Angiogenesis, hemocompatibility and bactericidal effect of bioactive natural polymer‐based bilayer adhesive skin substitute for infected burned wound healing

Thermal wounds are complex and lethal with irregular shapes, risk of infection, slow healing, and large surface area. The mortality rate in patients with infected burns is twice that of non-infected burns. Developing multifunctional skin substitutes to augment the healing rate of infected burns is vital. Herein, we 3D printed a hydrogel scaffold comprising carboxymethyl chitosan (CMCs) and oxidized alginate grafted catechol (O-AlgCat) on a hydrophobic electrospun layer, forming a bilayer skin substitute (BSS). The functional layer (FL) was fabricated by physiochemical crosslinking to ensure favorable biodegradability. The gallium-containing hydrophobic electrospun layer or backing layer (BL) could mimic the epidermis of skin, avoiding fluid penetration and offering antibacterial activity. 3D printed FL contains catechol, gallium, and biologically active platelet rich fibrin (PRF) to adhere to both tissue and BL, show antibacterial activity, encourage angiogenesis, cell growth, and migration. The fabricated bioactive BSS exhibited noticeable adhesive properties (P ≤ 0.05), significant antibacterial activity (P ≤ 0.05), faster clot formation, and the potential to promote proliferation (P ≤ 0.05) and migration (P ≤ 0.05) of L929 cells. Furthermore, the angiogenesis was significantly higher (P ≤ 0.05) when evaluated in vivo and in ovo. The BSS-covered wounds healed faster due to low inflammation and high collagen density. Based on the obtained results, the fabricated bioactive BSS could be an effective treatment for infected burn wounds.