Scarless wound repair: a human fetal skin model

Development ◽  
1992 ◽  
Vol 114 (1) ◽  
pp. 253-259 ◽  
Author(s):  
H.P. Lorenz ◽  
M.T. Longaker ◽  
L.A. Perkocha ◽  
R.W. Jennings ◽  
M.R. Harrison ◽  
...  
Keyword(s):  
Wound Healing ◽  
Gestational Age ◽  
Animal Studies ◽  
Wound Repair ◽  
Mouse Skin ◽  
Skin Wound ◽  
Scar Formation ◽  
Fetal Skin ◽  
Skin Wound Healing ◽  
Thickness Skin

Animal studies demonstrate that the fetus heals cutaneous wounds by reformation of normal tissue architecture without scar formation. We have developed a new model to study human fetal skin wound healing. Grafts of human fetal skin placed onto athymic mice retain the morphologic features of normal development, although they differentiate at an accelerated rate when placed cutaneously compared to subcutaneously. Full-thickness skin grafts from human fetuses at 15 (n = 12), 17 (n = 11), 18 (n = 25), 19 (n = 20) and 22 (n = 13) weeks gestational age were placed onto athymic (nu/nu) mice in 2 locations: (1) cutaneously onto a fascial bed and thereby exposed to air or (2) subcutaneously in a pocket under the murine panniculus carnosus. Linear incisions were made in each graft 7 days after transplantation. Grafts were harvested at 7, 14 and 21 days postwounding and analyzed histologically for scar formation. By hematoxylin & eosin and Mallory's trichrome stains, complete epidermal and dermal graft wound healing without scar formation was demonstrated in the subcutaneous grafts at each gestational age studied. In contrast, scar was seen at all time points in the cutaneous grafts in both the incisional wound and at the interface of the fetal human skin graft and adult mouse skin, regardless of fetal skin gestational age.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Increased glucocorticoid activation during mouse skin wound healing

2014 ◽  
Vol 221 (1) ◽  
pp. 51-61 ◽  
Author(s):  
Ana Tiganescu ◽  
Melanie Hupe ◽  
Yoshikazu Uchida ◽  
Theodora Mauro ◽  
Peter M Elias ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
De Novo ◽  
Mouse Skin ◽  
Inflammatory Cells ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Variable Expression ◽  
Before And After

Glucocorticoid (GC) excess inhibits wound healing causing increased patient discomfort and infection risk. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates GCs (converting 11-dehydrocorticosterone to corticosterone in rodents) in many tissues including skin, wherede novosteroidogenesis from cholesterol has also been reported. To examine the regulation of 11β-HSD1 and steroidogenic enzyme expression during wound healing, 5 mm wounds were generated in female SKH1 mice and compared at days 0, 2, 4, 8, 14, and 21 relative to unwounded skin. 11β-HSD1 expression (mRNA and protein) and enzyme activity were elevated at 2 and 4 days post-wounding, with 11β-HSD1 localizing to infiltrating inflammatory cells. 11β-HSD2 (GC-deactivating) mRNA expression and activity were undetectable. Although several steroidogenic enzymes displayed variable expression during healing, expression of the final enzyme required for the conversion of 11-deoxycorticosterone to corticosterone, 11β-hydroxylase (CYP11B1), was lacking in unwounded skin and post-wounding. Consequently, 11-deoxycorticosterone was the principal progesterone metabolite in mouse skin before and after wounding. Our findings demonstrate that 11β-HSD1 activates considerably more corticosterone than is generatedde novofrom progesterone in mouse skin and drives GC exposure during healing, demonstrating the basis for 11β-HSD1 inhibitors to accelerate wound repair.

Abstract 13373: Exercise Improves Angiogenic Function of Circulating Exosomes in Type 2 Diabetes: Role of Extracellular SOD

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Kareem Abdelsaid ◽  
Sudhahar Varadarajan ◽  
Archita Das ◽  
Yutao Liu ◽  
Xuexiu Fang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Wound Healing ◽  
Endothelial Dysfunction ◽  
Wound Repair ◽  
Cell Communication ◽  
Tube Formation ◽  
Skin Wound ◽  
Skin Wound Healing

Background: Exosomes, key mediators of cell-cell communication, derived from type 2 diabetes mellitus (T2DM) have detrimental effects. Exercise not only improves endothelial dysfunction and angiogenesis in T2DM but also induces secretion of exosomes into circulation. Extracellular superoxide dismutase (ecSOD) is a major secretory Cu containing antioxidant enzyme that catalyzes dismutation of O 2 •- to H 2 O 2 and its full activity requires Cu transporter ATP7A. We reported that ecSOD-derived H 2 O 2 in endothelial cells (ECs) enhances angiogenesis while impaired ATP7A-ecSOD axis in diabetes induces endothelial dysfunction. Here we examined whether exercise-derived exosomes (Exe-Exo) may have pro-angiogenic effects via regulating ATP7A-ecSOD axis in T2DM. Results: Two weeks of voluntary wheel exercise of control C57Bl6 mice increased plasma exosome levels (6.2-fold) characterized by Nanosight, TEM and exosome markers (CD63, CD81, Tsg101). Treatment of HUVECs with equal number of exosomes revealed that angiogenic responses such as EC migration (1.8-fold) and tube formation (1.7-fold) were significantly enhanced by Exe-Exo compared to sedentary-derived exosomes (Sed-Exo). This was associated with increased ATP7A (2.9-fold) and ecSOD (1.4-fold) expression in Exe-Exo. Sed-Exo from high fat-induced T2DM mice significantly decreased EC migration (40%) and tube formation (10%) as well as ATP7A expression (28%) compared to Sed-Exo from control mice, which were restored by T2DM Exe-Exo, but not by T2DM/ecSOD KO Exe-Exo. Furthermore, exosomes overexpressing ecSOD (ecSOD-Exo) which mimic exercise increased angiogenesis and H2O2 levels in ECs, which were inhibited by overexpression of catalase. In vivo, skin wound healing model showed that direct application of T2DM Sed-Exo delayed while T2DM Exe-Exo enhanced wound healing of control mice. Furthermore, defective wound healing in T2DM mice or ecSOD KO mice were rescued by ecSOD-Exo application. Conclusion: Exercise training improves pro-angiogenic function of circulating exosomes in T2DM via increasing ATP7A-ecSOD axis, which may provide an effective therapy for promoting angiogenesis and wound repair in metabolic and cardiovascular diseases.

scholarly journals Systemic and topical administration of spermidine accelerates skin wound healing

2020 ◽  
Author(s):  
Daisuke Ito ◽  
Hiroyasu Ito ◽  
Takayasu Ideta ◽  
Ayumu Kanbe ◽  
Soranobu Ninomiya ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Wound Healing ◽  
Wound Repair ◽  
Healing Process ◽  
Topical Administration ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

Abstract Background The skin wound healing process is regulated by various cytokines, chemokines, and growth factors. Recent reports have demonstrated that spermine/spermidine (SPD) promote wound healing through urokinase-type plasminogen activator (uPA)/uPA receptor (uPAR) signaling in vitro. Here, we investigated whether the systemic and topical administration of SPD would accelerate the skin wound-repair process in vivo.Methods A skin wound repair model was established using C57BL/6 J mice. SPD was mixed with white petrolatum for topical administration. For systemic administration, SPD mixed with drinking water was orally administered. Changes in wound size over time were calculated using digital photography.Results Systemic and topical SPD treatment significantly accelerated skin wound healing. The administration of SPD promoted the uPA/uPAR pathway in wound sites. Moreover, topical treatment with SPD enhanced the expression of IL-6 and TNF-α in wound sites. Scratch and cell proliferation assays revealed that SPD administration accelerated scratch wound closure and cell proliferation in vitro.Conclusion These results indicate that treatment with SPD promotes skin wound healing through activation of the uPA/uPAR pathway and induction of the inflammatory response in wound sites. The administration of SPD might contribute to new effective treatments to accelerate skin wound healing.

scholarly journals Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

2020 ◽  
Vol 8 ◽  
Author(s):  
Pengcheng Xu ◽  
Yaguang Wu ◽  
Lina Zhou ◽  
Zengjun Yang ◽  
Xiaorong Zhang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Chronic Wounds ◽  
Platelet Rich Plasma ◽  
Skin Wound ◽  
Local Inflammation ◽  
Skin Wound Healing

Abstract Background Autologous platelet-rich plasma (PRP) has been suggested to be effective for wound healing. However, evidence for its use in patients with acute and chronic wounds remains insufficient. The aims of this study were to comprehensively examine the effectiveness, synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair. Methods Full-thickness wounds were made on the back of C57/BL6 mice. PRP or saline solution as a control was administered to the wound area. Wound healing rate, local inflammation, angiogenesis, re-epithelialization and collagen deposition were measured at days 3, 5, 7 and 14 after skin injury. The biological character of epidermal stem cells (ESCs), which reflect the potential for re-epithelialization, was further evaluated in vitro and in vivo. Results PRP strongly improved skin wound healing, which was associated with regulation of local inflammation, enhancement of angiogenesis and re-epithelialization. PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β. An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1. Moreover, PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs, and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14. Conclusion PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization. However, the underlying regulatory mechanism needs to be investigated in the future. Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

scholarly journals Resveratrol-loaded peptide-hydrogels inhibit scar formation in wound healing through suppressing inflammation

2019 ◽  
Author(s):  
Chen-Chen Zhao ◽  
Lian Zhu ◽  
Zheng Wu ◽  
Rui Yang ◽  
Na Xu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Damage Model ◽  
Skin Wound ◽  
Scar Formation ◽  
Wound Dressings ◽  
Skin Damage ◽  
Skin Wound Healing ◽  
Accelerate Wound Healing ◽  
Peptide Hydrogels

Abstract Scar formation seriously affects the repair of damaged skin especially in adults and the excessive inflammation has been considered as the reason. The self-assembled peptide-hydrogels are ideal biomaterials for skin wound healing due to their similar nanostructure to natural extracellular matrix, hydration environment and serving as drug delivery systems. In our study, resveratrol, a polyphenol compound with anti-inflammatory effect, is loaded into peptide-hydrogel (Fmoc-FFGGRGD) to form a wound dressing (Pep/RES). Resveratrol is slowly released from the hydrogel in situ, and the release amount is controlled by the loading amount. The in vitro cell experiments demonstrate that the Pep/RES has no cytotoxicity and can inhibit the production of pro-inflammatory cytokines of macrophages. The Pep/RES hydrogels are used as wound dressings in rat skin damage model. The results suggest that the Pep/RES dressing can accelerate wound healing rate, exhibit well-organized collagen deposition, reduce inflammation and eventually prevent scar formation. The Pep/RES hydrogels supply a potential product to develop new skin wound dressings for the therapy of skin damage.

scholarly journals Enzyme-Crosslinked Gelatin Hydrogel with Adipose-Derived Stem Cell Spheroid Facilitating Wound Repair in the Murine Burn Model

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 2997
Author(s):  
Ting-Yu Lu ◽  
Kai-Fu Yu ◽  
Shuo-Hsiu Kuo ◽  
Nai-Chen Cheng ◽  
Er-Yuan Chuang ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Three Dimensional ◽  
Stromal Vascular Fraction ◽  
Skin Wound ◽  
3D Scaffold ◽  
Skin Wound Healing ◽  
Cell Spheroid ◽  
Cell Spheroids ◽  
Adipose Derived Stem Cell

Engineered skin that can facilitate tissue repair has been a great advance in the field of wound healing. A well-designed dressing material together with active biological cues such as cells or growth factors can overcome the limitation of using auto-grafts from patients. Recently, many studies showed that human adipose-derived stem cells (hASCs) can be used to promote wound healing and skin tissue engineering. hASCs have already been widely applied for clinical trials. hASCs can be harvested abundantly because they can be easily isolated from fat tissue known as the stromal vascular fraction (SVF). On the other hand, increasing studies have proven that cells from spheroids can better simulate the biological microenvironment and can enhance the expression of stemness markers. However, a three-dimensional (3D) scaffold that can harbor implanted cells and can serve as a skin-repaired substitute still suffers from deficiency. In this study, we applied a gelatin/microbial transglutaminase (mTG) hydrogel to encapsulate hASC spheroids to evaluate the performance of 3D cells on skin wound healing. The results showed that the hydrogel is not toxic to the wound and that cell spheroids have significantly improved wound healing compared to cell suspension encapsulated in the hydrogel. Additionally, a hydrogel with cell spheroids was much more effective than other groups in angiogenesis since the cell spheroid has the possibility of cell–cell signaling to promote vascular generation.

scholarly journals Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies

2019 ◽  
Vol 17 (2) ◽  
pp. 285-299 ◽  
Author(s):  
Yan Sun ◽  
Rei Ogawa ◽  
Bi‐Huan Xiao ◽  
Yu‐Xin Feng ◽  
Yan Wu ◽  
...  
Keyword(s):  
Systematic Review ◽  
Wound Healing ◽  
Photodynamic Therapy ◽  
Animal Studies ◽  
Skin Wound ◽  
Antimicrobial Photodynamic Therapy ◽  
Skin Wound Healing

scholarly journals Pharmaceutical application of frog skin on full-thickness skin wound healing in mice

2013 ◽  
Vol 51 (12) ◽  
pp. 1600-1606 ◽  
Author(s):  
Mahere Rezazade Bazaz ◽  
Mohammad Mashreghi ◽  
Nasser Mahdavi Shahri ◽  
Mansour Mashreghi ◽  
Ahmad Asoodeh ◽  
...  
Keyword(s):  
Wound Healing ◽  
Frog Skin ◽  
Skin Wound ◽  
Full Thickness ◽  
Skin Wound Healing ◽  
Full Thickness Skin ◽  
Pharmaceutical Application ◽  
Thickness Skin

scholarly journals Carbonic Anhydrase VI in Skin Wound Healing Study on Car6 Knockout Mice

2020 ◽  
Vol 21 (14) ◽  
pp. 5092
Author(s):  
Toini Pemmari ◽  
Jaakko Laakso ◽  
Maarit S. Patrikainen ◽  
Seppo Parkkila ◽  
Tero A. H. Järvinen
Keyword(s):  
Wound Healing ◽  
Knockout Mice ◽  
Wound Closure ◽  
Skin Wound ◽  
Carbonic Anhydrases ◽  
Skin Wound Healing ◽  
Tumor Cell Migration ◽  
Treatment Groups ◽  
Thickness Skin ◽  
Carbonic Anhydrase Vi

Carbonic anhydrases (CAs) contribute to tumor cell migration by generating an acidic environment through the conversion of carbon dioxide to bicarbonate and a proton. CA VI is secreted to milk and saliva, and it could contribute to wound closure, as a potential trophic factor, in animals that typically lick their wounds. Our aim was to investigate whether human CA VI improves skin-wound healing in full-thickness skin-wound models. The effect was studied in Car6 −/− knockout mice and wild type littermates. Half of both mice strains were given topically administered, milk-derived CA VI after wounding and eight hours later. The amount of topically given CA VI exceeded the predicted amount of natural saliva-delivered CA VI. The healing was followed for seven days and studied from photographs and histological sections. Our results showed no significant differences between the treatment groups in wound closure, re-epithelization, or granulation tissue formation, nor did the Car6 genotype affect the healing. Our results demonstrate that CA VI does not play a major role in skin-wound healing and also suggest that saliva-derived CA VI is not responsible for the licking-associated improved wound healing in animals.

Sign in / Sign up

Export Citation Format

Share Document