Hard palate mucosal wound is a common intraoral wound associated with implant surgery, periodontal surgery, and cleft palate surgery. The wound commonly affect the speech, chewing and swallowing of patients, and, in severe cases, may have adverse effects on patient mental health (Suzuki et al., 2021, Moss et al., 2016, Schularick et al., 2016). Given these concerns, the healing of postoperative hard palate mucosal wound has attracted much attention in the clinic, and timely healing of hard palate mucosal wound is very necessary. The hard palate mucosa is a masticatory mucosa composed of the superficial epithelium, basement membrane, lamina propria, and submucosa, and acts as the first line of defense against physical, chemical and biological damage in the oral cavity (Politis et al., 2016, Williams et al., 2021, Iglesias-Bartolome et al., 2018). However, the hard palate mucosa is generally fragile and susceptible to injury, and the healing of any damage can be difficult due to the constant presence of oral microorganisms and saliva (Bowler et al., 2001, Rodrigues Neves et al., 2019). Wound healing is further challenged by the special anatomical position of the hard palate mucosa, where it is subject to continuous chewing forces. Furthermore, full-thickness injury of the hard palate mucosa increases the risk of hard palate bone exposure and further affects the bone health of the hard palate region (Ding et al., 2022). Therefore, it is crucial to find an effective method to help treat the hard palate mucosal wound.

In recent years, a variety of methods have been proposed for enhancing hard palate mucosal wound healing. Traditional wound treatment strategies, including sutures and staples, are widely used in clinical wound closure, however, these strategies often cause damage to the surrounding tissue, leading to complications such as scarring, inflammation and infection (Gazivoda et al., 2015). In addition, growth factor therapy and biomaterial therapy have also been used for wound treatment of the hard palate mucosa. Although some results have been achieved, it is expensive and complicated to produce (Niu et al., 2019). For a long time, clinical practice has proved that traditional Chinese medicine has good wound repair effect and can act on the whole process of wound healing, which is a key treatment strategy (Zhang et al., 2022, Song et al., 2020, Akbik et al., 2014). Moreover, traditional Chinese medicine is typically lower in cost than mainstream Western pharmaceuticals, and traditional Chinese insect medicine is becoming increasingly popular among complementary and alternative therapies (Ning et al., 2022, Monika et al., 2022, El-Tantawy, 2015).

Periplaneta americana stands out as a typical Chinese medicine insect drug, which has a wide range of pharmacological activities and has shown benefits in the treatment of some diseases involving tissue repair (Li et al., 2022). Periplaneta americana dry powder is an early medicinal preparation of Periplaneta americana, which contains more inactive ingredients and may affect the efficacy of the active drug. Periplaneta americana extract was developed as a medicinal preparation of Periplaneta americana in the late 20th century, and Kangfuxin as one of the preparations has been used to treat skin wounds, gastrointestinal ulcers, cervical erosion, and radiation-induced mucositis (Zou et al., 2019, Qu et al., 2019, Luo et al., 2016). Hence, Periplaneta americana extract has shown potential for promoting soft tissue repair. More recently, improvements in extraction technology have enabled the further purification of Periplaneta americana extract, allowing the isolation of the main components, including peptides, amino acids and nucleosides. Existing researches on the use of Periplaneta americana extract in oral diseases have focused on evaluating its healing potential and mechanism of action in radiation-induced mucositis, chemotherapy-induced mucositis and ulcer (Luo et al., 2016, Bo et al., 2021). To our knowledge, no studies to date have explored the ability of Periplaneta americana extract to improve the healing of hard palate mucosal wound, which show unique progression compared to other regions. Based on the good ability of Periplaneta americana extract to enhance soft tissue repair, the newly purified Periplaneta americana extract is expected to be valuable in the treatment of hard palate mucosal wound.

Herein, this study focused on the novel therapeutic value of Periplaneta americana extract on hard palate mucosal wound healing. The effects of Periplaneta americana extract on hard palate mucosal wound healing were investigated in vivo and in vitro and the underlying mechanisms were revealed through RNA sequencing. Our study is expected to contribute to the development of new drug candidates for the clinical treatment of hard palate mucosal wound.