## 8 Conclusions and Future Perspectives
That includes releasing EV in a sustained manner while biodegradation. EV accelerate wound healing through modulation of different physiological processes, related to tissue regeneration. AgNP: silver nanoparticles; BMMSC, ADMSC, hUCMSC, SMSC and PMSC: MSC derived from bone marrow, adipose tissue, umbilical cord, synovium and placenta, respectively. References are shown in brackets. \begin{table}
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**Biomaterial** & **Origin** & **Culture** & **Isolation** & **[EV]** & **Model** & **Treatment *** & **Ref. ** \\ \hline Collagen & Rat Bone & \multicolumn{3}{c}{80\% confluent} & & & & \\ chitosan & marrow MSC & cells in & & & & & \\ scaffolds & marrow MSC & LG-DMEM & & & & & \\ scaffold & (BMMSC) & serum-free & & & & & \\  & medium for 48 h & & & & & \\ \hline  & Human & & & & & & \\  & Synovium & 50–60\% confluent & & & & & \\ Chitosan & MSC (SMSC) & cells in & & & & & \\  & and SMSC & MesenGro hMSC & & & & & \\  & overexpressing & medium for 48 h & & & & \\  & miR-126-3p & & & & & \\ \hline  & Human & & & & & \\  & & & & & & \\  & & & & & & \\  & & & & & & \\  & & & & & & \\  & & & & & & \\ \hline  & Human & & & & & \\  & endometrial & & & & & \\  
Another important element for further developing this strategy is the biomaterial or dressing, used as scaffolds to apply MSC-EV. As described in this review, there are numerous biomaterials with well-proven properties. Their use in wounds is approved by health authorities, with commercial products available [84, 85]. However, further progress is needed in the manufacture of new wound dressings at a low cost. They should have adequate properties to facilitate healing, with the capacity to encapsulate, protect and release EV in a sustained manner during the healing process. It is also important to note that the use of the wound dressings is not required in the manufacture of new wound dressings. \begin{table}
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that new wound dressings should not only serve the purpose of being a vehicle for MSC-EV, and create a barrier protecting wounds from external environments. They should also be biologically active, promoting healing. For example, they may have antimicrobial, antioxidant and wound pH-modulating activity, among softer properties. Another important aspect to be taken into account is the possible cytotoxicity of biomaterials, their components, such as the crosslinkers, and their degradation products. For this it is necessary to evaluate their possible cytotoxicity in vitro, using suitable cellular models, such as fibroblasts and endothelial cells [131; 132]. Thus, it may be convenient to evaluate, for instance, different crosslinkers when fabricating hydrogels, to obtain a product with low cytotoxicity [133]. Also, in relation to possible undesired effects in the application of MSC-EV encapsulated in biomaterials, it would be necessary to perform studies on possible adverse effects after the end of treatments. This is because the products derived from hydrogel degradation, and mainly the EV applied, can contain molecules with high biological activity. Therefore, it is important to ascertain potential undesired side-effects, as routinely done with pharmaceutical drugs-medicines. This could eventually manifest as alterations in immune responses, appearance of tumors or other consequences. In none of the studies reviewed has this type of research been carried out. Yet, this is an important aspect, in which progress must be made in the future. In conclusion, the combination of MSC-EV with multifunctional wound dressings may have positive synergistic effects on cutaneous-wound healing. Current data show great potential for clinical use. However, further progress is needed for a better understanding of the molecular mechanism of action of MSC-EV, optimization of industrial production for clinical purposes, and standardization of methodologies. Likewise, for the development of suitable wound dressings for encapsulation, protection and release of MSC-EV.