Multi-functional effects of a nitric oxide-conjugated copolymer for accelerating palatal wound healing

Highlights: • Exogenous nitric oxide donor is synthesized with co-polymer of Pluronic F68 and Branched polyethyleneimine. • The developed nitric oxide donor is biocompatible to improve cell migration and angiogenesis. • Nitric oxide delivered to the oral defects can accelerate the palatal wound healing. The damaged site of a palatal wound is difficult to repair and often remains unclosed due to failure of the healing process, which occurs in inadequate environments of the oral cavity. Nitric oxide (NO) has effective functions in repairing damaged tissues, but it has a limitation due to short lifetime and rapid diffusion. Here, we synthesize a donor to deliver exogenous NO gas and verify its therapeutic effect for the palatal wound healing, which is known to take longer for healing due to the poor environment of warm saliva containing millions of microbes. NO was incorporated into the synthetic polymer and the NO-donors were characterized based upon their ability to release NO. The NO donor not only reduced cytotoxicity but also increased migration and proliferation in gingival fibroblasts. Moreover, the angiogenic capacity was improved by NO-donor treatment. In the palatal wound model, the NO-treatment was involved in enhancing the biological responses associated with wound healing. This strategy suggests that treatment involving controlled NO release may have beneficial effects on palatal wound healing.