scholarly journals A Comparative Study of Engineered Dermal Templates for Skin Wound Repair in a Mouse Model

2020 ◽  
Vol 21 (12) ◽  
pp. 4508 ◽  
Author(s):  
Ilia Banakh ◽  
Perdita Cheshire ◽  
Mostafizur Rahman ◽  
Irena Carmichael ◽  
Premlatha Jagadeesan ◽  
...  
Keyword(s):  
Mouse Model ◽  
Wound Repair ◽  
Human Fibroblasts ◽  
Skin Wound ◽  
Tissue Growth ◽  
Skin Substitute ◽  
Protein Levels ◽  
Collagen Iii ◽  
Synthetic Grafts ◽  
Dermal Template

Engineered dermal templates have revolutionised the repair and reconstruction of skin defects. Their interaction with the wound microenvironment and linked molecular mediators of wound repair is still not clear. This study investigated the wound bed and acellular “off the shelf” dermal template interaction in a mouse model. Full-thickness wounds in nude mice were grafted with allogenic skin, and either collagen-based or fully synthetic dermal templates. Changes in the wound bed showed significantly higher vascularisation and fibroblast infiltration in synthetic grafts when compared to collagen-based grafts (P ≤ 0.05). Greater tissue growth was associated with higher prostaglandin-endoperoxide synthase 2 (Ptgs2) RNA and cyclooxygenase-2 (COX-2) protein levels in fully synthetic grafts. Collagen-based grafts had higher levels of collagen III and matrix metallopeptidase 2. To compare the capacity to form a double layer skin substitute, both templates were seeded with human fibroblasts and keratinocytes (so-called human skin equivalent or HSE). Mice were grafted with HSEs to test permanent wound closure with no further treatment required. We found the synthetic dermal template to have a significantly greater capacity to support human epidermal cells. In conclusion, the synthetic template showed advantages over the collagen-based template in a short-term mouse model of wound repair.

scholarly journals A New Role for Activin in Endometrial Repair after Menses

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1904-1911 ◽  
Author(s):  
Tu'uhevaha J. Kaitu'u-Lino ◽  
David J. Phillips ◽  
Naomi B. Morison ◽  
Lois A. Salamonsen
Keyword(s):  
Mouse Model ◽  
Wound Repair ◽  
Abnormal Uterine Bleeding ◽  
Transgenic Animals ◽  
Skin Wound ◽  
Uterine Bleeding ◽  
Epithelial Cell Line ◽  
Skin Wound Healing ◽  
Endometrial Epithelial Cell

Abnormal uterine bleeding can severely affect the quality of life for women. After menstruation, the endometrium must adequately repair to limit and stop bleeding. Abnormal uterine bleeding may result from incorrect or inadequate endometrial repair after menstruation. Previous studies have shown an important contribution of activin to skin wound healing, with severely delayed wound repair observed in animals transgenically induced to overexpress activin’s natural inhibitor, follistatin. Activin subunits have also been identified within human endometrium; however, their role in endometrial repair is unknown. We assessed the contribution of activin to endometrial repair after menses using a human in vitro cell wounding method and our well-characterized mouse model of endometrial breakdown and repair applied to mice overexpressing follistatin. Endometrial repair after menses is initiated with reepithelialization of the uterine surface. To mimic this repair, we utilized a human endometrial epithelial cell line (ECC-1) and demonstrated significant stimulation of wound closure after activin A administration, and attenuation of this response by addition of follistatin. Immunolocalization of activin subunits, βA and βB, in control endometrium from the mouse model demonstrated specific epithelial and stromal localization and some leukocyte staining (βA) around sites of endometrial repair, suggestive of a role for activin in this process. Follistatin-overexpressing animals had significantly higher circulating follistatin levels than wild-type littermates. There was a significant delay in endometrial repair after breakdown in follistatin transgenic animals compared with control animals. This study demonstrates for the first time a functional role for activin in endometrial repair after menses.

scholarly journals Stem cell–driven lymphatic remodeling coordinates tissue regeneration

Science ◽  
2019 ◽  
Vol 366 (6470) ◽  
pp. 1218-1225 ◽  
Author(s):  
Shiri Gur-Cohen ◽  
Hanseul Yang ◽  
Sanjeethan C. Baksh ◽  
Yuxuan Miao ◽  
John Levorse ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Mouse Model ◽  
Hair Follicle ◽  
Tissue Regeneration ◽  
Wound Repair ◽  
Lymphatic Drainage ◽  
Tissue Growth ◽  
Niche Components

Tissues rely on stem cells (SCs) for homeostasis and wound repair. SCs reside in specialized microenvironments (niches) whose complexities and roles in orchestrating tissue growth are still unfolding. Here, we identify lymphatic capillaries as critical SC-niche components. In skin, lymphatics form intimate networks around hair follicle (HF) SCs. When HFs regenerate, lymphatic–SC connections become dynamic. Using a mouse model, we unravel a secretome switch in SCs that controls lymphatic behavior. Resting SCs express angiopoietin-like protein 7 (Angptl7), promoting lymphatic drainage. Activated SCs switch to Angptl4, triggering transient lymphatic dissociation and reduced drainage. When lymphatics are perturbed or the secretome switch is disrupted, HFs cycle precociously and tissue regeneration becomes asynchronous. In unearthing lymphatic capillaries as a critical SC-niche element, we have learned how SCs coordinate their activity across a tissue.

scholarly journals Acute Exposure to Cigarette Smoking Followed by Myocardial Infarction Aggravates Renal Damage in an In Vivo Mouse Model

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Firas Kobeissy ◽  
Abdullah Shaito ◽  
Abdullah Kaplan ◽  
Lama Baki ◽  
Hassan Hayek ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cigarette Smoking ◽  
Mouse Model ◽  
Renal Dysfunction ◽  
Renal Damage ◽  
Smooth Muscle Actin ◽  
Tissue Growth ◽  
Mrna Levels ◽  
Protein Levels

Cigarette smoking (S) is a risk factor for progressive chronic kidney disease, renal dysfunction, and renal failure. In this study, the effect of smoking on kidney function was investigated in a mouse model of myocardial infarction (MI) using 4 groups: control (C), smoking (S), MI, and S+MI. Histological analysis of S+MI group showed alterations in kidney structure including swelling of the proximal convoluted tubules (PCTs), thinning of the epithelial lining, focal loss of the brush border of PCTs, and patchy glomerular retraction. Molecular analysis revealed that nephrin expression was significantly reduced in the S+MI group, whereas sodium-hydrogen exchanger-1 (NHE-1) was significantly increased, suggesting altered glomerular filtration and kidney functions. Moreover, S+MI group, but not S alone, showed a significant increase in the expression of connective tissue growth factor (CTGF) and fibrotic proteins fibronectin (FN) and α-smooth muscle actin (SMA), in comparison to controls, in addition to a significant increase in mRNA levels of IL-6 and TNF-α inflammatory markers. Finally, reactive oxygen species (ROS) production was significantly accentuated in S+MI group concomitant with a significant increase in NOX-4 protein levels. In conclusion, smoking aggravates murine acute renal damage caused by MI at the structural and molecular levels by exacerbating renal dysfunction.

scholarly journals Growth Factor-Reinforced ECM Fabricated from Chemically Hypoxic MSC Sheet with Improved In Vivo Wound Repair Activity

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Hui-Cong Du ◽  
Lin Jiang ◽  
Wen-Xin Geng ◽  
Jing Li ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Cost Effective ◽  
Tissue Growth ◽  
Wound Management ◽  
Skin Defect ◽  
Therapeutic Benefits ◽  
Collagen Iii

MSC treatment can promote cutaneous wound repair through multiple mechanisms, and paracrine mediators secreted by MSC are responsible for most of its therapeutic benefits. Recently, MSC sheet composed of live MSCs and their secreted ECMs was reported to promote wound healing; however, whether its ECM alone could accelerate wound closure remained unknown. In this study, Nc-ECM and Cc-ECM were prepared from nonconditioned and CoCl2-conditioned MSC sheets, respectively, and their wound healing properties were evaluated in a mouse model of full-thickness skin defect. Our results showed that Nc-ECM can significantly promote wound repair through early adipocyte recruitment, rapid reepithelialization, enhanced granulation tissue growth, and augmented angiogenesis. Moreover, conditioning of MSC sheet with CoCl2 dramatically enriched its ECM with collagen I, collagen III, TGF-β1, VEGF, and bFGF via activation of HIF-1α and hence remarkably improved its ECM’s in vivo wound healing potency. All the Cc-ECM-treated wounds completely healed on day 7, while Nc-ECM-treated wounds healed about 85.0%±8.6%, and no-treatment wounds only healed 69.8%±9.6% (p<0.05). Therefore, we believe that such growth factor-reinforced ECM fabricated from chemically hypoxic MSC sheet has the potential for clinical translation and will lead to a MSC-derived, cost-effective, bankable biomaterial for wound management.

scholarly journals A pulsatile release platform based on photo-induced imine-crosslinking hydrogel promotes scarless wound healing

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jian Zhang ◽  
Yongjun Zheng ◽  
Jimmy Lee ◽  
Jieyu Hua ◽  
Shilong Li ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Large Animal ◽  
Skin Wounds ◽  
Tgfβ Signaling ◽  
Pulsatile Release ◽  
Ecm Extracellular Matrix

AbstractEffective healing of skin wounds is essential for our survival. Although skin has strong regenerative potential, dysfunctional and disfiguring scars can result from aberrant wound repair. Skin scarring involves excessive deposition and misalignment of ECM (extracellular matrix), increased cellularity, and chronic inflammation. Transforming growth factor-β (TGFβ) signaling exerts pleiotropic effects on wound healing by regulating cell proliferation, migration, ECM production, and the immune response. Although blocking TGFβ signaling can reduce tissue fibrosis and scarring, systemic inhibition of TGFβ can lead to significant side effects and inhibit wound re-epithelization. In this study, we develop a wound dressing material based on an integrated photo-crosslinking strategy and a microcapsule platform with pulsatile release of TGF-β inhibitor to achieve spatiotemporal specificity for skin wounds. The material enhances skin wound closure while effectively suppressing scar formation in murine skin wounds and large animal preclinical models. Our study presents a strategy for scarless wound repair.

Current knowledge of immunomodulation strategies for chronic skin wound repair

2021 ◽  
Author(s):  
Parisa Heydari ◽  
Mahshid Kharaziha ◽  
Jaleh Varshosaz ◽  
Shaghayegh Haghjooy Javanmard
Keyword(s):  
Wound Repair ◽  
Current Knowledge ◽  
Skin Wound ◽  
Chronic Skin

scholarly journals A Prototype Skin Substitute, Made of Recycled Marine Collagen, Improves the Skin Regeneration of Sheep

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1219
Author(s):  
Luca Melotti ◽  
Tiziana Martinello ◽  
Anna Perazzi ◽  
Ilaria Iacopetti ◽  
Cinzia Ferrario ◽  
...  
Keyword(s):  
Gene Expression ◽  
Wound Healing ◽  
Sea Urchin ◽  
Healing Process ◽  
Skin Wound ◽  
Skin Substitute ◽  
Large Animal ◽  
Type I ◽  
Skin Wound Healing ◽  
Skin Adnexa

Skin wound healing is a complex and dynamic process that aims to restore lesioned tissues. Collagen-based skin substitutes are a promising treatment to promote wound healing by mimicking the native skin structure. Recently, collagen from marine organisms has gained interest as a source for producing biomaterials for skin regenerative strategies. This preliminary study aimed to describe the application of a collagen-based skin-like scaffold (CBSS), manufactured with collagen extracted from sea urchin food waste, to treat experimental skin wounds in a large animal. The wound-healing process was assessed over different time points by the means of clinical, histopathological, and molecular analysis. The CBSS treatment improved wound re-epithelialization along with cell proliferation, gene expression of growth factors (VEGF-A), and development of skin adnexa throughout the healing process. Furthermore, it regulated the gene expression of collagen type I and III, thus enhancing the maturation of the granulation tissue into a mature dermis without any signs of scarring as observed in untreated wounds. The observed results (reduced inflammation, better re-epithelialization, proper development of mature dermis and skin adnexa) suggest that sea urchin-derived CBSS is a promising biomaterial for skin wound healing in a “blue biotechnologies” perspective for animals of Veterinary interest.

scholarly journals A Bilayer Engineered Skin Substitute for Wound Repair in an Irradiation-Impeded Healing Model on Rat

2015 ◽  
Vol 4 (5) ◽  
pp. 312-320 ◽  
Author(s):  
A.B. Mohd Hilmi ◽  
Asma Hassan ◽  
Ahmad Sukari Halim
Keyword(s):  
Wound Repair ◽  
Skin Substitute ◽  
Healing Model
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