Traumatic oral ulcers are one of the most commonly encountered oral ulcers. Their healing may be delayed due to factors like the presence of opportunistic infectious microbes in the oral cavity, secondary trauma from sharp edges of teeth, and the systemic condition of the patient.
OBJECTIVE: To compare the efficacy of a newly developed neem extract containing herbal ointments (propolis and Hemidesmus indicus) in enhancing the wound contraction of traumatic oral ulcers and to determine the relationship between oxidative stress and oral ulcers.
METHODS: Ulcers were inflicted by trauma in the mouths of experimental rabbits using a 5 mm punch biopsy device. Forty-eight animals were randomly put into six groups (n = 12). Group 1 was the control group that did not receive any intervention; Group 2 had a systemic treatment of Hemidesmus indicus extract; Group 3 received a topical application of propolis; Group 4 had a topical application of a neem extract-based herbal ointment; Group 5 was administered a combination of Hemidesmus indicus and propolis; and Group 6 had a combination of a neem-based herbal ointment and Hemidesmus indicus. Oxidative stress levels were calculated by measuring superoxide dismutases and malondialdehyde levels in the blood on days 0, one, seven, and 14. Wound contraction scores of ulcers were also assessed on days seven and 14.
RESULTS: Significantly higher wound contraction scores were seen in groups treated with herbal ointment in comparison to groups treated without herbal ointment. Oxidative stress levels increased in all groups after the infliction of ulcers (day one) and then declined as the ulcers healed, reaching near-normal levels on day 14. Groups containing Hemidesmus indicus showed a significant reduction in oxidative stress in comparison to groups without Hemidesmus indicus. A p-value of <0.05 was considered significant.
CONCLUSIONS: A combined formulation of herbal ointment and Hemidesmus indicus proved to be the most efficacious in enhancing wound contraction of oral ulcers along with significantly reducing oxidative stress in experimental rabbits.

UNASSIGNED: Diabetes mellitus is among the disrupting factors of orchestrated events in wound healing. This necessitates the urge for tailored medications, which are continually offered by nano-sized materials. Herein, we present greenly synthesized copper oxide nanoparticles (CuO NPs), obtained from either Punica granatum L. (PG) or Pisidium guajava L. (GV) extract, to function as potent bactericidal and fungicidal materials that promote regeneration and healing of the targeted diabetic wounded tissues.
UNASSIGNED: PG or GV plant extracts were compared as source of reducing agents for CuO NPs synthesis process. The yield and photocatalytic degradation potential were compared. NPs obtained from the superior extract, PG, were characterized using particles size, zeta potential, XRD, TEM, SEM, and EDX. The antimicrobial effects were evaluated on multidrug-resistant human pathogens and then the percentage biofilm inhibitory concentration was determined. The cytotoxicity and wound scratch study were conducted on a normal human skin cell line. In-vivo wound healing activity in diabetic rats was assessed along with histopathological and immunohistochemical examination of CD45 and α-SMA.
UNASSIGNED: The greenly synthesized CuO NPs are spherical in shape having a diameter of 233nm. CuO NPs (250µg/mL) acted as promising biocontrol agent against a variety of multidrug-resistant human pathogens. They significantly exhibited 29.460±0.811% healing of the scratched wound compared to only 2.001±0.155% for the control. Wound healing experiments revealed the safety of a low CuO NPs concentration in a diabetic animal model as well as on human normal skin fibroblast cell line. The treated group with a dose of 2mg/cm2 showed superior results with a WC50 value of 7.2 days, and 92% wound contraction after 13-days. Immunohistochemical investigation of the same group demonstrated well-established fibrous tissue (5.7±3.7/HPF), and an amplified granulation tissue of recently developed blood vessels (70±1.5/HPF).
UNASSIGNED: Green synthesized CuO NPs could overcome drug resistance and promote wound healing process effectively.

Wound care management aims at stimulating and improving healing process without scar formation. Although various plants have been reported to possess wound healing properties in tribal and folklore medicines, there is a lack of scientific data to validate the claim. In this aspect, it becomes inevitable to prove the efficacy of naturally derived products at pharmacological levels. Couroupita guianensis as a whole plant has been reported to exhibit wound healing activity. The leaves and fruit of this plant have been utilized in folkloric medicine to cure skin diseases and infections for many years. However, to the best of our knowledge, no scientific studies have been conducted to verify the wound healing properties of C. guianensis fruit pulp. Therefore, the present study seeks to investigate the wound healing potential of C. guianensis fruit pulp using an excision wound model in Wistar albino male rats. This study indicated that the ointment prepared from crude ethanolic extract of C. guianensis fruit pulp facilitated wound contraction that were evidenced by a greater reduction in the wound area and epithelialization period and increased hydroxyproline content. The experimental groups treated with low and mid dose of C. guianensis ethanol extract (CGEE) ointments had shown a wound closure of 80.27% and 89.11% respectively within 15 days, which is comparable to the standard betadine ointment which showed 91.44% healing in the treated groups. Further, the extract influenced the expression of genes VEGF and TGF-β on post wounding days that clearly explained the strong correlation between these genes and wound healing in the experimental rats. The animals treated with 10% CGEE ointment showed a significant upregulation of both VEGF and TGF-β as compared with other test and standard groups. These findings provide credence to the conventional application of this plant in the healing of wounds and other dermatological conditions, and may represent a therapeutic strategy for the treatment of wounds.

Tissue formation and healing both require cell proliferation and migration, but also extracellular matrix production and tensioning. In addition to restricting proliferation of damaged cells, increasing evidence suggests that cellular senescence also has distinct modulatory effects during wound healing and fibrosis. Yet, a direct role of senescent cells during tissue formation beyond paracrine signaling remains unknown. We here report how individual modules of the senescence program differentially influence cell mechanics and ECM expression with relevance for tissue formation. We compared DNA damage-mediated and DNA damage-independent senescence which was achieved through over-expression of either p16Ink4a or p21Cip1 cyclin-dependent kinase inhibitors in primary human skin fibroblasts. Cellular senescence modulated focal adhesion size and composition. All senescent cells exhibited increased single cell forces which led to an increase in tissue stiffness and contraction in an in vitro 3D tissue formation model selectively for p16 and p21-overexpressing cells. The mechanical component was complemented by an altered expression profile of ECM-related genes including collagens, lysyl oxidases, and MMPs. We found that particularly the lack of collagen and lysyl oxidase expression in the case of DNA damage-mediated senescence foiled their intrinsic mechanical potential. These observations highlight the active mechanical role of cellular senescence during tissue formation as well as the need to synthesize a functional ECM network capable of transferring and storing cellular forces.

UNASSIGNED: Leaves of Urtica simensis (U. simensis) have been used traditionally for wound healing in different communities in Ethiopia. In spite of this, there were no scientific data documented regarding the wound healing activity of this plant. There is a need to investigate herbal remedies for the treatment of wounds in order to overcome the limitations of conventional drugs.
UNASSIGNED: Aim of the study was to evaluate the wound healing activity of extract and solvent fractions of the leaves of U. simensis in mice.
UNASSIGNED: Leaves of U. simensis were washed, dried under shade and ground into coarse powder and then extracted by 80% methanol with three consecutive macerations. Part of the extract was fractionated with n-hexane, chloroform and water. In excision and burn wounds, healing progress was measured by wound contraction, epithelialization period and histopathology investigation whereas incision wound healing was assessed by skin breaking strength.
UNASSIGNED: In excision wound model, the 5% and 10% crude extract ointments showed significant (p < 0.001) wound contractions during day 8 to day 16 evaluations. Similarly, in burn wound model, both 5% and 10% crude extract ointments produced significant (p < 0.001) wound contractions starting from day 12 and 10, respectively. In both models, the periods of epithelialization were also significantly reduced and favorable histopathologic changes were produced by the crude extract ointments. The solvent fractions of the crude extract as well produced significant wound contractions as evaluated in excision wound model. The fractions also significantly reduced the period of epithelialization in this model. The aqueous fraction found to be more active than either chloroform or n-hexane fraction in wound healing.
UNASSIGNED: Results of this study indicated that methanol extract and aqueous fractions of the leaves of U. simensis possess dose-dependent wound healing activity, thus supporting traditional claims.

BACKGROUND: Bergenia ciliata (Haw.) Sternb. is a plant growing in the Himalayan region of India where locals use its rhizomes for a variety of disease conditions including wounds and fractures. Although some of its pharmacological benefits have been documented, scientific validation of its wound healing property has not been done so far.
OBJECTIVE: To ensure use of this natural remedy as an alternative therapy to the faster wound healing, this study evaluated the wound healing activity of the ethanolic extract of Bergenia ciliata rhizome using excision wound model in Wistar rats.
METHODS: Four groups (n = 10) of rats were subjected to different topical wound regimens for 14 days. Simple paraffin-lanolin ointment was applied to the control group rats. One group was applied povidone-iodine 10% (w/w) ointment. The other two groups were treated with ointment of ethanolic extract of Bergenia ciliata at 5 or 10% (w/w) rhizome, respectively. Blood and wound tissue samples were collected on 7th and 14th day of treatment and were correspondingly subjected to histopathology, and the assays of L-hydroxyproline, D-glucosamine, antioxidants and pro-inflammatory cytokines.
RESULTS: Wound histology revealed increased collagenation, re-epithelialization and neovascularization while decreased bacterial colonies in the treatment groups. These histological changes and wound contraction were better in the 10% Bergenia ciliata group. Tissue L-hydroxyproline levels, blood enzymatic and non-enzymatic antioxidants were increased in the treatment groups. On 7th day of treatment glucosamine levels increased in the treatment groups, while as a reverse trend was observed on day 14. Plasma levels of TNF-α and IL-6 decreased in the treatment groups.
CONCLUSIONS: The results indicate that treatment with Bergenia ciliata extract ointment provides satisfactory wound healing which is comparable to that of the standard wound healing ointment, povidone-iodine and is surpassing simple lanolin-paraffin ointment. The improved wound healing, especially in the 10% Bergenia ciliata groups, can be attributed to satisfactory profile of the above studied parameters in these treatment groups which is also construed by the phytochemical analysis of its extract revealing the presence of antioxidant and anti-inflammatory compounds gallic acid, catechin, quercetin and rutin as the major active components.

To deal with permanent deformations and residual stresses, we consider a morphoelastic model for the scar formation as the result of wound healing after a skin trauma. Next to the mechanical components such as strain and displacements, the model accounts for biological constituents such as the concentration of signaling molecules, the cellular densities of fibroblasts and myofibroblasts, and the density of collagen. Here we present stability constraints for the one-dimensional counterpart of this morphoelastic model, for both the continuous and (semi-) discrete problem. We show that the truncation error between these eigenvalues associated with the continuous and semi-discrete problem is of order [Formula: see text]. Next we perform numerical validation to these constraints and provide a biological interpretation of the (in)stability. For the mechanical part of the model, the results show the components reach equilibria in a (non) monotonic way, depending on the value of the viscosity. The results show that the parameters of the chemical part of the model need to meet the stability constraint, depending on the decay rate of the signaling molecules, to avoid unrealistic results.

We consider a one-dimensional morphoelastic model describing post-burn scar contraction. Contraction can lead to a limited range of motion (contracture). Reported prevalence of burn scar contractures are 58.6% at 3-6 weeks and 20.9% at 12 months post-reconstructive surgery after burns. This model describes the displacement of the dermal layer of the skin and the development of the effective Eulerian strain in the tissue. Besides these components, the model also contains components that play a major role in the skin repair after trauma. These components are signaling molecules, fibroblasts, myofibroblasts, and collagen. We perform a sensitivity analysis for many parameters of the model and use the results for a feasibility study. In this study, we test whether the model is suitable for predicting the extent of contraction in different age groups. To this end, we conduct an extensive literature review to find parameter values. From the sensitivity analysis, we conclude that the most sensitive parameters are the equilibrium collagen concentration in the dermal layer, the apoptosis rate of fibroblasts and myofibroblasts, and the secretion rate of signaling molecules. Further, although we can use the model to simulate significant distinct contraction densities in different age groups, our results differ from what is seen in the clinic. This particularly concerns children and elderly patients. In children we see more intense contractures if the burn injury occurs near a joint, because the growth induces extra forces on the tissue. Elderly patients seem to suffer less from contractures, possibly because of excess skin.

A major impediment preventing normal wound healing is insufficient vascularization, which causes hypoxia, poor metabolic support, and dysregulated physiological responses to injury. To combat this, the delivery of angiogenic factors, such as vascular endothelial growth factor (VEGF), has been shown to provide modest improvement in wound healing. Here, the importance of specialty delivery systems is explored in controlling wound bed drug distribution and consequently improving healing rate and quality. Two intradermal drug delivery systems, miniaturized needle arrays (MNAs) and liquid jet injectors (LJIs), are evaluated to compare effective VEGF delivery into the wound bed. The administered drug\'s penetration depth and distribution in tissue are significantly different between the two technologies. These systems\' capability for efficient drug delivery is first confirmed in vitro and then assessed in vivo. While topical administration of VEGF shows limited effectiveness, intradermal delivery of VEGF in a diabetic murine model accelerates wound healing. To evaluate the translational feasibility of the strategy, the benefits of VEGF delivery using MNAs are assessed in a porcine model. The results demonstrate enhanced angiogenesis, reduced wound contraction, and increased regeneration. These findings show the importance of both therapeutics and delivery strategy in wound healing.

UNASSIGNED: Natural topical products have been used to enhance wound healing, especially in immunocompromised animals. The aims of this study were to evaluate and to compare the effects of moist exposed burn ointment (MEBO) and honey on the healing of full-thickness skin wounds in immunocompromised dogs.
UNASSIGNED: The study was conducted using 12 adults, apparently healthy mongrel dogs. Immunosuppression was induced in six dogs by oral administration of prednisone (2 mg/kg) and azathioprine (2 mg/kg), once a day for 21 days. On each dog, a total of 9, 1.5 cm in diameter full-thickness skin circular wounds were created aseptically in the thoracolumbar area under general anesthesia using customized skin punch biopsy kit. In a random fashion, three wounds in each dog were treatment using MEBO (contains b-sitosterol, baicalin, and berberine as active ingredients in a base of beeswax and sesame oil), honey or no treatment (control), once per day for 21 days. Wounds were grossly evaluated once a day for signs of inflammation or infection. In addition, biopsy specimens and digital imaging data of each wound were obtained on days 7, 14, and 21 for histopathological evaluation of the healing process.
UNASSIGNED: Wounds in immunocompromised dogs appeared to heal significantly in a slower fashion than in non-immunocompromised counterparts. Digital analysis data showed that MEBO-treated wounds expressed better epithelialization area, faster contraction, and smaller wound area percentage when compared with honey-treated wounds. Histopathological analysis showed significantly higher angiogenesis scores in MEBO-treated wounds when compared with other treatments.
UNASSIGNED: Results of this study showed that MEBO resulted in significant enhancement of wound healing in both healthy and immunocompromised dogs. However, when compared to honey, the wound healing effect of MEBO was superior to that of honey.