The primary function of the skin is to serve as a protective barrier against physical damage, pathogens, and dehydration, contributing to the maintenance of body health and homeostasis. Once skin damage occurs, the barrier loses its protective function. It is essential to accelerate wound healing to rapidly reconstruct damaged skin tissue and restore its integrity and functionality. A viable therapy should be able to not only take effect rapidly so as to accelerate skin wound closure in early stages, but also significantly promote re-epithelialization, collagen expression, angiogenesis as well as suppress excessive inflammation. In this thesis, we focused on exploring the feasibility and efficacy of administrating bioactive substances (PRP, Hst1, and Hst1-MAD) without or with ADM or SIS with the aim of achieving better therapeutic effect on skin wound healing. 1. The co-administration of SIS and PRP on acute wounds achieved a desirable effect on modulating the immune response of macrophages. In addition, the co-administration of them could accelerate wound healing, promoting angiogenesis, re-epithelialization, and collagen production as well as facilitating the transition of M1 into M2 macrophages, which presented a promising application in managing acute wound healing. 2. Topically administrated 10 Î¼M Hst1 could significantly accelerate wound healing by promoting angiogenesis, re-epithelialization, and collagen production as well as suppressing inflammation, which indicated a promising application in managing acute wound healing. 3. In vitro, Hst 1 can promote the migration of fibroblasts and the transformation of fibroblasts into myofibroblasts, thus enhancing wound contractile and collagen secretion functions through the activation of the PI3K/ AKT/ mTOR signaling pathway. In vivo, the wound healing rate was significantly accelerated and the mechanical properties of the healed skin were improved. The more detailed mechanism remains to be further studied. 4. The application of 1 Î¼M Hst1-MAD on acute wound could significantly accelerate wound healing by promoting wound closure, re-epithelialization, expression of tight junction proteins, collagen formation, and angiogenesis as well as alleviate inflammatory response in late inflammatory period, which indicated a promising application in managing acute wound healing. In conclusion, PRP is clinically ready to be co-administrated with SIS to manage acute skin wounds. Topical administration of Hst1 or Hst1-MAD could be novel and promising therapies to accelerate acute skin wound healing. Further studies will be needed to explore the underlying molecular and cellular mechanisms on wound healing. Large animal studies are still needed to further corroborate their clinical application potential. The thesis provides a theoretical basis to evaluate and develop favorable bioactive materials for acute skin wound healing.