Abstract
Chronic wounds constitute a significant medical, societal, and economic issue due to the significant delay in wound closure, leading to the increased risk of infection, which extends patients' time spent in the hospital and negatively impacts overall health. Biofunctional biomaterials have emerged as powerful tools to promote tissue regeneration by mimicking extracellular matrix properties and delivering therapeutic agents. Furthermore, wound closure is a complex and multi-stage process that requires coordination of molecular and cellular factors, such as growth factor signaling and matrix remodeling agents. To address this issue, hierarchically structured and compartmentalized multifunctional biomaterials that include hydrogels have emerged as an effective solution to promote wound healing. In the context of chronic wounds, Reactive Oxygen Species (ROS)-responsive hydrogels are interesting models which specifically trigger a response (e.g., gel opening followed by drug release) in the vicinity of high levels of ROS - specific biomarkers of a chronic state. In this study, we developed a hierarchical multi-layer hybrid biomaterial (HMHB) via the sequential combination of melt electrowriting (MEW) and electrospinning techniques. This HMHB will contain two parts: (i) a macro/micro structured polycaprolactone (PCL) support (MSS) printed via MEW onto which (ii) a polyvinyl alcohol (PVA) electrospun (micro)fibrous film (EFF) was deposited, resulting in a ROS-responsive bioactive antibacterial hydrogel meshwork upper layer that allows for further biofunctionalization. The final construct exhibited a hierarchical architecture composed of a mechanically robust PCL framework and a PVA nanotextured layer. This configuration ensured both structural integrity and homogeneous fiber coverage. Incorporation of Nisin (an antibacterial agent) directly into the EFF prior to the electrospinning step conferred effective antimicrobial activity against Staphylococcus epidermidis, without the need for additional chemical modification. These results establish the HMHB as a promising proof-of-concept for modular and multifunctional wound dressing elaboration.