Beta-caryophyllene as an antioxidant, anti-inflammatory and re-epithelialization activities in a rat skin wound excision model.

The skin is a critical organ for the maintenance of the integrity and protection of the organism. When a wound occurs, a sequence of healing mechanisms is triggered to reconstruct the wounded area. ß-caryophyllene is a sesquiterpene in Copaifera langsdorffii oleoresin with antioxidant and anti-inflammatory potential. On the basis of previous studies with C. langsdorffii, ß-caryophyllene was selected to evaluate its wound healing potential and pharmacological mechanisms. The excision wound model was used with male Wistar rats and macroscopic, histological, immunohistochemical and biochemical analyses were performed with skin samples, comparing the ß-caryophyllene-treated group with reference drugs. The results showed macroscopic retraction of the wounds treated with ß-caryophyllene. Biochemical assays revealed the antioxidant and anti-inflammatory mechanisms of the ß-caryophyllene-treated group with increasing levels of IL-10 and GPx and decreasing levels of pro-inflammatory molecules, including TNF-α, IFN-γ, IL-1ß and IL-6. After ß-caryophyllene treatment, immunohistochemical assays showed enhanced re-epithelialization, through the increase in laminin-γ2 and desmoglein-3 immunolabeling. ß-caryophyllene also act in the remodeling mechanism, increasing the collagen content in the Masson's trichrome staining. These findings indicated the wound-healing potential of ß-caryophyllene topical formulation in rat skin wounds, mediated by antioxidant, anti-inflammatory and re-epithelialization mechanisms.

Bioactive anti-oxidative polycaprolactone/gelatin electrospun nanofibers containing selenium nanoparticles/vitamin E for wound dressing applications.

In this study, polycaprolactone/gelatin (PCL/GEL) electrospun nanofibers containing biogenic selenium nanoparticles (Se NPs) and Se NPs/vitamin E (VE) with average diameters of 397.8 nm and 279.5 nm, respectively (as determined by SEM inspection) were prepared and their effect on wound healing was evaluated using in-vivo studies. The energy dispersive X-ray (EDX) mapping, TEM micrograph, and FTIR spectra of the prepared nanofibers strongly demonstrated well entrapment of Se NPs and VE into scaffolds. An amount of 57% Se NPs and 43% VE were gradually released from PCL/GEL/Se NPs/VE scaffold after 4 days immersion in PBS solution (pH 7.4). The both PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds supported 3T3 cell proliferation and attachment as confirmed by MTT assay and SEM imaging. Complete re-epithelialization, low level of edema and inflammatory cells in coordination with high level of oriented collagens demonstrated the wound healing activity of PCL/GEL/Se NPs/VE. Besides, significant antioxidant efficacy of PCL/GEL/Se NPs and PCL/GEL/Se NPs/VE scaffolds was demonstrated according to GSH and MDA assays. To sum up, the prepared PCL/GEL/Se NPs/VE scaffold in the present study represented suitable healing effect on animal model which candidate it for further studies.

In-vivo wound healing activity of a novel composite sponge loaded with mucilage and lipoidal matter of Hibiscus species.

Many researches have been undergone to hasten the natural wound healing process. In this study, several Hibiscus species (leaves) were extracted with petroleum ether, methanol, and their mucilage was separated. All the tested species extracts were assessed for their viability percentage using the water-soluble tetrazolium. H.syriacus was the plant of choice to be incorporated in a new drug delivery system and evaluated for its wound healing activity. H.syriacus petroleum ether extract (PEE) showed a high percentage of palmitic and oleic acids while its mucilage demonstrated high glucosamine and galacturonic acid. It was selected to be formulated and pharmaceutically evaluated into three different composite sponges using chitosan in various ratios. Fourier-transformed infrared spectroscopy investigated the chemical interaction between the utilized sponges' ingredients. Morphological characteristics were evaluated using scanning electron microscopy. H.syriacus composite sponge of mucilage: chitosan (1:5) was loaded with three different concentrations of PEE. Medicated formulations were assessed in rat model of excision wound model. The wound healing ability was clearly proved by the clinical acceleration, histopathological examination, and modulation of correlated inflammatory parameters as tumor necrosis factor in addition to vascular endothelial growth factor suggesting a promising valuable candidate that supports the management of excision wounds using single-dose preparation.

Omega-7 oil increases telomerase activity and accelerates healing of grafted burn and donor site wounds.

This study investigated the efficacy of Omega-7 isolated from the sea buckthorn oil (Polyvit Co., Ltd, Gangar Holding, Ulaanbaatar, Mongolia) in ovine burn wound healing models. In vitro, proliferation (colony-forming rate) and migration (scratch) assays using cultured primary ovine keratinocytes were performed with or without 0.025% and 0.08% Omega-7, respectively. The colony-forming rate of keratinocytes in the Omega-7 group at 72 and 96 h were significantly higher than in the control (P < 0.05). The percentage of closure in scratch assay in the Omega-7 group was significantly higher than in the control at 17 h (P < 0.05). In vivo, efficacy of 4% Omega-7 isolated from buckthorn oil was assessed at 7 and 14 days in grafted ovine burn and donor site wounds. Telomerase activity, keratinocyte growth factor, and wound nitrotyrosine levels were measured at day 14. Grafted sites: Un-epithelialized raw surface area was significantly lower and blood flow was significantly higher in the Omega-7-treated sites than in control sites at 7 and 14 days (P < 0.05). Telomerase activity and levels of keratinocyte growth factors were significantly higher in the Omega-7-treated sites after 14 days compared to those of control (P < 0.05). The wound 3-nitrotyrosine levels were significantly reduced by Omega-7. Donor sites: the complete epithelialization time was significantly shorter and blood flow at day 7 was significantly higher in the Omega-7-treated sites compared to control sites (P < 0.05). In summary, topical application of Omega-7 accelerates healing of both grafted burn and donor site wounds. Omega-7 should be considered as a cost-efficient and effective supplement therapy for burn wound healing.

In-vivo evaluation of Alginate-Pectin hydrogel film loaded with Simvastatin for diabetic wound healing in Streptozotocin-induced diabetic rats.

Previously we developed and characterized a novel hydrogel film wound dressing containing Sodium Alginate and Pectin loaded with Simvastatin with multi-functional properties. This study investigated the in-vivo efficacy of the developed wound dressing on type I diabetic wound model. Experiments were performed on male Wistar rats for the period of 21-days. Animals developed diabetes after intraperitoneal injection (50 mg/kg) of Streptozotocin then randomly divided into different groups. On days 7, 14, and 21 of post-wounding, animals were euthanized and the wounds tissue were harvested for analysis. The wound healing rate, hematology and histological analysis, hydroxyproline assay, and Vascular Endothelial Growth Factor A measurements were noted. The results revealed that the wound dressing healed the wounded area significantly (p < 0.05) higher than the control after 21-day treatment and wound closure was ~99% without any adverse systemic reactions. Histological analysis qualitatively revealed an enhanced re-epithelialization and collagen deposition. Moreover, results also showed an improved rate of collagen synthesis and angiogenesis in the group treated with the hydrogel film loaded with Simvastatin. Thus, the present study demonstrated that developed film holds great potential for the acceleration of diabetic wound healing by its pro-angiogenic effect, faster re-epithelialization and increased collagen deposition.

Thyroxine restores severely impaired cutaneous re-epithelialisation and angiogenesis in a novel preclinical assay for studying human skin wound healing under "pathological" conditions ex vivo.

Impaired cutaneous wound healing remains a major healthcare challenge. The enormity of this challenge is compounded by the lack of preclinical human skin wound healing models that recapitulate selected key factors underlying impaired healing, namely hypoxia/poor tissue perfusion, oxidative damage, defective innervation, and hyperglycaemia. Since organ-cultured human skin already represents a denervated and impaired perfusion state, we sought to further mimic "pathological" wound healing conditions by culturing experimentally wounded, healthy full-thickness frontotemporal skin from three healthy female subjects for three days in either serum-free supplemented Williams' E medium or in unsupplemented medium under "pathological" conditions (i.e. hypoxia [5% O2], oxidative damage [10 mM H2O2], absence of insulin, excess glucose). Under these "pathological" conditions, dermal-epidermal split formation and dyskeratosis were prominent in organ-cultured human skin, and epidermal reepithelialisation was significantly impaired (p < 0.001), associated with reduced keratinocyte proliferation (p < 0.001), cytokeratin 6 expression (p < 0.001) and increased apoptosis (p < 0.001). Moreover, markers of intracutaneous angiogenesis (CD31 immunoreactivity and the number of of CD31 positive cells and CD31 positive vessel lumina) were significantly reduced. Since we had previously shown that thyroxine promotes wound healing in healthy human skin ex vivo, we tested whether this in principle also occurs under "pathological" wound healing conditions. Indeed, thyroxine administration sufficed to rescue re-epithelialisation (p < 0.001) and promoted both epidermal keratinocyte proliferation (p < 0.01) and angiogenesis in terms of CD31 immunoreactivity and CD31 positive cells under "pathological" conditions (p < 0.001) ex vivo. This demonstrates the utility of this pragmatic short-term ex vivo model, which recapitulates some key parameters of impaired human skin wound healing, for the preclinical identification of promising wound healing promoters.

Effects and Characterization of Some Topical Ointments Based on Vegetal Extracts on Incision, Excision, and Thermal Wound Models.

The present paper aims to formulate and characterize four phytotherapeutic ointments based on Hippophae fructus, Calendulae flos, Bardanae folium, and Millefolii herba, which are included in a novel ointment base. In order to investigate the healing properties of the ointments, in vivo experimental wound models of linear incision, circular excision, and thermal burn were performed on Wistar rats. Topical treatment was performed daily for 21 days. Determination of the wound contraction rate (WCR), the period of reepithelization, and histopathological examination were achieved. Additionally, for the tested ointments, oscillatory and rotational rheological tests were carried out, and for the extracts, HPLC analysis was performed. The results demonstrate that the tested novel ointments are safe for use and the most effective ointment proved to be the one based on Arctium lappa, followed by that of Calendulae flos.

Carbon nanodot decorated acellular dermal matrix hydrogel augments chronic wound closure.

Impaired skin regeneration in chronic wounds like in diabetes corresponds to high oxidative stress, poor angiogenesis and insufficient collagen hyperplasia. Therefore, a multifaceted strategy for treatment is required to address critical issues associated with chronic wound healing. Fascinating application of nanomaterials in chronic wounds is still limited; hence, in the present work bioactive solubilized decellularized dermal matrix (sADM) was employed to form a hydrogel with chitosan (CTS) at physiological pH/temperature and modified with reactive oxygen species (ROS) scavenging carbon nanodots (ND). A detailed in vitro investigation found that the ND modified bioactive hydrogel (CsADMND) is suitable for human amniotic membrane derived stem cell (hAMSC) delivery. Also, CsADMND was observed to possess a good ROS scavenging property, hemocompatibility and pro-angiogenic potential as demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), haemolysis and chick chorioallantoic membrane (CAM) assay, respectively. The hybrid hydrogel promoted migration of cells in vitro in scratch assay owing to its antioxidant potential and the presence of bioactive moieties. Further, its efficacy in healing full thickness (FT) chronic wounds was evaluated in a streptozotocin (STZ) induced diabetic model. The CsADMND hydrogel after association with hAMSCs led to stimulation of early angiogenesis, superior collagen deposition, rapid wound closure, complete reepithelialisation, and formation of distinct organized dermal epidermal junctions (DEJ) post 21 days of healing. These results suggest that the hAMSC laden CsADMND hydrogel may serve as a promising therapeutic strategy for the management of chronic wounds.

Wound Healing Activity of Crassocephalum crepidioides (Benth.) S. Moore. Leaf Hydroethanolic Extract.

Crassocephalum crepidioides (Benth.) S. Moore. has been used to treat small wounds by minority people in Lam Dong, Vietnam. However, there has been no scientific evidences about its wound healing activity. This study is aimed at evaluating the wound healing activity of Crassocephalum crepidioides hydroethanolic extract via its antioxidant and anti-inflammation activities and healing capability on a mouse excision wound model. Crassocephalum crepidioides hydroethanolic extract (CCLE) at a dose of 50 mg/kg/day reduced the wound closure time about 3.5 days, compared to vehicle treatment. The granulation tissue on day 7 after surgery from the treated group showed a 2.8-fold decrease in the density of inflammatory cells, 1.9-fold increase in the fibroblast density, and a higher number of blood vessels. Real-time PCR analysis indicated that the mRNA expression level of NF-κB1 and TNF-α mRNA in CCLE-treated wounds decreased by 4.6 and 3.3 times, respectively, while TGF-ß1 and VEGF were found to increase by 3.3 and 2.4 times, respectively. Our experimental data provided proofs of Crassocephalum crepidioides leaf wound healing activity due to its antioxidant, anti-inflammation, fibroblast proliferation, wound contraction, and angiogenesis effects.

Epidermal Regeneration Induced by Comfrey Extract: A Study by Light and Electron Microscopy.

INTRODUCTION: An accelerated healing of superficial wounds was demonstrated in clinical trials with a topical comfrey preparation (Symphytum × uplandicum Nyman). The effect has previously not been examined in skin models. METHODS: An established in vitro model of epidermal cells with the typical strata was used for the observation of effects of applied substances on skin regeneration. Damage corresponding to a typical abrasion was created on day 1 by punching an opening into the epidermal fine structure down to the stratum basale. Samples were either untreated (controls) or exposed to comfrey cream on days 2, 3, 5, and 6. Tissue samples were taken for light and electron microscopy on days 1, 4, and 7. RESULTS AND CONCLUSIONS: Application of comfrey cream led to a quicker regeneration of skin cells and to an earlier differentiation of the cells towards a normal fine structure with a visible distinction of epidermal strata, keratin, and corneocyte formation within 4-7 days. The study covered the early days of skin regeneration and confirms the benefits observed in published clinical trials and non-interventional studies in patients with abrasions.

Fibroblast Proliferation and Migration in Wound Healing by Phytochemicals: Evidence for a Novel Synergic Outcome.

Wound-healing is a dynamic skin reparative process that results in a sequence of events, including inflammation, proliferation, and migration of different cell types as fibroblasts. Fibroblasts play a crucial role in repairing processes, from the late inflammatory phase until the fully final epithelization of the injured tissue. Within this context, identifying tools able to implement cell proliferation and migration could improve tissue regeneration. Recently, plants species from all over the world are coming out as novel tools for therapeutic applications thanks to their phytochemicals, which have antioxidant properties and can promote wound healing. In this paper, we aimed at investigating antioxidant activity of waste extracts from different medicinal plants, endemic of the Mediterranean area, on fibroblast proliferation and wound healing. We determined the amount of total phenols and anti-oxidant activity by ABTS assay. We then evaluated the cytotoxicity of the compounds and the proliferative capabilities of fibroblasts by scratch assay. Our results showed that waste extracts retain antioxidant and regenerative properties, inducing tissue re-establishment after environmental stress exposure. Taken together, our findings suggest that waste material could be used in the future also in combinations to stimulate wound healing processes and antioxidant responses in damaged skin.

Therapeutic Effect of a Traditional Chinese Medicine on the Treatment of Painful Leg Ulcer.

This study aimed to investigate the therapeutic effect of a traditional Chinese medicine on the treatment of painful leg ulcer. Twelve cases of painful leg ulcer were recruited and their characteristics (etiology, size, Visual Analog Scale score, and duration) were recorded. Then, an herbal medicine-oriented treatment protocol combining Zhi Tong Sheng Ji powder (ZTSJ) and SJXP (Sheng Ji Xiang Pi plaster) was applied to these patients. The results suggested that this therapeutic protocol contributed to pain relief and promoted wound healing simultaneously. Specifically, 2 days after applying ZTSJ on wounds, the intensity of pain reduced substantially, and the difference between pre- and post-treatment Visual Analog Scale scores (46 mm vs 23 mm, P < .001) was statistically significant. Epithelialization varied according to ulcer depth. If the wound was deep to the fascia, islands of epithelia did not form within wounds, but rather formed at the edge of wounds, generating island of epithelial cells (IECs) or newly formed epithelial tissue. If the wound was superficial and the dermis remained, scattered IECs appeared within ulcers and merged eventually. Furthermore, as wound pain decreased, IECs appeared, expanded, and merged, or epithelial proliferation and migration occurred in wound margin, eventually healing wounds. No infection spread, topical rashes, itching, or other allergies occurred in these 12 cases, and the time for recovery ranged from 16 to 163 days. ZTSJ is effective for the treatment of painful leg ulcers, but the specific mechanism is not clear.

Evaluation of the Effect of Topical Hypericum perforatum Oil on Excisional Palatal Wound Healing in Rabbits.

Aim: The aim of this study was to evaluate the effect of Hypericum perforatum (HP) oil on wound-healing process in rabbit palatal mucosa. Materials and Methods: Thirty-six New Zealand albino rabbits were randomly allocated to following groups; (1) HP oil (test, n = 18) and (2) olive oil (control, n = 18). Palatinal excisional wounds were created and the oils were topically applied (0.1 ml, 30 s, twice a day). Gingival biopsies were excised, and analyzed for re-epithelialization (RE) and granulation tissue maturation (GTM) on days 3, 7, and 14 after surgery. Levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) were assessed using the immunohistochemical method. Apoptotic cells (ACs) were evaluated using TUNEL staining. Enzyme-linked immunosorbent assay was used to assess tissue catalase (CAT) and malondialdehyde (MDA) levels. Results: RE and GTM were completed earlier in the HP oil group than in the control group. The number of positively stained cells/vessels was higher in olive oil than in the test group on day 3 for FGF-2 and on days 3 and 7 for VEGF (p < 0.05). In contrast, on day 14, a higher number of vessels was observed in the HP oil group than in the control group. HP oil treatment reduced the number of ACs compared to olive oil (p < 0.05), but the difference during the healing period did not reach significance. Tissue CAT and MDA levels between groups were not different, and also the results were the same when the levels were analyzed by the evaluated time periods (p > 0.05). Conclusions: The results of this study demonstrated that topical HP oil treatment did not provide an additional benefit to its base, olive oil, in the early phase of secondary wound healing.

Sorocea guilleminiana Gaudich.: Wound healing activity, action mechanisms, and chemical characterization of the leaf infusion.

ETHNOPHARMACOLOGICAL RELEVANCE: Sorocea guilleminina Gaudich. is a tree or shrub endemic to Brazil. Its leaves are used in Brazilian folk medicine for the healing of wounds, stomach problems, inflammation and as diuretic. The present study evaluates the activity and action mechanisms of the healing properties of the aqueous extract of S. guilleminiana leaves (AESg), in experimental models in vivo and in vitro, as well as performs a phytochemical analysis of the extract. MATERIALS AND METHODS: The AESg was prepared by infusion: Ten g of dry leaves powder in 1 L hot water, soaked for 15 min, filtered, lyophilized, and stored at -30 °C. Phytochemical analyses were realized by colorimetry and HPLC/ESI/MS. Its' in vitro cytotoxicity was evaluated on fibroblastic N3T3 cells. The potential of the wound healing activity in vivo was evaluated using excision and incision wound rat models, by histopathology of the injured skin along with the determination of nitric oxide, cytokines (IL-1ß, IL-10, and TNF-α), and antioxidant parameters (GSH, MPO and CAT). In vitro wound healing activity was also demonstrated in scratched N3T3 cells, by measuring the proliferation/migration rate. RESULTS: The phytochemical analysis of the AESg revealed a strong presence of polar compounds, especially flavonoids (4 majoritarian), as well as terpenes and/or sterols (2 majoritarian). The AESg showed no toxicity in the N3T3 cell line (IC50 > 800 µg/mL). Topical treatment with the AESg showed an increase (p < 0.05) in wound contraction with 2 mg/g cream on days 5 and 9 (43.56% and 6.70% increase, respectively), and with 50 mg/g on days 7 and 9 (10.88% and 7.91%, respectively), compared to the vehicle (non-ionic neutral cream). Topical application of AESg (2 or 50 mg/g non-ionic cream) in incised wounds caused an increase in the force necessary for the rupture of the wound when compared to the vehicle group. No changes in cytokines (IL-1ß, IL-10, or TNF-α) or NO accumulation was found with up to 50 mg/g AESg treatment. For antioxidant activity on the incision wound, an increase in GSH levels was denoted with the AESg use, at the lowest and highest dose (2 and 50 mg/g) by 75.86% and 61.20% respectively, when compared to the vehicle. Also, the CAT activity was accentuated by AESg at the highest dose (50 mg/g) by 85.87%. Finally, the AESg at all doses attenuated MPO activity significantly in the incision wound by 71.35%, 73.21%, 78.08%, respectively. In the scratch test on N3T3 cells, the treatment with AESg resulted also in an increase in fibroblast proliferation/migration rate, compared to the vehicle. CONCLUSION: AESg is not cytotoxic. The results confirm the popular use of the leaf infusion of S. guilleminiana for the treatment of cutaneous wounds, possibly by stimulating the proliferation of fibroblasts with a consequent deposition of collagen, fastening rearrangement of collagen fibers, and greater transformation into myofibroblasts, essential in the healing process. Preliminary chemical analyzes of AESg revealed the presence mainly of phenolic compounds, being salicylic acid, gallic acid, pinocembrin and isoquercitrin the majoritarian ones.

Activation of heme oxygenase-1 by Ginkgo biloba extract differentially modulates endothelial and smooth muscle-like progenitor cells for vascular repair.

Vascular progenitors such as endothelial progenitor cells (EPCs) and smooth muscle-like progenitor cells (SMPCs) may play different roles in vascular repair. Ginkgo biloba extract (GBE) is an exogenous activator of heme oxygenase (HO)-1, which has been suggested to improve vascular repair; however, the detailed mechanisms have yet to be elucidated. This study aimed to investigate whether GBE can modulate different vascular progenitor cells by activating HO-1 for vascular repair. A bone marrow transplantation mouse model was used to evaluate the in vivo effects of GBE treatment on wire-injury induced neointimal hyperplasia, which is representative of impaired vascular repair. On day 14 of GBE treatment, the mice were subjected to wire injury of the femoral artery to identify vascular reendothelialization. Compared to the mice without treatment, neointimal hyperplasia was reduced in the mice that received GBE treatment for 28 days in a dose-dependent manner. Furthermore, GBE treatment increased bone marrow-derived EPCs, accelerated endothelial recovery, and reduced the number of SMPCs attached to vascular injury sites. The effects of GBE treatment on neointimal hyperplasia could be abolished by co-treatment with zinc protoporphyrin IX, an HO-1 inhibitor, suggesting the in vivo role of HO-1. In this in vitro study, treatment with GBE activated human early and late EPCs and suppressed SMPC migration. These effects were abolished by HO-1 siRNA and an HO-1 inhibitor. Furthermore, GBE induced the expression of HO-1 by activating PI3K/Akt/eNOS signaling in human late EPCs and via p38 pathways in SMPCs, suggesting that GBE can induce HO-1 in vitro through different molecular mechanisms in different vascular progenitor cells. Accordingly, GBE could activate early and late EPCs, suppress the migration of SMPCs, and improve in vivo vascular repair after mechanical injury by activating HO-1, suggesting the potential role of pharmacological HO-1 activators, such as GBE, for vascular protection in atherosclerotic diseases.

Topical application of Cinnamomum hydroethanolic extract improves wound healing by enhancing re-epithelialization and keratin biosynthesis in streptozotocin-induced diabetic mice.

Context: Cinnamomum verum J. Presl. (Lauraceae) has a high number of polyphenols with insulin-like activity, increases glucose utilization in animal muscle, and might be beneficial for diabetic patients.Objective: This study evaluated the effectiveness of an ointment prepared from Cinnamomum verum hydroethanolic extract on wound healing in diabetic mice.Materials and methods: A total of 54 male BALB/c mice were divided into three groups: (1) diabetic non-treated group mice that were treated with soft yellow paraffin, (2 and 3) mice that were treated with 5 and 10% C. verum. Two circular full-thickness excisional wounds were created in each mouse, and the trial lasted for 16 d following induction of the wound. Further evaluation was made on the wound contraction ratio, histopathology parameters and mRNA levels of cyclin D1, insulin-like growth factor 1 (IGF-1), glucose transporter-1 (GLUT-1), total antioxidant capacity, and malondialdehyde of granulation tissue contents. HPLC apparatus was utilized to identify the compounds.Results: The HPLC data for cinnamon hydroethanolic extract identified cinnamaldehyde (11.26%) and 2-hydroxyl cinnamaldehyde (6.7%) as the major components. A significant increase was observed in wound contraction ratio, fibroblast proliferation, collagen deposition, re-epithelialization and keratin biosynthesis in the C. verum-treated groups in comparison to the diabetic non-treated group (p < 0.05). The expression level of cyclin D1, IGF1, GLUT 1 and antioxidant capacity increased in the C. verum-treated groups in comparison to the diabetic non-treated group (p < 0.05).Conclusions: Topical administration of C. verum accelerated wound healing and can possibly be employed in treating the wounds of diabetic patients.

A feasible biocompatible hydrogel film embedding Periplaneta americana extract for acute wound healing.

The wound healing effects of pharmaceutic preparations of Periplaneta americana, Kangfuxin liquid, have been widely utilized in clinics. However, its wound repair efficacy is limited due to short retention capability on cutaneous wound location. Herein, Periplaneta americana extract (PAE), which showed pro-fibrogenic and pro-angiogeneic effects, was embedded into hydrogel film (PAE/Film) by solution cast method by blending polyvinyl alcohol, hydroxypropyl chitosan and carbomer at the weight ratio of 78/6/3, with glycerol as plasticizer. PAE/Film exhibited smooth, flexible, and excellent swelling ability (WVTR of 2464 ±â€¯31.5 g/m2/day), characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry, meting the condition of ideal wound dressing. The superior wound healing capacity of PAE/Film was demonstrated that it significantly accelerated wound healing process in vivo in both full-thickness skin defect and scald wounded models. Compared to saline, blank vehicle (drug-free) and free PAE group, PAE/Film could accelerate wound healed, promote re-epithelialization and collagen deposition by means of TGF-ß/Smad signal pathway activation. Taken together, this novel hydrogel film-loading PAE would be a useful pharmaceutic candidate for acute cutaneous wound health care.

Characterization of burn wound healing gel prepared from human amniotic membrane and Aloe vera extract.

BACKGROUND: Skin burn wound is a notable medical burden worldwide. Rapid and effective treatment of burnt skin is vital to fasten wound closure and healing properly. Amniotic graft and Aloe vera are widely used as wound managing biomaterials. Sophisticated processing, high cost, availability, and the requirement of medics for transplantation limit the application of amnion grafts. We aim to prepare a novel gel from amnion combined with the Aloe vera extract for burn wound healing which overcome the limitations of graft. METHODS: Two percent human amniotic membrane (AM), Aloe vera (AV) and AM+AV gels were prepared. In vitro cytotoxicity, biocompatibility, cell attachment, proliferation, wound healing scratch assays were performed in presence of the distinct gels. After skin irritation study, second-degree burns were induced on dorsal region of Wistar rats; and gels were applied to observe the healing potential in vivo. Besides, macroscopical measurement of wound contraction and re-epithelialization; gel treated skin was histologically investigated by Hematoxylin and eosin (H&E) staining. Finally, quantitative assessment of angiogenesis, inflammation, and epithelialization was done. RESULTS: The gels were tested to be non-cytotoxic to nauplii and compatible with human blood and skin cells. Media containing 500 µg/mL AM+AV gel were observed to promote HaCaT and HFF1 cells attachment and proliferation. In vitro scratch assay demonstrated that AM+AV significantly accelerated wound closure through migration of HaCaT cells. No erythema and edema were observed in skin irritation experiments confirming the applicability of the gels. AV and AM+AV groups showed significantly accelerated wound closure through re-epithelialization and wound contraction with P < 0.01. Macroscopically, AM and AM+AV treated wound recovery rates were 87 and 90% respectively with P < 0.05. Histology analysis revealed significant epitheliazation and angiogenesis in AM+AV treated rats compared to control (P < 0.05). AM+AV treated wounds had thicker regenerated epidermis, increased number of blood vessels, and greater number of proliferating keratinocytes within the epidermis. CONCLUSION: We demonstrated that a gel consisting of a combination of amnion and Aloe vera extract has high efficacy as a burn wound healing product. Amniotic membrane combined with the carrier Aloe vera in gel format is easy to produce and to apply.

Topical administration of hydroethanolic extract of Lawsonia inermis (henna) accelerates excisional wound healing process by reducing tissue inflammation and amplifying glucose uptake.

Several studies have reported the beneficial effects of Lawsonia inermis on wound healing, but the mechanism of action is still unknown. This study aimed to investigate the effectiveness of a new ointment formulation of hydroethanolic extract leaves of L. inermis on wound healing by gene expression of glucose transporter-1 (Glut-1) and insulin-like growth factor I (Igf-1) in Wistar rats. The animals were topically treated with different doses of L. inermis. An experimentally induced circular excisional wound model of 314 mm2 surface area was surgically created. The percentage of wound contraction and histopathological changes was assessed at different time points following wound induction. The expression of Glut-1 and Igf-1 was evaluated by reverse-transcription PCR. Topical administration of L. inermis, dose dependently, shortened inflammatory phase, accelerated cellular proliferation, and enhanced wound contraction ratio. It also improved revascularization, collagen deposition, and re-epithelialization rate and promoted intracytoplasmic carbohydrate storage (P < 0.05). Moreover, the mRNA levels of Igf-1 and Glut-1 were significantly higher in the L. inermis-treated groups than the control group (P < 0.05). Topical administration of L. inermis promoted the healing process by reducing tissue inflammation and increasing glucose uptake, which was mediated by up-regulating the expression of Igf-1 and Glut-1.

Porous Se@SiO2 nanosphere-coated catheter accelerates prostatic urethra wound healing by modulating macrophage polarization through reactive oxygen species-NF-κB pathway inhibition.

Benign prostatic hyperplasia (BPH) patients experience complications after surgery. We studied oxidative stress scavenging by porous Se@SiO2 nanospheres in prostatic urethra wound healing after transurethral resection of the prostate (TURP). Beagle dogs were randomly distributed into two groups after establishing TURP models. Wound recovery and oxidative stress levels were evaluated. Re-epithelialization and the macrophage distribution at the wound site were assessed by histology. The mechanism by which porous Se@SiO2 nanospheres regulated macrophage polarization was investigated by qRT-PCR, western blotting, flow cytometry, immunofluorescence and dual luciferase reporter gene assays. Our results demonstrated that Porous Se@SiO2 nanosphere-coated catheters advance re-epithelization of the prostatic urethra, accelerating wound healing in beagle dogs after TURP, and improve the antioxidant capacity to inhibit oxidative stress and induced an M2 phenotype transition of macrophages at the wound. By restraining the function of reactive oxygen species (ROS), porous Se@SiO2 nanospheres downregulated Ikk, IκB and p65 phosphorylation to block the downstream NF-κB pathway in macrophages in vitro. Since activation of NF-κB signaling cascades drives macrophage polarization, porous Se@SiO2 nanospheres promoted macrophage phenotype conversion from M1 to M2. Our findings suggest that porous Se@SiO2 nanosphere-coated catheters promote postoperative wound recovery in the prostatic urethra by promoting macrophage polarization toward the M2 phenotype through suppression of the ROS-NF-κB pathway, attenuating the inflammatory response. STATEMENT OF SIGNIFICANCE: The inability to effectively control post-operative inflammatory responses after surgical treatment of benign prostatic hyperplasia (BPH) remains a challenge to researchers and surgeons, as it can lead to indirect cell death and ultimately delay wound healing. Macrophages at the wound site work as pivotal regulators of local inflammatory response. Here, we designed and produced a new type of catheter with a coating of porous Se@SiO2 nanosphere and demonstrated its role in promoting prostatic urethra wound repair by shifting macrophage polarization toward the anti-inflammatory M2 phenotype via suppressing ROS-NF-κB pathway. These results indicate that the use of porous Se@SiO2 nanosphere-coated catheter may provide a therapeutic strategy for postoperative complications during prostatic urethra wound healing to improve patient quality of life.