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.

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.

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)

Myostatin-null mice exhibit delayed skin wound healing through the blockade of transforming growth factor-β signaling by decorin

2012 ◽  
Vol 302 (8) ◽  
pp. C1213-C1225 ◽  
Author(s):  
Chen Zhang ◽  
Chek Kun Tan ◽  
Craig McFarlane ◽  
Mridula Sharma ◽  
Nguan Soon Tan ◽  
...  
Keyword(s):  
Wound Healing ◽  
Growth Factor ◽  
Wound Repair ◽  
Transforming Growth Factor ◽  
Healing Process ◽  
Critical Role ◽  
Transforming Growth Factor Β ◽  
Skin Wound ◽  
Wound Healing Process ◽  
Skin Wound Healing

Myostatin (Mstn) is a secreted growth and differentiation factor that belongs to the transforming growth factor-β (TGF-β) superfamily. Mstn has been well characterized as a regulator of myogenesis and has been shown to play a critical role in postnatal muscle regeneration. Herein, we report for the first time that Mstn is expressed in both epidermis and dermis of murine and human skin and that Mstn-null mice exhibited delayed skin wound healing attributable to a combination of effects resulting from delayed epidermal reepithelialization and dermal contraction. In epidermis, reduced keratinocyte migration and protracted keratinocyte proliferation were observed, which subsequently led to delayed recovery of epidermal thickness and slower reepithelialization. Furthermore, primary keratinocytes derived from Mstn-null mice displayed reduced migration capacity and increased proliferation rate as assessed through in vitro migration and adhesion assays, as well as bromodeoxyuridine incorporation and Western blot analysis. Moreover, in dermis, both fibroblast-to-myofibroblast transformation and collagen deposition were concomitantly reduced, resulting in a delayed dermal wound contraction. These decreases are due to the inhibition of TGF-β signaling. In agreement, the expression of decorin, a naturally occurring TGF-β suppressor, was elevated in Mstn-null mice; moreover, topical treatment with TGF-β1 protein rescued the impaired skin wound healing observed in Mstn-null mice. These observations highlight the interplay between TGF-β and Mstn signaling pathways, specifically through Mstn regulation of decorin levels during the skin wound healing process. Thus we propose that Mstn agonists might be beneficial for skin wound repair.

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.

scholarly journals Features of skin wound healing in rats with experimental chronic kidney disease

2021 ◽  
Vol 12 (4) ◽  
pp. 594-598
Author(s):  
S. B. Pavlov ◽  
O. B. Litvinova ◽  
N. M. Babenko
Keyword(s):  
Chronic Kidney Disease ◽  
Wound Healing ◽  
Growth Factors ◽  
Kidney Disease ◽  
Wound Repair ◽  
Histological Analysis ◽  
Kidney Diseases ◽  
Skin Wound ◽  
Control Group ◽  
Skin Wound Healing

Chronic kidney disease negatively affects the morphofunctional state of all organs due to hemodynamic and metabolic disorders. Changes in the content of cytokines observed in kidney diseases, which regulate the processes of inflammation and tissue repair, can complicate the course of the wound process. This research aimed to study disorders in the process of skin wound repair due to changes in the dynamics of production of interleukins IL-1β, IL-6, IL-10, IL-4, growth factors bFGF and VEGF in animals with experimental chronic kidney disease. The levels of interleukins and growth factors were determined on the 7th, 14th and 28th days after surgical modeling of wounds in the blood of rats with experimental chronic kidney disease and animals of the control group. To assess the dynamics and quality of wound healing, a semi-quantitative histological analysis was performed. The study showed an increase in the content of pro-inflammatory interleukins in the group of sick rats: on the 7th day the level of IL-1β was 1.19 times higher, and IL-6 – 1.55 times, on the 14th day the level of IL-1β was 1.37 times in comparison with the control group. The maximum increase in the concentration of anti-inflammatory interleukins was noted on the 28th day: IL-4 was 2.10 times higher, IL-10 – 1.39 times higher than in the control group. The content of bFGF and VEGF in animals of the control group reached its maximum on the 7th day, and in animals with chronic kidney disease – on the 15th day after surgery. Semi-quantitative histological analysis showed a decrease in indicators in the group of sick animals: the number of fibroblasts and collagen deposition – on the 7th day, reepithelialization – on the 28th day. A persistent increase in the number of polymorphonuclear leukocytes was also noted at all periods of the experiment: by 1.38, 1.99, and 9.82 times – on the 7th, 14th, and 28th days, respectively. The study showed that the dynamics of the production of interleukins and growth factors were impaired in rats with chronic kidney disease. In the process of damage regeneration in sick animals, pro-inflammatory mechanisms prevailed with the involvement of a large number of immunocompetent cells, as a result, skin wounds took longer to heal.

scholarly journals Pigment epithelium-derived factor as a multifunctional regulator of wound healing

2015 ◽  
Vol 309 (5) ◽  
pp. H812-H826 ◽  
Author(s):  
Mateusz S. Wietecha ◽  
Mateusz J. Król ◽  
Elizabeth R. Michalczyk ◽  
Lin Chen ◽  
Peter G. Gettins ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Repair ◽  
Pigment Epithelium ◽  
Skin Wound ◽  
Dermal Fibroblasts ◽  
Tissue Homeostasis ◽  
Skin Wound Healing ◽  
Pigment Epithelium Derived Factor ◽  
Vessel Regression ◽  
Treatment Of Wounds

During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury.

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