Platelet Extracellular Vesicles Loaded Gelatine Hydrogels for Wound Care.

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.