Mesenchymal Stem Cell Derived Extracellular Vesicles: Promising Nanomedicine for Cutaneous Wound Treatment

Abstract

A skin wound represents a rupture caused by external damage or the existence of underlying pathological conditions. Sometimes, skin wound healing processes may place a heavy burden on patients, families, and society. Wound healing processes mainly consist of several continuous, dynamic, but overlapping stages, namely, the coagulation stage, inflammation stage, proliferation stage, and remodeling stage. Bacterial infection, excessive inflammation, impaired angiogenesis, and scar formation constitute the four significant factors impeding the recovery efficacy of skin wounds. This encourages scientists to develop multifunctional nanomedicines to meet challenging needs. As we know, mesenchymal stem cells (MSCs) have been widely explored for wound repair owing to their unique capability for self-renewal and multipotency. However, problems including immune concerns and legal restrictions should be properly resolved before MSC-based therapeutics are safely and widely used in clinics. Besides, maintaining the high viability/proliferation capability of MSCs during administration processes and therapy procedures is also one of the biggest technical bottlenecks. Extracellular vesicles (EVs) are cell-derived nanovesicles, that not only possess the basic characteristics and functions of their corresponding maternal cells but also contain several outstanding advantages including abundant sources, excellent biocompatibility, and convenient administration routes. Furthermore, the membrane surface and cavity are easy to flexibly modify to meet versatile application needs. Recently, MSC-derived EVs have emerged as promising therapeutics for skin wound repair. However, current reviews are too broad and rarely focused on the specific roles of EVs in the different stages of wound recovery. Therefore, it is quite necessary to demonstrate the significance of stem cell-derived EVs in promoting wound healing from several specific aspects. Here, this review primarily tries to provide critical comments on current advances in EVs derived from MSCs for wound repair, particularly elaborating on their impressive roles in effectively eliminating infections, inhibiting inflammation, promoting angiogenesis, and reducing scar formation. Last but not least, current limitations and future prospects of EVs derived from MSCs in the areas of wound repair are also objectively analyzed.

Insights into the role of mesenchymal stem cells in cutaneous medical aesthetics: from basics to clinics

“…Bandages, hydrogels, and sponges are the main nanodrugs used to assist wound healing [175,176]. Mozafari et al designed thermosensitive hydrogel capsules to reduce the level of inflammation and promote wound recovery [177].…”

A bioinspired injectable antioxidant hydrogel for prevention of postoperative adhesion

“…The PU-OHA-D hydrogel exhibited notable tissue repair and anti-adhesion properties, stemming not only from the physical adhesion and isolation effects of the hydrogel itself but also from the exceptional tissue repair functionality of hyaluronic acid and the outstanding antioxidant capabilities of dopamine. 62,63 The adhesion-preventing efficacy of the PU-OHA-D hydrogel was assessed through H&E and Masson staining, with collection of damaged abdominal tissues from rats euthanized on days 7 and 14. As shown in Fig.…”

A comprehensive exploration of hydrogel applications in multi-stage skin wound healing

“…[1][2][3] A wound is the term used to describe an injury to the skin that causes its normal structure and function to be disrupted. 4 When there is a breakdown in the integrity of healthy skin, especially when there are large lesions or open wounds, the skin's physiological activities are affected, making natural healing difficult without assistance. [5][6][7] Wounds are usually divided into acute wounds and chronic wounds according to the nature of the repair process.…”

“…[16][17][18] These obstacles not only have a significant negative effect on patients' quality of life but also place a significant financial strain on healthcare systems. 19 Therefore, it goes without saying that effective techniques are necessary to accelerate wound healing.…”