3D printed bioengineered scaffold containing chitosan, alginate, and Barijeh-loaded niosomes enabled efficient antibiofilm activity and wound healing.

In this study, we developed a novel biocompatible wound scaffold by encapsulating Barijeh (Bar), a plant-derived antibacterial compound, with niosome (Nio). The Nio-Bar formulation was incorporated into a chitosan (CS) and alginate (AL) hydrogel mixture, followed by 3D printing to create a three-dimensional scaffold, namely Nio-Bar@CS-AL. The obtained scaffold showed notable degradation, reaching 68 % (w/w) within 14 days. Nio-Bar@CS-AL displayed strong antibacterial activity and led to a >5-log reduction of both Pseudomonas aeruginosa and Staphylococcus aureus, far surpassing the performance of CS-AL scaffolds. Further, it effectively reduced biofilm formation by 74 %-80 % for both pathogens, and showed no cytotoxicity toward human fibroblast (HFF) cells, ensuring safety for wound application. In an in vivo murine wound model, Nio-Bar@CS-AL facilitated over 90 % wound healing after 10-day. Tissue integration was signaled by a twofold increase of TGF-β expression and a reduction of IL-6 expression to near-baseline levels, thereby mitigating inflammation. Histopathological analysis revealed a much higher collagen deposition, a key indicator of effective healing, in scaffold-treated wounds compared to the control. These results suggest that Nio-Bar@CS-AL holds promising clinical potential for treating wound infections and defects, offering a multifaceted strategy to improve wound healing outcomes.