BACKGROUNDNitric oxide (NO) is a signaling molecule that plays many roles during infection, inflammation, and wound healing processes. Due to the role of NO in wound repair, a novel NO generation system was developed based on copper-chitosan complexes that can be used for the topical generation of NO. Chitosan, a biocompatible polymer, chelates copper ions. Copper in the +1 state can reduce nitrite (NO2-) and convert it into NO. With glucose, a reducing sugar, present in the system, Cu+2 can be returned to Cu+1 to complete the catalytic cycle. RESULTSCopper-chitosan milli- and micro-sized particles were produced using microfluidic techniques. Copper-chitosan milli-particles (Cu-chito) did produce nitric oxide (NO). The maximum rates of NO production were approximate to 1.40 nmol min(-1) g(-1) (Cu-chito) and 1.08 nmol min(-1) g(-1) (Cu-chito + glucose). The milli-particles were tested with ARPE-19 cell lines in cell proliferation assays. Cu-chito particle treatments with nitrite showed 130% more growth in comparison with chitosan milli-particles not containing copper. Furthermore, Cu-chito treatments of nitrite + glucose showed 152% more growth in comparison with control groups, and 118% in comparison with Cu-chito with nitrite alone. The activity of intracellular NO target, matrix metalloproteinases (MMP-2 and -9), were shown to increase by 60% after 48 h of Cu-chito glucose treatments. CONCLUSIONNO-releasing copper-chitosan derivatives were produced, with proof of concept for nitric oxide release and positive effects on a cell culture model of wound healing. (c) 2018 Society of Chemical Industry