Skin Wounds In Rats Research Articles

Moxibustion promoted transformation of inflammatory phase to facilitate wound healing in rats with full-thickness cutaneous wounds

Our previous study demonstrated that moxibustion could promote skin wound healing in rats with full-thickness cutaneous wounds. The present study was designed to observe the effect of moxibustion on the levels of pro-inflammatory and anti-inflammatory cytokines, and proliferation of vascular endothelial cells, so as to explore its mechanisms underlying facilitating wound-healing. A total of 84 adult SD male rats were randomly assigned to normal (n＝6), model(n＝39)and moxibustion(n＝39)groups. The skin wound model was established by removal of a piece of full-thickness skin from the median line of the rats' back (about 2 cm below the shoulder blade). Moxibustion was applied to the surrounding area of the focus for 25 min, once daily for 6 days. The blood samples were collected at day 1, 2, 3 and 5 after modeling for assaying serum contents of IL-1α， IL-1β， IL-6, IL-4, IL-10, IL-13, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophagecolony stimulating factor (GM-CSF, an inflammatory mediator), macrophage inhibitory protein-1α (MIP-1α) and vascular endothelial growth factor (VEGF) with liquid chip methods, and the topical wound tissues were collected after trans-cardiac perfusion with 4% paraforma-ldehyde solution for detecting the expression of CD31 proteins by using immunofluorescence staining. After modeling and in comparison with the model group, the contents of serum IL-1α and IL-6 at the 1st day were significantly increased (P<0.05), but notably decreased at the 3rd day after modeling in the moxibustion group (P<0.05). The contents of serum IL-1β on day 1 and 2 were significantly higher in the moxibustion group than those of the model group (P<0.05). After moxibustion, the contents of serum IL-4 and IL-10 were significantly up-regulated on day 1 after modeling (P<0.05), and obviously down-regulated from the 3rd day on (P<0.05). The contents of serum MIP-1α on the 2nd day and serum VEGF on day 1 and 2, and wound-skin VEGF on day 5 were obviously up-regulated in the moxibustion group in comparison with the model group (P<0.05, P<0.01)．. Moxibustion promotes the inflammatory response by regulating the levels of both pro-inflammatory and anti-inflammatory cytokines in the early phase of skin wounds in rats, which may be in favor of the transformation from the inflammatory phase to the proliferation phase in advance, promoting wound healing at last.

Effect of Honey/PVA Hydrogel Loaded by Erythromycin on Full-Thickness Skin Wound Healing in Rats; Stereological Study.

Background: Skin wounds are a significant public health risk, and treatment of wound remains a challenging clinical problem for medical teams and researchers. Materials and Methods: In the present study, we aimed to investigate the healing effects of honey/polyvinyl alcohol (PVA) hydrogel loaded with erythromycin as wound dressing on skin wounds in rats, based on histological studies. In this study, 60 male Wistar rats, with a 1.5 ×1.5 cm2 diameter full-thickness wounds on the backs were divided into four groups: honey/PVA with the erythromycin hydrogel group, honey group, PVA group, and the control group, with no treatment. Skin biopsies were prepared at days 4, 7, and 14 for microscopic analyses. The stereological analysis, including the mean area of the wound, length of vessels, numerical density of fibroblast, macrophage, basal cell and volume of the epidermis, dermis, and fibrous tissue were performed. Results: Wounds area in the honey/PVA hydrogel with the erythromycin group were significantly (P<0.05) smaller than in the other group. The numerical density of fibroblast, macrophage, basal cell and volume of the epidermis in the honey/PVA hydrogel with the erythromycin group were significantly higher than other groups. Conclusion: According to our results, honey/PVA hydrogel with erythromycin may promote early wound healing and has a positive influence on fibroblast proliferation and re-epithelialization, and its administration is recommended after further validation of clinical data.

Effect of Honey/PVA Hydrogel Loaded by Erythromycin on Full-Thickness

Background: Skin wounds are a significant public health risk, and treatment of wound remains a challenging clinical problem for medical teams and researchers.Materials and Methods: In the present study, we aimed to investigate the healing effects of honey/polyvinyl alcohol (PVA) hydrogel loaded with erythromycin as wound dressing on skin wounds in rats, based on histological studies. In this study, 60 male Wistar rats, with a 1.5 ×1.5 cm2 diameter full-thickness wounds on the backs were divided into four groups: honey/PVA with the erythromycin hydrogel group, honey group, PVA group, and the control group, with no treatment. Skin biopsies were prepared at days 4, 7, and 14 for microscopic analyses. The stereological analysis, including the mean area of the wound, length of vessels, numerical density of fibroblast, macrophage, basal cell and volume of the epidermis, dermis, and fibrous tissue were performed. Result: Wounds area in the honey/PVA hydrogel with the erythromycin group were significantly (P&lt;0.05) smaller than in the other group. The numerical density of fibroblast, macrophage, basal cell and volume of the epidermis in the honey/PVA hydrogel with the erythromycin group were significantly higher than other groups.Conclusion: According to our results, honey/PVA hydrogel with erythromycin may promote early wound healing and has a positive influence on fibroblast proliferation and re-epithelialization, and its administration is recommended after further validation of clinical data.[GMJ. 2019;8:e1362]

Coacervate-mediated exogenous growth factor delivery for scarless skin regeneration

Although there are numerous medical applications to recover damaged skin tissue, scarless wound healing is being extensively investigated to provide a better therapeutic outcome. The exogenous delivery of therapeutic growth factors (GFs) is one of the engineering strategies for skin regeneration. This study presents an exogenous GF delivery platform developed using coacervates (Coa), a tertiary complex of poly(ethylene argininyl aspartate diglyceride) (PEAD) polycation, heparin, and cargo GFs (i.e., transforming growth factor beta 3 (TGF-β3) and interleukin 10 (IL-10)). Coa encompasses the advantage of high biocompatibility, facile preparation, protection of cargo GFs, and sustained GF release. We therefore speculated that coacervate-mediated dual delivery of TGF-β3/IL-10 would exhibit synergistic effects for the reduction of scar formation during physiological wound healing. Our results indicate that the exogenous administration of dual GF via Coa enhances the proliferation and migration of skin-related cells. Gene expression profiles using RT-PCR revealed up-regulation of ECM formation at early stage of wound healing and down-regulation of scar-related genes at later stages. Furthermore, direct injection of the dual GF Coa into the edges of damaged skin in a rat skin wound defect model demonstrated accelerated wound closure and skin regeneration after 3 weeks. Histological evaluation and immunohistochemical staining also revealed enhanced formation of the epidermal layer along with facilitated angiogenesis following dual GF Coa delivery. Based on these results, we conclude that polycation-mediated Coa fabrication and exogenous dual GF delivery via the Coa platform effectively augments both the quantity and quality of regenerated skin tissues without scar formation. Statement of SignificanceThis study was conducted to develop a simple administration platform for scarless skin regeneration using polycation-based coacervates with dual GFs. Both in vitro and in vivo studies were performed to confirm the therapeutic efficacy of this platform toward scarless wound healing. Our results demonstrate that the platform developed by us enhances the proliferation and migration of skin-related cells. Sequential modulation in various gene expression profiles suggests a balanced collagen-remodeling process by dual GFs. Furthermore, in vivo histological evaluation demonstrates that our technique enhances clear epidermis formation with less scab and thicker woven structure of collagen bundle, similar to that of a normal tissue. We propose that simple administration of dual GFs with Coa has the potential to be applied as a clinical approach for fundamental scarless skin regeneration.

Fabrication of Xanthan gum: Gelatin (Xnt:Gel) Hybrid Composite Hydrogels for Evaluating Skin Wound Healing Efficacy

With the background of snowballing threat of skin wound to public health and economy, this study was undertaken utilizing xanthan gum (Xnt), citric acid (C), gelatin (Gel), glutaraldehyde (G) and HPLC-grade water to fabricate a series of composite hydrogels i.e. Xnt, Xnt:C, Xnt:Gel(3):G, Xnt:C:Gel(3):G, Xnt:Gel(5):G, Xnt:C:Gel(5):G for investigating their wound healing efficacy in experimental rat skin wound model. Physicochemical characterization revealed that all the composite hydrogels contained more than 90% water. The hydrogels displayed swelling ability, biodegradability, good polymeric networks and porosity. Fourier Transform Infrared Spectroscopy (FT-IR) studies confirmed the presence of bound water and free, intra and inter molecular bound hydrogen bonded OH and NH in the hydrogels. All the hydrogels showed significant wound healing potency in experimental deep second degree skin burns in rats compared to controls. 20 days post-application of hydrogels, Xnt:Gel(3):G, Xnt:Gel(5):G and Xnt:C:Gel(5):G-treated wounds showed better recovery compared to other composite hydrogels. We conclude that, Xnt:Gel(3):G, Xnt:Gel(5):G and Xnt:C:Gel(5):G might be effective wound dressing material.

Human umbilical cord mesenchymal stem cells implantation accelerates cutaneous wound healing in diabetic rats via the Wnt signaling pathway

ObjectiveDifficulty in wound healing is one common complication of diabetes mellitus. The study explored whether the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on diabetic ulcer wound was enhanced by the activation of the Wnt signaling pathway.MethodsRat diabetic model was established by intraperitoneal injection of Streptozotocin (STZ). hUCMSCs were purified and seeded on the collagen–chitosan laser drilling acellular dermal matrix (CCLDADM) scaffold, which was subsequently implanted into the cutaneous wound of normal and diabetic rats, followed by daily injection of Wnt signaling pathway agonist (Wnt3a) or antagonist (sFRP3) at the edge of the scaffold. Wound healing was checked on days 7, 14, and 21, and the fibrous tissue deposition, capillaries, and epidermal regeneration at the wound were examined by hematoxylin–eosin staining. The hUCMSCs-CCLDADM scaffold was cultured in vitro and treated with Wnt3a or sFRP3, followed by evaluation of cell proliferation, cell proliferation rate, survival status, and altered protein levels in the Wnt signaling pathway using BrdU staining, CCK-8 assay, live/dead staining, and Western blotting, respectively.ResultsOn days 7 and 14 postoperatively, the speed of wound healing was significantly lower in diabetic rats than that in normal control rats. This phenomenon was significantly improved by the activation of the Wnt signaling pathway that also elevated the fibrous protein deposition and the abundance of capillary in the granulation tissue. Conversely, blockade of Wnt signaling slowed the healing of skin wound in diabetic rats. The activation of Wnt signaling pathway promoted the proliferation and differentiation and decreased the apoptosis of hUCMSCs, thereby elevating the number of living hUCMSCs on the CCLDADM scaffold, while the suppression exerted a contrary effect.ConclusionThe activation of the Wnt signaling pathway promotes the healing of diabetic skin wound by the regulation of proliferation and differentiation of hUCMSCs on the CCLDADM scaffold.

Exosomes derived from clinical-grade oral mucosal epithelial cell sheets promote wound healing

ABSTRACTThe oral mucosa exhibits unique regenerative properties, sometimes referred to as foetal-like wound healing. Researchers from our institute have used sheets of oral mucosa epithelial cells (OMECs) for regenerative medicine applications including cornea replacement and oesophageal epithelial regeneration for stricture prevention. Here, we have isolated exosomes from clinical-grade production of OMEC sheets from healthy human donors (n = 8), aiming to evaluate the clinical potential of the exosomes to stimulate epithelial regeneration and to improve understanding of the mode-of-action of the cells. Exosomes were isolated from conditioned (cExo) and non-conditioned (ncExo) media. Characterization was performed using Western blot for common exosomal-markers: CD9 and flotillin were positive while annexin V, EpCam and contaminating marker GRP94 were negative. Nanoparticle tracking analysis revealed a diameter of ~120 nm and transmission electron microscopy showed a corresponding size and spherical appearance. Human skin fibroblasts exposed to exosomes showed dose-dependent reduction of proliferation and a considerable increase of growth factor gene expression (HGF, VEGFA, FGF2 and CTGF). The results were similar for both groups, but with a trend towards a larger effect from cExo. To study adhesion, fluorescently labelled exosomes were topically applied to pig oesophageal wound-beds ex vivo and subsequently washed. Positive signal could be detected after as little as 1 min of adhesion, but increased adhesion time produced a stronger signal. Next, labelled exosomes were added to full-thickness skin wounds in rats and signal was detected up to 5 days after application. cExo significantly reduced the wound size at days 6 and 17. In conclusion, exosomes from OMEC sheets showed pro-regenerative effects on skin wound healing. This is the first time that the healing capacity of the oral mucosa is studied from an exosome perspective. These findings might lead to a combinational therapy of cell sheets and exosomes for future patients with early oesophageal cancer.

EFFECT OF PROBIOTIC ORAL ADMINISTRATION ON SKIN WOUND HEALING IN RATS.

ABSTRACTBackground:Manipulating intestinal microbiota with probiotics might stimulate skin response. Understanding all stages of the healing process, as well as the gut-skin-healing response can improve the skin healing process. Aim:To evaluate the effect of perioperative oral administration of probiotics on the healing of skin wounds in rats. Methods:Seventy-two Wistar male adult rats were weighed and divided into two groups with 36 each, one control group (supplemented with oral maltodextrin 250 mg/day) and one probiotic group (supplemented with Lactobacillus paracasei LPC-37, Bifidobacterium lactis HN0019, Lactobacillus rhamnosus HN001, Lactobacillus acidophilus NCFM® at a dose of 250 mg/day), both given orally daily for 15 days. The two groups were subsequently divided into three subgroups according to the moment of euthanasia: in the 3rd, 7th and 10th postoperative days. Results:There were no significant changes in weight in both groups. Wound contraction was faster in probiotic group when compared to the controls, resulting in smaller wound area in the 7th postoperative day. As for histological aspects, the overall H&E score was lower in the probiotic group. The probiotic group showed increased fibrosis from 3rd to the 7th postoperative day. The type I collagen production was higher in the probiotic group at the 10th postoperative day, and the type III collagen increased in the 7th. Conclusion:The perioperative use of orally administrated probiotic was associated with a faster reduction of the wound area in rats probably by reducing the inflammatory phase, accelerating the fibrosis process and the deposition of collagen.

Polydopamine modification of silk fibroin membranes significantly promotes their wound healing effect.

Natural polymer-based wound dressings have gained great attention in skin tissue engineering. Silk fibroin (SF) spun from Bombyx mori (B. mori) is a potential wound dressing material due to its outstanding biocompatibility and biodegradability, however, its wound healing effect is still limited. To maximize the wound healing effect of SF-based wound dressing, we first fabricated fibrous electrospun SF (ESF) membranes with large porosity and specific surface area, and then formed polydopamine (PDA) coating on the ESF fibers to form PESF membranes. We found that PDA coating enabled the PESF membranes to outperform the ESF membranes in enhancing the hydrophilicity and protein adsorption ability of the membranes as well as the attachment, spreading and proliferation of fibroblasts on the membranes in vitro. Our further in vivo histological analysis confirmed that the PESF membranes accelerated wound healing in a rat skin wound model more effectively within 2 weeks than both the ESF membrane and a commercial dressing (3M™ Tegaderm™). The enhanced wound healing effect of the PESF membranes was further proved by the increase in the content of hydroxyproline (a constituent in collagen) in the wound treated by the PESF membranes. Therefore, the PESF membranes could be used as a promising wound dressing for wound healing and skin regeneration.

Physicochemical parameters of NO-containing gas flow affect wound healing therapy. An experimental study

Therapy of wounds and inflammatory diseases with NO-containing gas flows (NO-CGF) has proved to be effective in a longterm clinical practice. Plasma-chemical generation of nitric oxide occurs from atmospheric air in Plason device. For the purpose of modification and improvement of NO-therapy, effects of various physicochemical parameters of the NO-CGF on inflammatory and reparative processes in wounds were studied. Treatment of planar full-thickness skin wounds in laboratory rats was analyzed with morphological, immunohistochemical, morphometric and statistical methods. The study showed that the Plason device and the experimental device, which differs from Plason by the NO-CGF temperature, significantly reduce inflammatory and enhance regenerative processes in the wounds. The NO-CGF with an ambient temperature generated by the experimental device has noticeably facilitated the wound healing in direct ration to a nitric oxide content and flow velocity at the area of application. Temperature did not affect the course of wound healing process. The development of a new device for NO-therapy may be of use for both physicians and patients.

A MicroRNA-29 Mimic (Remlarsen) Represses Extracellular Matrix Expression and Fibroplasia in the Skin

MicroRNA-29 (miR-29) negatively regulates fibrosis and is downregulated in multiple fibrotic organs and tissues, including in the skin. miR-29 mimics prevent pulmonary fibrosis in mouse models but have not previously been tested in the skin. This study aimed to identify pharmacodynamic biomarkers of miR-29 in mouse skin, to translate those biomarkers across multiple species, and to assess the pharmacodynamic activity of a miR-29b mimic (remlarsen) in a clinical trial. miR-29 biomarkers were selected based on gene function and mRNA expression using quantitative reverse transcriptase polymerase chain reaction. Those biomarkers comprised multiple collagens and other miR-29 direct and indirect targets and were conserved across species; remlarsen regulated their expression in mouse, rat, and rabbit skin wounds and in human skin fibroblasts in culture, while a miR-29 inhibitor reciprocally regulated their expression. Biomarker expression translated to clinical proof-of-mechanism; in a double-blinded, placebo-randomized, within-subject controlled clinical trial of single and multiple ascending doses of remlarsen in normal healthy volunteers, remlarsen repressed collagen expression and the development of fibroplasia in incisional skin wounds. These results suggest that remlarsen may be an effective therapeutic to prevent formation of a fibrotic scar (hypertrophic scar or keloid) or to prevent cutaneous fibrosis, such as scleroderma.

MDia1 and Cdc42 Regulate Activin B-Induced Migration of Bone Marrow-Derived Mesenchymal Stromal Cells.

In a previous study, we have shown that Activin B is a potent chemoattractant for bone marrow‐derived mesenchymal stromal cells (BMSCs). As such, the combination of Activin B and BMSCs significantly accelerated rat skin wound healing. In another study, we showed that RhoA activation plays a key role in Activin B‐induced BMSC migration. However, the role of the immediate downstream effectors of RhoA in this process is unclear. Here, we demonstrated that mammalian homolog of Drosophila diaphanous‐1 (mDia1), a downstream effector of RhoA, exerts a crucial function in Activin B‐induced BMSC migration by promoting membrane ruffling, microtubule morphology, and adhesion signaling dynamics. Furthermore, we showed that Activin B does not change Rac1 activity but increases Cdc42 activity in BMSCs. Inactivation of Cdc42 inhibited Activin B‐stimulated Golgi reorientation and the cell migration of BMSCs. Furthermore, knockdown of mDia1 affected Activin B‐induced BMSC‐mediated wound healing in vivo. In conclusion, this study demonstrated that the RhoA‐mDia1 and Cdc42 pathways regulate Activin B‐induced BMSC migration. This study may help to optimize clinical MSC‐based transplantation strategies to promote skin wound healing. stem cells 2019;37:150–161

The Healing Effects of Conditioned Medium Derived from Mesenchymal Stem Cells on Radiation-Induced Skin Wounds in Rats

Radioactive dermatitis is caused by the exposure of skin and mucous membranes to radiation fields. The pathogenesis of radioactive dermatitis is complex and difficult to cure. Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) may serve as a promising candidate for the therapy of cutaneous wounds. The aim of this study was to investigate whether a WJ-MSC-derived conditioned medium (MSC-CM) could be used to treat radiation-induced skin wounds in rats using a radiation-induced cutaneous injury model. The present study was designed to examine MSC-CM therapy in the recovery of radiation-induced skin wounds in vitro and in vivo. Firstly, we prepared the MSC-CM and tested the effects of the MSC-CM on human umbilical vein endothelial cell proliferation in vitro. After that, we used a β-ray beam to make skin wounds in rats and tested the effects of MSC-CM on cutaneous wound healing in vivo. Our results indicated that MSC-CM secreted factors that promoted HUVEC proliferation, regeneration of sebaceous glands, and angiogenesis. Importantly, MSC-CM promoted wound healing in excess of the positive control (epidermal growth factor), with no, or smaller, scar formation. In conclusion, MSC-CM significantly accelerated wound closure and enhanced the wound healing quality. MSC-CM has a beneficial therapeutic effect on radiation-induced cutaneous injury skin in rats and in this way MSC-CM may serve as a basis of a novel cell-free therapeutic approach for radiation dermatitis.

Toxicology of skin of Rana catesbeiana as a biological dressing in skin wounds of rats

Purpose: The aim of this study was to evaluated the toxicity in rats’ kidney and liver by using Rana catesbeiana’s skin as biological dressing in skin wounds. Methods: Twenty Wistar rats were used; in all rats a back dorsum skin segment with 4 cm² was removed under anesthesia and aseptic technique. In group A (n=10) the wounds were treated with frog’s skin as a biological dressing. In group B (n=10) the wounds were treated with 1 mL of 0,9% saline solution. After 15 days, blood was collected for dosing serum AST, ALT, urea and creatinine. Results: Biochemical dosages evaluated liver and renal function tests. The values of AST, ALT, urea and creatinine showed no significant difference when the test and control groups were compared (p&gt;0.05). Conclusion: The use of Rana catesbeiana’s skin as a biological dressing of rats wounds did not show toxic effects for liver and kidney functions.

EFFECT OF JNK MAPK ON THE REPAIR OF DAMAGED SKELETAL MUSCLE

Regeneration of muscles after injuries, as well as the development of methods that stimulate this process, is an important problem in medicine and biology. The objective of the study was to evaluate the effect of local blocking of mitogen-activated protein kinase (MAPK) activity of the JNK group (c-Jun N-terminal kinase) on the repair of muscle tissue. Materials and methods. The effect of the JNK MAPK SP600125 blocker on the repair of muscle tissue was studied on a model of a skin and muscle wound in Wistar rats. The main group (n = 30) was injected with a drug plate containing SP600125 with a slow release of the active substance, the control group (n = 30) – the plate without the active substance. The number of dividing myosatellites and muscle kidneys in the damage zone was estimated. Results. Experimental studies have shown that when using a drug plate containing a JNK SP600125 blocker with a slow release of the active substance, the number of dividing myosatellites and forming muscle kidneys in the injury zone of the muscle in the main group on the 7th, 14th and 30th days was significantly higher (p &lt; 0.05) than in the control. Conclusion. Local blockade of JNK MAPK in the zone of muscle damage provides the ability to stimulate the repair of damaged skeletal muscle.

JAM-A knockdown accelerates the proliferation and migration of human keratinocytes, and improves wound healing in rats via FAK/Erk signaling

Junctional adhesion molecule-A (JAM-A) belongs to the immunoglobulin superfamily, it predominantly exists at the tight junctions of epithelial and endothelial cells. JAM-A is known to regulate leukocyte trans-endothelial migration, however, how it affects the proliferation and migration of keratinocytes, the two essential steps during wound healing, has less been explored. In this study, we showed that JAM-A was significantly expressed in normal skin epidermis. RNAi-mediated JAM-A knockdown remarkably promoted the proliferation and migration of keratinocytes. We also found that loss of JAM-A increased the protein levels of p-FAK, p-Erk1/2, and p-JNK; however, FAK inhibitor PF-562271 restrained the expression of p-FAK and p-Erk1/2 elevated by JAM-A RNAi, but not p-JNK, and also slowed down keratinocyte proliferation and migration. Finally, in a rat wound model we showed that absence of JAM-A significantly promoted the wound healing process, while the use of PF-562271 or Erk1/2 inhibitor PD98059 repressed those effects. These data collectively demonstrate that suppressing JAM-A expression could promote the proliferation and migration of keratinocytes and accelerate the healing process of rat skin wounds, potentially via FAK/Erk pathway, indicating that JAM-A might serve as a potential therapeutic target for the treatment of chronic refractory wounds.

Different Trypanosoma cruzi calreticulin domains mediate migration and proliferation of fibroblasts in vitro and skin wound healing in vivo.

Calreticulin is an endoplasmic reticulum-resident, calcium-binding, stress-produced, chaperone protein that serves multiple functions and is widely distributed in eukaryotic cells. Exogenously applied recombinant calreticulin solution, markedly enhanced the rate and quality of skin wound healing. These modulatory effects are more efficient than commercially available topic platelet-derived growth factor ointments (Regranex®). Trypanosoma cruzi calreticulin is more effective in equimolar terms to human counterpart in accelerating skin wound healing. While the effect of externally added recombinant parasite calreticulin on wound healing has been reported, the domains responsible for these modulatory effects have not yet been established. Here, recombinant parasite calreticulin and some of its domains were tested to assess their influence in increasing proliferation and migration of fibroblasts in vitro and rat skin wound healing in vivo. Herein, we propose that Trypanosoma cruzi whole calreticulin or some of its domains are differentially involved in the modulation of wound-healing cell migration and proliferation, and cosmetic outcome. Therefore, precise combination of the parasite protein and its domains could allow us to tailor-specific desired effects during the skin wound-healing process.

Potential adverse effects of antimicrobial chemotherapy based on ultraviolet-A irradiation of polyphenols against the oral mucosa in hamsters and wounded skin in rats

Antimicrobial chemotherapy based on ultraviolet-A (UVA) irradiation of polyphenol solution has been proposed as an adjunctive treatment for dental caries. However, the safety of this treatment has not been thoroughly evaluated. Therefore, the aim of the present study was to assess the influence of this treatment on the oral mucosa in hamsters and wounded skin in rats. An oral mucosal irritation test was performed in hamsters. The cheek pouch was everted and treated with UVA irradiation (wavelength: 365 nm) of pure water, 1 mg/mL of caffeic acid, or 1 mg/mL of grape seed extract using a light-emitting diode at an irradiance of 275 mW/cm2. Each treatment was performed for 2 or 5 min and repeated three times. Macroscopic and histological evaluations were performed 24 h after the last treatment. We also examined the effects of the treatment on the healing process of skin wounds in rats. Full-thickness skin wounds created on the back of the rats were treated for 2 min as described above, but only once. The wound area was then assessed daily for 9 days. The results demonstrated that the treatment induced oral mucosal irritation depending on the irradiation time; however, it did not influence the wound healing process. The oral mucosal irritation potential of three treatment sessions performed for 2 and 5 min was minimal and mild to moderate, respectively, according to histological analysis. These findings suggest that the duration of treatment based on UVA irradiation of polyphenols in the oral cavity should be as short as possible, considering the clinical efficacy of the antimicrobial effects and the irritation potential.

Effect of Mesenchymal Stromal Cells and Conditioned Media on Healing of Skin Wound.

We studied the effect of mesenchymal stromal cells and conditioned media on healing of full-thickness skin wound in rats. Cell transplantation to the wound bed did not accelerate wound closing and had no effect on the severity of inflammation, but increased vasculariza - tion of the granulation tissue in 14 days after injury. After injection of conditioned medium to the wound, less pronounced inflammation or enhanced epithelialization was observed. The angiogenic effect was observed only after repeated administration of conditioned medium and was associated with slower regeneration, probably due to skin traumatization by repeated injections. At the same time, fetal skin fibroblasts stimulated angiogenesis only after transplantation in high doses and the medium conditioned by these fibroblasts had no effect on wound healing.

Thermoresponsive polysaccharide-based composite hydrogel with antibacterial and healing-promoting activities for preventing recurrent adhesion after adhesiolysis

Postoperative adhesions are very common complications after general abdominal surgery. Although adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. The prevention of recurrent adhesion after adhesiolysis is more difficult because the injury is more severe and adhesion mechanism is more complicated compared with the primary adhesion. In this study, a thermoresponsive hydrogel contained galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC) was developed as a barrier device for recurrent adhesion prevention after adhesiolysis due to its injectability and spontaneous gelling behaviors at the body temperature without any chemical reactions or extra driving factors. First, mXG and HBC were synthesized via enzymatic modification and etherification reaction, respectively. Rheological measurements indicated that the mXG/HBC composite system showed excellent thermosensitivity properties, and their gelation temperature and time can be modulated via adjusting the mXG/HBC ratio. Moreover, the mXG/HBC hydrogel exhibited excellent cytocompatibility and hemocompatibility in vitro. Furthermore, the mXG/HBC hydrogel could promote wound healing in the rat skin wound model. Finally, the efficacy of the mXG/HBC composite hydrogel in the prevention of recurrent adhesion was evaluated in a more rigorous rat repeated-injury adhesion model. The results demonstrated that the composite hydrogel could not only effectively prevent recurrent adhesion after adhesiolysis, but also promote wound healing and reduce scare formation. These results suggested that the mXG/HBC composite hydrogel may be a promising candidate as an injectable anti-adhesion system for clinical applications. Statement of SignificanceAlthough adhesiolysis has been proven effective in eliminating the preexisting adhesions, the new trauma caused by surgical lysis can induce recurrent adhesion. So far, most of the existing barrier systems and pharmacological approaches were developed for primary adhesion prevention while few attention has paid on prevention of recurrent adhesion after adhesiolysis. In the present study, we developed a thermoresponsive polysaccharide-based composite hydrogel by simple mixing galactose modified xyloglucan (mXG) and hydroxybutyl chitosan (HBC). The resulting mXG/HBC composite hydrogel not only was easy to handle and highly effective in preventing the recurrent adhesion after adhesiolysis, but also could promote wound healing and reduce scare formation. Our study provide an effective anti-adhesion system for preventing recurrent adhesion after adhesiolysis.