Bioresponsive nanodrug delivery systems have excellent
potential
in tissue engineering applications. Poly-anionic and poly-cationic
biopolymers have provided a superior platform for designing pH-sensitive
drug delivery systems. In this regard, hyaluronic acid–chitosan–polyvinyl
alcohol complex nanofibers with high quality and reproducibility were
produced by optimizing the solution preparation process. In addition,
the synthesized composite nanofiber, with 66.82 kN/mm toughness, 200%
swelling ratio, and 60% porosity, exhibited excellent properties to
meet the requirements of the ideal wound dressing. Green cross-linking
with citric acid prevented the destruction of the nanofiber even after
prolonged immersion in biological solutions. ζ potential studies
demonstrated that the synthesized nanofiber has a negative surface
charge (∼−30) at physiological pH. The pK
a of the temporin-Ra peptide is about 10, and as a result
the peptide molecules have a net positive charge in physiological
conditions. Therefore, peptide molecules immobilized on the synthesized
scaffold based on surface adsorption. In vivo evaluation has proven
that the wound bed has an alkaline environment, facilitating peptide
release from the nanofiber scaffold. Electrospun nanofibers can imitate
the architecture of the extracellular matrix for accelerating wound
healing. In vitro investigation showed better adhesion, proliferation,
migration, and fibroblast cell growth on peptide-loaded nanofiber
samples than other groups. In vivo studies on full-thickness wounds
in the mouse model indicated that the designed nanofiber was gradually
absorbed without causing dryness or infection. On day 6, the peptide-loaded
nanofiber revealed 60% wound closure compared to the control group
(17%). In addition, based on histological studies, the composite nanofiber
demonstrated excellent tissue repair ability, hence these active nanofiber
mats can be a good alternative to existing wound dressings. Gene expression
studies show that the antimicrobial peptide promotes the inflammatory
phase of wound healing in a shorter time frame by accelerating the
tumor necrosis factor-α cytokine response.