β‑Caryophyllene-Loaded Sunflower Oil Nanoemulsion Incorporated into Chitosan Films for Wound Healing Applications

Skin wounds, particularly chronic lesions, represent a major global clinical challenge, as current treatments remain limited in their ability to provide effective, accessible, and biologically active therapies that accelerate tissue repair. This challenge has driven increasing interest in the development of advanced wound dressings based on multifunctional biomaterials. In this study, we hypothesized possible combination of three natural compounds (two nonpolar and one hydrogel), with well-recognized healing properties, in a single multifunctional device. Thus, sunflower oil nanoemulsion containing a bicyclic sesquiterpene β-caryophyllene (BCP) was incorporated into chitosan-based dressing formulations as a potential wound-healing device. The optimized nanoemulsion containing 0.5% BCP presented a mean droplet diameter of about 114 nm, narrow size distribution (PdI = 0.136), and high encapsulation efficiency (96%). The presence of nanoemulsion induced formation of homogeneous and flexible chitosan films, with skin-compatible pH, and contained 13.3 mg BCP per g of multifunctional device. The dressing was characterized in terms of physicochemical, morphological, thermal, and mechanical properties, as well as in vitro biological activity. Spectroscopic and thermal analyses confirmed intermolecular interactions between the components and maintenance of thermal and structural stability. The BCP-loaded film displayed excellent cytocompatibility, antioxidant activity, and a pronounced stimulatory effect on L929 fibroblast migration, resulting in complete in vitro wound closure within 24 h. Overall, the device exhibits suitable structural integrity and in vitro biological performance, supporting its potential as a promising platform for topical wound-healing applications.