**1. Introduction**

Skin trauma especially severe wound is a common clinical problem, and is more challenging to cure. The foremost aim for the treatment of skin defects is to rapidly restore the construction and function of the wound to the levels of normal tissue, involving acute and chronic inflammations, cell division, migration, and differentiation, regeneration and vascularization [1]. In recent years, the mechanism of wound healing properties of the biomaterials is becoming a research hotspot. Wound healing is a multifactorial process that is characterized by angiogenesis, collagen deposition, granulation tissue formation and re-epithelialization. All these phases involve complex biomolecular interactions among cells, soluble cytokines, adherence factors and chemokines. The clinical treatment of skin wound by traditional medicine has a long history from ancient times, however, the major drawback

of traditional medicine dressing is less effective and prolonged treatment time. Many researchers focus on finding the new medical tissue engineering materials for wound healing. The medical tissue engineering materials can replace the damaged skin to provide temporary barrier function and avoid the wound being infected [2]. It provides a platform for cellular proliferation, adhesion and differentiation leading to the development of new functional tissues [3,4]. It can promote tissue repair, regeneration, and recovery to accelerate and complete wound healing [5]. Therefore, grafting tissue engineering material for the healing of a full-thickness wound is preferably a suitable model.

As a new tissue engineering material, collagen has good physical and mechanical properties [6], low immunogenicity [7–9], good biocompatibility, and biodegradability [10–12]. Due to minimal inflammation response, cytotoxicity effect, ability to promote cellular growth and good biocompatibility, collagen is the most promising skin substitute or wound dressing biomaterial [13]. Collagen can promote cellular adhesion and proliferation [14,15], collagen synthesis [16] and increase various growth factors [17], in order to accelerate wound-healing process. In earlier reports, collagen sponge from marine fish up-regulated the fibroblasts and keratinocytes growth, proliferation and wound healing potential in rat model [18]. Liane et al. [19] stated that neurotensin-loaded collagen dressings significantly reduced inflammatory cytokine expression, increased fibroblast migration, enhanced collagen I/III expression and deposition. Tian et al. [20] also reported that electrospun tilapia collagen nanofibers could significantly promote the proliferation of human keratinocytes (HaCaTs), stimulate epidermal differentiation and facilitate rat skin regeneration. All these findings claim that collagen is an excellent biomaterial to be used in wound healing purpose.

Biomimetic environment is also essential for tissue regeneration. Electrospun nanofibrous matrix has been proved to be very effective in skin regeneration because of its superiority features including adjustable diameters, porosity, mimic the structure and function of native extracellular matrix (ECM) and high surface-to-volume ratio, which are beneficial for cell adhesion and proliferation [21]. If collagen could be prepared as nanofibers by electrospinning, it might be helpful for its future application.

Our earlier study showed that collagens from Tilapia skin (PCS, ACS) have significant biocompatibility and can be absorbed and degraded by tissues [22]. Bovine collagen electrospun has been confirmed significant biocompatibility and no cytotoxicity. In continuation to our earlier research [23–26], in vivo wound healing properties of tilapia collagen sponges and bovine collagen electrospun were studied in rat models in order to evaluate its mechanism on accelerating wound healing properties.

#### **2. Results**
