A review of the current state of natural biomaterials in wound healing applications. Mojtaba Ansari and Ahmad Darvishi. Department of Biomedical Engineering, Meybod University, Meybod, Iran. Skin, the largest biological organ, consists of three main parts: the epidermis, dermis, and subcutaneous tissue. Wounds are abnormal wounds in various forms, such as lacerations, burns, chronic wounds, diabetic wounds, acute wounds, and fractures. The wound healing process is dynamic, complex, and lengthy in four stages involving cells, macrophages, and growth factors. Wound dressing refers to a substance that covers the surface of a wound to prevent infection and secondary damage. Biomaterials applied in wound management have advanced significantly. Natural biomaterials are increasingly used due to their advantages including biomimicry of ECM, convenient accessibility, and involvement in native wound healing. However, there are still limitations such as low mechanical properties and expensive extraction methods. Therefore, their combination with synthetic biomaterials and/or adding bioactive agents has become an option for researchers in this field. In the present study, the stages of natural wound healing and the effect of biomaterials on its direction, type, and level will be investigated. Then, different types of polysaccharides and proteins were selected as desirable natural biomaterials, polymers as synthetic biomaterials with variable and suitable properties, and bioactive agents as effective additives. In the following, the structure of selected biomaterials, their extraction and production methods, their participation in wound healing, and quality control techniques of biomaterials-based wound dressings will be discussed. Keywords: wound healing, wound dressing, skin tissue engineering, natural biomaterials, synthetic biomaterials. 1 Introduction The skin is the largest and widest organ in the human body, making it more susceptible to disease, injury, and burns. An important disease is skin damage due to superficial and local wounds that require treatment (Nisar et al., 2023). Skin wounds are injuries in the form of tears, fractures, or abnormal defects that may be caused by pathological conditions, endogenous factors (e.g., diabetes, malignancy, vascular disease, etc.), physical trauma, and burns (Percival, 2002). Wound healing and repair are typically long-term, slow, complex, multifaceted, and dynamic biological processes. Simple and small wounds can heal on their own, but acute and large wounds heal slowly and heal, usually within 8–12 years, which may be affected by bacterial infections and dust particles during the wound healing process (Koehler et al., 2018; Shen et al., 2021). Therefore, the treatment of wounds against bacterial infections (e.g., infections caused by Escherichia coli, Staphylococcus aureus, and Bacillus subA review of the current state of natural biomaterials in wound healing applications. Mojtaba Ansari and Ahmad Darvishi. Department of Biomedical Engineering, Meybod University, Meybod, Iran. Skin, the largest biological organ, consists of three main parts: the epidermis, dermis, and subcutaneous tissue. Wounds are abnormal wounds in various forms, such as lacerations, burns, chronic wounds, diabetic wounds, acute wounds, and fractures. The wound healing process is dynamic, complex, and lengthy in four stages involving cells, macrophages, and growth factors. Wound dressing refers to a substance that covers the surface of a wound to prevent infection and secondary damage. Biomaterials applied in wound management have advanced significantly. Natural biomaterials are increasingly used due to their advantages including biomimicry of ECM, convenient accessibility, and involvement in native wound healing. However, there are still limitations such as low mechanical properties and expensive extraction methods. Therefore, their combination with synthetic biomaterials and/or adding bioactive agents has become an option for researchers in this field. In the present study, the stages of natural wound healing and the effect of biomaterials on its direction, type, and level will be investigated. Then, different types of polysaccharides and proteins were selected as desirable natural biomaterials, polymers as synthetic biomaterials with variable and suitable properties, and bioactive agents as effective additives. In the following, the structure of selected biomaterials, their extraction and production methods, their participation in wound healing, and quality control techniques of biomaterials-based wound dressings will be discussed. Keywords: wound healing, wound dressing, skin tissue engineering, natural biomaterials, synthetic biomaterials. 1 Introduction The skin is the largest and widest organ in the human body, making it more susceptible to disease, injury, and burns. An important disease is skin damage due to superficial and local wounds that require treatment (Nisar et al., 2023). Skin wounds are injuries in the form of tears, fractures, or abnormal defects that may be caused by pathological conditions, endogenous factors (e.g., diabetes, malignancy, vascular disease, etc.), physical trauma, and burns (Percival, 2002). Wound healing and repair are typically long-term, slow, complex, multifaceted, and dynamic biological processes. Simple and small wounds can heal on their own, but acute and large wounds heal slowly and heal, usually within 8–12 years, which may be affected by bacterial infections and dust particles during the wound healing process (Koehler et al., 2018; Shen et al., 2021). Therefore, the treatment of wounds against bacterial infections (e.g., infections caused by Escherichia coli, Staphylococcus aureus, and Bacillus sub