Cytosine-Functionalized Supramolecular Polymer-Mediated Cellular Behavior and Wound Healing

Physically cross-linked supramolecular polymers composed of a hydrophobic poly(epichlorohydrin) backbone with hydrogen-bonding cytosine pendant groups and hydrophilic poly(ethylene glycol) (PEG) side chains spontaneously self-assemble to form highly controlled, reversible supramolecular polymer networks (SPNs) because of cytosine-induced transient cross-linking. Owing to their simple synthesis procedure and ease of tuning the cytosine and PEG contents to obtain varying degrees of SPNs within the polymer matrix, the resulting polymers exhibit a unique surface morphology, wide-range tunable mechanical/rheological properties, and surface wettability behavior as well as high biocompatibility and structural stability in normal cell- and red blood cell-rich media. Cell culture experiments and fluorescent images clearly demonstrated that the incorporation of cytosine and PEG units into the SPN-based polymer substrates efficiently promoted cellular attachment and accelerated cell growth. Importantly, scratch wound-healing assays revealed that the cytosine-functionalized substrates promoted rapid cell spreading and migration into the damaged cellular surface and accelerated the wound-healing rate. These results indicate that the presence of cytosine units within polymer substrates is crucial for the construction of multifunctional tissue engineering scaffolds with tailorable physical characteristics in order to promote cell adhesion, proliferation, and differentiation.