Wound repair is a worldwide medical issue implicating a number of highly controlled and complex reactions triggered by tissue break down to restore the functionality and integrity of affected tissues (Xu et al., 2020). Different kinds of wounds, including pressure, vascular, and diabetic ulcers, affect between 2.4 and 4.5 million people in the United States (Ahmed, 2022). An estimated 2 million patients are treated for acute or chronic wounds in Europe (Frydrych et al., 2019). Chronic wounds often represent a complication of chronic illnesses like diabetes (Beyene et al., 2020, Lindholm and Searle, 2016). Chen et al. have reported that the 5-year mortality rate in diabetic foot ulcers is comparable to cancer deaths (Armstrong et al., 2020). Chronic wounds significantly decrease the quality of life and add to the medical pressure (Olsson et al., 2019). Wound healing is a complicated and dynamic process involving hemostasis, inflammation, proliferation, remodeling, and bacterial infection may hinder these processes (Deng, 2022, Liang et al., 2021). Microorganisms [especially Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli)] can compete with the host immune system to invade injured tissues, causing infection, prolonged inflammation, and severe tissue damage (Ciofu, 2022). As a result of their elevated mortality and morbidity, diseases associated with bacterial infections have emerged as major public health issues.

The healing of skin wounds goes through four main steps, including hematoma formation, inflammation, proliferation, and tissue remodeling (Kaur et al., 2022, Wang, 2022, El Ayadi et al., 2020). These four steps overlap considerably and are supported by different mediators including immune cells, fibroblast, pro- and anti-inflammatory cytokines, and growth factors that contribute to new tissue formation (Kaur et al., 2022, Venugopal et al., 2023). Advanced biomaterials were shown useful in all stages of wound healing by removing wound exudate, providing wound coverage, transporting oxygen to the wound site, and preventing infection (Kaur et al., 2022, Yu et al., 2022). In addition, advanced biomaterials act as transport vehicles for proteins, drugs, growth factors, and antimicrobial agents (Kaur et al., 2022, Yu et al., 2022).

Graphene quantum dots (GQDs) are advanced biomaterials and potential candidates for biomedical applications, owing to their solubility in aqueous solutions and high biocompatibility (Abbas et al., 2018, Iravani and Varma, 2020). GQDs are nanostructures of graphene in the size range of 2–20 nm with a set of unique chemical and physical properties (Haque et al., 2018). Photostable GQDs can absorb a suitable wavelength for photon energy and transfer to specific activation, then generate heating effects and/or reactive oxygen species (ROS), known as cytotoxic agents in phototherapy (Zhang et al., 2019, Kumar, 2022). GQDs were shown efficient when treating various wounds and inflammatory conditions because of their low toxicity, non-invasive nature, and flexibility. In general, GQDs have no apparent toxicity, they have demonstrated a high potential for utilization in cellular imaging, as antibacterial material, and in drug delivery (Sangam et al., 2018, Cui et al., 2021, Henna and Pramod, 2020). To meet industrial needs, it is crucial to produce GQDs on a large scale with cost-effectiveness, adaptability, and environmental friendliness in mind.

The focus on sustainable and eco-conscious materials derived from natural origins has witnessed a remarkable upswing, primarily owing to their inherent traits such as recyclability, biodegradability, compatibility, and non-toxicity (Khalid et al., 2021). Materials sourced from plants are valuable resources for eco-friendly GQD synthesis, given their higher carbon content ideal for GQD production (Saleem et al., 2023). Kumawat et al. utilized GQDs produced from mango leaves using an eco-friendly approach for near-infrared bioimaging applications (Kumawat et al., 2017). The same research team employed grape seed extracts as a green carbon source for GQD synthesis (Kumawat et al., 2017). Teymourinia et al. employed corn powder as a precursor for the green chemistry-based synthesis of GQDs (Teymourinia et al., 2017). In another study, GQDs crafted from Clitoria Ternatea flowers via a one-pot microwave-assisted green synthesis method were used as an adjuvant for the treatment of Alzheimer's disease (Tak et al., 2020). Recently, GQDs were derived from date palm leaf powder, exhibiting sizes ranging from 3.5 to 8 nm, allowing for large-scale production that can be available for biomedical applications (Saleem et al., 2023). The outcomes of these aforementioned studies inspired our investigation into the potential to develop GQDs from renewable, cost-effective, natural, and sustainable sources such as green plants.

In the present work, Cannabis sativa L. seeds GQDs (termed here as C-GQDs) were generated through a novel eco-friendly approach using cannabis seeds as precursor and without the addition of strong oxidants, thus avoiding the production of toxic gases. As shown in Fig. 1, C-GQDs were synthesized by the simple microwave approach. Cannabis seeds offer an opportunity in regard to versatility, cost, and availability. They are a rich source of fiber and have significant medicinal value (Rashid, 2021). They contain antibacterial cannabinoids with the potential to kill antibiotic-resistant bacteria (Farha et al., 2020). They also possess analgesics and anti-inflammatory effects that can be used in various biomedical applications (Tiwari et al., 2019, Balant, 2021, Raina, 2020). The as-synthesized C-GQDs were comprehensively characterized and systematically evaluated. In vivo and in vitro results revealed that the C-GQDs exhibit excellent biocompatibility and significantly augmented capability for killing both S. aureus and E. coli with a minimal inhibitory concentration (MIC) of 236 µg/mL for both strains compared with povidone-iodine alone. More importantly, we found that C-GQDs accelerate the healing process by killing S. aureus and E. coli implicated in skin wound infection. The antibacterial and anti-inflammatory activities of C-GQDs against S. aureus and E. coli were demonstrated by increased neutrophil levels in serum and wounded tissue. The neurobehavioral impairments of incisional wounds including stress and anxiogenic-like effect were evaluated using the open-field behavioral test and serum cortisol level quantification. A clear anxiolytic-like effect with increased vertical locomotor activity in C-GQDs treated mice was confirmed by reduced cortisol levels implicated in wound healing impairment. The C-GQDs, via their antibacterial, anti-inflammatory, anti-stress, anxiolytic-like effects showed an accelerative potential of wound closure in mice models of incisional wounds.