Radiation-induced Skin Damage Research Articles

Application and clinical efficacy of Sufu medical chitosan hydrogel dressing in radiation skin damage caused by radiotherapy for cervical cancer.

To investigate the benefits of Sufu medical chitosan hydrogel dressing(Sufu) in the prevention and control of radiation skin damage during radiotherapy for cervical cancer as a combined modality. Ninety-seven cervical cancer patients who underwent radiotherapy at the Cancer Hospital of China Medical University between May 2017 and November 2018 were recruited according to given inclusion and exclusion criteria. The patients were assigned to a control group (n=48, washing the perineal area with normal saline) and an observation group (n=49, application of Sufu onto the site of radiotherapy in addition to washing the perineal area with normal saline). The treatment regimens for the two groups continued until the end of radiotherapy. A comparison of the RTOG (Radiation Therapy Oncology Group) grading of acute radiation-induced skin reactions (ARISRs), pain intensity (measured by the verbal rating scale (VRS)) and post-treatment wound healing was drawn between the two groups. In the observation group, 81.6% (40/49) of the patients had radiation dermatitis, which was significantly lower than the incidence rate (95.8%, 46/48) in the control group (P <0.05). The observation group was at higher risk of radiation dermatitis when given a high radiation dose, while the control group was more likely to have radiation dermatitis when administered with a moderate radiation dose (P <0.05). The median time of occurrence of pain and the median time of onset of skin reactions were significantly later in the observation group as compared with the control group (P <0.05, respectively). In the observation group, the pain relief rate was 92.50% at Day-3, and the wound healing rate was 95.0% at Day-7, significantly higher than in the control group (73.9% and 80.4%) (P <0.05, respectively). During radiotherapy for cervical cancer, Sufu can effectively prevent and control radiation-induced skin and mucous membrane damage, delay the onset of radiation dermatitis and substantially reduce the incidence rate, relieve radiation dermatitis and pain and promote wound healing.

Modulation of autophagy, apoptosis and oxidative stress: a clue for repurposing metformin in photoaging

Long-term sun exposure is the commonest cause of photoaging, where mutual interplay between autophagy, oxidative stress, and apoptosis is incriminated. In combating photoaging, pharmacological approaches targeted to modulate autophagy are currently gaining more ground. This study aimed to examine repurposing metformin use in such context with or without the antioxidant coenzyme Q10 (coQ10) in ultraviolet A (UVA) irradiation-induced skin damage. The study was conducted on 70 female CD1 mice that were randomly assigned into seven groups (10/group): normal control, vehicle-treated-UVA-exposed mice, three metformin UVA-exposed groups (Topical 1 and 10%, and oral 300 mg/kg), topical coQ10 (1%)-treated mice, and combined oral metformin with topical coQ10-treated UVA-exposed mice. After UVA-exposure for 10 weeks (3 times/week), macroscopic signs of photoaging were evaluated. Mice were then euthanized, and the skin was harvested for biochemical estimation of markers for oxidative stress, inflammation, matrix breakdown, and lysosomal function. Histopathological signs of photoaging were also evaluated with immunohistochemical detection of associated changes in autophagic and apoptotic markers. Metformin, mainly by topical application, improved clinical and histologic signs of photoaging. This was associated with suppression of the elevated oxidative stress, IL-6, matrix metalloproteinase 1, and caspase, with induction of cathepsin D and subsequent change in anti-LC3 and P62 staining in skin tissue. In addition to metformin antioxidant, anti-inflammatory, and antiapoptotic activities, its anti-photoaging effect is mainly attributed to enhancing autophagic flux by inducing cathepsin D. Its protective effect is boosted by coQ10, which supports their potential use in photoaging.

Hesperetin-Based Hydrogels Protect the Skin against UV Radiation-Induced Damage.

UV radiation can cause damages, such as erythema, skin photoaging, and carcinogenesis. The adoption of protective measures against sun exposure is essential to prevent these damages, and the interest in using natural substances as an alternative for photoprotection is growing. Thus, hesperetin with antioxidant, anti-inflammatory, and anticancer properties is a promising substance to be used with photochemopreventive action and to protect the skin from damage induced by UV radiation. Therefore, the present study aimed to develop a topical formulation based on AAMVPC gel containing hesperetin and evaluate its photoprotective effect on the skin of rats exposed to UVA-UVB radiation. The animals were submitted to the irradiation protocol UVA-UVB, and at the end, erythema, lipid peroxidation, and activity of the antioxidant enzyme catalase and superoxide dismutase were evaluated. Additionally, it evaluated the activity of myeloperoxidase and histological changes. The formulation presented a rheological and spreadability profile suitable for cutaneous application. In vivo results demonstrated that the topical formulation of AAMVPC gel containing hesperetin at a concentration of 10% protected the skin from damage induced by UVA-UVB radiation, with the absence of erythema, lipid lipoperoxidation, and inflammation (low myeloperoxidase activity), and increased catalase and superoxide dismutase activities. The morphology and architecture of the dermo-epidermal tissue of these animals were like those observed under normal conditions (non-irradiated animals). Thus, the results showed that hesperetin was able to protect the animals' skin against UV radiation-induced skin damage and the protection mechanisms may be related to the antioxidant and anti-inflammatory properties of this natural product.

Clinical applications of the chimeric anterolateral thigh (ALT) flap in head and neck reconstruction

Background Surgical site infection (SSI) is a common complication following head and neck surgery. Dead space at the excision site can increase the risk of infection, abscess formation, and mortality. Herein, we evaluated the performance of the chimeric anterolateral thigh (ALT) flap in addressing these concerns. Methods Patients who underwent oncologic head and neck reconstruction between October 2016 and November 2021 were divided in two groups: a normal ALT flap and a chimeric dead space filling (DSF) ALT-vastus lateralis flap group. We evaluated the postoperative outcomes. Results Twenty-five patients treated with normal ALT flaps (34.7%) and 47 with DSF ALT flap group (65.2%) were included. Only one ALT per case was necessary. Most of the cases involved tongue (31.9%) and lower gingival reconstruction (27.8%). The time to harvest the DSF ALT flap was 134.3 min when compared to the normal ALT flap (116.2 min, p < .001). Vascular occlusion, flap loss, partial necrosis, and fat necrosis were not observed among the different groups. Conclusion The DSF process can be used as a preventive measure for SSI or vessel exposure due to radiation-induced skin damage. This flap allows same-site reconstruction if the primary tumor recurs by using the pedicle of the chimeric flap for reattachment of another free flap.

Transcriptomics of Wet Skin Biopsies Predict Early Radiation-Induced Hematological Damage in a Mouse Model.

The lack of an easy and fast radiation-exposure testing method with a dosimetric ability complicates triage and treatment in response to a nuclear detonation, radioactive material release, or clandestine exposure. The potential of transcriptomics in radiation diagnosis and prognosis were assessed here using wet skin (blood/skin) biopsies obtained at hour 2 and days 4, 7, 21, and 28 from a mouse radiation model. Analysis of significantly differentially transcribed genes (SDTG; p ≤ 0.05 and FC ≥ 2) during the first post-exposure week identified the glycoprotein 6 (GP-VI) signaling, the dendritic cell maturation, and the intrinsic prothrombin activation pathways as the top modulated pathways with stable inactivation after lethal exposures (20 Gy) and intermittent activation after sublethal (1, 3, 6 Gy) exposure time points (TPs). Interestingly, these pathways were inactivated in the late TPs after sublethal exposure in concordance with a delayed deleterious effect. Modulated transcription of a variety of collagen types, laminin, and peptidase genes underlay the modulated functions of these hematologically important pathways. Several other SDTGs related to platelet and leukocyte development and functions were identified. These results outlined genetic determinants that were crucial to clinically documented radiation-induced hematological and skin damage with potential countermeasure applications.

Quantitative evaluation of radiodermatitis following whole-breast radiotherapy with various color space models: A feasibility study.

PurposeWe analyzed skin images with various color space models to objectively assess radiodermatitis severity in patients receiving whole-breast radiotherapy.MethodsTwenty female patients diagnosed with breast cancer were enrolled prospectively. All patients received whole-breast radiotherapy without boost irradiation. Skin images for both irradiated and unirradiated breasts were recorded in red-green-blue (RGB) color space using a mobile skin analysis device. For longitudinal analysis, the images were acquired before radiotherapy (RTbefore), approximately 7 days after the first fraction of radiotherapy (RT7days), RT14days, and approximately 10 days after radiotherapy completion (RTafter). Four color space models (RGB, hue-saturation-value (HSV), L*a*b*, and YCbCr models) were employed to calculate twelve color space parameters for each skin image. Skin dose measurements for irradiated breasts were performed using nanoDot optically stimulated luminescent dosimeters on the first fraction of radiotherapy. Subsequently, acute radiation dermatitis in each patient was assessed according to the Radiation Therapy Oncology Group scoring criteria at both RT14days and RTafter. Finally, several statistical analysis methods were applied to investigate the performance of the color space parameters to objectively assess the radiodermatitis.ResultsOwing to radiation-induced skin damage, R value of RGB model as well as S and V values of the HSV model for irradiated breasts increased significantly, while those for unirradiated breasts showed smaller increases. These parameters showed the longitudinal changes in color space parameters within each group and between groups over time with statistical significance. Strong correlations of the parameters for irradiated breasts at RT7days with skin doses and those at RTafter were observed with statistical significance.ConclusionThe R value of RGB model as well as the S and V values of HSV model showed relatively better performance in evaluating the acute radiation dermatitis. These color space parameters could therefore serve as useful tools to assess radiodermatitis severity in a dose-dependent manner.

Selenium-Rich Yeast Peptide Fraction Ameliorates Imiquimod-Induced Psoriasis-like Dermatitis in Mice by Inhibiting Inflammation via MAPK and NF-κB Signaling Pathways.

Psoriasis, a chronic and immune-mediated inflammatory disease, adversely affects patients’ lives. We previously prepared selenium-rich yeast peptide fraction (SeP) from selenium-rich yeast protein hydrolysate and found that SeP could effectively alleviate ultraviolet radiation-induced skin damage in mice and inhibited H2O2-induced cytotoxicity in cultured human epidermal keratinocyte (HaCaT) cells. This study aimed to investigate whether SeP had a protective effect on imiquimod (IMQ)-induced psoriasis-like dermatitis in mice and the underlying mechanisms. Results showed that SeP significantly ameliorated the severity of skin lesion in IMQ-induced psoriasis-like mouse model. Moreover, SeP treatment significantly attenuated the expression of key inflammatory cytokines, including interleukin (IL)-23, IL-17A, and IL-17F, in the dorsal skin of mice. Mechanistically, SeP application not only inhibited the activation of JNK and p38 MAPK, but also the translocation of NF-κB into the nucleus in the dorsal skin. Furthermore, SeP treatment inhibited the levels of inflammatory cytokines and the activation of MAPK and NF-κB signaling induced by lipopolysaccharide in HaCaT cells and macrophage cell line RAW264.7. Overall, our findings showed that SeP alleviated psoriasis-like skin inflammation by inhibiting MAPK and NF-κB signaling pathways, which suggested that SeP would have a potential therapeutic effect against psoriasis.

512 Phenylene Bis-Diphenyltriazine (TriAsorB), a new full-spectrum photoprotector against sunlight radiation induced skin damage

512 Phenylene Bis-Diphenyltriazine (TriAsorB), a new full-spectrum photoprotector against sunlight radiation induced skin damage

NLRP3 protects mice from radiation-induced colon and skin damage via attenuating cGAS-STING signaling

In the present study, the effects of NLRP3 on radiation-induced tissue damage, including colon and skin damage in mice, and the possible mechanisms were explored in vivo and in vitro. The mice were subjected to whole abdomen radiation by timed exposure to X-ray at a cumulative dose of 14 Gy. The survival rate showed that NLRP3 deficiency increased the mortality rate in mice. Furthermore, colon damage, evaluated by H&E staining and barrier function analysis, were significantly aggravated by NLRP3 deficiency. Enhanced phosphorylation of p-TBK1 and p-IRF3 in colonic tissue as well as elevated IFN-β levels in the serum indicated hyperactivation of cGAS-STING signaling. Moreover, radiation-induced expression of p-TBK1, p-IRF3, and IFN-β in BMDMs increased in vitro after NLRP3 knockout. Thus, our study outcomes suggest that NLRP3 may protect mice from radiation-induced tissue damage via attenuating cGAS-STING signaling.

Hyptis mociniana: phytochemical fingerprint and photochemoprotective effect against UV-B radiation-induced erythema and skin carcinogenesis

Skin cancer is a public health problem due to its high incidence. Ultraviolet radiation (UVR) is the main etiological agent of this disease. Photochemoprotection involves the use of substances to avoid damage caused by UV exposure. The aim of this work was to determine the phytochemical fingerprint and photochemoprotective effect against UVB radiation-induced skin damage such as erythema and carcinogenesis of H. mociniana methanolic extract (MEHm). The chemical composition of the MEHm was analysed by LC/ESI-MS/MS. Three quercetin derivatives, two pectinolides, and two caffeic acid derivatives were identified in the methanolic extract. MEHm has antioxidant effect and it is not cytotoxic in HaCaT cells. Phytochemicals from H. mociniana have a photochemopreventive effect because they absorb UV light and protect HaCaT cells from UVR-induced cell death. Also, in SKH-1 mice -acute exposure-, it decreased erythema formation, modulating the inflammatory response, reduced the skin damage according to histological analysis and diminished p53 expression. Finally, MEHm protects from photocarcinogenesis by reducing the incidence and multiplicity of skin carcinomas in SKH-1 mice exposed chronically to UVB radiation.

Radiation dermatitis: the evaluation of a new topical therapy for the treatment and prevention of radiation-induced skin damage and moist desquamation: a multicentre UK case cohort study

AbstractIntroduction:Radiotherapy is a mainstay of cancer therapy for a wide variety of anatomical areas. An unfortunate side effect of treatment can be radiation damage to the skin which can be a painful and debilitating problem. Previous experience from the experimental use of Flamigel® in two large-scale clinical studies on affected skin has proven sufficiently positive for the addition of a new product in the Flamigel® family (now commercially available in the UK as Flamigel RT®, Flen Health UK). The aim of this investigation is to evaluate the use of this new product to study how effective it is in the prevention and/or treatment of radiation-induced skin damage.Materials and methods:A survey was conducted among radiotherapy specialist teams in dedicated UK radiotherapy centres between 1 January 2017 and 31 October 2017. This report is of a preliminary evaluation conducted by UK-based specialists on 108 patients undergoing radiotherapy. The scoring system for skin reactions of the ‘Radiation Therapy Oncology Group’ was used.Results:Results show that the use of Flamigel® has the potential to soothe (p = 0·0001), reduce pain (p = 0·0001) and reduce pruritus (p = 0·004). The product met the expectations of the clinicians involved (p &lt; 0·0001) of whom most were happy to continue use or to recommend its use to colleagues (p &lt; 0·0001).Conclusions:Flamigel® is an effective treatment in the management of radiation-induced skin reactions. Erythema was unchanged through the study period (p = 0·42). No adverse reactions were reported after the use of Flamigel from twice to six times a day.

Glabridin Liposome Ameliorating UVB-Induced Erythema and Lethery Skin by Suppressing Inflammatory Cytokine Production.

Glabridin, a compound of the flavonoid, has shown outstanding skin-whitening and anti-aging properties, but its water insolubility limits its wide application. Therefore, glabridin liposome (GL) has been developed to improve its poor bioavailability, while there are few studies to evaluate its amelioration of UVB- induced photoaging. This study is performed to investigate the amelioration of GL against UVB- induced cutaneous photoaging. The prepared GL has a spheroidal morphology with an average diameter of 200 nm. The GL shows lower cytotoxicity than glabridin, but it has a more effective role in inhibition of melanin. Moreover, the application of GL can effectively relieve UV radiation induced erythema and leathery skin, associated with the down-regulated expression of inflammatory cytokines (TNF-α, IL-6 and IL-10). Taken together, these results demonstrate that GL has potentials as topical therapeutic agents against UVB radiation induced skin damage through inhibiting inflammation.

Ethanol consumption synergistically increases ultraviolet radiation induced skin damage and immune dysfunction

BackgroundExcessive UV radiation disrupts skin homeostasis by multiple mechanisms that extend beyond the simple erythema associated with sunburns including reduction of antioxidants, increased DNA damage, and impairment of skin immune responses. Recreational UV exposure frequently occurs concurrently with excessive ethanol (EtOH). Epidemiological studies suggest a harmful, dose-dependent impact of EtOH in the setting of high UV exposure, leading to increased severity of sunburns relative to those generated in the absence of EtOH. Furthermore, EtOH consumption and UV radiation have multiple overlapping effects on the skin that could account for the epidemiological association. ObjectiveTo elucidate the relationship between excessive EtOH ingestion and UV exposures on early skin damage and downstream immune dysfunction. MethodsWe examined the impact of UVB on local skin damage, including inflammation, sunburned cells, apoptotic cells, melanin and antioxidant levels, DNA damage and immune dysfunction in the presence or absence of EtOH ingestion by combining standard mouse models of EtOH consumption and UVB exposure models. To confirm that the observed changes in mouse skin were relevant to human skin, we investigated the effects of EtOH on UV-induced skin damage with human skin explants. ResultsWe demonstrated that EtOH consumption and UV exposure act synergistically to increase the severity of local skin damage resulting in impaired melanin responses, reduced antioxidants, greater DNA damage, and immune dysfunction as measured by reduced contact hypersensitivity. ConclusionsThe results support incorporation of the risks of combined UV exposure and excessive alcohol consumption into public health campaigns.

Evaluation of the Antioxidant Properties of Vitellaria paradoxa Seed Extract and Its Effect of Ultra Violet Radiation Induced Skin Damage

Ultra violet radiation (UVR) is relevant in nature, but despite its importance it has been labeled as a causative agent in skin damage. This study was done to evaluate the antioxidant properties of shea butter and its role in the prevention of skin damage. Six groups of albino rats with three rats per group were used, group 2-5 were exposed to UVR at the dose of 180 mJ/cm2 with group 1 serving as the normal control, group 2 (negative control), group 2-5 (treated groups) and group 6 (normal + treated). The treatment was done by topical application of Vitellaria parodoxa seed extract 5 minutes after exposure to UVR. The in-vitro antioxidant properties determined using DPPH radical scavenging activity revealed that the aqueous extract of Vitellaria paradoxa possesses high antioxidant activity. There was an increase in the concentration of GSH of the treated animals when compared to the negative control (p&lt;0.05). The histopathology result shows the extract had a protective effect on the skin tissue of the experimental animals. This study suggests the extract has the potential to serve as a chemopreventive agent against UV-induced skin damage by neutralizing the effects of free radicals generated by ultraviolet radiation and as such can be recommended for use as UVR screen which could in turn reduce the risk of UVR skin damage.

Antioxidant activity and inhibition of ultraviolet radiation-induced skin damage of Selenium-rich peptide fraction from selenium-rich yeast protein hydrolysate

The bioactive peptides and trace element selenium (Se) both have good antioxidant activity. However, whether combined Se and bioactive peptides have more excellent antioxidant activity remain unknown. The aim of this study is to prepare a Se-rich peptide fraction containing both Se and peptides from Se-rich yeast protein hydrolysate and investigated its antioxidant activity and effect on ultraviolet B (UVB) radiation-induced skin oxidative damage. The peptide fractions with different molecular weight (MW) and Se content were obtained by enzymatically hydrolyzing normal or Se-rich yeast proteins followed by a filtration process. In vitro free radical scavenging and lipid peroxidation inhibition assays showed that Se-rich peptides fraction with lower MW of <1 kDa (sSeP) had the highest antioxidant activity compared with Se-rich peptide fractions with higher MW of <3 kDa or normal peptide fractions. Oral administration of sSeP significantly decreased the level of malonaldehyde (MDA) in liver and serum, and increased the activity of glutathione peroxidase (GPx) in liver and serum in normal mice. When topically applied on the dorsal skin of mice, sSeP effectively alleviate UVB radiation-induced skin damage and oxidative stress by increasing GPx and catalase activities and glutathione content in skin or serum. Furthermore, sSeP showed a protective effect against H2O2-induced cytotoxicity in cultured human epidermal keratinocytes (HaCaT) cells probably by increasing aquaporin-3 expression and attenuating the phosphorylation of p38 MAPK. Overall, the results showed that Se-rich yeast peptide fraction containing Se and bioactive peptides could be a promising antioxidant nutrient used as food additive to enhance the body’s antioxidant ability or as cosmeceutical product to minimize the skin oxidative damage.

Metformin effect on driving cell survival pathway through inhibition of UVB-induced ROS formation in human keratinocytes

Human skin functions go beyond serving only as a mechanical barrier. As a complex organ, the skin is capable to cope with external stressors cutaneous by neuroendocrine systems to control homeostasis. However, constant skin exposure to ultraviolet (UV) radiation causes progressive damage to cellular skin constituents, mainly due excessive reactive oxygen species (ROS) production. The present study shows new approaches of metformin (MET) as an antioxidant agent. Currently, MET is the first line treatment of type 2 diabetes and has attracted attention, based on its broad mechanism of action. Therefore, we evaluated MET antioxidant potential in cell-free systems and in UVB irradiated human keratinocyte HaCaT cells. In cell-free system assays MET did not show intrinsic scavenging activity on DPPH radicals or superoxide (O2−) xanthine/luminol/xanthine oxidase-generated. Cell-based results demonstrated that MET was able to reduce UVB-induced intracellular ROS and NADPH oxidase-dependent superoxide (O2−) production. MET posttreatment of HaCaT cells reduced ERK 1/2 phosphorylation, NADPH oxidase activity, and cell death by apoptosis. These findings suggest that the protection mechanism of MET may be through the inhibition of ROS formation enzyme. These results showed that MET might be a promising antioxidant agent against UV radiation induced skin damage.

Innate lymphoid cells regulate radiation-induced skin damage via CCR10 signaling

Objective To assess the role of CCR10 in innate lymphoid cells (ILCs) response in radiation-induced skin damage. Material and methods CCR10+/− and CCR10−/− mice were treated with either a single dose of 5 Gy or 5 Gy everyday for 6 days with a total dose of 30 Gy with X-ray. ILCs from the skin were isolated and analyzed by flow cytometry 3 and 10 days after irradiation. A mouse model of radio-dermatitis was used to assess the skin damage 10 days after 6 × 5 Gy irradiation. Results Skin ILCs were decreased in both CCR10+/− and CCR10−/− mice 3 days after single irradiation (p < .05). However, the skin inflammation disappeared and ILCs returned to normal levels 10 days after single irradiation. ILCs of both genotypes were also decreased after 6 × 5 Gy irradiation, but the percentage of skin ILCs in CCR10−/− mice was lower than that in CCR10+/− mice 10 days after irradiation. The immunohistochemistry results showed that CCR10−/− mice had more severe skin inflammation than CCR10+/− mice. Conclusion CCR10−/− mice had lower percentages of ILCs and more skin damage than CCR10+/− mice after irradiation. These findings indicate that skin ILCs are regulated by CCR10, which might be a potential target for reducing the radio-dermatitis.

Clinical effect and mechanism of alkaline reduced water

Recently, alkaline ionized water (AIW) generated by water electrolysis has received increasing attention because of its shown benefits in treatment and prevention of diseases. The Korean and the Japanese governments officially acknowledged the efficacy of AIW as a novel material for the improvement of abnormal intestinal fermentation, chronic diarrhea, gastric hyperacidity and dyspepsia. It was reported that intake of AIW has various beneficial effects such as removal of reactive oxygen species, improving constipation, suppressed accumulation of body fats, early expulsion of melamine, reduction of ultraviolet radiation-induced skin damage, modulation of immune response and ameliorating diabetes. The effect of AIW is thought to be accounted to its negative oxidation reduction potential, and abundant dissolved hydrogen. The major role of AIW as an antioxidant due to its high content of hydrogen had long been established. Furthermore, drinking hydrogen water and inhaling hydrogen gas demonstrated protection against oxidative diseases. However, our recent study on alkaline reduced water (ARW) from spring water which exhibits different properties from AIW showed a salutary effect through oral administration and bathing. This finding led us to explore further the potential benefits of alkaline reduced water on health and its accompanying mechanism.

Therapeutic effect of adipose-derived mesenchymal stem cells (ASCs) on radiation-induced skin damage in rats.

Radiation-induced skin injury remains a serious concern, which may limit the duration and dose of radiation treatment. The concept that stem cell injection may reduce tissue injury or assist its recovery after radiation has been recently argued. Herein, we examined the effect of adipose-derived mesenchymal stem cells (ASCs) on radiation-induced skin damage in rats. This study is an experimental case control study. ASCs were isolated from peri uterine fat tissue of the rats. Then the rats received a 30 Gy single dose radiation to their buttocks skin using gamma radiation. Next day stem cells were transplanted subcutaneously in 16 rats as the case group. A group of 16 rats was considered as control group with radiation but no transplantation of stem cells. Then rats were examined and observed by macroscopic analysis and phenotypic scores during 4 weeks of follow up. The wound size in control group was significantly higher than case group in the second, third and fourth weeks of evaluation (P<0.05). There was no significant difference in skin lesion severity, pathological factors, and the onset of recovery signs between two groups (P>0.05). It seems that using ASCs alone has not profound effects on reducing radiation-induced cutaneous complications, while combination of these cells with growth factors may produce more promising results.

Abstract 1: Transdermal Deferoxamine Alleviates Radiation-Induced Damage In Porcine Skin

Purpose: Adjuvant radiation therapy is an effective treatment for oncologic malignancies; however, it can cause adverse collateral effects to surrounding soft tissue such as dermal thickening, destruction of vessels, and loss of skin elasticity making reconstruction a burden. To alleviate these detrimental effects, we tested the efficacy of a novel transdermal drug delivery system (TDDS) to provide cutaneous delivery of deferoxamine (DFO) to irradiated porcine skin. DFO is an FDA approved drug which stabilizes hypoxia-inducible factor-1 alpha to increase tissue vascularization. Direct inject of DFO has previously been shown to improve irradiated mouse skin. We hypothesize that application of the DFO TDDS to irradiated soft tissue will also improve radiation-induced fibrosis in our pig model. Methods: Three, red Duroc pigs (three months old) were irradiated with a single fraction of 30 Gray delivered to 5 equal localized regions on either side. The pigs were allowed to recover for eight weeks allowing for chronic radiation damage to develop. At the end of recovery period, the pigs were divided into 3 treatment conditions: 1% DFO TDDS patch, control TDDS patch with not medication, and no treatment. Biopsies from each group, with their respective adjacent non-irradiated skin, were acquired at 1, 2, 3, 4, and 8 week time points. Histological sections were stained with hematoxylin and eosin and Picrosirius Red to evaluate dermal thickness and collagen deposition. Vascularity was determined by CD31 immunofluorescence staining. Mechanical testing was performed to determine skin stiffness, and cutometer readings for each condition were performed to test for skin deformation. Results: Skin histology revealed that DFO TDDS treated irradiated skin demonstrated significant reduction in dermal thickness (hematoxylin and eosin), lower collagen content (Picrosirius Red), and higher vascularity (CD31 immunofluorescence) compared to no patch (***p<0.001, **p<0.01, *p<0.05, respectively) and control patch treated skin (*p<0.05, ****p<0.0001, **p<0.01, respectively). Furthermore, mechanical testing of DFO treated skin exhibited decreased stiffness starting from week 2 onwards after patch placement. Finally, overall skin deformation, from cutometer data, was higher for DFO treated skin compared to the control and no patch treatment groups. Conclusions: Currently, there are limited effective treatments for radiation-induced skin damage. The DFO TDDS patch provides a method to mitigate the chronic effects of radiation-induced skin damage for oncological patients who are in need of reconstructive surgery. The histological and immunofluorescent data indicate the morphological characteristics of the irradiated skin after DFO TDDS patches are similar to normal skin. Furthermore, the mechanical properties of the irradiated skin after DFO TDDS patches mirror normal skin. As porcine skin closely resembles human skin, our findings establish incredible potential to treat patients with radiation induced soft tissue fibrosis.