Dental Pulp Stem\nCell Lysate-Based Hydrogel Improves\nDiabetic Wound Healing via the Regulation of Anti-Inflammatory Macrophages\nand Keratinocytes

The prolonged existence of chronic wounds heightens the\nrisk of\npatients experiencing chronic pain, necrosis, and amputation. Dental\npulp stem cells (DPSCs) have garnered attention due to their potential\nimmunomodulatory and tissue repair regenerative effects in the management\nof chronic wounds. However, stem-cell-based therapy faces challenges\nsuch as malignant differentiation, immune rejection, and long-term\neffectiveness. To overcome these challenges, we proposed a chronic\nwound therapy using a hydrogel derived from human-originated dental\npulp stem cell lysate (DPSCL). Our data indicate that, with the degradation\nof the dental pulp stem cell lysate-based hydrogel (DPSCLH), the slowly\nreleased cell lysates recruit anti-inflammatory M2 macrophages and\npromote the proliferation, migration, and keratinization of HacaT\ncells. In addition, <i>in vivo</i> studies revealed that\nDPSCLH avoids immune rejection reactions and induces a long-term accumulation\nof endogenous M2 macrophages. In a mouse model of diabetic wounds,\nDPSCLH effectively modulates the inflammatory microenvironment around\ndiabetic wounds, promotes the formation of the stratum corneum, and\nfacilitates the healing of wounds, thus holding tremendous potential\nfor the treatment of diabetic wounds.