IJMMS_2025v15n5

International Journal of Molecular Medical Science, 2025, Vol.15, No.5, 214-223 http://medscipublisher.com/index.php/ijmms 216 3 Molecular Regulation of Wound Healing 3.1 Cytokines and immune regulation in the inflammatory phase The inflammatory stage of wound healing is regulated by multiple cytokines and immune cells together. After injury, pro-inflammatory factors such as IL-1β, IL-6, TNF-α, as well as various chemokines, will be released rapidly, attracting neutrophils and monocytes to the wound site to clear necrotic tissue and resist infection (Cioce et al, 2024). These factors can not only initiate the immune response, but also promote the production of growth factors, laying the foundation for the subsequent repair process (Wong et al., 2025). The intensity and duration of these inflammatory signals need to be appropriately adjusted. If the inflammatory response is too intense or lasts for too long, it will interfere with the normal healing process and subsequently form chronic wounds (Raziyeva et al., 2021; Zhu, 2025). As the inflammatory phase progresses, anti-inflammatory factors such as IL-10 and IL-4 gradually gain the upper hand, helping to calm the inflammation and guide tissue repair (Allen, 2022). Macrophages are particularly crucial among them. They will change from pro-inflammatory type (M1) to repair type (M2) and secrete anti-inflammatory and pro-regeneration molecules (Cioce et al., 2024). When this conversion is blocked, for example, when m1 type is chronically active or the anti-inflammatory signal is insufficient, the wound is prone to be difficult to heal (Raziyeva et al., 2021; Sousa et al., 2022). Therefore, precisely regulating the immune response is the prerequisite for effective healing and also the core direction of regenerative therapy. 3.2 Proliferative angiogenesis and extracellular matrix remodeling During the proliferative phase, the key to tissue repair lies in the formation of new blood vessels and the reconstruction of the extracellular matrix (ECM). Angiogenesis can form new blood vessels to supply oxygen to tissues and is controlled by various growth factors such as VEGF, FGF, and TGF-β (Shi et al., 2023). Endothelial cells help form the capillary network through division and movement, while fibroblasts and keratinocytes promote granulation tissue growth and epidermal repair (Dikici et al., 2021). The interaction between inflammatory cells and pro-angiogenic signals helps the wound smoothly enter the tissue reconstruction stage from this period (Shi et al., 2023). The renewal of ECM relies on the generation and degradation of matrices such as collagen to provide scaffold support for new tissues. Fibroblasts are responsible for the production and arrangement of collagen, and matrix metalloproteinases (MMPs) and their inhibitors, together, maintain the stability of the matrix. Appropriate ECM remodeling is helpful for functional recovery, but too much or too little may cause fibrosis or slow down healing (Kim et al., 2022). Therefore, coordinating well with the processes of angiogenesis and ECM remodeling is of great significance for wound repair and the design of related dressings. 3.3 Signal pathways and tissue maturation mechanisms during the remodeling period Under the regulation of multiple signaling pathways, the main goal of the remodeling period is to make the newly formed tissues more mature and stable. At this stage, type III collagen is gradually replaced by type I collagen, tissue strength increases, and the structure also tends to be complete. Myofibroblasts and macrophages prevent excessive scar formation by secreting MMPs. MMPs are involved in ECM recombination and remove residual substances, while regulating the growth and death of excess cells (Cioce et al., 2024). The key signaling pathways include TGF-β, ERK and p38 MAPK, etc., which together regulate fibroblast function, collagen synthesis and matrix renewal. Anti-inflammatory factors such as IL-10 and TGF-β1 can help tissues grow better, completely eliminate inflammation, and also assist in the remodeling of normal scars. If these signals are unbalanced, it may cause abnormal healing, such as prolonged wound failure or excessive scar growth, which indicates that molecular regulation plays a key role in the later stage of healing (Kim et al., 2022). 4 Types and Characteristics of Recycled Dressings 4.1 Natural polymer materials Natural polymer dressings, such as those made from collagen, chitosan, hyaluronic acid, alginate and gelatin, are widely used in wound care due to their good biocompatibility, degradability and structural resemblance to human

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