Platelet Extracellular Vesicles Loaded Gelatine Hydrogels for Wound Care

Abstract Platelet extracellular vesicles (pEVs) isolated from clinical‐grade human platelet concentrates are 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, PAH 0.24 G 37 , displayed an elastic modulus G’ = 8.5 kPa at 37 °C and retained a rubbery state at elevated temperatures. The excellent swelling properties of PAH 0.24 G 37 allowed to easily absorb pEVs at high concentration (1 × 10 11 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 PAH 0.24 G 37 @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 PAH 0.24 G 37 @pEVs addressed the complex challenges associated with chronic diabetic wounds, representing a significant advance toward personalized treatment regimens for these conditions.