Abstract
Platelet extracellular vesicles (pEVs)isolated from clinical-grade human platelet concentratesare attracting attention as a promising agent for wound healing therapies. Although pEVs have shown potential for skin regeneration, their incorporation into wound bandages has remained limitedly explored. Herein, gelatine-based hydrogel (PAH-G) foams for pEVs loading and release are formulated by crosslinking gelatine with poly(allylamine) hydrochloride (PAH) in the presence of glutaraldehyde and sodium bicarbonate. The optimized PAH-G hydrogel foam, PAH0.24G37, displayed an elastic modulus G' = 8.5 kPa at 37°C and retained a rubbery state at elevated temperatures. The excellent swelling properties of PAH0.24G37 allowed to easily absorb pEVs at high concentration (1×1011 particles mL-1). The therapeutic effect of pEVs was evaluated in vivo on a chronic wound rat model. These studies demonstrated full wound closure after 14 days upon treatment with PAH0.24G37@pEVs. The maintenance of a reduced-inflammatory environment from the onset of treatment promoted a quicker transition to skin remodeling. Promotion of follicle activation and angiogenesis as well as M1-M2 macrophage modulation are evidenced. Altogether, the multifunctional properties of PAH0.24G37@pEVs addressed the complex challenges associated with chronic diabetic wounds, representing a significant advance toward personalized treatment regimens for these conditions.
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