Multifunctional bilayer wound dressing based on 3D-printed sodium alginate/gelatin hydrogel and polycaprolactone nanofibers for accelerating diabetic wound healing.

Millions of diabetic patients endure serious complications, particularly chronic wounds. Prolonged inflammation, oxidative stress, bacterial infection, and impaired vascularization are characteristics of the diabetic wound that impede tissue regeneration and result in inappropriate healing. Therefore, fabricating antioxidant, antibacterial, and anti-inflammatory wound dressing is highly desirable. Due to this demand, a new multifunctional bilayer dressing was fabricated utilizing electrospinning and 3D-printing techniques. The nanofibrous top layer comprises polycaprolactone and cellulose acetate (PCL/CA) and is loaded with synthesized antibacterial chitosan/selenium nanoparticles (CS/SeNPs). The 3D-printed hydrogel bottom layer is composed of sodium alginate, gelatin, and polyvinyl alcohol (SGPH) incorporating mixed pluronics nanomicelles individually loaded with antioxidant rutin and anti-inflammatory simvastatin drugs (RLN and SLN). Morphology, physicochemical, and biological characteristics were evaluated. According to the results, the developed bilayer wound dressing (PCL/CA2/LSGPH) displayed significant antibacterial capability against E. coli and S. aureus with a rate of inhibition of 99 %, and cell viability up to 97 % after 24 h, and cell migration of 95 % within 48 h. PCL/CA2/LSGPH significantly increased the wound healing rate by 95 % after 14 days in the in-vivo diabetic wound healing experiment. The histology examination demonstrated that the entire epidermal layer was generated following treatment with PCL/CA2/LSGPH, enhancing neovascularization, collagen deposition, and re-epithelialization by decreasing proinflammatory cytokines TNF-α and IL-6 level and upregulating antioxidant SOD level. These results suggest that the newly developed bilayer wound dressing PCL/CA2/LSGPH emerged as a promising dressing for treating diabetic wounds and other tissue regeneration applications.