Skin injuries can be caused by different factors such as acute trauma, chronic wound, genetic disorders, and complex surgeries that may cause disability or even death[1]. Current treatments such as autografts, allografts, and xenografts have limitations including donor site morbidity, limited supply, various disease risks, high manufacturing costs, and excessive inflammation[2]. Recently, remarkable advances in biological scaffolds derived from decellularized tissues or organs have raised new hopes for solving the problems. The decellularized scaffolds provide a favorable microenvironment that mimics normal tissue and contains many biological factors necessary for cell proliferation, migration, and differentiation[3–5]. Skin, bone, heart valve, precordium, and placental tissues (placenta, chorion, and amniotic membrane) collected from humans and animals are excellent sources for the fabrication of allograft and xenograft decellularized scaffolds [6]. Among the candidate tissues for decellularization, the human placenta is a frequently available source of tissue after birth [7, 8]. They can be retrieved without undergoing an invasive operation, which gives them a significant advantage over other tissues and organs[9, 10]. The human placenta is a complex organ with a rich reservoir for various growth factors and cytokines such as epidermal growth factor (EGF), fibroblast growth factor (FGF), transforming growth factor-β (TGF- β), platelet-derived growth factor (PDGF), and vascular endothelial growth factor (VEGF), etc. [11]. These growth factors and cytokines are crucial for fibroblast and keratinocyte proliferation and migration mesenchymal stem cell homing re-epithelialization, and neovascularization[12]. All of these substances are thought to be essential for tissue regeneration. Additionally, its anti-scarring, anti-inflammatory, and low immunogenicity make it an excellent choice for skin wound healing[13]. Co-treatment of defects with scaffold and exogenous stem cells significantly accelerated the healing process. Some studies have found that the re-cellularization of decellularized scaffolds with stem cells can significantly improve healing when compared to scaffolding alone [14][15]. Among the stem cells in cell therapy applications, mesenchymal stem cells (MSCs) have been extensively studied in the treatment of various defects, and are now being utilized therapeutically in the healing of burns and the re-epithelization of chronically untreated skin[16, 17]. Unique immune-modulatory and anti-inflammatory capabilities, easy availability, and expansion method, potential multipotency have made MSCs a prospective source of cells for many regenerative processes[18, 19]. The stem cell niche, directly and indirectly regulates stem cell functions like self-renewal and differentiation, and the extracellular matrix (ECM) plays a vital role in regulating cell behavior[20]. The bone marrow MSC niche is composed of numerous matrix proteins, including fibronectin, laminin, collagen I, and collagen IV, and typically, cells would be exposed to tissues by cultivating cells within a 3D scaffold. The 3D geometry of a biomimetic scaffold plays a significant role in enhancing its potential for regeneration, highlighting the need of replicating the actual physical geometry of the native cellular niche[21–23]. In the present study, the DPS scaffold was fabricated and re-cellularized with MSCs. The potential of DPS for supporting MSCs growth and attachment, and as a carrier for delivery of these cells to wounds sites and accelerating angiogenesis and wound healing has been thoroughly investigated in vitro and in vivo.