Cutaneous Wound Healing Process Research Articles

Evaluation of the Effectiveness of Medical-Grade Honey and Hypericum Perforatum Ointment on Second-Intention Healing of Full-Thickness Skin Wounds in Cats.

This study aimed to determine the effects of two topical treatments on second-intention wound healing in cats. Eight 2 × 2 cm full-thickness wounds were created, four on each side of the dorsal midline of eight laboratory cats, to receive either medical-grade honey ointment (MGH) and its control (HC), or Hypericum-based ointment (HP) and its control (HPC). MGH or HP ointment was applied to four wounds on the same side, while the remaining four were used as controls, chosen at random. Planimetry, laser Doppler flowmetry, daily physical examinations, and histologic examinations on days 0, 7, 14, and 25 were used to assess the healing of wounds. Tissue perfusion was better in the MGH-treated (2.14 ± 0.18 mm/s) and HP-treated wounds (2.02 ± 0.13 mm/s) than in the untreated controls HC (1.59 ± 0.11 mm/s) and HPC (1.60 ± 0.05 mm/s), respectively (p = 0.001). Histopathology revealed that the median edema score was lower in the MGH-treated (2; range 1-4) compared to the HC-treated wounds (3; range 2-4) on day 7 (p < 0.05). The median angiogenesis score was higher on day 7 in the MGH-treated (2; range 1-3) compared to the HP-treated wounds (2; range 1-2) (p = 0.046). The fibroblast concentration was increased in the MGH-treated wounds (3.5; range 3-4) compared to the HP-treated wounds (3; range 2-4) on day 25 (p = 0.046). MGH and HP increased tissue perfusion compared to the untreated controls. The MGH-treated wounds had histologic parameters superior to the HP-treated wounds regarding angiogenesis and fibroblast concentration in cutaneous wound healing in cats. Topical application of MGH and HP did not accelerate the healing process of feline cutaneous wounds.

MiRn-3 inhibits cutaneous wound healing by targeting gelsolin in the sea cucumber Apostichopus japonicus

The microRNA novel-3 (miRn-3) is a 23-nt small endogenous noncoding RNA of unknown function. To enrich our knowledge of the regulatory function of miRn-3 in the process of wound healing, the sea cucumber Apostichopus japonicus was used as a target model in this study. Gelsolin (AjGSN), a potential target gene of miRn-3, was cloned and characterized, and the interaction between miRn-3 and AjGSN was verified. The function of the miRn-3/AjGSN axis in regulating cutaneous wound healing was explored in the sea cucumber A. japonicus. The results showed that 1) the full-length cDNA of AjGSN was 2935 bp, with a high level of sequence conservation across the echinoderms; 2) miRn-3 could bind to the 3’UTR of AjGSN and negatively regulate the expression of AjGSN; 3) overexpression of miRn-3 and inhibition of the expression of AjGSN suppressed cutaneous wound healing in A. japonicus. In general, all observations of this study suggest that miRn-3 plays an important role in the early process of cutaneous wound healing by negatively targeting AjGSN, and that it may be a potential biomarker in wound healing.

Stem Cells and Exosome Applications for Cutaneous Wound Healing: From Ground to Microgravity Environment.

The increasing number of astronauts entering microgravity environments for long-term space missions has resulted in serious health problems, including accidental injury and trauma. Skin, as the largest organ and outermost layer of the human body, has the ability to self-renew and withstand a variety of harmful biological and environmental influences. Recent spaceflight experiments and simulated studies have begun to concern the effects of microgravity on the growth of skin cells and the process of cutaneous wound healing. However, the mechanisms of the adverse effects of microgravity on skin cells and potential intervention measures are still limited. Stem cells and their exosomes provide unique opportunities for the cutaneous wound healing as they have been used to improve skin repair. This review discusses the effects of microgravity on wound healing, from cell morphological changes to molecular level alterations. Furthermore, the current research on wound healing treatment utilizing stem cells and their exosomes on the ground is summarized. Finally, this review proposes promising therapeutic strategies using stem cells or exosomes for wound healing in the microgravity environment. Graphical Abstract.

In vitro and in vivo evaluation of electrospun poly (ε-caprolactone)/collagen scaffolds and Wharton's jelly mesenchymal stromal cells (hWJ-MSCs) constructs as potential alternative for skin tissue engineering

Dermal substitutes bear a high clinical demand because of their ability to promote the healing process of cutaneous wounds by reducing the healing time the appearance and improving the functionality of the repaired tissue. Despite the increasing development of dermal substitutes, most of them are only composed of biological or biosynthetic matrices. This demonstrates the need for new developments focused on using scaffolds with cells (tissue construct) that promote the production of factors for biological signaling, wound coverage, and general support of the tissue repair process. Here, we fabricate by electrospinning two scaffolds: poly(ε-caprolactone) (PCL) as a control and poly(ε-caprolactone)/collagen type I (PCol) in a ratio lower collagen than previously reported, 19:1, respectively. Then, characterize their physicochemical and mechanical properties. As we bear in mind the creation of a biologically functional construct, we characterize and assess in vitro the implications of seeding human Wharton's jelly mesenchymal stromal cells (hWJ-MSCs) on both scaffolds. Finally, to determine the potential functionality of the constructs in vivo, their efficiency was evaluated in a porcine biomodel. Our findings demonstrated that collagen incorporation in the scaffolds produces fibers with similar diameters to those in the human native extracellular matrix, increases wettability, and enhances the presence of nitrogen on the scaffold surface, improving cell adhesion and proliferation. These synthetic scaffolds improved the secretion of factors by hWJ-MSCs involved in skin repair processes such as b-FGF and Angiopoietin I and induced its differentiation towards epithelial lineage, as shown by the increased expression of Involucrin and JUP. In vivo experiments confirmed that lesions treated with the PCol/hWJ-MSCs constructs might reproduce a morphological organization that seems relatively equivalent to normal skin. These results suggest that the PCol/hWJ-MSCs construct is a promising alternative for skin lesions repair in the clinic.

Modulation of NK cell activation by exogenous calcium from alginate dressings in vitro.

Natural Killer (NK) cells participate in the defense against infection by killing pathogens and infected cells and secreting immuno-modulatory cytokines. Defects in NK cell activity have been reported in obese, diabetic, and elderly patients that are at high risk of developing infected chronic wounds. Calcium alginate dressings are indicated for the debridement during the inflammatory phase of healing. Since calcium ions are major activators of NK cells, we hypothesized that these dressings could enhance NK functions, as investigated in vitro herein. Primary human blood NK cells were freshly-isolated from healthy volunteers and exposed to conditioned media (CM) from two alginate dressings, Algosteril® (ALG, pure Ca2+ alginate) and Biatain® Alginate (BIA, Ca2+ alginate with CMC), in comparison with an exogenous 3mM calcium solution. Our results demonstrated that exogenous calcium and ALG-CM, but not BIA-CM, induced NK cell activation and enhanced their capacity to kill their targets as a result of increased degranulation. NK cell stimulation by ALG depended on the influx of extracellular Ca2+ via the SOCE Ca2+ permeable plasma membrane channels. ALG-CM also activated NK cell cytokine production of IFN-γ and TNF-α through a partly Ca2+-independent mechanism. This work highlights the non-equivalence between alginate dressings for NK cell stimulation and shows that the pure calcium alginate dressing Algosteril® enhances NK cell cytotoxic and immuno-modulatory activities. Altogether, these results underline a specific property of this medical device in innate defense that is key for the cutaneous wound healing process.

COMPARATIVE STUDY OF PLACENTREX GEL DRESSING'S VS AMORPHOUS HYDROGEL WITH COLLOIDAL SILVER IN CHRONIC CLEAN WOUNDS

Background: The process of cutaneous wound healing is incredibly complex, dependent on an intricate interplay between number of highly regulated factors working in concert to restore injured skin towards repaired barrier function.Any surgical practice primarily depends upon the healing of wounds without serious complications and infection occurring ,It accounts for considerable patient morbidity, discomfort and prolonged hospitalization. Objective :To compare between the use of Placentrex gel dressingvs Amorphous Hydrogel with colloidal silver in Patients who having chronic clean wounds Methodology:This comparative study was conducted among 140 patients with chronic clean wounds came getting admitted in the department of General Surgery,AVMC with Informed consent were included in the study. Placentrex gel dressing and Amorphous Hydrogel with colloidal silver dressing's was done .Patients were monitored daily and Data was calculated and analysed byusing SPSS version 22.0 (IBM SPSS, US) software operating on windows 10 Result:Total of 140 patients included in the study and divided into two groups of 70 based on the type of dressings done for the Patients .Found signicant lower duration of the hospitalization and cost for the Patients whoreceived Placentrex gel compared to Amorohous hydrogel with colloidal silver .Number of dressings needed for Patients who received placentrex is less comparedwith Amorophous hydrogel with colloidal silver . The patients who given placentrex gel were found to have Signicantly fast wound healing 20 vs 30 days (P&lt;0.005). Conclusion: Placentrex gel is more effective in wound healing than hydrogel and the duration of hospital stay is decreased for patients who have chronic wounds. This study results found that placentrex gel ismore effective against acute and chronic clean wounds.

The combined effect of the human umbilical cord blood with chitosan scaffold on the full-thickness wound healing process in rats

This studyaimed to investigate the role of a low dose of human umbilical cord blood mesenchymal stem cells (HUCB-MSCs) with chitosan scaffold (ChSc) on the progress of the cutaneous wound healing process in male Albino rats. A full-thickness cutaneous wound with a circular shape with a diameter of about 2 cm was induced on the dorsum of thirty-six Albino male rats, divided into four groups: the first group, the wounds were left without treatment as a control group. In the second group, the wounds were covered by freeze-dried ChSc. While in the third group, the wounds were treated through injection of the HUCB-MSCs intradermally, and in the fourth group, the ChSc seeded with HUCB-MSCs were used together to treat the wounds. The progress of wound healing was monitored by histological, immunohistochemical, and biochemical assays for all experimental groups at 3, 8, and 21 postoperative days. Both ChSc and the low dose of HUCB-MSCs alone performed moderate healing progress.The (HUCB-MSCs) ChSc group exhibited an increased healing rate more than the other groups and reported an appropriate collagen deposition without scarring signs, effective mast cell regulation, and well vascularization. In conclusion, the fourth group (the HUCB-MSCs with ChSc) improved the healing process, revealing the highest healing rate and performance without complications.

Centella asiatica and Its Metabolite Asiatic Acid: Wound Healing Effects and Therapeutic Potential.

An intense effort has been focused on new therapeutic approaches and the development of technologies for more efficient and rapid wound healing. The research for plants used for long time in traditional medicine in the treatment of wound has become a promising strategy to obtain drugs therapeutically useful in the acute and chronic wound management. In this context, Centella asiatica (Apiaceae) has been used to treat a variety of skin diseases, such as leprosy, lupus, varicose ulcers, eczema and psoriasis, in Asiatic traditional medicine for thousands of years. Studies have shown that Centella asiatica extracts (CAE) display activity in tissue regeneration, cell migration and wound repair process by promoting fibroblast proliferation and collagen synthesis. Preliminary findings have shown that the asiatic acid is one of the main active constituents of C. asiatica, directly associated with its healing activity. Thus, this study discusses aspects of the effects of Centella asiatica and its active component, asiatic acid, in different stages of the healing process of cutaneous wounds, including phytochemical and antimicrobial aspects that contribute to its therapeutic potential.

Role of Senescent Cells in Cutaneous Wound Healing.

Cellular senescence has gained increasing attention in the field of aging research. Senescent cells have been implicated in biological aging processes, tumorigenesis, development, and wound repair amongst other processes and pathologies. Recent findings reveal that senescent cells can both promote and inhibit cutaneous wound healing processes. Relating senescent cells in acute and chronic wounds will help to clarify their role in wound healing processes and inform our understanding of senescent cell heterogeneity. To clarify this apparent contradiction and guide future research and therapeutic development, we will review the rapidly growing field of cellular senescence and its role in wound healing biology.

Heparin-Loaded Alginate Hydrogels: Characterization and Molecular Mechanisms of Their Angiogenic and Anti-Microbial Potential.

Background: Chronic wounds continue to be a global concern that demands substantial resources from the healthcare system. The process of cutaneous wound healing is complex, involving inflammation, blood clotting, angiogenesis, migration and remodeling. In the present study, commercially available alginate wound dressings were loaded with heparin. The purpose of the study was to enhance the angiogenic potential of alginate wound dressings and analyze the antibacterial activity, biocompatibility and other relevant properties. We also aimed to conduct some molecular and gene expression studies to elaborate on the mechanisms through which heparin induces angiogenesis. Methods: The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Swelling ability was measured by soaking hydrogels in the Phosphate buffer at 37 °C, and cell studies were conducted to evaluate the cytotoxicity and biocompatibility of hydrogels in NIH3T3 (fibroblasts). Real-time PCR was conducted to check the molecular mechanisms of heparin/alginate-induced angiogenesis. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Results: FTIR confirmed the formation of heparin-loaded alginate wound dressing and the compatibility of both heparin and alginate. Among all, 10 µg/mL concentration of heparin showed the best antibacterial activity against E. coli. The swelling was considerably increased up to 1500% within 1 h. Alamar Blue assay revealed no cytotoxic effect on NIH3T3. Heparin showed good anti-microbial properties and inhibited the growth of E. coli in zones with a diameter of 18 mm. The expression analysis suggested that heparin probably exerts its pro-angiogenetic effect through VEGF and cPGE. Conclusions: We report that heparin-loaded alginate dressings are not cytotoxic and offer increased angiogenic and anti-bacterial potential. The angiogenesis is apparently taken through the VEGF pathway.

Lack of transient receptor potential ankyrin 1 (TRPA1) retards cutaneous wound healing in mice: A preliminary study

Wound healing is an important process in various diseases, and elucidating the underlying mechanism is essential for developing therapeutic strategies. We investigated whether the loss of transient receptor potential ankyrin 1 (TRPA1) affects the cutaneous wound healing process in mice. We assessed the formation of granulation tissue by myofibroblasts and macrophages, re-epithelialization, and related gene expression. TRPA1-null (KO) and wild-type (WT) C57BL/6 mice were used for establishing the wound model. Two round full-thickness excision wounds (diameter, 5.0 mm) were produced in the dorsal skin of mice under general anesthesia. After specific intervals, healing was evaluated using macroscopic observation, histology, immunohistochemistry, and real-time reverse transcription-polymerase chain reaction (RT-PCR). TRPA1 KO retarded the formation of granulation tissue and re-epithelialization in the healing of cutaneous wound. Furthermore, TRPA1 KO suppressed the appearance of myofibroblasts, macrophage infiltration, and mRNA expression of αSMA, F4/80, and Col-1α2. These findings indicate that TRPA1 is required for cutaneous wound healing in mice. The lack of TRPA1 retards macrophage infiltration and the subsequent fibrotic tissue formation, which might further impair the fibrogenic behavior of fibroblasts.

Polysaccharide extract of Caesalpiniaferrea (Mart) pods attenuates inflammation and enhances the proliferative phase of rat cutaneous wounds.

Pods of Caesalpiniaferrea, popularly used to treat inflammatory processes, were collected to obtain the polysaccharide-rich extract, presenting anti-inflammatory and antinociceptive effects in acute inflammation models. This study aimed to evaluate the anti-inflammatory, antinociceptive and healing activities of the polysaccharide-rich extract from Caesalpiniaferrea pods (PEp-Cf) in the rat model of cutaneous excisional wound. PEp-Cf (0.025-0.1%) or 0.9% NaCl was topically applied in the wounds at dorsal thoracic region (2×/day) during 21days for measurement of clinical signs (hyperemia, inflammatory exudate, edema, nociception), wound size, histopathological/histomorphometric, oxidative/inflammatory markers and systemic toxicity. PEp-Cf at 0.1% reduced wound area and increased ulcer contraction [days 2 and 10 (21-78%)]. PEp-Cf reduced clinical signs [days 2 and 5 (2.2-2.8×)] and modulated the healing inflammatory phase via stimulation of epithelialization (days 10 and 14), and inhibition of polymorphonuclears [days 2 and 5 (71-74%)], protein leakage [days 2 and 5 (28-41%)], nitrate [days 2 and 5 (2.2-6×)] and malondialdehyde [days 2 and 5 (46-49%)]. PEp-Cf increased the number of blood vessels [days 5 and 7 (3.1-9.6×)], fibroblasts [days 5 and 7 (2.1-6.4×)] and collagen [days 5 to 14 (1.5-1.8×)]. In conclusion, the topical application of PEp-Cf at 0.1% accelerates the healing process of rat cutaneous wounds via modulation of the inflammatory and proliferative phases, being devoid of systemic alterations.

Effects of the Application of Decellularized Amniotic Membrane Solubilized with Hyaluronic Acid on Wound Healing.

A perfect graft for wound care must be readily available without affecting the immune response, covering and protecting the wound bed. Considering previous studies have already established the use of hyaluronic acid (HA) for the treatment of wounds but the data presented on the amniotic membrane (AM) and its promising effects on healing still requires further investigation, this study aimed to evaluate the effects of the application of a decellularized amniotic membrane solubilized with hyaluronic acid on the healing process of cutaneous wounds on the 7th and 14th day, to evaluate the evolution of the wound and the inflammatory phases in these two times. Cutaneous lesions were excised from the dorsal region and 96 Wistar rats were divided into four groups: I-Excisional wound (EW); II-EW + AM; III-EW + HA; IV-EW + AM + HA. The present study demonstrated that the proposed combined therapy favors the tissue repair process of the epithelial lesion. Results showed a reduction in pro-inflammatory cytokines, an increase in anti-inflammatory cytokines, an increase in TGF-β, and attenuation of oxidative stress, reducing the acute inflammatory response and promoting the beginning of tissue repair. We concluded that the proposed therapies accelerated the inflammatory process with anticipation of the repair phase.

The Efficacy of Mesenchymal Stem Cells loaded in Acacia Gum Hydrogel and Acacia Gum Hydrogel on Skin Wounds Healing in Rats

Cutaneous wound healing processes start at the beginning of the trauma leading to impairment of physical and functional tissue continuity. The present work aimed to clarify the efficacy of stem cells loaded in acacia gum hydrogel and acacia gum hydrogel on skin wound healing in rats. Thirty-six adult male rats (Wister rats). The weight of the rats was estimated between 150-160 grams and the animals were divided into three groups (n=12). In Group A (control group), the surgical skin wound was established and treated with normal saline only. Group B: surgical skin wound was made and covered with Acacia gum hydrogel. Group C: surgical skin wound was made and covered with mesenchymal stem cells loaded in Acacia gum hydrogel. Examination of wound healing on days 3, 7, 14 and 21 for gross and microscopic pathological changes. The gross pathological evaluation showed no significant difference between all groups but the histopathological result showed the Acacia gum improved wound recovery better than the control group, although the wound was not completely closed on day 21 in Acacia gum and control groups contrary to the stem cells treated group, which showed complete wound closure. The best ever histopathological result of wounds healing in mesenchymal stem cells loaded in acacia gum hydrogel treated groups.

Cutaneous Wound Healing: A Review about Innate Immune Response and Current Therapeutic Applications.

Skin wounds and compromised wound healing are major concerns for the public. Although skin wound healing has been studied for decades, the molecular and cellular mechanisms behind the process are still not completely clear. The systemic responses to trauma involve the body's inflammatory and immunomodulatory cellular and humoral networks. Studies over the years provided essential insights into a complex and dynamic immunity during the cutaneous wound healing process. This review will focus on innate cell populations involved in the initial phase of this orchestrated process, including innate cells from both the skin and the immune system.

Bio-Hybrid Hydrogels Incorporated into a System of Salicylic Acid-pH/Thermosensitive Nanocarriers Intended for Cutaneous Wound-Healing Processes.

In this paper, the preparation method of bio-hybrid hydrogels incorporated into a system of salicylic acid-pH/thermosensitive nanocarriers to speed up the wound-healing process was developed. This combination creates a dual drug delivery system, which releases the model hydrophobic active substance—salicylic acid—in a gradual and controlled manner for an extended time. Our research team has determined the various properties of bio-hybrid hydrogels based on their physicochemical (swelling degree, and degradation), structural (FT-IR), morphological (SEM), and mechanical (elongation tests) traits. Moreover, empty pH/thermosensitive nanocarriers and their salicylic acid-containing systems were characterized using the following methods: DLS, TG/DTG, and DSC. Additionally, salicylic acid release profiles directly from thermosensitive nanocarriers were compared to the bio-hybrid matrix. These studies were conducted in PBS (pH = 7.4) for 7 days using the USP4 method. To evaluate the antibacterial properties of the obtained materials, the inhibition of growth of Staphylococcus aureus, Escherichia coli, Candida albicans, and Aspergillus niger—as the main microorganisms responsible for human infections—were tested. The obtained results indicated that the pH/thermosensitive nanocarrier–salicylic acid system and bio-hybrid hydrogels are characterized by antibacterial activity against both S. aureus and E. coli.

The influence of CD26+ and CD26\u2212 fibroblasts on the regeneration of human dermo-epidermal skin substitutes

CD26, also known as dipeptidyl peptidase IV (DPPIV), is a multifunctional transmembrane protein playing a significant role in the cutaneous wound healing processes in the mouse skin. However, only scarce data are available regarding the distribution and function of this protein in the human skin. Therefore, the aim of this study was to investigate the impact of CD26 deficiency in human primary fibroblasts on the regeneration of human tissue-engineered skin substitutes in vivo. Dermo-epidermal skin analogs, based on collagen type I hydrogels, were populated either with human CD26+ or CD26knockout fibroblasts and seeded with human epidermal keratinocytes. These skin substitutes were transplanted onto the back of immune-incompetent rodents. Three weeks post-transplantation, the grafts were excised and analyzed with respect to specific epidermal and dermal maturation markers. For the first time, we show here that the expression of CD26 protein in human dermis is age-dependent. Furthermore, we prove that CD26+ fibroblasts are more active in the production of extracellular matrix (ECM) both in vitro and in vivo and are necessary to achieve rapid epidermal and dermal homeostasis after transplantation.

PH-responsive hierarchical H2S-releasing nano-disinfectant with deep-penetrating and anti-inflammatory properties for synergistically enhanced eradication of bacterial biofilms and wound infection

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) biofilm-associated bacterial infection is the primary cause of nosocomial infection and has long been an ongoing threat to public health. MRSA biofilms are often resistant to multiple antimicrobial strategies, mainly due to the existence of a compact protective barrier; thus, protecting themselves from the innate immune system and antibiotic treatment via limited drug penetration.ResultsA hierarchically structured hydrogen sulfide (H2S)-releasing nano-disinfectant was presented, which was composed of a zinc sulfide (ZnS) core as a H2S generator and indocyanine green (ICG) as a photosensitizer. This nano-disinfectant (ICG-ZnS NPs) sensitively responded to the biofilm microenvironment and demonstrated efficient eradication of MRSA biofilms via a synergistic effect of Zn2+, gas molecule-mediated therapy, and hyperthermia. Physically boosted by released H2S and a near-infrared spectroscopy-induced hyperthermia effect, ICG-ZnS NPs destroyed the compactness of MRSA biofilms showing remarkable deep-penetration capability. Moreover, on-site generation of H2S gas adequately ameliorated excessive inflammation, suppressed secretion of inflammatory cytokines, and expedited angiogenesis, therefore markedly accelerating the in vivo healing process of cutaneous wounds infected with MRSA biofilms.ConclusionICG-ZnS NPs combined with NIR laser irradiation exhibited significant anti-biofilm activity in MRSA biofilms, can accelerate the healing process through deep-penetration and anti-inflammatory effectuation. The proposed strategy has great potential as an alternative to antibiotic treatment when combating multidrug-resistant bacterial biofilms.Graphical

High-resolution polarization-sensitive optical coherence tomography and optical coherence tomography angiography for zebrafish skin imaging

Zebrafish is an important animal model, which is used to study development, pathology, and genetic research. The zebrafish skin model is widely used in cutaneous research, and angiogenesis is critical for cutaneous wound healing. However, limited by the penetration depth, the available optical methods are difficult to describe the internal skin structure and the connection of blood vessels between the skin and subcutaneous tissue. By a homemade high-resolution polarization-sensitive optical coherence tomography (PS-OCT) system, we imaged the polarization contrast of zebrafish skin and the zebrafish skin vasculature with optical coherence tomography angiography (OCTA). Based on these OCT images, the spatial distribution of the zebrafish skin vasculature was described. Furthermore, we monitored the healing process of zebrafish cutaneous wounds. We think the high-resolution PS-OCT system will be a promising tool in studying cutaneous models of zebrafish.

Extracellular Vesicles as Therapeutic Tools for the Treatment of Chronic Wounds.

Chronic wounds develop when the orderly process of cutaneous wound healing is delayed or disrupted. Development of a chronic wound is associated with significant morbidity and financial burden to the individual and health-care system. Therefore, new therapeutic modalities are needed to address this serious condition. Mesenchymal stem cells (MSCs) promote skin repair, but their clinical use has been limited due to technical challenges. Extracellular vesicles (EVs) are particles released by cells that carry bioactive molecules (lipids, proteins, and nucleic acids) and regulate intercellular communication. EVs (exosomes, microvesicles, and apoptotic bodies) mediate key therapeutic effects of MSCs. In this review we examine the experimental data establishing a role for EVs in wound healing. Then, we explore techniques for designing EVs to function as a targeted drug delivery system and how EVs can be incorporated into biomaterials to produce a personalized wound dressing. Finally, we discuss the status of clinically deploying EVs as a therapeutic agent in wound care.