Biomedical Multilayer Composite Systems for Wound Healing: Design Strategies, Therapeutic Functions and Future Perspectives
Acute and chronic wounds remain a major clinical burden, motivating the design of multilayer biomedical composite systems capable of combining structural support, antimicrobial protection, and controlled release of therapeutic agents within a single device. These architectures integrate natural and synthetic biomaterials, hydrogels, electrospun membranes, bioactive nanoparticles, and 3D-printed scaffolds to reproduce the multifunctionality of the native extracellular matrix. This review examines how layer-by-layer design and biomaterial selection govern mechanical strength, as well as bioactivity, and how these parameters can be tuned to the distinct phases of wound repair. Particular emphasis is placed on strategies for incorporating growth factors, antimicrobial agents, metal/metal-oxide nanoparticles to enhance re-epithelialization, angiogenesis, and infection control; emerging gene-based delivery strategies are also discussed. The main technologies and biomaterial combinations reported to date are compared, alongside a critical overview of their in vitro and in vivo performance. Reproducibility, scalability, and regulatory standardization remain the main barriers to clinical translation. We conclude by outlining priority research directions to advance multilayer composites from bench-scale prototypes toward approved wound-care products.