Auto Micro Atomization Delivery of Human Epidermal Organoids Improves Therapeutic Effects for Skin Wound Healing

Abstract Background As the major interface between the body and the external environment, the skin is liable to various injuries. Skin injuries often lead to severe disability, and the exploration of promising therapeutic strategies is of great importance. Exogenous mesenchymal stem cell (MSC)-based therapy is a potential strategy due to the apparent therapeutic effects, while the underlying mechanism is still elusive. Interestingly, we observed the extensive apoptosis of exogenous bone marrow mesenchymal stem cells (BMMSCs) in a short time after transplantation in mouse skin wound healing models. Considering the roles of extracellular vesicles (EVs) in intercellular communication, we hypothesized that the numerous apoptotic bodies (ABs) released during apoptosis may partially contribute to the therapeutic effects. Methods ABs derived from MSCs were extracted, characterized, and applied in mouse skin wound healing models, and the therapeutic effects were evaluated. Then, the target cells of ABs were explored, and the effects of ABs on macrophages were investigated in vitro. Results We found ABs derived from MSCs promoted cutaneous wound healing via triggering the polarization of macrophages towards M2 phenotype. In addition, the functional converted macrophages further enhanced the migration and proliferation abilities of fibroblasts, which together facilitated the wound healing process. Conclusions Collectively, our study demonstrated that transplanted MSCs promoted cutaneous wound healing partially through releasing apoptotic bodies which could convert the macrophages towards an anti-inflammatory phenotype that plays a crucial role in the tissue repair process.

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Comparison of the Therapeutic Effects of Native and Anionic Nanofibrillar Cellulose Hydrogels for Full-Thickness Skin Wound Healing

Micro ◽

10.3390/micro1020015 ◽

2021 ◽

Vol 1 (2) ◽

pp. 194-214

Author(s):

Raili Koivuniemi ◽

Qian Xu ◽

Jasmi Snirvi ◽

Irene Lara-Sáez ◽

Arto Merivaara ◽

...

Keyword(s):

Mechanical Properties ◽

Wound Healing ◽

Early Stage ◽

Skin Wound ◽

Therapeutic Effects ◽

Full Thickness ◽

Skin Wound Healing ◽

Full Thickness Skin ◽

Nanofibrillar Cellulose ◽

Thickness Skin

Nanofibrillar cellulose (NFC)-derived dressings such as films, hydrogels, and aerogels are one of the favorable materials for wound healing due to their proper mechanical properties and water holding ability. However, the therapeutic differences between native and anionic NFC materials are rarely studied. In this report, we compared the differences and addressed the regenerative potential of native and anionic wood-derived NFC hydrogels for wound treatment. In vitro characteristics of the hydrogels were detected using scanning electron microscopy, rheological measurements, and swelling and hemolytic activity assays. Skin regeneration at an early stage after hydrogel treatment was analyzed using an in vivo splinted excisional full-thickness skin wound model in C57BL/6 mice. Both native NFC and anionic NFC (ANFC) hydrogel with differing mechanical and surface properties were shown to be biocompatible. Surprisingly, wounds treated with NFC and ANFC hydrogel did not show any statistical difference compared with control wounds and progressed through normal wound closure, inflammatory response, re-epithelialization, vascularization, and tissue maturation with no signs of fibrosis. The data show here for the first time the therapeutic performance of native and anionic NFC hydrogel in a wound mimicking human wound healing mechanisms. The mechanical properties of native and anionic NFC hydrogels such as the capability to modify material stiffness may also prove to be valuable in the management of wounds in the future.

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Epigallocatechin-3-gallate augments therapeutic effects of mesenchymal stem cells in skin wound healing

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.12652 ◽

2016 ◽

Vol 43 (11) ◽

pp. 1115-1124 ◽

Cited By ~ 7

Author(s):

Min Li ◽

Jingxing Xu ◽

Tongxin Shi ◽

Haiyang Yu ◽

Jianping Bi ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Skin Wound ◽

Therapeutic Effects ◽

Skin Wound Healing

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The Therapeutic Effects of Oral Intake of Hydrogen Rich Water on Cutaneous Wound Healing in Dogs

Veterinary Sciences ◽

10.3390/vetsci8110264 ◽

2021 ◽

Vol 8 (11) ◽

pp. 264

Author(s):

Dong-Dong Qi ◽

Meng-Yuan Ding ◽

Ting Wang ◽

Muhammad Abid Hayat ◽

Tao Liu ◽

...

Keyword(s):

Wound Healing ◽

Blood Vessels ◽

Oral Intake ◽

Healing Time ◽

Skin Wound ◽

Control Group ◽

Therapeutic Effects ◽

Sod Activity ◽

Skin Wound Healing ◽

Wound Healing Time

This study explored the effects of drinking Hydrogen-rich water (HRW) on skin wound healing in dogs. Eight circular wounds were analyzed in each dog. The experimental group was treated with HRW thrice daily, while the control group was provided with distilled water (DW). The wound tissues of dogs were examined histopathologically. The fibroblasts, inflammatory cell infiltration, the average number of new blood vessels, and the level of malondialdehyde (MDA) and superoxide dismutase (SOD) activity in the skin homogenate of the wound was measured using the corresponding kits. The expressions of Nrf-2, HO-1, NQO-1, VEGF, and PDGF were measured using the real-time fluorescence quantitative method. We observed that HRW wounds showed an increased rate of wound healing, and a faster average healing time compared with DW. Histopathology showed that in the HRW group, the average thickness of the epidermis was significantly lower than the DW group. The average number of blood vessels in the HRW group was higher than the DW group. The MDA levels were higher in the DW group than in the HRW group, but the SOD levels were higher in the HRW group than in the DW group. The results of qRT-PCR showed that the expression of each gene was significantly different between the two groups. HRW treatment promoted skin wound healing in dogs, accelerated wound epithelization, reduced inflammatory reaction, stimulated the expression of cytokines related to wound healing, and shortened wound healing time.

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NANOPARTICLES FOR SKIN WOUND HEALING

Nano LIFE ◽

10.1142/s179398441342004x ◽

2013 ◽

Vol 03 (03) ◽

pp. 1342004 ◽

Cited By ~ 1

Author(s):

MELISSA PRZYBOROWSKI ◽

FRANCOIS BERTHIAUME

Keyword(s):

Wound Healing ◽

Bacterial Load ◽

Skin Wound ◽

Bioactive Molecules ◽

Therapeutic Effects ◽

Skin Substitutes ◽

Skin Wound Healing ◽

Design Elements ◽

Design Options ◽

Bioengineered Skin

Over the past two decades, there has been a surge in the development of nanoparticle technologies for therapeutic applications. In the area of skin wound healing, silver nanoparticles have been long used as topical antibacterials, but new types of multifunctional nanosystems that can provide more comprehensive therapeutic effects on wounds are being rolled out. The ability to provide a reservoir of bioactive molecules that can be released over time is a feature of many of these systems, which is critically important for nonhealing wounds, where there often is a persistent bacterial load and a chronic lack of growth factors necessary for healing. A great advantage of nanosystems is that by virtue of their extremely small size, they can be easily incorporated into a wide variety of topical treatments that are currently available for use in the clinic. For example, nanoparticles can be easily introduced into decellularized skin products as well as other bioengineered skin substitutes. The design options available for the nanocarriers are very diverse, including encapsulating the drug in the particle's core or presenting it on the outside of the particle, which can also be decorated with a targeting agent, and the ability to change conformation in response to environmental cues (e.g., pH). These various design elements have been optimized differently to treat different types of wounds.

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Skin wound healing in the first generation (F1) offspring of Yorkshire and red Duroc pigs: Evidence for genetic inheritance of wound phenotype

Yearbook of Surgery ◽

10.1016/s0090-3671(08)70054-5 ◽

2007 ◽

Vol 2007 ◽

pp. 63-64

Author(s):

D.W. Mozingo

Keyword(s):

Wound Healing ◽

First Generation ◽

Skin Wound ◽

Genetic Inheritance ◽

Skin Wound Healing

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Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

International Journal of Molecular Sciences ◽

10.3390/ijms20153679 ◽

2019 ◽

Vol 20 (15) ◽

pp. 3679 ◽

Cited By ~ 3

Author(s):

Lin Chen ◽

Alyne Simões ◽

Zujian Chen ◽

Yan Zhao ◽

Xinming Wu ◽

...

Keyword(s):

Wound Healing ◽

Oral Mucosa ◽

Wound Closure ◽

Expression Patterns ◽

Skin Wound ◽

Skin Wound Healing ◽

Specific Expression ◽

Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

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The Effect of a Polyester Nanofibrous Membrane with a Fibrin-Platelet Lysate Coating on Keratinocytes and Endothelial Cells in a Co-Culture System

Nanomaterials ◽

10.3390/nano11020457 ◽

2021 ◽

Vol 11 (2) ◽

pp. 457

Author(s):

Andreu Blanquer ◽

Jana Musilkova ◽

Elena Filova ◽

Johanka Taborska ◽

Eduard Brynda ◽

...

Keyword(s):

Wound Healing ◽

Endothelial Cells ◽

Chronic Wounds ◽

Human Keratinocytes ◽

Skin Wound ◽

Platelet Lysate ◽

Therapeutic Approaches ◽

Skin Wound Healing ◽

New Therapeutic Approaches ◽

Proliferation And Differentiation

Chronic wounds affect millions of patients worldwide, and it is estimated that this number will increase steadily in the future due to population ageing. The research of new therapeutic approaches to wound healing includes the development of nanofibrous meshes and the use of platelet lysate (PL) to stimulate skin regeneration. This study considers a combination of a degradable electrospun nanofibrous blend of poly(L-lactide-co-ε-caprolactone) and poly(ε-caprolactone) (PLCL/PCL) membranes (NF) and fibrin loaded with various concentrations of PL aimed at the development of bioactive skin wound healing dressings. The cytocompatibility of the NF membranes, as well as the effect of PL, was evaluated in both monocultures and co-cultures of human keratinocytes and human endothelial cells. We determined that the keratinocytes were able to adhere on all the membranes, and their increased proliferation and differentiation was observed on the membranes that contained fibrin with at least 50% of PL (Fbg + PL) after 14 days. With respect to the co-culture experiments, the membranes with fibrin with 20% of PL were observed to enhance the metabolic activity of endothelial cells and their migration, and the proliferation and differentiation of keratinocytes. The results suggest that the newly developed NF combined with fibrin and PL, described in the study, provides a promising dressing for chronic wound healing purposes.

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