Browsing by Subject "wound healing"

Now showing 1 - 7 of 7
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    Adipose stromal cells enhance keratinocyte survival and migration in vitro, and graft revascularization in mouse wound healing model
    (2013-12-11) Knowles, Kellen Alexander; Berbari, Edward J.; March, Keith Leonard, 1963-; Ji, Julie
    In the US, more than 1 million burn injuries are reported annually. About 45,000 injuries due to fires and burns result in hospitalization and ten percent of these result in death every year. Advances in burn treatment have led to a reduction in mortality rate over the last decades. Since more patients are surviving the initial resuscitation phase even with very large areas of skin being burned away, wound care has become increasingly important to ensure continued patient survival and improvement. While currently a common treatment for third degree burn wounds, skin grafts have several drawbacks. The availability of donor sites for autografts may be limited, especially in incidences of extensive skin loss. The rejection associated with the use of allografts and xenografts may render them inadequate or undesirable. Even if a suitable graft is found, poor retention due to infection, hematoma, and low vascularity at the recipient site are other drawbacks associated with the use of skin grafts as a primary treatment for severe burn wounds. As such, research has been done into alternative treatments, which include but are not limited to artificial skin, cell therapy, and growth factor application. We propose the delivery of adipose derived stem cells (ASC) in combination with endothelial progenitor cells (EC) via Integra Dermal Regenerative Template (DRT) to promote faster graft vascularization and thus faster healing of wounds. Integra DRT is an acellular skin substitute that consists of a dermal layer composed of bovine collagen and chondroitin-6-sulfate glycosaminoglycan, and an "epidermal" layer, which consists of silicone polymer. This silicone layer is removed after the collagen matrix is adequately vascularized (usually takes 2-3 weeks), and then a thin layer autograft is applied to the top of the neo-dermis. ASC are derived from the stromal-vascular fraction (SVF) of adipose tissue and are a readily available, pluripotent, mesenchymal cell known to promote angiogenesis. They are being explored as a treatment for a myriad of diseases and conditions, including wound healing. In combination with ECs, they form stable microvessel networks in vitro and in vivo. In our work, we found that ASC+EC form stable microvessel networks when cultured on Integra DRT. Also, ASC and ASC+EC conditioned media promoted both survival and migration of human epidermal keratinocytes compared to control medium. In a full thickness wound healing model, using healthy NSG mice, the ASC+EC case showed a significantly higher rate of wound closure compared to control. Based on best linear unbiased estimates (BLUE), the difference between the healing rates of ASC alone treatment and the Control treatment group is -0.45 +/- 0.22 mm²/day (p=0.041), which is not less than 0.025 and thus not statistically significant (Bonferroni Adjusted). However, the BLUE for the difference between the ASC+EC group and the Control group healing rates is -0.55 +/- 0.28 mm²/day (p = 0.017<0.025, Bonferroni Adjusted), which is statistically significant. Histology revealed a significantly higher number of vessels compared to control in both ASC alone and ASC+EC case. CD31 staining revealed the presence of human vessels in ASC+EC treatment scaffolds. We conclude that the combination of ASC and EC can be used to accelerate healing of full-thickness wounds when delivered to site of the wound via Integra. This result is especially compelling due to the fact that the mice used were all healthy. Thus our treatment shows an improvement in healing rate even compared to normal wound healing.
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    Constitutive overexpression of periostin delays wound healing in mouse skin
    (Wiley, 2018) Nunomura, Satoshi; Nanri, Yasuhiro; Ogawa, Masahiro; Arima, Kazuhiko; Mitamura, Yasutaka; Yoshihara, Tomohito; Hasuwa, Hidetoshi; Conway, Simon J.; Izuhara, Kenji; Pediatrics, School of Medicine
    Periostin is a matricellular protein involved in development, maintenance and regulation of tissues and organs via by binding to cell surface integrin receptors. Pathologically, periostin plays an important role in the process of wound healing: as a deficiency of the Postn gene delays wound closure and periostin is consistently upregulated in response to injury and skin diseases. However, the functional role of elevated periostin in the process of wound healing has not been tested. In this study, we generated Postn-transgenic mice under the control of the CAG promoter/enhancer to investigate the effects of constitutive overexpression of full length periostin during its pathophysiological roles. Transgenic mice showed significant overexpression of periostin in skin, lung, and heart, but no morphological changes were observed. However, when these transgenic mice were injured, periostin overexpression delayed the closure of excisional wounds. Expression of IL-1β and TNFα, pro-inflammatory cytokines important for wound healing, was significantly decreased in the transgenic mice, prior to delayed healing. Infiltration of neutrophils and macrophages, the main sources of IL-1β and TNFα, was also downregulated in the transgenic wound sites. From these data, we conclude that enforced expression of periostin delays wound closure due to reduced infiltration of neutrophils and macrophages followed by downregulation of IL-1β and TNFα expression. This suggests that regulated spatiotemporal expression of periostin is important for efficient wound healing and that constitutive periostin overexpression interrupts the normal process of wound closure.
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    Cutaneous Epithelial to Mesenchymal Transition Activator ZEB1 Regulates Wound Angiogenesis and Closure in a Glycemic Status–Dependent Manner
    (American Diabetes Association, 2019-11) Singh, Kanhaiya; Sinha, Mithun; Pal, Durba; Tabasum, Saba; Gnyawali, Surya C.; Khona, Dolly; Sarkar, Subendu; Mohanty, Sujit K.; Soto-Gonzalez, Fidel; Khanna, Savita; Roy, Sashwati; Sen, Chandan K.; Surgery, School of Medicine
    Epithelial to mesenchymal transition (EMT) and wound vascularization are two critical interrelated processes that enable cutaneous wound healing. Zinc finger E-box binding homeobox 1 (ZEB1), primarily studied in the context of tumor biology, is a potent EMT activator. ZEB1 is also known to contribute to endothelial cell survival as well as stimulate tumor angiogenesis. The role of ZEB1 in cutaneous wounds was assessed using Zeb1+/− mice, as Zeb1−/− mice are not viable. Quantitative stable isotope labeling by amino acids in cell culture (SILAC) proteomics was used to elucidate the effect of elevated ZEB1, as noted during hyperglycemia. Under different glycemic conditions, ZEB1 binding to E-cadherin promoter was investigated using chromatin immunoprecipitation. Cutaneous wounding resulted in loss of epithelial marker E-cadherin with concomitant gain of ZEB1. The dominant proteins downregulated after ZEB1 overexpression functionally represented adherens junction pathway. Zeb1+/− mice exhibited compromised wound closure complicated by defective EMT and poor wound angiogenesis. Under hyperglycemic conditions, ZEB1 lost its ability to bind E-cadherin promoter. Keratinocyte E-cadherin, thus upregulated, resisted EMT required for wound healing. Diabetic wound healing was improved in ZEB+/− as well as in db/db mice subjected to ZEB1 knockdown. This work recognizes ZEB1 as a key regulator of cutaneous wound healing that is of particular relevance to diabetic wound complication.
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    From the Cochrane Library: Hydrosurgical Debridement Versus Conventional Surgical Debridement for Acute Partial-Thickness Burns
    (JMIR Publications, 2022-04) Kokoska, Ryan E.; Szeto, Mindy D.; Sivesind, Torunn E.; Dellavalle, Robert P.; Wormald, Justin C. R.; Dermatology, School of Medicine
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    An in-vitro comparison of four antibacterial agents with and without nicotine and their effects on human gingival fibroblasts
    (Wiley, 2021) Batra, Chandni; Alalshaikh, Marwa; Gregory, Richard L.; Windsor, L. Jack; Blanchard, Steven B.; Hamada, Yusuke; Periodontology, School of Dentistry
    Background To compare anti-bacterial activity of 0.12% Chlorhexidine (CHX), 10% Povidone Iodine (PVD), Vega Oral Care Gel (VEGA), and Antioxidant Gel (AO) on Streptococcus mutans, Streptococcus sanguis, Fusobacterium nucleatum, and Porphyromonas gingivalis with and without nicotine and to evaluate their effects on human gingival fibroblasts (HGFs). Methods S. mutans, S. sanguis, P. gingivalis, and F. nucleatum were incubated with serial dilutions (1/4, 1/8, 1/16, 1/32, and 1/64) of anti-bacterial agents in media (with and without nicotine). Minimum inhibitory and minimum bactericidal concentrations (MIC/MBC) were measured, and confocal microscopy was performed. HGFs were exposed to serial dilutions (1/10, 1/100, 1/1000, and 1/10,000) of antibacterial agents with media. Water-soluble tetrazolium-1 (WST-1) assay and lactate dehydrogenase (LDH) assay were used to assess proliferation and cytotoxicity towards HGFs. Results CHX and PVD significantly inhibited growth of all bacterial species (P < 0.0001) at all dilutions. AO and VEGA inhibited growth of all bacterial species up to only the 1/4 dilution. CHX and PVD decreased HGF proliferation at 1/10 and 1/100 dilution, whereas AO at all dilutions (P < 0.05). CHX and AO were cytotoxic at all dilutions (P < 0.05). VEGA was not cytotoxic to HGFs and did not affect HGF proliferation at any dilution (P > 0.05). An increased bacterial growth was seen for all species except P. gingivalis with addition of nicotine. Conclusion CHX and PVD demonstrate superior antibacterial properties, but significantly reduce HGF proliferation. AO is bacteriostatic at lower dilutions but is highly toxic to HGFs. VEGA was bacteriostatic and demonstrated no detrimental effects on HGF's.
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    Risks of ozonated oil and ozonated water on human skin: A systematic review
    (Wiley, 2022-01-13) Leon, Brian R.; Romary, Daniel J.; Landsberger, Sarah A.; Bradner, K. Nicole; Ramirez, Mirian; Lubitz, Robert M.
    Ozonated water and oil are emerging as potential dermatologic therapeutics, particularly for the treatment of various wounds. However, the safety of these liquids has not been extensively studied. The aim of this systematic review was to evaluate the risks of ozonated liquids to human skin tissue based on the available literature. We completed a structured search of five scientific databases and identified 378 articles for consideration. Based on pre-established inclusion/exclusion criteria, nine studies were included in this review. Two studies specifically evaluated the cytotoxicity of ozonated liquids on human cells, five studies evaluated ozonated liquids in randomised controlled trials(RCTs), one was a post-market surveillance study, and one was a cross over study in humans. None of the included studies found any significant human dermatologic risks associated with ozonated water or liquid. Because of the small sample size, however, additional short- and long-term RCTs specifically designed to evaluate the dermatological risks of ozonated liquids are recommended.
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    Skin Regeneration Using Dermal Substrates that Contain Autologous Cells and Silver Nanoparticles to Promote Antibacterial Activity: In Vitro Studies
    (AMSUS, 2017-03) Zieger, Michael A. J.; Ochoa, Manuel; Rahimi, Rahim; Campana, Gonzalo; Tholpady, Sunil; Ziaie, Babak; Sood, Rajiv; Surgery, School of Medicine
    We hypothesized that the addition of silver nanoparticles (AgNP) to a dermal substrate would impart antibacterial properties without inhibiting the proliferation of contained cells. Our in vitro model was based on the commercial substrate, Integra. The substrate was prepared by simple immersion into 0 to 1% suspension of AgNP (75 or 200 nm diameter) followed by rinsing for 20 minutes and sterilization under an ultraviolet C lamp. A total of 107 human adipose stem cells per cubic centimeter were injected and after 1 hour, 6 × 105 keratinocytes/cm2 were seeded and cultured for up to 14 days. Constructs were evaluated using a metabolic assay (WST-1), and hematoxylin and eosin and immunoperoxidase staining. Bactericidal activity was measured using a log reduction assay against bacteria that are prevalent in burns. The presence of AgNP did not significantly change the metabolic activity of constructs after 14 days of culture, and the distribution of cells within the substrate was unchanged from the controls that did not have AgNP. Antibacterial activity of Integra containing AgNP (75 nm diameter) was concentration dependent. In conclusion, the addition of AgNP to the dermal substrate suppressed bacterial growth but did not significantly affect cell proliferation, and may represent an important property to incorporate into a future clinical skin regeneration system.