Graphene oxide crosslinked-zein nanofibrous scaffolds for prominent Cu-adsorption as tissue regeneration promoters in diabetic rats: Nanofibers optimization and in vivo assessment

Diabetic ulcers are prone to bacterial contamination and can severely affect patient's quality of life. This study is first report to explore copper-grafted graphene oxide-crosslinked zein scaffolds (Cu-GZS) for promoting cutaneous excision wounds healing as a promising therapeutic modality in diabetic male-rats. Cu-GZS scaffolds were fabricated using electrospinning technique, where GO was employed as an echo-friendly crosslinker to meliorate mechanical stability and swellability of scaffolds. To circumvent risk of infection, copper ions were grafted into GZS as bactericidal agents and angiogenesis promoters, through soaking GZS nanofibers into Cu-solution or direct loading during electrospinning process. SEM images showed GO encapsulation by wrapping around/or trapping within nanofibrous. Interestingly, formation of chemical amide bond between zein and GO was proven by FTIR spectra. Crosslinking of zein nanofibers with GO increased tensile strength of nanofibrous by 3-folds compared to uncrosslinked zein nanofibers. Optimized Cu-GZS exhibited constant release rate of copper over a period of 8 days (~53.42%). Cu-GZS immensely accelerated wound closure demonstrated by diminished infiltration of leukocytes, absence of α-SMA positive cells, presence of fully intact epithelium with normal keratinization and accelerated wound size reduction, compared to control. Cu-GZS scaffolds could serve as promising biomaterials for effective topical wound healing in diabetic rats.