Autologous keratinocyte cultures and combinations of scaffolds, different cell types, solutions of macromolecules, or growth factors have contributed to the resurfacing of burns and large wounds. There are, however, significant limitations with these therapies. No tissue-engineered substitute can fully replace the split-thickness skin graft for permanent coverage of full-thickness skin loss in one step, and none contain a functional vascular plexus. Current research characterizes skin as more than a barrier with sensory function, but as an intricate biological factory participating in cell signaling, metabolism, and protein synthesis, and as a vital component of the nervous, immune and endocrine systems. This paper provides a comprehensive review of the structure and function of skin, highlighting the importance of regenerating an organ that will function physiologically.
The clinical use of honey has gained significant importance in regenerative medicine owing to its constructive properties that abets the rapid healing of broad-spectrum of injuries. The salient characteristics of honey are attributable to its active ingredients which include sugars, enzymes and vitamins. Moreover, the evidence based results exert that honey acts in synergy with its immunologic modulators and physiologic mediators in multitude of signalling pathways and molecular targets offering beneficial vigor effects in wound healing. The aim of this present study is to systematically review the literature in PubMed database in order to identify the available pre-clinical results in support to rational use of honey in wound management. The results revealed that the active biomolecules of honey assisted in improved autolytic debridement and tissue granulation. This review highlights the physiological basis for the use of honey in wound healing, its current pre-clinical uses and its future recommendations.
The major problem in the management of burn wounds are infections. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major cause of infection in burn wounds. Antibiotic resistant bacteria around the world has become a major therapeutic challenge. Bacteriophages and their lysine are suggested as an antimicrobial alternative agent. Phage display technique is suggested for production of recombinant lysine by Nano carrier technology. The approach of this study was to evaluate the potential of recombinant Nano phage efficacy in MRSA burn wound infection in vivo. The 3rd degree burn wounds were induced in 54 rats and infected with MRSA ATCC 33591 via the topical route in four groups. Burn wound size was measured in 0, 14, 21, 28 days. The efficacy of Nano phage gel was assessed on the basis of percentage collagen deposition, granulation tissue, neovascularization, fibroblastic maturity, re-epithelization, and scar formation in rats following treatment in 14, 21, 28 days. The results showed that the percentage of wound size were 3 cm on base line day and the average macroscopic wound healing rates were increased in the prevention groups receiving the recombinant Nano phage gel and natural phage gel, in the treatment groups with secondary infection receiving the recombinant Nano phage gel and the natural phage gel, and in the two control groups respectively. The average microscopic wound healing rates were increased in the prevention groups receiving the recombinant Nano phage gel and natural phage gel, in the treatment groups with secondary infection receiving the recombinant Nano phage gel and the natural phage gel, and in the two control groups respectively. In conclusion the recombinant Nano phage gel is efficacy to treat and prevent MRSA burn wound infection.
Abstract Background The use of Theresienol® (T.O.) a traditional Austrian natural product has been traced back to1350. Medical wound care has always been a major concern and problem for people, especially in the Middle Ages. Еven the smallest injuries or open wounds to become fatal due to poor hygienic conditions. Access to natural fats and vegetable ingredients made it possible to create a unique ointment named Theresienol® which successfully treated multiple skin injuries including wounds, burns and scars. Methods 1,354 patients suffering of therapy-refractory skin injuries treated with T.O. within 38 centers between 2004–2020 in a cohort study. These were used for this review. Patients were divided by clinical criteria based on application duration and daily rate of reapplication strictly individualized depending on the degree of damage and efficiency results depending on the duration of the problem and the presence of chronic concomitant diseases. With a simplified application process a fine film of 2 drops/1 cm of the product (Depending on the vehicle of choice) over the wound or the affected areas, with a waiting time until partial absorption takes place followed by the dressing. It can be applied directly over the wound or over sterile bandages. The Primary endpoints were pain reduction, patient satisfaction both physically and aesthetically. Additionally we performed dermatological testing for irritation and allergy potential and rule out further side effects. Results After further evaluation of the 1,354 cases, statistically it showed an averaged of 89 % improvement rate in inflammation, an 88 % reduction rate in pruritus, 87 % of improved epithelisation, 93 % in patient benefit, and 91 % show improvement in wound closure. The Visual Analogue Scale of pain started at 8.29 a marked reduction was noted in the first 24 h with an average of 2.41. followed by a stable slow reduction of 1.73 on the 7th day. Conclusion Treatment of Therapy-Refractory skin injuries including burns, scars, acute in addition to chronic wounds with T.O., which is nearly 700 years old has shown for the first time exceptional results in an outpatient setting and was successful in alleviating inflammation, pain, itching and discomfort associated with wound care, thus providing an optimal opportunity for the wound to heal sufficiently and quickly without reported side effects.
•Overview of matrix therapy agent CACIPLIQ20® used as last resort for chronic wounds.•119 healed wounds were evaluated to assess healing time with CACIPLIQ20® treatment.•Wound types included diabetic foot ulcers, burns, post-amputation/surgical wounds.•Complete healing was achieved in 2 months regardless of wound size, age or etiology.•CACIPLIQ®20 treatment was cost-effective costing 74 euros/64 GBP per wound.•Marked pain relief as a consequence of healing was also reported.
Extralevator Abdominoperineal excision (ELAPE) for low rectal cancer results in a large perineal defect, often requiring reconstruction by a biological or absorbable mesh or a flap as compared to conventional Abdominoperineal excision (CAPE). Although there are indications for oncological superiority with ELAPE, the incidence of wound-related complications is postulated to be higher when compared to CAPE due to the removal of more amount of tissue around the anorectum. On the other hand, the incidence of inadvertent rectal tube perforation during dissection is lesser in ELAPE and hence perineal wound breakdown and infection are postulated to be lesser in some other studies. We conducted a retrospective study in the department of colorectal surgery, Christian Medical College; Vellore from 2011 to 2017 to compare the perineal wound-related complications following CAPE and ELAPE. The data were retrieved from the prospectively maintained computerized inpatient and out-patient follow up records and comparisons were made in terms of incidence of perineal wound outcomes, need for reoperations and duration of hospital stay. A total of 138 patients underwent CAPE and 57 patients underwent ELAPE over a period of 7 years. There was no statistical difference in baseline characteristics and patients who underwent neo-adjuvant chemoradiation between the two groups. Perineal wound complications were seen in 63% (87) of the patients after CAPE compared to 64.9% (37) of the patients after ELAPE. There was no perineal herniation or wound dehiscence following ELAPE, whereas these complications occurred in 1 and 5 patients respectively after CAPE. Similarly, the incidence of reoperations was 8% in CAPE as compared to 5.4% in ELAPE although not statistically significant. There was no difference in the length of hospital stay. Hence, in our experience, perineal wound complications were similar in the Extralevator approach to APE (ELAPE) as compared to conventional APE (CAPE) for rectal adenocarcinoma.
Type 2 diabetes is one of the most prevalent diseases throughout the world. The foot ulcers are severe complications of this disease. Foot ulcers induce the high rate of morbidity, impair quality of life, bring about extreme costs to health service providers, and give rise to waste of time. Recently, platelet-rich plasma (PRP) and platelet gel (PG) have been used for the treatment of chronic wounds. In the present randomized, double-blind, placebo-controlled study, platelet gel derived from umbilical cord blood (UCB) was used to heal the diabetic foot. The patients were randomly divided into three groups, under the categories of PG, platelet-poor plasma (PPP) and lubricant gel (placebo) (ratio 1:1:1). The processes of gels application were launched for the subject of each group twice per week with 3–4 days' interval. This mechanism protracted for eight weeks. After completion of 8 weeks, the patients were followed up after two weeks and then continued for nine months with one-month interval. 30 patients underwent statistical analysis. Except for diastolic blood pressure which was significant between groups, there were no statistically significant differences in patients' baseline demographics. No significant differences were detected between groups at baseline of wounds (P = 0.09). The results revealed that there is no statistically significant interaction among three groups during follow-up time. The present study provides evidence that there are no significant differences in the size of wound among PG, PPP, and placebo groups.
•The percentage of graft take at the end of 15th post-operative day was higher in fibrin sealant group.•At end of six months, modified Vancouver scar scale score was better in fibrin sealant group.•Fibrin sealant group, less resting pain over the skin grafted site was reported.•Histopathological and immuno-histochemical staining showed better scar characteristics in fibrin sealant group at the end of six months follow up.
Dimethyl sulfoxide (DMSO) is one of the commonly used vehicles to dissolve water insoluble drugs, including used for wound healing purposes, for different experiments. The present study was aimed to investigate the gross effects and histopathological changes produced by topical DMSO on granulation tissue at wound site. Open excision cutaneous wounds were created on the back of ten male rats and equally divided into two groups. Distilled water and DMSO (10 %) were topically applied once daily for 21 days on wounds of Group I (control group) and Group II, respectively. Grossly, wounds revealed that DMSO facilitated wound closure on day 7 and 12. On day 21, the wound was still not closed in DMSO treated group in comparison to control group. The H & E stained sections of control group showed formation of complete, immature and thin epithelial layer, collagen deposition and infiltration of abundant number of mononuclear cells. Sections of DMSO treated group showed blood vessels, scattered infiltration of inflammatory cells, collagen fibers and partially formed epithelial layer. Semi-quantitative score for inflammatory cells and epithelialization was significantly lower in DMSO treated group. Picrosirius red stained sections showed dominance of orange-red (thicker) collagen fibers in control group and yellow-green (thinner) collagen fibers in DMSO treated group. DMSO treated group showed higher and lower thin collagen and thick collagen fiber fraction, respectively in comparison to control group. Thus, it might be concluded that DMSO facilitates wound closure during the early stages and delays the wound closure during at later stages of wound healing.
Caiman yacare visceral fat oil was extracted, analyzed, and tested for healing potential. In vivo assays were performed by excisional wounds in rats and treated topically daily with Caiman oil for 10 days. The positive and negative controls were, respectively, with Dersani® (Essential Fatty Acids – EFA, reference substance) and saline solution (SS). The scattered area was measured daily, and at 3rd and 10th days the rats were euthanized and samples were processed for histological analyses. The cytotoxicity was evaluated by the MTT assay in non-tumor retinal pigment epithelium cells. The Caiman oil composition was 42.95 ± 1.03 % of saturated fatty acids and 43.74 ± 0.74 % of unsaturated ones. After 10 days of excisional wounds, the Caiman oil-treated animals present a larger scarred area than the negative control ones. Caiman oil and EFA treated animals present significantly more epidermal papillae than in SS-treated ones on day 10. Caiman oil treated animals, at 10th day, present a relative increased area of collagen fibers, as well as an elevated number of fibroblasts and monomorphonuclear cells in the wound region in comparison to both SS and EFA treated ones. The oil showed no significant cytotoxicity up to 500 μg/mL. Taken together, Caiman oil, extracted as a by-product of the C. yacare zootechnical disposal, demonstrated wound healing properties equal to the commercial available solution, subsidizing its ethnoknowledge.
Graphene and its derivatives have attracted much attention in recent years due to their unique properties and functionalization ability in tissue engineering. In this work, effect of biomolecule adding in three groups of Graphene family (consisting of Graphene, Graphene Oxide and reduced Graphene Oxide), their composites and modified forms are studied. Although the Graphene family induces differentiation of stem cells, adding appropriate factors (such as growth factors, inducers and gene activator proteins) helps improve the adhesion, proliferation and differentiation of cells. The novelty of this work is to verifying the capability of specifically-induced differentiation and bioactive controlled release of biomolecules on Graphene-based substrates, Graphene filled substrates or Graphene coated substrates and explaining the important role of biomolecules in stem cells fate. The study indicates that Graphene family can release biomolecules (including growth factors and proteins) in a controlled manner and these additives significantly enhance or accelerate the adhesion, proliferation and differentiation of stem cells and induce the differentiation of stem cells to specific cells.
Burns are one of the most common and devastating forms of trauma. Patients with serious thermal injury require immediate specialized care in order to minimize morbidity and mortality. The objective of this study was to evaluate the healing potential of porcine decellularized small intestinal submucosa (SIS) matrix and chitosan with mesenchymal stem cells (rMSC) and epidermal growth factor (mEGF) on the healing of full thickness burn wound in rat model. One 2 × 2 cm2 size full thickness burn wound was created on the dorsum of each animal under general anaesthesia. Burn wounds were treated with silver sulfadiazine; medical grade chitosan; chitosan with rMSC; chitosan with rMSC and mEGF; decellularized porcine SIS; rMSC seeded with SIS; rMSC seeded with SIS and mEGF in groups A, B, C, D, E, F and G, respectively. Healing was evaluated on the basis of percentage of wound contraction, colour digital imaging, immunological, histopathological, immunohistochemistry and gelatin zymography observations. A decrease in wound area was noticed in stem cell and m-EGF treated groups. Early angiogenesis and epithelialisation was observed in groups, where decellularized SIS matrix was combined with r-MSC and m-EGF. Type III collagen was found more in control group by immunohistochemistry which indicated abnormal collagen deposition. Gelatin zymography revealed expression of MMPs in the control group suggesting a chronic nature of wound. Chitosan in combination of rMSC and mEGF proved to be efficient for full-thickness burn wound healing. Decellularized SIS matrix when combined with r-MSC and m-EGF has healing potential and showed best healing response than conventional treatment for the reconstruction of full-thickness skin burn wounds in rats.
Biological membranes are widely used as dressings to prevent contamination during the open wound healing process. The amniotic membrane has been clinically demonstrated to be an accelerator of wound healing. However, this membrane is fragile and technically sensitive. The platelet-rich fibrin membrane has good physical properties and contains growth factors. However, few controlled studies have compared the effects of these membranes on wound healing, specifically during the proliferation phase. The proliferation phase is an important stage in the development of more effective therapeutic interventions. This study investigated the differences in the wound healing process during the proliferation phase after applying platelet-rich fibrin and amniotic membranes. This quasi-experimental study used 36 rabbits that were divided into three groups. A 4 mm x 4 mm section of the labial gingiva was de-epithelized using a scalpel. Gingival biopsies were taken on days one, three, five, and seven and stained with hematoxylin and eosin and Mallory's trichrome stain. Observations were done in a double-blind manner. The number of fibroblasts and blood vessels, as well as epithelial thickness were tested using two-way analysis of variance followed by a post-hoc LSD test. Collagen density was tested with the Kruskal–Wallis test followed by the Mann–Whitney test using SPSS software. The number of fibroblasts, angiogenesis, collagen density, and epithelial thickness were higher in group II than in the other groups (P < 0.05). Histological parameters measured during the proliferation phase showed that the platelet-rich fibrin membrane may accelerate wound healing better than the amniotic membrane.
Our aim was to determine the treatment outcome using HBOT for both acute and chronic problematic wounds. This was a case-control study conducted at Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand between 2012 and 2017. The inclusion criterion was all patients with either acute or chronic wounds with delayed wound healing treated with hyperbaric oxygen therapy (HBOT). Wound improvement was the primary outcome. Eighty-eight patients were included. Sixty-eight patients (77 %) had improved wound healing while 20 (23 %) had a poor treatment outcome. In the improved wound healing group, the outcome of wound healing was classified into 2 groups: Group 1–40 patients (58.8 %) experienced wound healing while Group 2–28 patients (41.2 %) experienced decreased wound size and reduced pain. The factors prognostic for a poor treatment outcome were arterial occlusion (OR 19.667, 95 % CI 5.740–67.378), diabetes (OR 3.405, 95 % CI 1.198–9.679), and bone exposure (OR 10.389, 95 % CI 2.763–39.058). Among patients with problematic wounds undergoing HBOT, the factors associated with a poor prognosis were arterial occlusion, DM, and wound with bone exposure.
•Rooibos extract loaded hydrogels (RH) displayed therapeutic properties in vivo.•RH dressing accelerated healing of uncomplicated acute surgical wounds.•Fermented rooibos extract was more effective than green rooibos extract.•Rooibos extracts reduced infiltration of inflammatory cells in granulation tissues.
Tridax procumbens(L.) leaves are traditionally used in wound healing by tribal people. The matured leaves are crushed to make a paste and applied on the surface of the wound. The aim of the present investigation was to evaluate the wound healing activity of ethanolic extract of Tridax procumbens (L.) (EETP) in streptozotocin induced diabetic and non- diabetic laboratory animals. There is no scientific literature, claiming the use of leaves of Tridax procumbens (L.) in diabetic wounds. The simple ointment base (2.5 % and 5% w/w) of EETP was formulated to evaluate the wound healing potential on diabetic and non-diabetic rats, using incision, excision and burn wound model. In incision wound model, epithelization period, wound index, % contraction area, hydroxyproline content, DNA estimation, total protein and histopathological evaluations were done. In excision wound model, tensile strength was measured. In burn model, contraction rate, wound contraction (%) and epithelization period were evaluated. Secondary metabolite as tannin, flavonoids were present. In the excision model, animals treated with 2.5 % and 5% w/w EETP showed significant result in wound contraction, epithelization period and wound index. Hydroxyproline, total protein and DNA concentration in healing tissue were more in comparison to control and as well as standard in diabetic and non- diabetic. The parameters evaluated showed significant response at 2.5 % and 5% w/w EETP. Flavonoids and tannin were accountable for wound healing. The findings confirmed the ethanomedicinal claim of Tridax procumbens(L.) in wound healing in diabetic and nondiabetic conditions.
Wound closure is the prime objective in the treatment of deep and extensive burns, where the dermis layer is partially or completely destroyed and the inherent capability of spontaneous re-epithelialization is greatly reduced or absent leading to high mortality rate. Scar formation as a result of burn wounds results in aesthetic and functional impairment, causing emotional distress in patients. Induced regeneration of skin could be a solution to improve the quality of life of burned patients. Nano calcium oxide (NCO) was prepared by thermal decomposition method. In situ gels (ISG) were formulated using micronized xanthan gum and NCO in different concentrations by geometric mixing. The formulations were evaluated for their particle size, surface morphology, elemental composition, clarity, pH, gelling and in vivo burn wound healing properties. The average particle size and polydispersity index of NCO was found to be 345.3 nm and 0.23 respectively. Three formulations were prepared, each containing varied concentrations of NCO (12.5, 25 and 50 ppm). The SEM analysis of the formulation exhibited particle sizes ranging from 1 nm to 468 nm and EDX characterization showed intense peaks of calcium and oxygen. The percentage of wound size reduction was significantly increased in wounds treated with prepared in situ gels in contrast to commercial product (calcium alginate dressing) and control (untreated) group. With an increase in concentration of NCO, the rate of healing also increased. In situ gels containing 50 ppm of NCO exhibited a better rate of wound healing in comparison to other formulations, within a period of 15 days. Histopathological analysis indicated that in situ gels had better wound healing properties. In situ gels of NCO were developed as a formulation for effective treatment of burns and to aid in skin regeneration.
Weakly acidic hypochlorous acid (HClO; 200 ppm, pH 6.5) is effective against a broad range of microorganisms. We have previously reported a study of developing antimicrobial biomaterials made up of chitin-nanofiber sheet (CNFS) -immobilized silver nanoparticles (CNFS/Ag NPs) and showed that either cleansing with HClO or covering with CNFS/Ag NPs daily for more than 7 days resulted in delayed wound healing. This study aimed to evaluate disinfection and wound healing by a combination of cleansing with HClO and covering with CNFS/Ag NPs daily for 3 days. Applying HClO + CNFS/Ag NPs daily for 3 days and then cleansing with just pure water and covering with CNFS alone daily for 9 days were performed for Pseudomonas aeruginosa-infected wounds in db/db diabetic mice. We found a significant enhancement of wound healing and a reduction of bacteria counts compared to the controls. Histological examination showed significantly advanced granulation tissue and capillary formations in the wounds on Day 12. These results suggest that limited disinfection to 3 days with HClO + CNFS/Ag NPs may be sufficient to avoid negative effects on wound repair.
Honey, pomegranate peel extract and bee venom, were used in combination with polyvinyl alcohol to develop a novel nanofibrous wound dressing. Methanolic pomegranate peel extract was prepared and mixed with either Manuka honey or lyophilized multiflora honey powder together with bee venom. The formulas were tested for their antibacterial activity, cytotoxicity, and wound healing activity in an excisional wound rat model. Scanning electron microscopy showed that lyophilized honey fibers had smaller and more uniform diameter than Manuka honey fibers. Moderate swelling and higher weight loss capacities were detected when compared to polyvinyl alcohol mats. Antibacterial tests showed significant antibacterial activity against S. aureus and E. coli compared to negative controls (P < 0.0001). No cytotoxicity was observed. In vivo wound healing study showed that all treatment groups enhanced wound healing as shown by increased wound closure percentages compared to negative control groups at days 3,5 and 10 (P < 0.0001), and histological examination. In comparison to treatment groups, Medihoney® calcium alginate dressing significantly enhanced healing compared to negative controls at days 3 and 5. However, healing was delayed afterwards. These results indicate that Manuka honey/Pomegranate/Bee Venom nanofibers are promising for wound healing.
Wound healing is a general repair response or process of the body immediately after the disruption of the skin integrity. However wound healing is a complex process in which body repairs itself. The aim of this research is to study the wound healing activity of ethanolic extract of Plumeria obtusa L. leaves and to study the efficacy of formulated 2.5%, 5% and 10% Plumeria obtusa sprays in in-vivo wound healing models. The spray was prepared in three formulations F1, F2 and F3 containing 2.5% (50 mg/kg BW), 5% (100 mg/kg BW) and 10% (200 mg/kg BW) extract of P. obtusa leaves respectively. The wound healing activity was studied by invivo method. In excision model the % wound closure rate on epidermal skin of white Wistar albino rats was studied and was compared with standard Hansaplast Wound spray. The tensile strength or skin breaking strength was measured on the 10th post wounding day in anesthetized experimental rats in incision model. The results obtained by 3 formulations F1, F2 and F3 were studied and compared with the control group. The formula F3 shows complete wound healing on day 17, while the F1 and F2 showed complete healing on day 21 and 19 respectively in excision wound model. In incision wound model the tensile strength was found to be high about 404 gm by application of formula F3 spray. Formula F1 and F2 showed 354 gm and 385 gm tensile strength respectively. The conclusion is ethanolic extract of the leaves of plant P. obtusa showed promising wound healing activity as studied by the invivo models. The study shows that Formula F3 with 10% (200 mg/kg BW) P. obtusa extract spray shows better and efficient wound healing activity than formula F1 with 2.5% (50 mg/kg BW) and formula F2 with 5% (100 mg/kg BW) extract spray.
