Development and characterization of contraction-suppressed full-thickness skin wound model in rabbits.

The wound healing process in rodents (rats and mice) and lagomorphs (rabbits) predominantly relies on wound contraction rather than re-epithelialization and granulation tissue formation. As a result, existing laboratory animal models for wound healing often fail to mimic human wound healing mechanisms accurately. This study introduces a standardized rabbit model with superior translational potential for skin wound healing research. Two full-thickness dermal wounds were created on the posterior dorsal surface of each rabbit using a standard 2 ×2 cm² template. One of these wounds was randomly selected to be treated as a contraction-suppressed wound by applying a transparent adhesive elastic bandage. At the same time, the other was retained as a standard full-thickness wound. Wound contraction was measured on 7, 14, 21, 28, and 35 days. Histomorphological evaluation was done on day 35 to evaluate the quality of wound healing. The findings indicate that transparent adhesive elastic bandage prolonged the wound healing time and suppressed wound contraction in rabbits. In addition, the healed contraction-suppressed full-thickness wounds had denser and thicker collagen fibers than the healed standard full-thickness wounds, indicating better collagen fiber deposition. Our model achieved a 100 % success rate in maintaining the transparent adhesive elastic bandage in the rabbits. Therefore, we have developed a simple, non-invasive, cost-effective method for preventing wound contraction. Further studies are required to establish the utility of this model for studying wound healing mechanisms and evaluating therapeutic interventions.

Pluronic F127 composite hydrogel for the repair of contraction suppressed full-thickness skin wounds in a rabbit model.

Hydrogels are commonly used as carriers for cell delivery due to their similarities to the extracellular matrix. A contraction-suppressed full-thickness wound model was used to evaluate the therapeutic potential of Pluronic F127 (PF127) hydrogel loaded with adipose-derived stromal vascular fraction (AdSVF), mesenchymal stem cells (AdMSC), and conditioned media (AdMSC-CM) for the repair of wounds in a rabbit model. The experimental study was conducted on forty-eight healthy adult New Zealand white rabbits randomly divided into eight groups with six animals each and treated with AdSVF, AdMSC, and AdMSC-CM as an injectable or topical preparation. The healing potential of different adipose-derived cell-based and cell-free therapeutics was evaluated based on percentage wound healing, period of epithelialization, epidermal thickness, scar evaluation, histopathology analysis, histochemical evaluation, immunohistochemistry (collagen type I), and hydroxyproline assay by comparing with the positive and negative control. Collagen density analysis using different staining methods, immunohistochemistry, and hydroxyproline assay consistently showed that delivering AdMSC and AdMSC-CM in PF127 hydrogel enhanced epithelialization, collagen production, and organization, contributing to improved tissue strength and quality. Even though allogeneic AdSVF was found to promote wound healing in rabbits, it has a lower potential than AdMSC and AdMSC-CM. The wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. Even though wounds treated with AdMSC outperformed AdMSC-CM, a significant difference in the healing quality was not observed in most instances, indicating almost similar therapeutic potential. The findings indicate that the wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. These treatments promoted collagen production, tissue organization, and epidermal regeneration, ultimately improving overall healing outcomes.

Lab on chip based self-adjustable liposomes for rapid wound healing: An in depth in vitro, in vivo and higher dose toxicity investigation.

Thanks to microfluidic technology, different nano-delivery systems are becoming clinically viable. Using a novel and rapid microfluidic hydrodynamic focusing (MHF) method (lipids on chip) we developed self-adaptable liposomes (SLs) containing cefpodoxime proxetil (CP) for the treatment of skin infections caused by Staphylococcus aureus. SLs were optimized using different flow rate ratios in the MHF method and the final formulation CPT3 was found to be the best in terms of particle size (68.27 ± 01.15 nm), % entrapment efficiency (% EE: 82 ± 1.5), polydispersity (PDI: 0.2 ± 0.012), and degree of deformability (DOD: 4.7 ± 0.18 nm). Rats (Sprague Dawley) treated with a self-adaptable CPT3 liposomal formulation recuperate skin injury, exhibited reduced bacterial counts (<106 CFU/mL) in the wounded region, and completely restored (100 %) on day 21. Rat survival, in vivo dermal pharmacokinetics and ex vivo-in vivo relationship were also investigated. Rats treated with an even 10-fold higher dose (100 mg/kg/day) of CP using an equivalent CPT3 formulation did not show any symptoms of toxicity as revealed by hematological, biochemical, and internal organ assessment observations. Finally, the developed CPT3 formulation with special interest in patients with high-risk skin injuries not only delivered CP in a controlled manner but was also clinically effective and safe as it did not produce any serious adverse events even at 10× higher doses in the infected rats.

Evaluation of the Efficacy of a Neem Extract-Based Herbal Ointment, Herbal Antioxidant, and Propolis on Oxidative Stress Related to Oral Ulcers: An Interventional Animal Study.

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. AIM: 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. METHOD: 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. CONCLUSION: 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.

Preliminary Evaluation of Wound Healing Potential of Leonurus japonicus Houtt. Extracts.

Leonurus japonicus Houtt. is a medicinal plant popular in Brazil as "rubim", used in local folk medicine for several applications as an anti-inflammatory, antioxidant, analgesic, and antimicrobial phytomedicine. The traditional use for wound healing is related; however, few studies have evaluated the wound healing activity. Thus, this study aimed to analyse the popular indication of the hydroalcoholic and aqueous extracts of L. japonicus aerial parts in a rat wound healing model. The initial chemical characterization was performed using flavonoid quantification and complemented with mass spectroscopy/chemometrics analysis. The wound's lesion contraction and tissue regeneration (histological study stained with hematoxylin-eosin and picrosirius) were determined. Hydroalcoholic and aqueous extracts presented high flavonoid content, and mass spectrometry analysis of the extracts demonstrated the presence of compounds with a mass between 100-650, reinforcing the presence of polyphenolic constituents. The extracts of L. japonicus improve various wound healing phases, like inflammatory modulation, wound contraction, and collagen synthesis, resulting in faster healing in rats. These effects could be related to the extracts' polyphenolic compounds.

Mikania micrantha extract enhances cutaneous wound healing activity through the activation of FAK/Akt/mTOR cell signaling pathway.

Mikania micrantha (MM) has been traditionally used for various health benefits, including mental health, anti-inflammatory, wound dressing, and healing of sores. However, the molecular mechanisms and dose required for the wound healing activity of MM have yet to be reported. Therefore, a study was conducted to evaluate the wound healing potential of a cold methanolic extract of MM through in vitro and in vivo studies. Human dermal fibroblast adult (HDFa) cells were treated with 0 (control), 75 ng/ml, 125 ng/ml, 250 ng/ml, and 500 ng/ml of MMmethanolic extract (MME) for 24 h. MME at 75 ng/ml has significantly (p˂0.05) promoted HDFa cell proliferation and migration. Further, MME has also been shown to enhance the invasiveness of human umbilical vascular endothelial cells (HUVECs), indicating the neovasculature for wound healing. The tube formation assay demonstrated a significant (p<0.05) increase in the angiogenic effect of the MME starting at a concentration of 75 ng/ml as compared to the control. Treatment of excision wounds in Wistar rats with 5% and 10% MME ointment significantly enhanced wound contraction compared to control animals. Incision wounds in rats treated with 5% and 10% MME showed a significant (p<0.01) increase in tensile strength compared to control. HDFa cells, and granulation tissue collected on day 14 post-wounding, revealed the modulation of the FAK/Akt/mTOR cell signaling pathway during the enhancement of wound healing. The results of gel zymography showed increased activity of MMP-2 and MMP-9 in the HDFa cells after treatment with the extract.  It is concluded that MMEcan potentially accelerate cutaneous wound healing.

Diabetic wound healing potential of silk sericin protein based hydrogels enriched with plant extracts.

The complications associated with diabetic wounds make their healing process prolonged. Hydrogels could be ideal wound dressings therefore present research was conducted to prepare silk sericin (an adhesive protein polymer) based hydrogels in combination with plant extracts and to evaluate its effectiveness against wound healing process in mice with alloxan induced diabetes. Excision wounds were formed via a biopsy puncture (6 mm). Experimental hydrogels were prepared and applied topically on the diabetic wounds. All the hydrogel treatment groups showed significantly higher (P < 0.001) percent wound contraction from day 3 to day 11 as compared to the negative diabetic control group. The serum level of anti-inflammatory cytokine (Interleukin-10) and tissue inhibitor metalloproteinase (TIMP) was significantly higher (P < 0.001), while the level of pro-inflammatory cytokines (tumor necrosis factor-α, Interleukin-6) and matrix metalloproteinases (MMP-2, MMP-9) was significantly lower (P < 0.001) in hydrogels treatment groups as compared to diabetic control group. Although all the hydrogels showed effective results, however the best results were shown by 4 % sericin+4 % banyan+4 % onion based hydrogel. It can be concluded that Sericin based hydrogel enriched with banyan and onion extracts can be used as an effective remedy for the treatment of diabetic wounds due to their high healing and regenerative properties.

Concurrent Tissue Engineering for Wound Healing in Diabetic Rats Utilizing Dual Actions of Green Synthesized CuO NPs Prepared from Two Plants Grown in Egypt.

Purpose: 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. Methods: 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. Results: 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). Conclusion: Green synthesized CuO NPs could overcome drug resistance and promote wound healing process effectively.

Topical delivery of mupirocin calcium nanostructured lipid carriers using a full-thickness excision wound healing model.

OBJECTIVE: Treatment of contaminated wounds represents a significant challenge in healthcare and there is a need to develop approaches maximising skin retention to maintain therapeutic concentrations of anti-infectives at the wound site. The objective of the present study was to develop and evaluate mupirocin calcium nanolipid emulgels to enhance wound healing performance and patient acceptability. METHODS: Nanostructured lipid carriers (NLCs) of mupirocin calcium were prepared by the phase inversion temperature method using Precirol ATO 5 (Gattefosse, India) and oleic acid as lipids and Kolliphor RH 40 (BASF, India) as surfactant and further incorporated into a gel base for topical delivery. RESULTS: The particle size, polydispersity index and zeta potential of mupirocin NLCs were found to be 128.8±1.25nm, 0.283±0.003 and -24.2±0.56mV, respectively. In vitro release studies from developed emulgel showed sustained drug release over 24 hours. Ex vivo drug permeation studies through excised rat abdominal skin showed better skin permeation (1712.38±15. 57µg/cm2) from developed emulgel compared to marketed ointment (827.92±21.42µg/cm2) after 8 hours, which was in agreement with in vitro antibacterial activity. Studies on Wistar rats indicated the nonirritant potential of developed emulgels. Further, mupirocin emulgels showed improved efficacy in percent wound contraction of acute contaminated open wounds in Wistar rats using a full-thickness excision wound healing model. CONCLUSION: The emulgels of mupirocin calcium NLCs appear to be effective in the treatment of contaminated wounds due to increased skin deposition and sustained release, thereby enhancing the wound healing potential of existing molecules.

Wound Healing Potential of Couroupita guianensis Aubl. Fruit Pulp Investigated on Excision Wound Model.

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-ß 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-ß 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.

Stability of a two-dimensional biomorphoelastic model for post-burn contraction.

We consider the stability analysis of a two-dimensional model for post-burn contraction. The model is based on morphoelasticity for permanent deformations and combined with a chemical-biological model that incorporates cellular densities, collagen density, and the concentration of chemoattractants. We formulate stability conditions depending on the decay rate of signaling molecules for both the continuous partial differential equations-based problem and the (semi-)discrete representation. We analyze the difference and convergence between the resulting spatial eigenvalues from the continuous and semi-discrete problems.

Wound contraction rate in excised and unexcised burn wounds with laser photobiomodulation: Systematic review and meta-analysis of preclinical studies.

INTRODUCTION: Laser photobiomodulation (laser PBM) is an effective means of accelerating burn wound contraction, however it is still unclear whether laser PBM produces greater benefit when applied directly to excised and unexcised burn wounds . The aim of this systematic review of preclinical studies was to determine the effectiveness of laser PBM in the wound contraction rate in excised and unexcised burn wounds. MATERIALS AND METHODS: A systematic search was conducted in the EMBASE, MEDLINE and LILACS databases. Preclinical studies were included that analysed the effectiveness of laser PBM in burn wound contraction, and assessed wound closure. The SYRCLE risk of bias tool was used. Random effects models were used to estimate the pooled effect. RESULTS: Thirteen studies were included in the qualitative analysis and six in the quantitative analysis. Two weeks after the lesion, laser PBM favoured the wound contraction percentage, increasing the closure rate in excised burn wounds (SMD= 1.34, CI 95% 0.41 to 2.27, 0.41-2.27, I2=0%, =0%, low certainty of evidence. In unexcised burns, it was uncertain whether laser PBM increased or diminished the wound contraction rate (SMD=1.22(SMD=1.22 CI 95% -0.05 to 2.49, I2=68%; =68%; very low certainty of evidence). CONCLUSIONS: In the animal model, laser PBM is effective in increasing the wound contraction rate in excised burns. However, due to the low certainty of the evidence, uncertainty remains about the true magnitude of the effect of laser on wound contraction in animals; our results should therefore be interpreted with caution.

Modernization of a Traditional Siddha Medicine Paccai eruvai into a Novel Nanogel Formulation for the Potent Wound Healing Activity-A Phyto- Pharmaceutical Approach.

BACKGROUND: Paccai eruvai formulation has been widely used in traditional Siddha practice to treat ulcerous wounds due to the content of potentially active compounds. OBJECTIVE: The present study aimed to determine the enhancement potency of wound healing of nanogels containing Paccai eruvai in an incision and excision wound models. METHODS: Paccai eruvai nanogel was synthesized using the high-energy milling method, and characterization and enhancement of the wound healing potential of Paccai eruvai nanogel were assessed. RESULTS: Reportedly, Paccai eruvai nanogel has been produced successfully and its chemical properties confirmed, and physical properties characterized. Paccai eruvai nanogel showed homogeneity, green color, transparency, and an average size of 19.73 nm. We observed a significant reduction of wound area (p<0.001) in the Paccai eruvai nanogel-treated rats. The percentage of wound contraction on the 16th day was higher than the traditional formulation and nitrofurazone treatment. Notably, a lesser epithelialization period (14.33 days) and higher hydroxyproline content were observed in the 10% Paccai eruvai nanogel rats. We found that 10 % Paccai eruvai nanogel treatment increased tensile strength suggesting a better therapeutic indication. CONCLUSION: The present findings indicate that Paccai eruvai nanogel significantly contributes wound healing activities with the enhancement of collagen synthesis, wound contraction, and wound tensile strength.

Dissecting the influence of cellular senescence on cell mechanics and extracellular matrix formation in vitro.

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.

Sensitivity of a two-dimensional biomorphoelastic model for post-burn contraction.

We consider a two-dimensional biomorphoelastic model describing post-burn scar contraction. This model describes skin displacement and the development of the effective Eulerian strain in the tissue. Besides these mechanical components, signaling molecules, fibroblasts, myofibroblasts, and collagen also play a significant role in the model. We perform a sensitivity analysis for the independent parameters of the model and focus on the effects on features of the relative surface area and the total strain energy density. We conclude that the most sensitive parameters are the Poisson's ratio, the equilibrium collagen concentration, the contraction inhibitor constant, and the myofibroblast apoptosis rate. Next to these insights, we perform a sensitivity analysis where the proliferation rates of fibroblasts and myofibroblasts are not the same. The impact of this model adaptation is significant.

Schinus terebinthifolius Leaf Lectin (SteLL) Reduces the Bacterial and Inflammatory Burden of Wounds Infected by Staphylococcus aureus Promoting Skin Repair.

Staphylococcus aureus is commonly found in wound infections where this pathogen impairs skin repair. The lectin isolated from leaves of Schinus terebinthifolius (named SteLL) has antimicrobial and antivirulence action against S. aureus. This study evaluated the effects of topical administration of SteLL on mice wounds infected by S. aureus. Seventy-two C57/BL6 mice (6−8 weeks old) were allocated into four groups: (i) uninfected wounds; (ii) infected wounds, (iii) infected wounds treated with 32 µg/mL SteLL solution; (iv) infected wounds treated with 64 µg/mL SteLL solution. The excisional wounds (64 mm2) were induced on the dorsum and infected by S. aureus 432170 (4.0 × 106 CFU/wound). The daily treatment started 1-day post-infection (dpi). The topical application of both SteLL concentrations significantly accelerated the healing of S. aureus-infected wounds until the 7th dpi, when compared to untreated infected lesions (reductions of 1.95−4.55-fold and 1.79−2.90-fold for SteLL at 32 µg/mL and 64 µg/mL, respectively). The SteLL-based treatment also amended the severity of wound infection and reduced the bacterial load (12-fold to 72-fold for 32 µg/mL, and 14-fold to 282-fold for 64 µg/mL). SteLL-treated wounds show higher collagen deposition and restoration of skin structure than other groups. The bacterial load and the levels of inflammatory markers (IL-6, MCP-1, TNF-α, and VEGF) were also reduced by both SteLL concentrations. These results corroborate the reported anti-infective properties of SteLL, making this lectin a lead candidate for developing alternative agents for the treatment of S. aureus-infected skin lesions.

Determination of the effectiveness of Dorema ammoniacum gum on wound healing: an experimental study.

OBJECTIVE: For a long time, natural compounds have been used to accelerate wound healing. In this study, the topical effects of ammoniacum gum extract on wound healing were investigated in white male rats. METHOD: Following skin wound induction in aseptic conditions, 48 Wistar rats were divided into six equal groups; phenytoin cream 1% (standard), untreated (control), Eucerin (control), and 5%, 10% and 20% ointments of Dorema ammoniacum gum extract (treatment groups). All experimental groups received topical drugs daily for 14 days. The percentage of wound healing, hydroxyproline content, histological parameters, and growth factors (endothelial growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-α) were measured in experimental groups. RESULTS: The areas of the wounds in the treatment groups were significantly decreased compared with the wound areas of control groups at 5, 7 and 10 days after wounding. On the 12th day, the wounds in the treatment groups were completely healed. Hydroxyproline contents were significantly increased in the treatment groups compared with the control groups (p<0.001). In histological evaluation, the re-epithelialisation, increasing thickness of the epithelial layer, granulation tissue and neovascularisation parameters in the treatment groups showed significant increases compared with the control groups. Also, serum levels of TGF-ß, PDGF, EGF and VEGF in the treatment groups were significantly increased compared to the control groups. CONCLUSION: The topical application of ammoniacum gum extract significantly increases the percentage of wound healing in rats and reduces the time of wound closure.

Healing Potential of Propolis Extract-Passiflora edulis Seed Oil Emulgel Against Excisional Wound: Biochemical, Histopathological, and Cytokines Level Evidence.

Propolis is rich in natural bioactive compounds, and considering its importance for many skin therapies, emulgel was prepared. This study examines how a propolis extract (PE) and Passiflora edulis seed (PS) oil emulgel affect rat deep skin wound healing. Based on preset criteria of maximum drug content and optimum drug permeation through the stratum corneum along with drug retention in the skin layers, an optimized emulgel formula based on Box-Behnken factorial design was prepared and used for subsequent in vitro and in vivo evaluations. In vivo wound-healing activities of emulgel and control treatments were investigated in a rat model. The optimized emulgel formula exhibited superior healing activity compared with plain PE suspension-treated rats on day 14 of wounding. Histopathological investigations of hematoxylin and eosin and Masson's Trichrome-stained skin sections supported this effect. Emulgel promotes cutaneous wound healing through a variety of mechanisms, including anti-inflammatory through modulation of cytokines tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 production, and promotion of collagen fiber formation, all of which contribute to tissue remodeling. Furthermore, when compared with propolis suspension, emulgel showed significant antioxidant and anti-inflammatory effects. Emulgel significantly increased the skin's hydroxyproline level, antioxidant potential, wound contraction, increased penetration, and localized propolis deposition across the skin. Incorporation of PS oil into the emulgel accelerates the tissue regeneration process. The findings suggest that 5% propolis emulgel could be used as an alternative to treat wounds.

Effects of resveratrol topical ointment on wound healing of full-thickness cutaneous burns in albino rats.

OBJECTIVE: In this study, the effects of resveratrol topical ointment on wound contraction and histopathology of full-thickness cutaneous burn wounds were evaluated. METHOD: Adult albino rats were grouped into four equal-sized groups of 15 rats each, as follows: Group A-no wound, no treatment (control); Group B-1% silver sulphadiazine; Group C-5% resveratrol, and Group D-wound without treatment (control). A burn wound measuring 23.5mm was created on the skin at the dorsum of all rats in groups B-D after shaving. The percentage of wound contraction was measured using a digital Vernier Caliper on days 1, 3, 5, 7, 10, 14, 16, 18 and 21, post-wounding. From each group, five rats were then euthanised and tissue samples of the skin, liver and kidney were collected in 10% buffered formalin for histopathology. RESULTS: The percentage of wound contraction was significant (p<0.05) on 7, 14 and 18 days post treatment. Histopathologically, 5% resveratrol topical ointment application resulted in a thicker epidermis with neovascularisation and an increased collagen distribution. Resveratrol topical ointment ameliorated the extent of hepatocellular and nephrotubular injuries following burn-induced hepatocellular and acute kidney injuries. CONCLUSION: In this study, topical application of 5% resveratrol ointment appeared to enhance burn wound healing by increasing the rate of wound contraction through collagen fibre synthesis, granulation tissue formation and epithelial regeneration.

Effect of bromelain on mast cell numbers and degranulation in diabetic rat wound healing.

OBJECTIVE: Many studies have revealed the prominent roles of mast cells in wound healing, including inflammatory reactions, angiogenesis and extracellular matrix reabsorption. In the present study, we aimed to assess the probable therapeutic features of bromelain on wound contraction and mast cell degranulation in wound healing in experimental diabetic animals. METHOD: Male rats were grouped as control, vehicle and experiment. Skin wounds were generated in all groups. Treatments were applied with distilled water and with bromelain (BR) intraperitoneally in the vehicle and experimental groups, respectively. Following skin wound generation, animals were euthanised on days 3, 5, 7 and 15. We gathered 16,800 microscopic images to count the mast cells and degranulation level (Image J software). The wound contraction index was assessed both microscopically (Image J software) and macroscopically (time-lapse photography). The meshwork evaluation method was used to assess wound healing. RESULTS: Time-lapse photography revealed that the BR significantly (p<0.05) accelerated wound contraction and healing. BR significantly (p<0.05) increased the total number of mast cells in all experimental groups on days 5 and 7. The count of grade III (degranulated) mast cells was reduced significantly (p<0.05) on days 5 and 7 in experimental groups compared to control and vehicle groups. CONCLUSION: In this study, the rate of wound healing was accelerated considerably following BR administration. In addition, this agent decreased the count of degranulated mast cells, leading to wound contraction and healing.