Antibacterial and bioactive multilayer electrospun wound dressings based on hyaluronic acid and lactose-modified chitosan

Abstract

Antibacterial multilayer electrospun matrices based on hyaluronic acid (HA) and a lactose-modified chitosan (CTL) were synthetized (i) by combining electrospun polycaprolactone (PCL) and polysaccharidic matrices in a bilayer device and (ii) by sequentially coating the PCL mat with CTL and HA. In both cases, the antibacterial activity was provided by loading rifampicin within the PCL support. All matrices disclosed suitable morphology and physicochemical properties to be employed as wound dressings. Indeed, both the bilayer and coated fibers showed an optimal swelling capacity (3426 ± 492 % and 1435 ± 251 % after 7 days, respectively) and water vapor permeability (160 ± 0.78 g/m²h and 170 ± 12 g/m²h at 7 days, respectively). On the other hand, the polysaccharidic dressings were completely wettable in the presence of various types of fluids. Depending on the preparation method, a different release of both polysaccharides and rifampicin was detected, and the immediate polysaccharide dissolution from the bilayer structure impacted the antibiotic release (42 ± 4 % from the bilayer structure against 25 ± 2 % from the coated fibers in 4 h). All the multilayer matrices, regardless of their production strategy and composition, revealed optimal biocompatibility and bioactivity with human dermal fibroblasts, as the released bioactive polysaccharides induced a faster wound closure in the cell monolayer (100 % in 24 h) compared to the controls (78 ± 8 % for untreated cells and 89 ± 5 % for cells treated with PCL alone, after 24 h). The inhibitory and bactericidal effects of the rifampicin loaded matrices were assessed on S. aureus, S. epidermidis, E. coli, and P. aeruginosa. The antibacterial matrices were found to be highly effective except for E. coli, which was more resistant even at higher amounts of rifampicin, with a bacterial concentration of 6.4 ± 0.4 log CFU/mL and 6.8 ± 0.3 log CFU/mL after 4 h in the presence of the rifampicin-loaded bilayer and coated matrices, respectively.

Keywords: Chronic wounds; Electrospinning; Hyaluronic acid; Lactose-modified chitosan; Multilayer; Rifampicin.