# The Application of Mesenchymal Stem Cells on Wound Repair and Regeneration
## 9 Stem Cell Delivery Methods  
Regarding treatment, cell delivery methods are a very important aspect that is often neglected [62]. Stem cells can be applied in several ways: systemically, which does not allow local specific treatment and is less efficient as local injections; topical, which is  
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**MSCs** & **Advantages** & **Limitations** \\ \hline
**BM-MSCs** & & & \\  & \(\bullet\) & Well-Described & \(\bullet\) & Invasive and Painful \\  & \(\bullet\) & Low Immunogenicity & Harvest Method \\  & \(\bullet\) & Promising Healing Capacity (Chronic Wounds) & \(\bullet\) & Low Performance in \\  & & & & Culture \\ \hline
**ASCs** & & & \\  & \(\bullet\) & Easy to Isolate and Collect & \(\bullet\) & Heterogeneous \\  & \(\bullet\) & Ready to Use & & Population \\  & \(\bullet\) & Better for Autotransplantation & & \\  & \(\bullet\) & Promote Tissue Regeneration & & \\ \hline
**UC-MSCs** & & & \\  & \(\bullet\) & Safe and Non-Invasive Collection & \(\bullet\) & Non Relevant \\  & \(\bullet\) & Higher Proliferation and Expansion Capacity & & \\  & \(\bullet\) & Promote Regeneration and Tissue Repair & & \\  & \(\bullet\) & Possibility to Differentiate Into Epidermal Tissue & & \\ \hline
**EPSCs** & & & \\  & \(\bullet\) & Simple to Isolate & \(\bullet\) & Skin Lesion for Cell \\  & \(\bullet\) & Abundance and Accessibility & & Collection \\  & \(\bullet\) & Skin Regenerative Capacity & & \\ \hline \hline \end{tabular}
\end{table}
Table 1: Advantages and limitations of different types of MSC.  
an excellent alternative in cases of skin wounds; and bioscaffolds, which are the most promising delivery method (Figure 4) [7,63].  
Bioscaffolds are 3D-printed with biocompatible materials generating 3D patterns, which enable the incorporation of cells (in this case stem cells) or biomolecules that remain viable. They are composed of natural organic materials, synthetic organic materials or even inorganic porous materials, allowing stem cells to be seeded in controlled spaces, protected and promoting their self-renewal and survival [7,64,65,66,67]. The advantages of this method are due to the ability to produce an identical scaffold with homogeneous distribution, that can incorporate an identical and well-defined dose, being easy to apply [64,65,66]. In addition, some studies have shown that using bioscaffolds accelerates wound healing when compared to other techniques, increasing cell graft longevity, remodeling of ECM and improving cell viability [7,14,62]. Thus, when compared with intradermal injection, bioscaffolds have shown better results in wound healing, reducing scar formation and improving the skin's biomechanical properties [63].  
On the other hand, there are some disadvantages in the use of stem-cell therapies, for example, the delivery methods that are not yet optimized, the best stem cell populations are not identified yet and there is a risk of tumorigenicity and immunogenicity. The wound itself can have a hostile environment for stem cells due to inflammation, hypoxia or even oxidative stress. Also, topical application does not allow the control of cell density that is placed locally and delivers the cells in a non-protected way [7].