932 Development of an early wound model in human ex vivo skin explant as a preclinical model of wound healing

AbstractA large body of literature is available on wound healing in humans. Nonetheless, a standardized ex vivo wound model without disruption of the dermal compartment has not been put forward with compelling justification. Here, we present a novel wound model based on application of negative pressure and its effects for epidermal regeneration and immune cell behaviour. Importantly, the basement membrane remained intact after blister roof removal and keratinocytes were absent in the wounded area. Upon six days of culture, the wound was covered with one to three-cell thick K14+Ki67+ keratinocyte layers, indicating that proliferation and migration were involved in wound closure. After eight to twelve days, a multi-layered epidermis was formed expressing epidermal differentiation markers (K10, filaggrin, DSG-1, CDSN). Investigations about immune cell-specific manners revealed more T cells in the blister roof epidermis compared to normal epidermis. We identified several cell populations in blister roof epidermis and suction blister fluid that are absent in normal epidermis which correlated with their decrease in the dermis, indicating a dermal efflux upon negative pressure. Together, our model recapitulates the main features of epithelial wound regeneration, and can be applied for testing wound healing therapies and investigating underlying mechanisms.

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Octenidine-based hydrogel shows anti-inflammatory and protease-inhibitory capacities in wounded human skin

Scientific Reports ◽

10.1038/s41598-020-79378-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Saskia Seiser ◽

Lukas Janker ◽

Nina Zila ◽

Michael Mildner ◽

Ana Rakita ◽

...

Keyword(s):

Wound Healing ◽

Human Skin ◽

Ex Vivo ◽

Skin Wound ◽

Enzyme Linked Immunosorbent Assay ◽

Tape Stripping ◽

Skin Wound Healing ◽

Wound Model ◽

Octenidine Dihydrochloride ◽

Anti Inflammatory

AbstractOctenidine dihydrochloride (OCT) is a widely used antiseptic molecule, promoting skin wound healing accompanied with improved scar quality after surgical procedures. However, the mechanisms by which OCT is contributing to tissue regeneration are not yet completely clear. In this study, we have used a superficial wound model by tape stripping of ex vivo human skin. Protein profiles of wounded skin biopsies treated with OCT-containing hydrogel and the released secretome were analyzed using liquid chromatography-mass spectrometry (LC–MS) and enzyme-linked immunosorbent assay (ELISA), respectively. Proteomics analysis of OCT-treated skin wounds revealed significant lower levels of key players in tissue remodeling as well as reepithelization after wounding such as pro-inflammatory cytokines (IL-8, IL-6) and matrix-metalloproteinases (MMP1, MMP2, MMP3, MMP9) when compared to controls. In addition, enzymatic activity of several released MMPs into culture supernatants was significantly lower in OCT-treated samples. Our data give insights on the mode of action based on which OCT positively influences wound healing and identified anti-inflammatory and protease-inhibitory activities of OCT.

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Somatostatin Inhibits Cell Migration and Reduces Cell Counts of Human Keratinocytes and Delays Epidermal Wound Healing in an Ex Vivo Wound Model

PLoS ONE ◽

10.1371/journal.pone.0019740 ◽

2011 ◽

Vol 6 (5) ◽

pp. e19740 ◽

Cited By ~ 14

Author(s):

Matthias Vockel ◽

Simone Pollok ◽

Ute Breitenbach ◽

Ina Ridderbusch ◽

Hans-Jürgen Kreienkamp ◽

...

Keyword(s):

Wound Healing ◽

Cell Migration ◽

Ex Vivo ◽

Human Keratinocytes ◽

Wound Model ◽

Cell Counts

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ultrastructural process of intestinal wound healing

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100141494 ◽

1995 ◽

Vol 53 ◽

pp. 1024-1025

Author(s):

Rick L. Vaughn ◽

Shailendra K. Saxena ◽

John G. Sharp

Keyword(s):

Wound Healing ◽

Epithelial Cells ◽

Smooth Muscles ◽

Microscopic Level ◽

Light Microscopic Level ◽

Ileal Mucosa ◽

Wound Model ◽

Serosal Surface ◽

Complex Process ◽

Orderly Fashion

We have developed an intestinal wound model that includes surgical construction of an ileo-cecal patch to study the complex process of intestinal wound healing. This allows approximation of ileal mucosa to the cecal serosa and facilitates regeneration of ileal mucosa onto the serosal surface of the cecum. The regeneration of ileal mucosa can then be evaluated at different times. The wound model also allows us to determine the rate of intestinal regeneration for a known size of intestinal wound and can be compared in different situations (e.g. with and without EGF and Peyer’s patches).At the light microscopic level it appeared that epithelial cells involved in regeneration of ileal mucosa originated from the enlarged crypts adjacent to the intestinal wound and migrated in an orderly fashion onto the serosal surface of the cecum. The migrating epithelial cells later formed crypts and villi by the process of invagination and evagination respectively. There were also signs of proliferation of smooth muscles underneath the migratory epithelial cells.

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Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530321666201230113018 ◽

2020 ◽

Vol 21 ◽

Author(s):

Hana M. Hammad ◽

Amer Imraish ◽

Maysa Al-Hussaini ◽

Malek Zihlif ◽

Amani A. Harb ◽

...

Keyword(s):

Wound Healing ◽

Rural Communities ◽

Ex Vivo ◽

Ethanol Extract ◽

Aortic Ring ◽

Treated Group ◽

Control Group ◽

Dependent Manner ◽

Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

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Injectable Self-Healing Adhesive pH-Responsive Hydrogels Accelerate Gastric Hemostasis and Wound Healing

Nano-Micro Letters ◽

10.1007/s40820-020-00585-0 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Jiahui He ◽

Zixi Zhang ◽

Yutong Yang ◽

Fenggang Ren ◽

Jipeng Li ◽

...

Keyword(s):

Wound Healing ◽

Endoscopic Treatment ◽

Healing Process ◽

Gelation Time ◽

Type I ◽

Self Healing ◽

Ph Responsive ◽

Gastric Hemorrhage ◽

Wound Model ◽

Arterial Bleeding

AbstractEndoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are well-established therapeutics for gastrointestinal neoplasias, but complications after EMR/ESD, including bleeding and perforation, result in additional treatment morbidity and even threaten the lives of patients. Thus, designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge. Herein, a series of injectable pH-responsive self-healing adhesive hydrogels based on acryloyl-6-aminocaproic acid (AA) and AA-g-N-hydroxysuccinimide (AA-NHS) were developed, and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model. The hydrogels showed a suitable gelation time, an autonomous and efficient self-healing capacity, hemostatic properties, and good biocompatibility. With the introduction of AA-NHS as a micro-cross-linker, the hydrogels exhibited enhanced adhesive strength. A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding. A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition, α-SMA expression, and blood vessel formation. These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.

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Wound Healing Composite Materials of Bacterial Cellulose and Zinc Oxide Nanoparticles with Immobilized Betulin Diphosphate

Nanomaterials ◽

10.3390/nano11030713 ◽

2021 ◽

Vol 11 (3) ◽

pp. 713

Author(s):

Nina Melnikova ◽

Alexander Knyazev ◽

Viktor Nikolskiy ◽

Peter Peretyagin ◽

Kseniia Belyaeva ◽

...

Keyword(s):

Wound Healing ◽

Zinc Oxide ◽

Bacterial Cellulose ◽

Zinc Oxide Nanoparticles ◽

Wound Dressings ◽

Oxide Nanoparticles ◽

Burn Wound ◽

Zno Nps ◽

Wound Model ◽

And Oxidative Stress

A design of new nanocomposites of bacterial cellulose (BC) and betulin diphosphate (BDP) pre-impregnated into the surface of zinc oxide nanoparticles (ZnO NPs) for the production of wound dressings is proposed. The sizes of crystalline BC and ZnO NPs (5–25%) corresponded to 5–6 nm and 10–18 nm, respectively (powder X-ray diffractometry (PXRD), Fourier-infrared (FTIR), ultraviolet (UV), atomic absorption (AAS) and photoluminescence (PL) spectroscopies). The biological activity of the wound dressings “BC-ZnO NPs-BDP” was investigated in rats using a burn wound model. Morpho-histological studies have shown that more intensive healing was observed during treatment with hydrophilic nanocomposites than the oleophilic standard (ZnO NPs-BDP oleogel; p < 0.001). Treatment by both hydrophilic and lipophilic agents led to increases in antioxidant enzyme activity (superoxide dismutase (SOD), catalase) in erythrocytes and decreases in the malondialdehyde (MDA) concentration by 7, 10 and 21 days (p < 0.001). The microcirculation index was restored on the 3rd day after burn under treatment with BC-ZnO NPs-BDP wound dressings. The results of effective wound healing with BC-ZnO NPs-BDP nanocomposites can be explained by the synergistic effect of all nanocomposite components, which regulate oxygenation and microcirculation, reducing hypoxia and oxidative stress in a burn wound.

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Evaluation of Potential Application of Wharton’s Jelly-Derived Human Mesenchymal Stromal Cells and its Conditioned Media for Dermal Regeneration using Rat Wound Healing Model

Cells Tissues Organs ◽

10.1159/000513895 ◽

2021 ◽

pp. 1-14

Author(s):

Caroline Mathen ◽

Mrunal Ghag Sawant ◽

Raghubansh Gupta ◽

Wilfrid Dsouza ◽

Shilpa G. Krishna

Keyword(s):

Wound Healing ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Therapeutic Potential ◽

Wound Care ◽

Free Cell ◽

Conditioned Media ◽

Human Umbilical Cord ◽

Human Mscs ◽

Wound Model

Mesenchymal stromal cells and the derived conditioned media represent an area of tremendous medical interest and, among other clinical applications, are currently being extensively explored for wound healing. The aim of this study was to comparatively evaluate the wound healing potential of xeno-free human umbilical cord-derived mesenchymal stromal cells (MSCs) and the conditioned media (CM) in a full-thickness excision wound model in rats. The evaluation parameters included rate of wound healing, serum cytokine analyses, collagen content, histopathology, and hyperspectral imaging as an independent qualitative and quantitative tool. Both the cell-based and cell-free approaches scored better in lower inflammation, as evidenced in lower IL-10 and stable IL-6 levels, and improved rate of wound healing (<i>p</i> < 0.0001). More importantly, no adverse reaction or rejection was observed although human MSCs and CM were used in a xenogeneic model. The presence of hFGF, hHGF, hGCSF, hIL-1Ra, hVEGF, and hIL-6 in the secretome may elucidate the regenerative potential of the xeno-free cell-based and cell-free approaches which have translational value for advanced wound care. The results revealed the therapeutic potential of both the cell-based and cell-free approaches for wound healing.

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Development of a Three-Dimensional Human Skin Equivalent Wound Model for Investigating Novel Wound Healing Therapies

Tissue Engineering Part C Methods ◽

10.1089/ten.tec.2009.0725 ◽

2010 ◽

Vol 16 (5) ◽

pp. 1111-1123 ◽

Cited By ~ 58

Author(s):

Yan Xie ◽

Simone C. Rizzi ◽

Rebecca Dawson ◽

Emily Lynam ◽

Sean Richards ◽

...

Keyword(s):

Wound Healing ◽

Human Skin ◽

Three Dimensional ◽

Skin Equivalent ◽

Wound Model ◽

Human Skin Equivalent

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In Vivo and ex Vivo Approaches to Studying the Biomechanical Properties of Healing Wounds in Rat Skin

Journal of Biomechanical Engineering ◽

10.1115/1.4025109 ◽

2013 ◽

Vol 135 (10) ◽

Cited By ~ 14

Author(s):

Clare Y. L. Chao ◽

Gabriel Y. F. Ng ◽

Kwok-Kuen Cheung ◽

Yong-Ping Zheng ◽

Li-Ke Wang ◽

...

Keyword(s):

Wound Healing ◽

Ex Vivo ◽

Normal Skin ◽

Biomechanical Properties ◽

Skin Wound ◽

Sprague Dawley ◽

Rat Skin ◽

Mechanical Stiffness ◽

Air Jet

An evaluation of wound mechanics is crucial in reflecting the wound healing status. The present study examined the biomechanical properties of healing rat skin wounds in vivo and ex vivo. Thirty male Sprague-Dawley rats, each with a 6 mm full-thickness circular punch biopsied wound at both posterior hind limbs were used. The mechanical stiffness at both the central and margins of the wound was measured repeatedly in five rats over the same wound sites to monitor the longitudinal changes over time of before wounding, and on days 0, 3, 7, 10, 14, and 21 after wounding in vivo by using an optical coherence tomography-based air-jet indentation system. Five rats were euthanized at each time point, and the biomechanical properties of the wound tissues were assessed ex vivo using a tensiometer. At the central wound bed region, the stiffness measured by the air-jet system increased significantly from day 0 (17.2%), peaked at day 7 (208.3%), and then decreased progressively until day 21 (40.2%) as compared with baseline prewounding status. The biomechanical parameters of the skin wound samples measured by the tensiometer showed a marked reduction upon wounding, then increased with time (all p < 0.05). On day 21, the ultimate tensile strength of the skin wound tissue approached 50% of the normal skin; while the stiffness of tissue recovered at a faster rate, reaching 97% of its prewounded state. Our results suggested that it took less time for healing wound tissues to recover their stiffness than their maximal strength in rat skin. The stiffness of wound tissues measured by air-jet could be an indicator for monitoring wound healing and contraction.

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