of Dentin Tissues

In calcified tissues such as bones and teeth, mineralization is regulated by an extracellular matrix that includes noncollagenous proteins (NCP). This natural process has been adapted or mimicked to restore tissues following physical damage or demineralization by using polyanionic acids in place of NCPs, but the remineralized tissues fail to fully recover their mechanical properties. Here, we show that pretreatment with certain amphiphilic peptoids, a class of peptide-like polymers consisting of N-substituted glycines that have defined monomer sequences, enhances ordering and mineralization of collagen and induces functional remineralization of dentin lesions in vitro. In the vicinity of dentin tubules, the newly formed apatite nanocrystals are coaligned with the c-axis parallel to the tubular periphery, and recovery of tissue ultrastructure is accompanied by development of high mechanical strength. The observed effects are highly sequence-dependent with alternating polar and nonpolar groups leading to positive outcomes, whereas diblock sequences have no effect. The observations suggest aromatic groups interact with the collagen while the hydrophilic side chains bind the mineralizing constituents and highlight the potential of synthetic sequence-defined biomimetic polymers to serve as NCP mimics in tissue remineralization.