Lignin-Incorporated Nanogel Serving As an Antioxidant Biomaterial for Wound Healing

Oxidative phosphorylation is an important biological process in the body to produce energy, during which oxygen free radicals are generated as byproduct. Excessive oxygen free radicals cause cell death and reduce the rate of tissue regeneration and healing in a wound. Lignin is a natural antioxidant derived from plants, but its biomedical application is restricted because of the uncertain biocompatibility. In this work, we developed a lignin-incorporated nanogel and explored its application for wound healing. Lignin was extracted from coconut husks and determined to have strong antioxidant activity (IC₅₀ = 25.7 ppm). Various amounts of lignin were incorporated into thermoresponsive nanogels, which were produced from polyurethane copolymers of polyethylene glycol (PEG), polypropylene glycol (PPG), and polydimethylsiloxane (PDMS). It was shown that the addition of lignin had minimal effects on the gelation and rheological properties of the nanogel but slightly increased the critical micelle concentration (CMC) of poly(PEG/PPG/PDMS urethane) copolymer from 3.38 × 10^-4 g mL^-1 to 4.61 × 10^-4 g mL^-1. The lignin-incorporated nanogels did not display detectable cytotoxicity. The lignin-incorporated nanogel possessed antioxidant activity, as it reduced the active oxygen level, protecting the LO2 cells from apoptosis caused by oxidative stress. More importantly, in vivo studies demonstrated that the lignin-incorporated nanogels accelerated the healing of burn wounds in mice as proved by the increased expression of Ki67, one marker of cell proliferation. The present work demonstrates that lignin-incorporated nanogel could serve as an antioxidant wound-dressing material and facilitate the wound healing.