Treat Skin Injuries Research Articles

Fabrication and Characterization of Chitosan-Polyethylene Glycol (Ch-Peg) Based Hydrogels and Evaluation of Their Potency in Rat Skin Wound Model.

Thermal burns are a major cause of death and suffering around the globe. They can cause debilitating, life-altering injuries as well as lead to significant psychological and financial consequences. Several research works have been conducted in attempt to find a wound healing therapy that is successful. At present, hydrogels have been widely used in cutting-edge research for this purpose because they have suitable properties. This study aimed to see how therapy with chitosan-polyethylene glycol (Ch-Peg) based hydrogels affected the healing of burn wounds in rats. With the concern of public health, xanthan gum (X), boric acid (B), gelatin (Ge), polyethylene glycol (Peg), chitosan (Ch), glutaraldehyde (G), and HPLC-grade water were prepared using X : Ge : G, X : Ge : Peg : G, X : Ge : Ch : G, X : Ge : Peg : Ch : G, X : Ge : B : Ch : G, X : Ge : B : Peg : G, and X : Ge : B : Peg : Ch : G. The produced composite hydrogels were examined for swelling ability, biodegradability, rheological characteristics, and porosity. The 3D structure of the hydrogel was revealed by scanning electron microscopy (SEM). After that, the structural characterization technique named Fourier-transform infrared spectroscopy (FTIR) was used to describe the composites (SEM). Lastly, in a rat skin wound model, the efficacy of the produced hydrogels was studied. Swelling ability, biodegradability, rheological properties, and porosity were all demonstrated in composite hydrogels that contained over 90% water. Hydrogels with good polymeric networks and porosity were observed using SEM. The existence of bound water and free, intra- and intermolecule hydrogen-linked OH and NH in the hydrogels was confirmed using FTIR. In a secondary burned rat model, all hydrogels showed significant wound healing effectiveness when compared to controls. When compared to other composite hydrogels, wounds treated with X : Ge : Peg : Ch : G, X : Ge : B : Peg : G, and X : Ge : B : Peg : Ch:G recovered faster after 28 days. In conclusion, this research suggests that X : Ge : Peg : Ch : G, X : Ge : B : Peg : G, and X : Ge : B : Peg : Ch : G could be used to treat skin injuries in the clinic.

Self-Assembled Nanofibrous Marine Collagen Matrix Accelerates Healing of Full-Thickness Wounds.

There is an urgent clinical need for wound dressings to treat skin injuries, particularly full-thickness wounds caused by acute and chronic wounds. Marine collagen has emerged as an attractive and safer alternative due to its biocompatibility, diversity, and sustainability. It has minimum risk of zoonotic diseases and less religious constraints as compared to mammalian collagen. In this study, we reported the development of a self-assembled nanofibrous barramundi (Lates calcarifer) collagen matrix (Nano-BCM), which showed good biocompatibility for full-thickness wound-healing applications. The collagen was extracted and purified from barramundi scales and skin. Thereafter, the physicochemical properties of collagen were systematically evaluated. The process to extract barramundi skin collagen (BC) gave an excellent 45% yield and superior purity (∼100%). More importantly, BC demonstrated structural integrity, native triple helix structure, and good thermal stability. BC demonstrated its efficacy in promoting human primary dermal fibroblast (HDF) and immortalized human keratinocytes (HaCaT) proliferation and migration. Nano-BCM has been prepared via self-assembly of collagen molecules in physiological conditions, which resembled the native extracellular matrix (ECM). The clinical therapeutic efficacy of the Nano-BCM was further evaluated in a full-thickness splinted skin wound mice model. In comparison to a clinically used wound dressing (DuoDerm), the Nano-BCM demonstrated significantly accelerated wound closure and re-epithelization. Moreover, Nano-BCM nanofibrous architecture and its ability to facilitate early inflammatory response significantly promoted angiogenesis and differentiated myofibroblast, leading to enhanced wound healing. Consequently, Nano-BCM demonstrates great potential as an economical and effective nonmammalian substitute to achieve skin regeneration.

Bilayered electrospun membranes composed of poly(lactic-acid)/natural rubber: A strategy against curcumin photodegradation for wound dressing application

Curcumin is a natural phenolic compound renowned for its beneficial anti-carcinogenic, anti-oxidant, antibacterial and anti-inflammatory properties. More recently, this active compound has also demonstrated wound healing capability and antibacterial properties, which are essential prerequisites to treat skin injuries. However, the practical application of curcumin in wound-healing dressing is limited by its susceptibility to photodegradation when exposed to artificial or natural sunlight. To maintain the pharmacological and antibacterial properties of curcumin and prevent its photodegradation, we have developed a bilayered asymmetric membrane for wound healing application composed of two layers of electrospun fibers. The bottom layer is composed of a biodegradable blend of poly(lactic acid)(PLA)/natural rubber(NR) microfibers containing curcumin in the bulk. In contrast, the top layer is composed solely of PLA nanofibers to simultaneously protect curcumin against photodegradation and avoid bacterial penetration. Scanning electron microscopy, Fourier transform infrared spectroscopy, UV–Vis spectroscopy, thermal analyses, contact angle measurements and antibacterial assay were employed to investigate the properties of the membranes. Our results demonstrated the top layer of PLA was crucial to prevent the photodegradation of curcumin contained in the PLA/NR microfibers bottom layer and also avoided the penetration of bacteria for 10 days. Additionally, the PLA/NR microfibers showed strong antibacterial activity against Staphylococcus aureus. Our results demonstrated the potential of bilayered nano/microfibrous membranes to be applied in the design of wound dressings containing active compounds susceptible to photodegradation.

Criteria to evaluate the quality of alginate wound dressings.

to validate an instrument with criteria to evaluate the quality of calcium alginate wound dressings to treat skin injuries. methodological study, developed in two stages: the elaboration of criteria to evaluate the quality of the alginate wound dressing based on literature; validation of these criteria by a group of evaluators in two moments. Data was analyzed using descriptive statistics, central tendency measures and the Content Validity Index. seven articles were selected, leading to the elaboration of 7 criteria and 11 expected results. The Content Validity Index was 0.98 in stage 1 and 0.93 in stage 2. After adjustments, 8 criteria were validated, and 13 results were expected. the study allowed the validation of criteria to evaluate the quality of calcium alginate wound dressings, helping the nurses to choose with more autonomy and assertiveness.

Natural Film Based on Pectin and Allantoin for Wound Healing: Obtaining, Characterization, and Rat Model.

Introduction In our days, several approaches reported the use of natural compounds in medical applications. Among them, pectin and allantoin are nontoxic, biocompatible, and biodegradable; however, its use for possible wound healing therapeutics is still limited. Pectin and allantoin have been applied in pharmaceutical industry and beauty cosmetic and could be also applied as scaffolds for tissue regeneration, wound healing, and so on. The aim of this study was to combine by the first time two natural ingredients to develop a new biomaterial to treat skin injuries in a rat model. Methods For the hydrogel development, new synthesis parameters were established for the obtaining of the film such as temperature, mixing velocity and time, and drying temperatures as well. To enrich the film, the allantoin concentrations were set at 90 wt% and 100 wt% of pectin used. By in vivo assay, films were tested in wound healing in female Wistar rats, 190 ± 10 g in weight and 2 months aged. Results The obtained films comprise 2 well-differentiated layers, one layer rich in allantoin, which will be the regenerative layer, and one rich in pectin, which will work as an antimicrobial and protective layer to the wound. These were characterized by swelling kinetics, Fourier transform of the infrared spectrum of absorption (FTIR) spectroscopy, and contact angle. The morphology and topography were determined by scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM). In vivo assay showed remarkable reduce in a time period in a wound healing process when the film was used. The results show that the use of PA (Pectin-Allantoin) hydrogel reduces the total healing time by 25% approximately. Conclusions Pectin-Allantoin (PA) film has potential use in medical applications as wound healing material promoting healthy tissue renewal.

Concentration Dependent Effect of Human Dermal Fibroblast Conditioned Medium (DFCM) from Three Various Origins on Keratinocytes Wound Healing.

Fibroblasts secrete many essential factors that can be collected from fibroblast culture medium, which is termed dermal fibroblast conditioned medium (DFCM). Fibroblasts isolated from human skin samples were cultured in vitro using the serum-free keratinocyte-specific medium (Epilife (KM1), or define keratinocytes serum-free medium, DKSFM (KM2) and serum-free fibroblast-specific medium (FM) to collect DFCM-KM1, DFCM-KM2, and DFCM-FM, respectively). We characterised and evaluated the effects of 100–1600 µg/mL DFCM on keratinocytes based on attachment, proliferation, migration and gene expression. Supplementation with 200–400 µg/mL keratinocyte-specific DFCM-KM1 and DFCM-KM2 enhanced the attachment, proliferation and migration of sub-confluent keratinocytes, whereas 200–1600 µg/mL DFCM-FM significantly increased the healing rate in the wound healing assay, and 400–800 µg/mL DFCM-FM was suitable to enhance keratinocyte attachment and proliferation. A real-time (RT2) profiler polymerase chain reaction (PCR) array showed that 42 genes in the DFCM groups had similar fold regulation compared to the control group and most of the genes were directly involved in wound healing. In conclusion, in vitro keratinocyte re-epithelialisation is supported by the fibroblast-secreted proteins in 200–400 µg/mL DFCM-KM1 and DFCM-KM2, and 400–800 µg/mL DFCM-FM, which could be useful for treating skin injuries.

Inhibition of Proinflammatory Enzymes and Attenuation of IL-6 in LPS-Challenged RAW 264.7 Macrophages Substantiates the Ethnomedicinal Use of the Herbal Drug Homalium bhamoense Cubitt & W.W.Sm.

Commonly used to treat skin injuries in Asia, several Homalium spp. have been found to promote skin regeneration and wound healing. While ethnobotanical surveys report the use of H. bhamoense trunk bark as a wound salve, there are no studies covering bioactive properties. As impaired cutaneous healing is characterized by excessive inflammation, a series of inflammatory mediators involved in wound healing were targeted with a methanol extract obtained from H. bhamoense trunk bark. Results showed concentration-dependent inhibition of hyaluronidase and 5-lipoxygenase upon exposure to the extract, with IC50 values of 396.9 ± 25.7 and 29.0 ± 2.3 µg mL−1, respectively. H. bhamoense trunk bark extract also exerted anti-inflammatory activity by significantly suppressing the overproduction of interleukin 6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages at concentrations ranging from 125 to 1000 µg mL−1, while leading to a biphasic effect on nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) levels. The phenolic profile was elucidated by HPLC-DAD, being characterized by the occurrence of ellagic acid as the main constituent, in addition to a series of methylated derivatives, which might underlie the observed anti-inflammatory effects. Our findings provide in vitro data on anti-inflammatory ability of H. bhamoense trunk bark, disclosing also potential cutaneous toxicity as assessed in HaCaT keratinocytes.

Pharmacological Update Properties of Aloe Vera and its Major Active Constituents.

Aloe vera has been traditionally used to treat skin injuries (burns, cuts, insect bites, and eczemas) and digestive problems because its anti-inflammatory, antimicrobial, and wound healing properties. Research on this medicinal plant has been aimed at validating traditional uses and deepening the mechanism of action, identifying the compounds responsible for these activities. The most investigated active compounds are aloe-emodin, aloin, aloesin, emodin, and acemannan. Likewise, new actions have been investigated for Aloe vera and its active compounds. This review provides an overview of current pharmacological studies (in vitro, in vivo, and clinical trials), written in English during the last six years (2014–2019). In particular, new pharmacological data research has shown that most studies refer to anti-cancer action, skin and digestive protective activity, and antimicrobial properties. Most recent works are in vitro and in vivo. Clinical trials have been conducted just with Aloe vera, but not with isolated compounds; therefore, it would be interesting to study the clinical effect of relevant metabolites in different human conditions and pathologies. The promising results of these studies in basic research encourage a greater number of clinical trials to test the clinical application of Aloe vera and its main compounds, particularly on bone protection, cancer, and diabetes.

Accelerating healing of excisional wound with alginate hydrogel containing naringenin in rat model.

Wounds have always been considered as one of the most common physical damages. Therefore, various researches have been conducted to find an appropriate method to improve wound healing process. Among various materials, since hydrogels have appropriate properties for wound healing, they are widely used for this purpose. In this study, to develop a potential wound dressing, different concentrations of naringenin (0%, 1%, 10% and 20%) were incorporated in alginate hydrogel followed by evaluating its characters such as morphology, swelling properties, weight loss, antibacterial activity, releasing profile of the naringenin, hemo-, and cytocompatibility. Finally, to evaluate the effect of developed hydrogels on wound healing, the full-thickness dermal wound model in rat was used. Our results provided that the prepared hydrogels have appropriate porosity (86.7 ± 5.3%) with the interconnected pores. Moreover, weight loss assessment confirmed that fabricated hydrogels have suitable biodegradability (about 89% after 14days). MTT assay also revealed the positive effect of hydrogels on cell viabilities, and they have no toxicity effect on cells. In vivo study indicated that the prepared hydrogels had better wound closure than the gauze-treated wound (the control), and alginate/20% naringenin group had the best wound closure among other groups. All in all, this study concluded that alginate/naringenin hydrogel has positive effect on wound healing process, and it can be used to treat skin injuries in the clinic. Graphical abstract.

Identification of Flavonoids and Bufadienolides and Cytotoxic Effects of Kalanchoe daigremontiana Extracts on Human Cancer Cell Lines.

Kalanchoe species are well-known medicinal plants used in traditional medicine as anti-inflammatory and analgesic remedies. Recently, it has been reported that Kalanchoe plants have cytotoxic properties; however, data on traditional use of these plants in tumor treatment are extremely limited. Kalanchoe daigremontiana is one of the most popular species cultivated in Europe, and it is used, among other things, as a remedy in treating skin injuries and wounds. Studies on the biological activity of this species are scarce, and there is a lack of data on the cytotoxic activity of K. daigremontiana extracts on epithelial cancer cells in the literature. In our present study, we analyzed the phytochemical composition of K. daigremontiana ethanol extract and fractions-water and dichloromethane-by the HPLC-DAD-ESI-MS method and estimated cytotoxic activity of the extracts on human adenocarcinoma (HeLa), ovarian (SKOV-3), breast (MCF-7), and melanoma (A375) cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, real-time cell analyzer (RTCA), and flow cytometry. We identified 6 bufadienolide compounds and 19 flavonoids, mostly kaempferol, quercetin, isorhamnetin, and myricetin glycosides, of which only 3 flavonoids have been identified in K. daigremontiana to date. Other flavonoids that were characterized in our study have not yet been found in this plant. The ethanol extract and water fraction of K. daigremontiana did not show significant cytotoxic activity on the tested cell lines. In contrast, the dichloromethane fraction showed the strongest activity against all cell lines with IC50 values of ≤ 10 µg/mL. The results indicated that this activity is mainly due to the presence of bersaldegenin-1,3,5-orthoacetate.

Wound healing with alginate/chitosan hydrogel containing hesperidin in rat model

Skin damages have always been considered as one of the most common physical injuries. Therefore, many researches have been conducted to find an efficient method for wound healing. Since hydrogels have suitable characteristics, they are widely used for this purpose. In this study, based on the high efficiency of alginate and chitosan hydrogels in the wound healing, different concentrations of hesperidin were loaded to alginate and chitosan hydrogels followed by evaluating their morphology, swelling properties, release, weight loss, hemo- and cytocompatibility, antibacterial and toxicity properties. Finally, the therapeutic function of the prepared hydrogels was evaluated in the full-thickness dermal wound in a rat model. Our results indicated that the hydrogels have appropriate porosity (91.2 ± 5.33%) with the interconnected pores. Biodegradability of the prepared hydrogel was confirmed with weight loss assessment (almost 80% after 14 days). Moreover, the time-kill assay showed the antibacterial properties of hydrogels, and MTT assay revealed the positive effect of hydrogels on cell proliferation, and they have no toxicity effect on cells. Also, the in vivo results indicated that the prepared hydrogels had better wound closure than the gauze-treated wound (the control group), and the highest wound closure percentage was observed for the alginate/chitosan/10% hesperidin group. All in all, this study shows that alginate/chitosan hydrogels loaded with 10% of hesperidin can be used to treat skin injuries in humans.

Enhanced wound healing by PVA/Chitosan/Curcumin patches: In vitro and in vivo study

Biocompatible polymers are being used in recent times for treating skin injuries and burn wounds. Polymers like Poly Vinyl Alcohol and Chitosan are proven to be biocompatible with least toxic to treat injuries with minimal side-effects. Curcumin, a primary component of turmeric has anti-inflammatory properties and anti-microbial activity but has extremely low bioavailability. Converting Curcumin to its nano form increased its bioavailability exponentially allowing it to play a vital role in the process of wound healing. This PVA/Chi/Cur patch increased cell proliferation as shown by the results of cell line studies and MTT assay. Its anti-bacterial activity against four major bacterial strains commonly found in wound sites and water retainability indicates it to be a perfect material for wound treatment. Results of in-vivo studies conducted on wistar rats by testing the patch's healing ability on a surgically induced wound displayed its superiority over commercial ointment. This treatment for epidermal wounds reduces the frequency in which the patch has to be replaced and increases the rate of wound rehabilitation.

A simplified fabrication technique for cellularized high-collagen dermal equivalents

Human autologous bioengineered skin has been successfully developed and used to treat skin injuries in a growing number of cases. In current clinical studies, the biomaterial used is fabricated via plastic compression of collagen hydrogel to increase the density and stability of the tissue. To further facilitate clinical adoption of bioengineered skin, the fabrication technique needs to be improved in terms of standardization and automation. Here, we present a one-step mixing technique using highly concentrated collagen and human fibroblasts to simplify fabrication of stable dermal equivalents. As controls, we prepared cellularized dermal equivalents with three varying collagen compositions. We found that the dermal equivalents produced using the simplified mixing technique were stable and pliable, showed viable fibroblast distribution throughout the tissue, and were comparable to highly concentrated manually produced collagen gels. Because no subsequent plastic compression of collagen is required in the simplified mixing technique, the fabrication steps and production time for dermal equivalents are consistently reduced. The present study provides a basis for further investigations to optimize the technique, which has significant promise in enabling efficient clinical production of bioengineered skin in the future.

Anti-inflammatory and burn injury wound healing properties of the shell of Haliotis diversicolor.

BackgroundThe shell of Haliotis diversicolor, or shijueming (SJM), is a type of traditional Chinese medicine. The SJM has appeared in historical records as early as the third and fourth centuries. Historical records have revealed that SJM had mainly been used to treat eye diseases. After the Qing Dynasty (1757), records had emerged, detailing the use of SJM for treating skin injuries, particularly for treating poorly managed ulcers or traumatic wounds. Furthermore, in our anti-inflammation-screening system, SJM significantly inhibited the expression of pro-inflammatory proteins. Previous studies have yet to adopt an animal model to verify the phenomenon and described in the historical records regarding the efficacy of SJM in promoting wound healing. Besides, the mechanism of wound healing effect of SJM is also not clear.MethodsThis study applied in vitro and in vivo models, tissue section analysis, and western blotting to evaluate the effect of SJM on wound healing. The RAW 264.7 cells were used in anti-inflammatory activity assay and phagocytic assay. Male Wistar rats were used to evaluate the effect of SJM on burn injury healing. A copper block (2 × 2 cm, 150 g) preheated to 165 °C in a dry bath was used to contact the skin area for 10 s, thus creating a full-thickness burn injury. The results were analyzed by hematoxylin and eosin staining, picrosirius red staining and Western blotting.ResultsThe results revealed that in the in vitro model, the presence of SJM decreased the inducible nitric oxide synthase (iNOS) expression and enhanced the functions of macrophages. The results of the rat burn injury model revealed that SJM decreased neutrophil infiltration, promoted wound healing, thus increasing the collagen I content and promoting the expression of transforming growth factor-beta 1 (TGF-β1) protein. We speculate that the effect and mechanism of SJM on promoting wound healing is related to macrophage activation. In the inflammation phase, SJM alleviates inflammation by inhibiting iNOS expression and removing neutrophils through phagocytosis. Furthermore, SJM induces the secretion of TGF-β1, converting collagen during the tissue remodeling phase.ConclusionsAccording to our review of relevant literature, this is the first study that applied an evidence-based method to verify that SJM alleviates inflammation, enhances phagocytosis, and triggers wound healing after burn injury. The study findings reveal that SJM provides a promising therapeutic option for treating burn injury.

Skin Rounds: A Quality Improvement Approach to Enhance Skin Care in the Neonatal Intensive Care Unit.

Skin injuries are common among neonatal intensive care unit (NICU) patients and may lead to significant complications. Standardized methods of preventing, detecting, and treating skin injuries are needed. The aim of this project was to standardize the assessment, documentation, and tracking of skin injuries among hospitalized neonatal patients and to determine the incidence of pressure ulcers in this patient population. (1) Creation of an interdisciplinary skin team to identify skin injuries through weekly skin rounds. (2) Assessment of all patients at least twice daily for the presence of skin injuries. Interventions were implemented upon identification of a skin injury. Pressure ulcers of Stage II or more were further assessed by wound/ostomy nurses. A total of 2299 NICU patients were hospitalized and assessed between July 2011 and December 2015. After the initiation of skin rounds, the baseline incidence of pressure ulcers increased from 0.49 per 1000 patient days to 4.6 per 1000 patient days, reflecting an improvement in detection and reporting. The most common skin injuries detected included erythema, skin tears, and ecchymosis; the most common cause of injuries was medical devices. A dedicated skin team can improve the detection and reporting of skin injuries among NICU patients. Determination of the incidence of pressure ulcers in this population is critical to develop targeted interventions. Further research is needed to determine the most effective interventions to prevent and treat skin injuries among hospitalized neonates.

Repair and Regeneration of Skin Injury by Transplanting Microparticles Mixed With Wharton’s Jelly and MSCs From the Human Umbilical Cord

The prognosis for extensive and deep skin injury is not satisfactory because of scar formation and the loss of normal function and skin appendages. Several novel therapies for skin repair and regeneration have emerged. Currently, stem cell-based therapies are attractive candidates in regenerative medicine to treat skin injuries. Human umbilical cord Wharton's jelly-derived mesenchymal stem cells (hUC-MSCs) have become a unique, accessible, and noncontroversial source of regeneration in medicine. The aim of this study was to explore a new strategy for treating skin wounds. A mixture of hUC-MSCs, Wharton's jelly, and skin microparticles were transplanted to 10-mm diameter, full-thickness, middorsal, excisional skin wounds of mice. After 7 days, the tissue sections were sampled for reconstruction analysis and histological examination. After transplantation, there was a remarkable development of newborn skin and its appendages. We could see newly generated layers of epidermis, sebaceous glands, hair follicle, and sweat glands clearly. This innovative strategy could be very promising and may significantly increase the quality of repair and regeneration of skin in injuries.

Synthesis and Chemical Characterization of a Polymeric Prodrug for Prolonged Release of Nitrofurazone

AbstractChitosan, a natural polysaccharide obtained from partial or total deacetylation of chitin, is a linear copolymer composed of β(1→4) linked N‐acetyl glucosamine and glucosamine monomer residues. Owing to its biological properties (such as biocompatibility, low toxicity, antimicrobial activity and haemostatic effect) chitosan has been widely exploited in the pharmaceutical industry to produce tablets, gels, nanoparticles and films. The aim of this study was to develop a polymeric prodrug for prolonged drug release of nitrofurazone (NF) on the skin, with chitosan as the carrier. The drug is conjugated to chitosan by means of ester bonds and the cleavage of these bonds by non‐specific cutaneous esterases provides the prolonged release of NF. This prodrug could be formulated in films or gels to accelerate wound healing, by acting as a physical barrier that prevents both loss of natural skin humidity and secondary microbial contamination, as well as to treat skin injuries caused by microorganisms susceptible to NF, whose antimicrobial spectrum is added to that of chitosan.