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Using an in situ sol-gel technique, new nanoarchitectonics of propolis loaded zinc oxide nanoarchitectonics (PP/ZnO-NPs) were developed in order to improve the in vivo outcomes of collagen-chitosan gel in wounded rats. The obtained nanoarchitectonics were fully characterized. The XRD results indicate the presence of a Zincite phase for ZnO-NPs and Zincite accompanied by a minor amount of zinc hydroxide for PP/ZnO-NPs samples. While the TEM findings illustrate the transfer of the ZnO-NPs from agglomerated spheres with an average particle size of 230 ± 29 nm to needle-like NPs of 323 ± 173 nm length (PP1/ZnO-NPs) and to a sheet-like NPs of 500 ± 173 nm diameter (PP2/ZnO-NPs). In addition, the incorporation of PP results in an increase in the surface negativity of ZnO-NPs to -31.4 ± 6.4 mV for PP2/ZnO-NPs. The antimicrobial activities of the nanocomposite gel loaded with 10%PP1/ZnO-NPs (G6) revealed the highest inhibition zone against E. coli (26 ± 2.31 mm). Remarkably, the in vivo outcomes showed that the nanocomposite gel (G6) has exceptional collagen deposition, quick wound closure rates, and re-epithelization. The outcomes demonstrate the nanocomposite gel encouraging biological properties for the treatment of damaged and infected wounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)