# The Application of Mesenchymal Stem Cells on Wound Repair and Regeneration
## 6 Recent Innovative Strategies in Wound-Healing Regeneration  
Recent studies support the concept that MSCs can be appropriated for treating chronic wounds. Moreover, autologous stem cells are the most popular approach, mainly MSCs derived from adipose tissue (ASCs) and from the bone-marrow (BM-MSCs). However, umbilical cord blood was also mentioned because of the beneficial effects shown on wound healing [23, 38, 39]. The skin tissue engineering process is truly complex because it relies on various factors: the appropriate choice of biomaterial, the design of a convenient platform (to mimic functional and structural properties of skin) and cell selection. One of the aims is to develop scaffolds containing cells and other molecules to restore damaged tissues. Moreover, the  
Figure 2: Wound healing is a complex process that can be divided into different phases: hemostasis, inflammation, proliferation and tissue remodeling. Promptly after injury, hemostasis and inflammation occur, which is characterized by the influx of inflammatory cells. Consequently, the proliferative phase is marked by collagen deposition, angiogenesis, granulation tissue formation and epithelization. At the very least, the tissue remodeling phase is characterized by declined cellularity and matrix remodeling. Moreover, it is during this phase that the wound undergoes contraction which can result in the formation of a scar. Based on [20] and adapted and modified from Servier Medical Art. Servier is licensed under a Creative Commons Attribution 3.0 Unported License. matrix provided by the scaffold is good for the cells to reside and proliferate, but it also needs instructive cues to multiply in a regenerative microenvironment [34]. For instance, continued and slow release of molecules, such as growth factors from scaffolds, can help in the skin regeneration process. The combination of stem cells and a 3D biomaterial printing (capable of mimicking the extracellular matrix) has several advantages, such as the regeneration properties placed locally [3]. This technique limitations are related to the biomaterials properties that need to be compatible with the cells and the printing requirements [3]. The primary features that the hydrogel scaffold needs to have are biocompatibility, anti-bacterial capacity, proper mechanical characteristics, injectable capacity and water retention [40]. Furthermore, the ability to sustain damage by external forces, maintaining the stability of its structure, is fundamental. The injective capacity is relevant due to the ability to attach to the wound (long term) and an excellent cell biocompatibility that is capable of increasing differentiation and proliferation [40]. On the other hand, there are still several points that need improvement, such as the crosslinking reagents added to hydrogels. They are necessary because otherwise the hydrogels would have weak mechanical properties, which means they would be incapable of maintaining their shape and size [41]. The process of healing is based on four healing phases, as mentioned before, which implicate interactions between different cell types, a platform and bioactive factors [34]. In addition, structural engineering of scaffolds or hydrogels is another approach, which obligates the study of different matrices and their properties. It is important to consider that a particular design of a scaffold is appropriate for each specific type of wound [42; 43]. In addition, 3D bioprinting of skin is a promising technology which has long been anticipated in the fields of drug and cosmetic development, mainly due to the decrease of ethical issues related to animal testing. This innovative technology allows the production of in vitro skin tissues for wound healing applications and shows great potential in fields like transplantation and development of skin equivalents [42; 43]. In 2015, Procter and Gamble (P&G) and Rokit started working on research projects that focus on bioprinted human skin models [42; 43].