Chronic wounds, such as diabetic ulcers and pressure sores, pose significant challenges in modern healthcare due to their prolonged healing times and susceptibility to infections. This study aims to engineer a bilayered wound dressing (BLWD) composed of soy protein isolate/collagen with the ability to release Cinnamaldehyde, Artemisia absinthium (AA), and oxygen. Cinnamaldehyde, magnesium peroxide (MgO2), and AA extract were encapsulated. Nanoparticles were evaluated using scanning electron microscopy (SEM), dynamic light scattering, and ZETA potential tests. Swelling, degradation, water vapor penetration, tensile, MTT, SEM, oxygen release, AA extract release, and antibacterial properties were performed. An in vivo study was carried out to assess the final wound dressing under Hematoxiline&Eosin and Masson trichrome staining analysis and compared to a commercial product. According to the results, the synthesized nanoparticles had an average diameter of about 20 nm with a zeta potential in the range of −20 to −30 mV. The layers had uniform and dense surfaces. The maximum swelling and degradation of the dressing was about 130 and 13% respectively. Generally, better mechanical properties were observed in BLWD than in the single-layer case. More than 90% biocompatibility for the wound dressing was reported. The BLWD could inhibit the growth of Gram-positive and Gram-negative microorganisms. Histopathological analysis showed an acceptable wound-healing property. To sum up, the engineered wound dressing can be a good candidate for more clinical trials
