Polyvinyl pyrrolidone/carboxymethyl chitosan hydrogel loaded with Paris polyphylla var. yunnanensis extracellular vesicles promotes wound healing.

Wound healing presents a persistent challenge, particularly in enhancing tissue regeneration and mitigating inflammation. Conventional wound dressings often fall short in providing adequate protection against microbial infections and do not fully support the regenerative processes necessary for effective healing. In this study, extracellular vesicles (PPEVs) were successfully isolated from Paris polyphylla var. yunnanensis, with an average particle size of 156.8 ± 13.15 nm and a zeta potential of -15 ± 2.54 mV. Transmission electron microscopy (TEM) images confirmed that the PPEVs exhibited an irregular spherical shape, characteristics of extracellular vesicles. PPEVs demonstrated significant anti-inflammatory properties, reducing the expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α by >1.5 times relative to the model group. Additionally, PPEVs promoted the expression of epidermal growth factor and collagen mRNA, exhibiting potent reactive oxygen species (ROS) scavenging activity, with 50 % reduction in ROS levels in the high-concentration group compared to the positive control. To facilitate the controlled delivery of PPEVs and promote wound healing, a composite hydrogel was developed by incorporating polyvinylpyrrolidone (PVP) and carboxymethyl chitosan (CMC) through physical crosslinking. The hydrogel exhibited high porosity (43.6 ± 7.2 %) and remarkable swelling capacity (445.4 ± 38.3 %), with a drug release of 61.3 ± 11.8 % within 6 h. Rheological analysis revealed that the hydrogel exhibited pseudoplastic behavior and elastic characteristics, with good thermal stability. In vivo studies demonstrated that the wound healing rate in the PPEVs@PVP/CMC hydrogel group on day 7 (82.17 ± 5.44 %) was significantly higher than that of the control group (58.5 ± 12.15 %). On day 14, the wounds in the PPEVs@PVP/CMC group were nearly completely healed, with a healing rate of 99.66 ± 0.42 %, significantly surpassing the control group (95.85 ± 0.90 %). Therefore, the PPEVs@PVP/CMC hydrogel can serve as a safe and efficient wound dressing to regulate the inflammatory response and accelerate wound healing in mice. This finding suggests that utilizing the PPEVs@PVP/CMC hydrogel may be a promising strategy for wound healing.