Extracellular vesicles (EVs) are lipid bilayer vesicles that are secreted from almost all cell types, serve as “messengers” in intercellular and inter-organismal communication, and encapsulate a variety of functional nucleic acids, proteins, and other component [[1], [2], [3]]. Plant-derived EVs are abundant in resources, with low production costs and high yield. Regarding safety, plant-derived EVs do not harbor any zoonotic or human pathogens and have lower immune risks in vivo [4,5]. Recent research indicated that plant-derived EVs had anti-inflammatory and anti-cancer properties [6,7], even though the fundamental processes behind their wound-healing [8] process remain unclear. Ginger is the rhizome of Zingiber and is traditionally used for both medicine and food [9]. In addition to being used as a natural medicine, ginger extracts come in various forms and are currently used to treat various ailments [10]. Due to ginger's high concentration of bioactive contents, it has anti-inflammatory and antioxidant characteristics [11]. These properties are utilized to treat diseases including cancer and other related conditions [12].

Human skin exposure to terrestrial solar ultraviolet (UV) radiation causes a number of well-known acute and long-term effects [13]. UV radiation is a primary factor contributing to skin cancer [14] and premature aging [15,16] due to its deep penetration and high photon energy levels. UVA (320–400 nm) is the main component of solar UV irradiation component, making up as much as 95% of the total. It is linked to numerous pathological processes and determines the possible degree of harm might cause to skin [17]. UVA has oxidizing properties that decomposing collagen and elastic fibers [18], causing wrinkles and color spots, and altering the dermal connective tissue [19,20]. There is a noticeable increasing in the production of ROS [21] in skin cells after prolonged UVA irradiation. ROS is a general term for oxygen-containing and active substances in the body that are involved in the formation of cell damage [22,23] and cell-to-cell transmission [24]. It can activate NF-κB and MAPK signaling pathways to encourage the expression of AP-1 and MMPs [25,26], causing the extracellular matrix to degrade and speeding up the aging process of the skin. The degree of photodamage is directly correlated with ROS concentration [27].

For the treatment of skin injury, functional hydrogels provide a viable choice. A unique local drug delivery preparation known as thermosensitive gel has the ability to display several physical states in response to temperature changes. It will rapidly transition into a semi-solid gel state when the temperature rises to the phase transition temperature or near body temperature. The reason for this transformation is that the gel's molecular structure has a great number of hydrophilic polymer groups. Because of the unique interactions between the molecules of the polymer, like hydrogen bonds, ionic bonds, or hydrophobic interactions, these interactions will change as the temperature rises and cause the gel to solidify or liquefy. Polymer molecules primarily exist as a dissolved form at low temperature, but combine and undergo gel transition at high temperature, forming a dense three-dimensional network structure [28,29].

The morphology of the skin and its constant temperature properties led us to select a temperature-sensitive hydrogel as an effective EVs carrier. At room temperature or low temperature, the gel stays liquid, it is easier for EVs to mix completely and uniformly and preserve their stability and activity. By slowing down the release of EVs, encapsulating EVs in gel improves their mechanical stability, integrity, and activity [30], all while being shielded from quick clearance. Additionally, the loading of gel increases the stability and retention rate of EVs [31] and provides high-quality extracellular matrix at the site of skin injury, keeping the wound moist and encouraging tissue repair. For these reasons, there is hope for designing EVs loaded into thermosensitive gel for skin injury.

In this study, it is the first time to utilize ginger-derived extracellular vesicles (gEVs) to promote the proliferation and migration of cells as well as to treat inflammatory skin lesions caused by UVA rays. The thermosensitive gel was loaded with gEVs, which effectively treated the wounded area and offered some guidance for repairing skin irritation. Because of its low cost, good efficacy, dependability, and safety, the manufacture of gEVs as an ingredient therapy has become a novel therapeutic strategy.