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Preparation of nanocomposite membranes loaded with taxifolin liposome and its mechanism of wound healing in diabetic mice
Abstract
In this study, a new wound dressing was developed to speed up the healing process of diabetic wounds. First of all, taxifolin liposome (TL) was manufactured in this study. Then, taxifolin (TAX) and TL were mixed with polyvinyl alcohol (PVA) and chitosan (CS) by electrostatic spinning to prepare nanocomposite membranes. Finally, the mechanism of nanocomposite membranes to accelerate diabetic wound healing was investigated. The diameter of TL-loaded polyvinyl alcohol/chitosan nanocomposite membranes (PVA/CS/TL) was 429.43 ± 78.07 nm. The results of in vitro experiments demonstrated that the PVA/CS/TL had better water absorption, water vapor transmission rate (WVTR), porosity, hydrophilicity, mechanical properties, slow-release, antioxidant capacity, and antibacterial properties. The results of in vivo experiments demonstrated that the wound healing rate of mice treated with PVA/CS/TL for eighteen days was 98.39 ± 0.34 %. Histopathological staining, immunohistochemical staining, and western blot experiments also demonstrated that PVA/CS/TL could promote wound healing in diabetic mice by inhibiting the activation of inhibitor kappa B alpha (IκBα)/nuclear factor-kappa B (NF-κB) signaling pathway and related pro-inflammatory factors to increase the expression of CD31 and VEGF in skin tissues. These results suggested that PVA/CS/TL could be a potential candidate for wound dressing to promote chronic skin wound healing.
... In order to inhibit the formation of wound scars, Ding et al. mixed TAX and dihydroquercetin protein liposome (TL) with polyvinyl alcohol (PVA) and CS by electrostatic spinning to prepare a nanocomposite membrane [80]. The results show that PVA/CS/TL can increase the expression of CD and VEGF in skin tissue and promote the wound healing of diabetic mice by inhibiting the activation of the κB α(IκBα)/nuclear factor κ B (NF-κB) signaling pathway and related pro-inflammatory factors. ...
... As shown in Figure 1. In order to inhibit the formation of wound scars, Ding et al. mixed TAX and dihydroquercetin protein liposome (TL) with polyvinyl alcohol (PVA) and CS by electrostatic spinning to prepare a nanocomposite membrane [80]. The results show that PVA/CS/TL can increase the expression of CD and VEGF in skin tissue and promote the wound healing of diabetic mice by inhibiting the activation of the κB α(IκBα)/nuclear factor κ B (NF-κB) signaling pathway and related pro-inflammatory factors. ...
Skin is a barrier to maintaining the stability of the human environment and preventing the invasion of pathogens. When skin tissue is exposed to the external environment, it will inevitably develop defects due to trauma, injury, burns, ulcers, surgery, and chronic diseases. Rapid skin repair is the key to reducing infection, relieving pain, and improving quality of life. Dihydroquercetin is a kind of flavonoid that has a wide range of pharmacological activities and can improve skin repair, skin inflammation, skin cancer, and so on. In this paper, the application of dihydroquercetin in medical dressings and the research progress in the treatment of skin-related diseases are reviewed, so as to provide reference for further developing dihydroquercetin as a drug for the treatment of skin diseases.
... These findings serve as a reference for improving the bioavailability and promoting the angiogenesis of other substances using similar methods and materials. 24 In addition, some studies have added the traditional iron ion chelator deferoxamine (DFO) to the hydrogel to improve the redox reaction caused by iron ion accumulation, thereby reducing the oxidative damage caused by the release of hydroxyl radicals, increasing the level of vascular endothelial growth factor (VEGF) in blood vessels, and significantly improving the ability to promote angiogenesis and improve tissue blood supply. 25 In addition to conventional iron ion chelators, it has been discovered that the synthesis of a three-dimensional porous hydrogel by grafting protocatechuic acid onto carboxymethyl chitosan through freeze-drying and secondary crosslinking can significantly enhance the chelation activity of iron ions, thereby reducing oxidative stress. ...
Hydrogels can be rationally designed as multifunctional platforms with structures and functions for various biomedical applications. Because of their excellent biochemical and mechanical properties, hydrogels have shown great potential for promoting angiogenesis, and an increasing amount of research has been devoted to designing and developing new hydrogels. However, a systematic and detailed review of hydrogels that promote angiogenesis is lacking. This paper comprehensively summarizes the design strategies of different kinds of functional hydrogels that promote angiogenesis, with anti-oxidant, substance-delivery, stimulus-responsive, self-healing, conductive, and wound-monitoring properties. The applications of hydrogels in wound healing, bone regeneration, and treatment of myocardial ischemia are discussed. Finally, future development directions of functional hydrogels promoting angiogenesis are proposed along with new strategies for the treatment of related diseases.
... The characteristic peaks around 1150 and 1065 cm − 1 correspond to the bending vibration of the C-O-C bond and the stretching vibration of the C-O bond in CS, respectively. The peaks near 1567 and 1642 cm − 1 correspond to the stretching vibrations of N-H and C-O, respectively, mainly due to the typical C2 symmetry of chitosan's type 2 crystal structure [39]. In addition, Fig. S3 showed that no new absorption peaks were observed during the synthesis of PVA/CS/-DES/CuTA 500 , indicating that the synthesis is an irreversible physical process and no new chemical bonds are formed. ...
Bacterial-infected wounds could cause delayed wound healing due to increased inflammation, especially wounds infected by drug-resistant bacteria remain a major clinical problem. However, traditional treatment strategies were gradually losing efficacy, such as the abuse of antibiotics leading to enhanced bacterial resistance. Therefore, there was an urgent need to develop an antibiotic-free multifunctional dressing for bacterially infected wound healing. This study demonstrated the preparation of a multifunctional injectable hydrogel and evaluated its efficacy in treating acute and infected wounds. The hydrogel was prepared by a one-step mixing method, and cross-linked by natural deep eutectic solvent (DES), polyvinyl alcohol (PVA), chitosan (CS), tannic acid (TA), and Cu2+ through non-covalent interactions (hydrogen bonds and metal coordination bonds). PVA/CS/DES/CuTA500 hydrogel has multiple functional properties, including injectability, tissue adhesion, biocompatibility, hemostasis, broad-spectrum antibacterial, anti-inflammatory, and angiogenesis. Most importantly, in the MRSA-infected skin wound model, PVA/CS/DES/CuTA500 hydrogel could ultimately accelerate infected wound healing by killing bacteria, activating M2 polarization, inhibiting inflammation, and promoting angiogenesis. In summary, the PVA/CS/DES/CuTA500 hydrogel showed great potential as a wound dressing for bacterial infected wounds treatment in the clinic.
... They come with hydrogel, gauze film, foam, scaffold, and hydrocolloid, all of which are commonly prepared with antimicrobial properties. [14][15][16] An ideal wound dressing material should demonstrate biocompatibility, adhere to the wound without leaving sticky residues, have optimal water absorption capacity, the adaptable to environmental changes such as pH or moisture levels, and have the ability to sustain a moist environment that is favorable for wound recovery. [17][18][19][20][21][22] Nevertheless, an ideal wound dressing system to the body's response to the injury. ...
Background
Conventional wound dressings often adhere to wounds and can cause secondary injury due to their lack of anti-inflammatory and antibacterial properties. In contrast, collagen-based nanoparticles (NPs) as drug delivery systems exhibit both biocompatibility and biodegradability, presenting a promising avenue for accelerating wound healing processes.
Aims of Study
This review aims to provide a comprehensive overview of the mechanisms involved in wound healing, description of the attributes of ideal wound dressings, understanding of wound healing efficacy of collagen, exploring NPs-mediated drug delivery mechanisms in wound therapy, detailing the synthesis and fabrication techniques of collagen-based NPs, and delineating the applications of various collagen-based NPs infused wound dressings on wound healing.
Methodology
This review synthesizes relevant literature from reputable databases such as Scopus, Science Direct, Google Scholar, and PubMed.
Results
A diverse array of collagen-based NPs, including nanopolymers, metal NPs, nanoemulsions, nanoliposomes, and nanofibers, demonstrate pronounced efficacy in promoting wound closure and tissue regeneration. The incorporation of collagen-based NPs has not only become an agent for the delivery of therapeutics but also actively contributes to the wound healing cascade.
Conclusion
In conclusion, In brief, the use of collagen-based NPs presents a compelling strategy for expediting wound healing processes.
... This is predicated on the benefits of nanoencapsulation and administration, such as improved stability and bioavailability of encapsulated com-pounds. 8 Therefore, various nanocarriers, including nanoliposomes, 9 nano emulsions, 10 microcapsules, 11 and hydrogels, 12 have been produced to encapsulate bioactive materials. The goal is to improve the stability, dispersion, bioavailability, and bioactive characteristics of phytochemicals for use as nano active carriers. ...
... In tandem with nitric oxide-releasing nanoparticles, exploration into liposomes and microfluidics as nanoparticle-based systems for drug delivery in diabetic wound healing has been undertaken. [191][192][193][194][195][196][197][198] Liposomes, characterized by lipid-based vesicles, have undergone extensive scrutiny in this domain. These vesicles, composed of a lipid bilayer structure, proficiently encapsulate therapeutic agents, shielding them from degradation and facilitating their controlled discharge at the wound site. ...
Diabetic wounds pose a significant challenge in healthcare due to impaired healing and increased risk of complications. In recent years, various drug delivery systems with stimuli-responsive features have been developed to address these issues. These systems enable precise dosage control and tailored drug release, promoting comprehensive tissue repair and regeneration. This review explores targeted therapeutic agents, such as carboxymethyl chitosan-alginate hydrogel formulations, nanofiber mats, and core-shell nanostructures, for diabetic wound healing. Additionally, the integration of nanotechnology and multifunctional biomimetic scaffolds shows promise in enhancing wound healing outcomes. Future research should focus on optimizing the design, materials, and printing parameters of 3D-bio-printed wound dressings, as well as exploring combined strategies involving the simultaneous release of antibiotics and nitric oxide for improved wound healing.
... This encapsulation enables controlled and targeted drug delivery to the wound site, optimizing treatment outcomes. 37 The lipid bilayers of liposomes mimic cell membranes, facilitating their interaction with cells at the wound site. This property enhances the penetration of drugs or bioactive compounds into tissues, including those with impaired circulation often seen in diabetic wounds. ...
Diabetic wounds pose a significant challenge in modern healthcare due to their chronic and complex nature, often resulting in delayed healing, infections, and, in severe cases, amputations. In recent years, nanotherapeutic approaches have emerged as promising strategies to address the unique pathophysiological characteristics of diabetic wounds. This review paper provides a comprehensive overview of the latest advancements in nanotherapeutics for diabetic wound treatment. We discuss various nanomaterials and delivery systems employed in these emerging therapies. Furthermore, we explore the integration of biomaterials to enhance the efficacy of nanotherapeutic interventions. By examining the current state-of-the-art research, challenges, and prospects, this review aims to offer valuable insights for researchers, clinicians, and healthcare professionals working in the field of diabetic wound care.
... [55] Pilitidepsin A plitidepsin-containing carrier demonstrated similar anticancer activity in four cancer cell lines. [56] Erlotinib A target-sustained-release mechanism for erlotinib may be achieved using cationic G4 dendrimers. [57] Liposome Taxifolin Increase the expression of CD31 and VEGF in skin tissues by inhibiting the NF-kappa B/Ikappa B signaling pathway and related pro-inflammatory factors in diabetic mice. ...
Modern nanostructures must fulfill a wide range of functions to be valuable, leading to the combination of various nano-objects into hierarchical assemblies. Hybrid Nanoparticles (HNPs), comprised of multiple types of nanoparticles, are emerging as nanoscale structures with versatile applications. HNPs offer enhanced medical benefits compared to basic combinations of distinct components. They address the limitations of traditional nanoparticle delivery systems, such as poor water solubility, nonspecific targeting, and suboptimal therapeutic outcomes. HNPs also facilitate the transition from anatomical to molecular imaging in lung cancer diagnosis, ensuring precision. In clinical settings, the selection of nanoplatforms with superior reproducibility, cost-effectiveness, easy preparation, and advanced functional and structural characteristics is paramount. This study aims toextensively examine hybrid nanoparticles, focusing on their classification, drug delivery mechanisms, properties of hybrid inorganic nanoparticles, advancements in hybrid nanoparticle technology, and their biomedical applications, particularly emphasizing the utilization of smart hybrid nanoparticles. PHNPs enable the delivery of numerous anticancer, anti-leishmanial, and antifungal drugs, enhancing cellular absorption, bioavailability, and targeted drug delivery while reducing toxic side effects.
... Dihydroquercetin, also known as paclitaxel, is a potent flavonoid antioxidant. It is commonly found in onion, silymarin, French marine bark, and Douglas fir bark [67,68]. Ding et al. fabricated hydrogels sensitive to temperature by incorporating the bioactive compound taxifolin (TAX) into Poloxamer 407, chitosan (CS), and hyaluronic acid (HA). ...
Chitosan is a linear polyelectrolyte with active hydroxyl and amino groups that can be made into chitosan-based hydrogels by different cross-linking methods. Chitosan-based hydrogels also have a three-dimensional network of hydrogels, which can accommodate a large number of aqueous solvents and biofluids. CS, as an ideal drug-carrying material, can effectively encapsulate and protect drugs and has the advantages of being nontoxic, biocompatible, and biodegradable. These advantages make it an ideal material for the preparation of functional hydrogels that can act as wound dressings for skin injuries. This review reports the role of chitosan-based hydrogels in promoting skin repair in the context of the mechanisms involved in skin injury repair. Chitosan-based hydrogels were found to promote skin repair at different process stages. Various functional chitosan-based hydrogels are also discussed.
... Another research group, led by Ding et al. [51], conducted experiments on nanocomposite membranes containing liposomes. This team developed an innovative wound dressing to accelerate the healing process of wounds in diabetic patients. ...
Studies on bionanocomposite drug carriers are a key area in the field of active substance delivery, introducing innovative approaches to improve drug therapy. Such drug carriers play a crucial role in enhancing the bioavailability of active substances, affecting therapy efficiency and precision. The targeted delivery of drugs to the targeted sites of action and minimization of toxicity to the body is becoming possible through the use of these advanced carriers. Recent research has focused on bionanocomposite structures based on biopolymers, including lipids, polysaccharides, and proteins. This review paper is focused on the description of lipid-containing nanocomposite carriers (including liposomes, lipid emulsions, lipid nanoparticles, solid lipid nanoparticles, and nanostructured lipid carriers), polysaccharide-containing nanocomposite carriers (including alginate and cellulose), and protein-containing nanocomposite carriers (e.g., gelatin and albumin). It was demonstrated in many investigations that such carriers show the ability to load therapeutic substances efficiently and precisely control drug release. They also demonstrated desirable biocompatibility, which is a promising sign for their potential application in drug therapy. The development of bionanocomposite drug carriers indicates a novel approach to improving drug delivery processes, which has the potential to contribute to significant advances in the field of pharmacology, improving therapeutic efficacy while minimizing side effects.
... The network structure of hydrogels has been reported to facilitate the proliferation and adhesion of osteoblasts, and the structure of hydrogels is very similar to the extracellular matrix of bone and cartilage, which makes hydrogels suitable for bone repair and regeneration [17]. Meanwhile, the excellent swelling properties of hydrogel can absorb tissue exudate from the damaged area of the tissue, thus reducing recurrent inflammatory infiltration and infection [18][19][20][21]. Hydrogels also have excellent hemostatic properties and tissue adhesion, which also positively modulate the repair of bone defects [22][23][24]. ...
Large bone defects due to trauma, infections, and tumors are difficult to heal spontaneously by the body’s repair mechanisms and have become a major hindrance to people’s daily lives and economic development. However, autologous and allogeneic bone grafts, with their lack of donors, more invasive surgery, immune rejection, and potential viral transmission, hinder the development of bone repair. Hydrogel tissue bioengineered scaffolds have gained widespread attention in the field of bone repair due to their good biocompatibility and three-dimensional network structure that facilitates cell adhesion and proliferation. In addition, loading natural products with nanoparticles and incorporating them into hydrogel tissue bioengineered scaffolds is one of the most effective strategies to promote bone repair due to the good bioactivity and limitations of natural products. Therefore, this paper presents a brief review of the application of hydrogels with different gel-forming properties, hydrogels with different matrices, and nanoparticle-loaded natural products loaded and incorporated into hydrogels for bone defect repair in recent years.
... It can be observed in the figure that the blood vessels were more prominently located in the group V and VI (black arrows), indicating a more mature dermis. This is also indicative of a more advanced CD 68 is a marker of pro-inflammatory macrophages, whereas CD163 indicates anti-inflammatory macrophages An increase in CD 68 expression indicates more active inflammation, and an increase in CD 163 indicates a resolving stage of inflammation [45][46][47]. It can be observed from Fig. 7(a), that CD-68 expression was higher in group I, II, III and IV. ...
This study focuses on development of a nanocomposite hydrogel for wound healing purposes. Poly-vinyl alcohol and poly-ethylene glycol-4000 were used to fabricate the hydrogel, physically crosslinking through freeze-thaw method, and magnesium oxide nanoparticles were incoprorated onto them. Notably, the integration of these nanoparticles induced significant changes in the hydrogel's properties, leading to marked improvements in its swelling ratio, water content, and tensile strength. This, in conjunction with their intrinsic moisture retention ability and enhanced antibacterial efficacy, makes these hydrogel nanocomposites as highly promising candidates for wound healing applications. Also, the minimal leaching of nanoparticles from these films reduced the risk of metal accumulation on wounds. To evaluate their performance in wound contraction, assessments were conducted using a live Wister rat model. It was observed that both bare and unloaded hydrogels promoted cell proliferation, and addition of human epidermal growth factor exponentially accelerated the process.The hydrogel films demonstrated biocompatibility and stimulated cell growth. Various parameters, including wound size contraction, angiogenesis, and reconstruction of the damaged epithelial layer, were examined using microscopic methods to assess the rate of wound healing.
A more profound understanding of the pathogenesis of acute or chronic wounds has recently been made possible by unprecedented developments in molecular science, leading to the discovery of imaginative bio-molecular targets and the development of advanced health care. In addition to its multi-functional approaches, the nanobiomaterials implanted technique demonstrated several benefits beyond traditional ways in a broad-spectrum operation for wound management. The healthcare challenges introduced by wound contagion have become incredible and exert a substantial influence on patient health and mortality along with the expenses of therapy. The intricate nature of typical wound-therapeutic procedures, cell sensitivity, and plenty of governing components, especially the molecular mechanism of persistent wounds, can all be targeted by nano-tech-based detection and therapies, which have endorsed exciting opportunities in wound management. Biomaterials using a nano-delivery platform is an emergent approach due to its ability to speed up and multi-functionality for comprehensive implementation in the field of distinctive wound management. The principles of fundamental mechanisms underlying the healing stages of wounds with potential wound treatment strategies have been highlighted in this chapter, with particular attention paid to various types of nanobiomaterials employed in cutaneous wound repair.
Introduction:
Wounds, resulting from traumas, surgery, burns or diabetes, are important medical problems due to the complexity of wound healing process regarding healing times and healthcare costs. Nanosystems have emerged as promising candidates in this field thank to their properties and versatile applications in drugs delivery.
Areas covered:
Lipid-based nanosystems (LBN) are described for wound treatment, highlighting their different behaviors when interacting with the cutaneous tissue. The role of nanosystems in delivering mostly natural compounds on skin as well as the technological and engineering strategies to increase their efficiency in wound healing effect are reviewed. Finally, in vitro, ex-vivo and in vivo studies are reported.
Expert opinion:
LBN have shown promise in addressing the challenges of wound healing as they can improve the stability of drugs used in wound therapy, leading to higher efficacy and fewer adverse effects as compared to traditional formulations. LBNs being involved in the inflammatory and proliferation stages of the wound healing process, enable the modification of wound healing through multiple ways. In addition, the use of new technologies, including 3D bioprinting and photobiomodulation, may lead to potential breakthroughs in wound healing. This would provide clinicians with more potent forms of therapy for wound healing.
Nanoparticles are structures that possess unique properties with high surface area-to-volume ratio. Their small size, up to 100 nm, and potential for surface modifications have enabled their use in a wide range of applications. Various factors influence the properties and applications of NPs, including the synthesis method and physical attributes such as size and shape. Additionally, the materials used in the synthesis of NPs are primary determinants of their application. Based on the chosen material, NPs are generally classified into three categories: organic, inorganic, and carbon-based. These categories include a variety of materials, such as proteins, polymers, metal ions, lipids and derivatives, magnetic minerals, and so on. Each material possesses unique attributes that influence the activity and application of the NPs. Consequently, certain NPs are typically used in particular areas because they possess higher efficiency along with tenable toxicity. Therefore, the classification and the base material in the NP synthesis hold significant importance in both NP research and application. In this paper, we discuss these classifications, exemplify most of the major materials, and categorize them according to their preferred area of application. This review provides an overall review of the materials, including their application, and toxicity.
Antimicrobial agents, cancer treatments, diabetes drugs, hypertension drugs, antifungal drugs, peptide hormones, enzymes, vaccines, and genetic materials are just some of the many drugs that Hesperidin loaded Liposomes (HLLs) have been shown to improve the delivery of in recent years. Liposomes can be broken down further into subgroups based on lamellarity, size, charge, and function due to variations in preparation processes and lipid compositions. They can be used for drug delivery via several routes of administration thanks to their adaptable behaviour, which is not dependent on their solubility. Liposomes loaded with hesperidin have the ability to target a chemical to specific tissues, potentially improving the therapeutic efficacy of several drugs. Medications' in vitro and in vivo efficacy can both be boosted by a drug delivery technology called hesperidin-loaded liposomes it can also decrease its toxicity, and increase its efficacy by delivering the molecule in a more regulated fashion. This article discusses analytical methods for managing physical, chemical, and biological characteristics in the production of various drugs, as well as ways for creating hesperidin-loaded liposomes. The main characteristics of the formation and manufacturing processes of liposome nanocarriers are covered in this article, with a focus on the structural characteristics and crucial factors that govern the development of acceptable and stable formulations. We detail the primary benefits (and drawbacks) of each method, as well as their suitability for mass industrial manufacturing.
Pomegranate peel extract (PPE) hydrogel films filled with citric acid (CA) and β-cyclodextrin-carboxymethyl tapioca starch (CMS) were designed mainly to prevent wound infections and speed up the healing process. FTIR and NMR studies corroborated the carboxymethylation of neat tapioca starch (NS). CMS exhibited superior swelling behavior than NS. The amount of CA and β-CD controlled the physicochemical parameters of developed PPE/CA/β-CD/CMS films. Optimized film (OF) exhibited acceptable swellability, wound fluid absorptivity, water vapor transmission rate, water contact angle, and mechanical properties. Biodegradable, biocompatible, and antibacterial films exhibited pH dependence in the release of ellagic acid for up to 24 h. In mice model, PPE/CA/β-CD/CMS hydrogel film treatment showed promising wound healing effects, including increased collagen deposition, reduced inflammation, activation of the Wingless-related integration site (wnt) pathway leading to cell division, proliferation, and migration to the wound site. The expression of the WNT3A gene did not show any significant differences among all the studied groups. Developed PPE-loaded CA/β-CD/CMS film promoted wound healing by epithelialization, granulation tissue thickness, collagen deposition, and angiogenesis, hence could be recommended as a biodegradable and antibacterial hydrogel platform to improve the cell proliferation during the healing of diabetic wounds.
Diabetes-related ulcers are still a therapeutic problem because of their susceptibility to infection, ongoing inflammation, and diminished vascularization. The design and development of novel dressings are clinically urgent for the treatment of chronic wounds due to diabetic ulcers. In this study, we made taxifolin (TAX) loaded sodium alginate (SA)/poly(vinyl alcohol) (PVA) nanofibers for the treatment of chronic wounds. The SA/PVA/TAX nanofibers that have been created are smooth and bead-free, with good thermal stability, hydrophilicity, and mechanical properties. The release profile indicated a sustained drug release, with a cumulative release rate of 64.6 ± 3.7 % at 24 h. In vitro experiments have shown that SA/PVA/TAX has good antibacterial activity, antioxidant activity, and biocompatibility. In vivo experiments have shown that SA/PVA/TAX exhibits desirable biochemical properties and is involved in the diabetic wound healing process by promoting cell proliferation (Ki67), angiogenesis (CD31, VEGFA), and alleviating inflammation (CD68). Western blotting experiments suggest that SA/PVA/TAX may promote diabetic wound healing by inhibiting the TLR4/NF-κB/NLRP3 signaling pathway and upregulating the expression of VEGFA and PDGFA. The 16S rRNA sequencing results showed that SA/PVA/TAX increased the wound surface flora's diversity and reversed the skin microbiota's structural imbalance. Therefore, SA/PVA/TAX can promote diabetic wound healing by modulating the inflammatory response, angiogenesis, and skin flora and has the potential to be an excellent wound dressing.
Jujube peel pigment (JP), an ideal natural water‐soluble pigment extracted from jujube peel, mainly consists of flavonoids and possesses a wide range of physiological activities. In this study, JP‐loaded multivesicular liposomes (JP‐MVL) were prepared using the double emulsification method. JP‐MVL was characterized, and its encapsulation efficiency was determined using the UV‐Vis method. Furthermore, the release behavior and antioxidant capacity of JP‐MVL were evaluated in vitro. The results displayed in the structure of JP‐MVL were spherical with internal vesicles; the average particle size of JP‐MVL was 5.63 μm, and the zeta potential was −69.50 mV. Analysis of the release results indicated that the best‐fitting models in PBS (Phosphate buffered saline pH 7.4) and 0.9% NaCl were the Higuchi and first‐order kinetic models, respectively. The cytotoxicity of JP‐MVL at the appropriate concentrations was negligible and had a good protective effect against UVB‐induced photodamage.
Wound healing is a complex and dynamic process, and metabolic disturbances in the microenvironment of chronic wounds and the severe symptoms they cause remain major challenges to be addressed. The inherent properties of hydrogels make them promising wound dressings. In addition, biomembrane-based nanostructures and microstructures (such as liposomes, exosomes, membrane-coated nanostructures, bacteria and algae) have significant advantages in the promotion of wound healing, including special biological activities, flexible drug loading and targeting. Therefore, biomembrane-based nanostructure- and microstructure-loaded hydrogels can compensate for their respective disadvantages and combine the advantages of both to significantly promote chronic wound healing. In this review, we outline the loading strategies, mechanisms of action and applications of different types of biomembrane-based nanostructure- and microstructure-loaded hydrogels in chronic wound healing.
Taxifolin (TAX) is a hepatoprotective flavanol compound, which is severely limited by poor solubility and low bioavailability. Liposomes (Lips) are used as well-recognized drug carrier systems that improve the water solubility and bioavailability of drugs, but are easily damaged by gastric juice after oral administration, resulting in the release of drugs in the gastric juice. Therefore, it is important to find materials that modify liposomes and avoid the destruction of the liposomal phospholipid bilayer structure by the gastrointestinal environment. Taxifolin liposomes (TAX-Lips) were modified by polyvinylpyrrolidone-k30 (PVP-TAX-Lips) and manufactured using a thin-film hydration technique. Particle size (109.27 ± 0.50 nm), zeta potential (−51.12 ± 3.79 mV), polydispersity coefficient (PDI) (0.189 ± 0.007), and EE (84.7 ± 0.2%) of PVP-TAX-Lips were studied. In addition, the results of in vitro release experiments indicated that the cumulative release rates of TAX-Lips and PVP-TAX-Lips were 89.73 ± 5.18% and 65.66 ± 4.86% in the simulated gastric fluid after 24 h, respectively, while the cumulative release rates were 68.20 ± 4.98% and 55.66 ± 3.92% in the simulated intestinal fluid after 24 h, respectively. Moreover, PVP-TAX-Lips were able to reverse lipopolysaccharide and D-galactosamine (LPS/D-GalN)-induced acute liver injury (ALI) by inducing autophagy to inhibit the expression levels of the TLR4/NF-κB signaling pathway and inflammatory factors, which suggested that PVP-TAX-Lips played an important role in the prevention of ALI and also provided a promising drug delivery system for the application of TAX.
Chronic wounds are a major health problem with increasing global prevalence, which endangers the physical and mental health of those affected and is a heavy burden to healthcare providers. Artemisia argyi extract (AE) has excellent antibacterial and anti-inflammatory properties. In this research, we developed AE loaded composite hydrogel scaffold based on methacrylate gelatin (GelMA)/methacrylate hyaluronic acid (HAMA) and mesoporous silica nanoparticle (MSN) as sustained-release drug carrier vehicles for the treatment of chronic wounds. The presented GelMA/1%HAMA hydrogel possessed stable rheological properties, suitable mechanical properties, appropriate biodegradability, swelling, sustained-release AE capacity. In vitro antibacterial and cell experiments showed that the GelMA/HAMA/MSN@AE hydrogel had excellent antibacterial activity and biocompatibility and induced macrophages to differentiate into M2 phenotype. In vivo wound healing of rat full-thickness cutaneous wounds further demonstrated that the prepared GelMA/HAMA/MSN@AE hydrogel could significantly promote chronic wound healing by upregulating the expression of IL-4, TGF-β1, CD31, and α-SMA but downregulating the expression of TNF-α and IFN-γ and promoting M1-M2 macrophages polarization. Altogether, we believe that the GelMA/HAMA/MSN@AE hydrogel will have wide application prospects in healing chronic wounds.
To obtain long‐lasting preservation materials, the tea polyphenol liposomes (TP‐Lips)/lysozyme (LZM)–chitosan (CS) composite coating with the gradual sustained property was prepared by tape casting method. These coatings were characterised, and their physicochemical properties were measured. Meanwhile, the antibacterial mechanisms of coatings were studied using the spoilage bacteria of aquatic products (Shewanella putrefaciens and Pseudomonas fluorescens) as target strains. Compared with CS coating, the incorporation of TP‐Lips makes the cracks and granular matter of the coatings increase. Except for the oxygen permeabilities (OP) and carbon dioxide permeabilities (CDP), the rest of the physicochemical properties are decreased, including tensile strength (Ts), elongation at break (EB) and light transmittance (T). Antibacterial mechanisms indicate that TP and LZM have a synergistic antibacterial effect. The slow‐release system composed of liposomes and coating prolongs the action time of TP and LZM. Hence, the TP‐Lips/LZM‐CS coating could be a hopeful material in food preservation field with excellent antibacterial properties.
With the worldwide prevalence of diabetes and considering the complicated microenvironment of diabetic wounds, the design and development of innovative multifunctional wound dressing materials are much wanted for the treatment of hard-to-heal wounds in diabetic patients. In the present study, anti-inflammatory ingredients loaded with nanofibrous wound dressing materials were manufactured by a promising blend-electrospinning strategy, and their capability for treating the diabetic wound was also systematically explored. A polymer blend consisting of Chitosan (CS) and polyvinyl alcohol (PVA) was electrospun into CS-PVA nanofibrous mats as control groups. In the meanwhile, a bioactive ingredient of Chinese medicine Pulsatilla, anemoside B4(ANE), with different contents were loaded into the electrospinning solution to construct CS-PVA-ANE nanofibrous mats. The developed CS-PVA-ANE wound dressing materials exhibited multifunctional properties including prominent water absorption, biomimetic elastic mechanical properties, and sustained ANE releasing behavior, as well as outstanding hemostatic properties. The in vitro studies showed that the CS-PVA-ANE nanofiber mats could significantly suppress lipopolysaccharide (LPS)-stimulated differentiation of pro-inflammatory (M1) macrophage subsets, and notably reduce the reactive oxygen species (ROS) generation, as well as obviously decrease inflammatory cytokine release. The in vivo animal studies showed that the CS-PVA-ANE nanofiber mats promoted the healing of diabetic wounds by significantly enhancing wound closure rates, accelerating excellent angiogenesis, promoting re-epithelization and collagen matrix deposition throughout all stages of wound healing. The present study demonstrated that CS-PVA-ANE nanofiber mats could effectively shorten the wound-healing time by inhibiting inflammatory activity, which makes them promising candidates for the treatment of hard-to-heal wounds caused by diabetes.
Diabetic wounds are complications of diabetes which are caused by skin dystrophy because of local ischemia and hypoxia. Diabetes causes wounds in a pathological state of inflammation, resulting in delayed wound healing. The structure of electrospun nanofibers is similar to that of the extracellular matrix (ECM), which is conducive to the attachment, growth, and migration of fibroblasts, thus favoring the formation of new skin tissue at the wound. The composition and size of electrospun nanofiber membranes can be easily adjusted, and the controlled release of loaded drugs can be realized by regulating the fiber structure. The porous structure of the fiber membrane is beneficial to gas exchange and exudate absorption at the wound, and the fiber surface can be easily modified to give it function. Electrospun fibers can be used as wound dressing and have great application potential in the treatment of diabetic wounds. In this study, the applications of polymer electrospun fibers, nanoparticle-loaded electrospun fibers, drug-loaded electrospun fibers, and cell-loaded electrospun fibers, in the treatment of diabetic wounds were reviewed, and provide new ideas for the effective treatment of diabetic wounds.
Complex dermal wounds represent major medical and financial burdens, especially in the context of comorbidities such as diabetes, infection and advanced age. New approaches to accelerate and improve, or "fine tune" the healing process, so as to improve the quality of cutaneous wound healing and management, are the focus of intense investigation. Here, we investigate the topical application of a recombinant immune modulating protein which inhibits the interactions of chemokines with glycosaminoglycans, reducing damaging or excess inflammation responses in a splinted full-thickness excisional wound model in mice. M-T7 is a 37 kDa-secreted, virus-derived glycoprotein that has demonstrated therapeutic efficacy in numerous animal models of inflammatory immunopathology. Topical treatment with recombinant M-T7 significantly accelerated wound healing when compared to saline treatment alone. Healed wounds exhibited properties of improved tissue remodeling, as determined by collagen maturation. M-T7 treatment accelerated the rate of peri-wound angiogenesis in the healing wounds with increased levels of TNF, VEGF and CD31. The immune cell response after M-T7 treatment was associated with a retention of CCL2 levels, and increased abundances of arginase-1-expressing M2 macrophages and CD4 T cells. Thus, topical treatment with recombinant M-T7 promotes a pro-resolution environment in healing wounds, and has potential as a novel treatment approach for cutaneous tissue repair.
An increase in the spread of antibiotic-resistant opportunistic microorganisms causes serious problems in the treatment of purulent infections, burns, and trophic ulcers. We tested the antimicrobial activity in vivo of three polyphenols, Resveratrol, Dihydroquercetin (Taxifolin), and Dihydromyricetin (Ampelopsin) from Norway spruce bark to promote the elimination of Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans from wounds. Purulent infection was modelled on wounds in rats infected with suspensions containing 109 CFU (colony-forming unit)/mL of pathogens. The wound area was treated daily with solutions of the polyphenols or placebo for 14 days after the beginning of the treatment. The animals were examined daily, and each stage of the wound healing (inflammation, granulation, and maturation (marginal epithelialisation) was documented. The planimetric analysis of the wound recovery percentage was performed on the 3rd, 10th, and 14th day after the start of curing. Then, one echelon (three or four animals from each subgroup) was withdrawn from the experiment on days 3 (three animals), 10 (three animals), and 14 (four animals) for microscopy analysis of cytological composition of their wound defects by microscopy and microbiological analysis of their contamination with pathogens. Our results show that they are also able to suppress mast cell infiltration and stimulate lymphocyte and macrophage (monocyte) infiltration into the wound. Resveratrol stimulated the replacement of the scar with normal tissue (with a clear boundary between the dermis and epidermis) and the restoration of hair follicles. Resveratrol turned out to be significantly better than some commercial antimicrobial (Levomecol) and antifungal (Clotrimazole) ointments and can be proposed as a promising drug for topical use for the treatment of trophic ulcers and burns.
In this study, daidzein long-circulating liposomes (DLCL) were prepared using the ultrasonication and lipid film-hydration method. The optimized preparation conditions by the orthogonal design was as follows: 55 to 40 for the molar ratio of soybean phosphatidylcholine (SPC) to cholesterol, 1 to 10 for the mass ratio of daidzein to total lipid (SPC and cholesterol) (w:w), the indicated concentration of 5% DSPE-mPEG2000 (w:w), 50 °C for the hydration temperature, and 24 min for the ultrasonic time. Under these conditions, the encapsulation efficiency and drug loading of DLCL were 85.3 ± 3.6% and 8.2 ± 1.4%, respectively. The complete release times of DLCL in the medium of pH 1.2 and pH 6.9 increased by four- and twofold of that of free drugs, respectively. After rats were orally administered, a single dose of daidzein (30 mg/kg) and DLCL (containing equal dose of daidzein), respectively, and the MRT0-t (mean residence time, which is the time required for the elimination of 63.2% of drug in the body), t1/2 (the elimination half-life, which is the time required to halve the plasma drug concentration of the terminal phase), and AUC0-t (the area under the plasma drug concentration-time curve, which represents the total absorption after a single dose and reflects the drug absorption degree) of daidzein in DLCL group, increased by 1.6-, 1.8- and 2.5-fold as compared with those in the free group daidzein. Our results indicated that DLCL could not only reduce the first-pass effect of daidzein to promote its oral absorption, but also prolong its mean resident time to achieve the slow-release effect.
The objective of this study was to develop an ultrasonic-assisted procedure for the extraction of total phenolics from Citrus aurantium L. blossoms (CAB) and evaluate the free radical scavenging activity and anti-HMG-CoA reductase activity of the total phenolics. In this work, a Box– Behnken design based on single-factor experiments was used to explore the optimum extraction process. Under the optimum conditions (extraction solvent 70.31% ethanol, extraction temperature 61.94 °C, extraction time 51.73 min, and liquid-to-solid ratio 35.63 mL/g), the extraction yield of total phenolics was 95.84 mg gallic acid equivalents (GAE)/g dry matter (DM), which was highly consistent with the theoretical value (96.12 mg GAE/g DM). The higher contents of total phenolics and five main phenolic compounds obtained from the optimized ultrasonic-assisted extraction (UAE) proved its efficiency when compared with conventional heat reflux extraction (HRE). The total phenolic extract showed excellent free radical scavenging properties against 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·), 2,2’-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) radical (ABTS+·), hydroxyl radical (·OH) and superoxide anion radical (·O2−), with IC50 values of 197.007, 83.878, 218.643, and 158.885 μg/mL, respectively; the extracts also showed good inhibition of β-hydroxy-β-methylglutaryl-CoA reductase (HMG-CoA reductase) activity, with an IC50 value of 117.165 μg/mL. Total phenolics from CAB could be a potential source of natural free radical scavenger and HMG-CoA reductase inhibitor.
Developed over 70 years, antibiotics are the most effective strategies to treat bacterial biofilm and infections. However, overuse of antibiotics in human healthcare and industrial applications has caused development of serious resistant bacteria. Therefore, alternative ways to prevent bacteria attachment and biofilm formation are urgently needed. Recently, mediated biofilm formation processes and smart antibacterial surfaces have emerged as promising strategies to prevent and treat bacterial infections. This review discusses the recent progress in biofilm interference and smart antibacterial surfaces. The smart antibacterial and anti-biofilm surface should be responsive to the bacterial infections environment, switchable between various antibacterial functions or with a special bionic structure and function. The major contents are: (i) smart anti-biofilm surfaces through preventing biofilm formation or promoting mature biofilms dissolution, (ii) smart materials for reversible killing and/or release of bacteria, (iii) smart surfaces responsive to bacterial infections microenvironment or external stimulus and (iv) bionic surfaces with antifouling and bactericidal properties.
Objective
The peptide lycosin-I has anti-bacterial and anti-cancer capacities. However, the anti-inflammatory activity of lycosin-I remains unknown. We investigated whether lycosin-I could attenuate inflammation. Materials and methodsHuman umbilical vein endothelial cells (HUVECs) were treated with lycosin-I before exposure to tumor necrosis factor-α (TNF-α). The expression of intercellular cell adhesion molecule-1 (ICAM-1), nuclear transcription factor-kappa B (NF-κB) p65 and inhibitory subunit of NF-κB alpha (IκBα) was evaluated by western blot. The expression of interleukin-6 (IL-6) and interleukin-8 (IL-8) was detected by quantitative RT-PCR or ELISA. Immunofluorescence analysis was used to determine the impact of lycosin-I on NF-κB pathway. C57BL/6 mice were pretreated with lycosin-I before exposure with lipopolysaccharide (LPS). ResultsLycosin-I significantly reduced the TNF-α-enhanced expression of IL-6, IL-8 and ICAM-1. Lycosin-I also inhibited the human monocyte cells adhesion to HUVECs. We further demonstrated that lycosin-I could effectively suppress the reaction of endothelial cells to TNF-α by inhibiting IκBα degradation. Subsequently, the phosphorylation and translocation of NF-κB p65 could also be attenuated. Furthermore, lycosin-I exhibited a significant protection of C57BL/6 mice against LPS-induced death. Conclusions
Our results suggested that the anti-inflammatory activity of lycosin-I was associated with NF-κB activation and lycosin-I had potential to be a novel therapeutic candidate for inflammatory diseases.
The mechanical properties of the skin are important for various applications. Numerous tests have been conducted to characterize the mechanical behavior of this tissue, and this article presents a review on different experimental methods used. A discussion on the general mechanical behavior of the skin, including nonlinearity, viscoelasticity, anisotropy, loading history dependency, failure properties, and aging effects, is presented. Finally, commonly used constitutive models for simulating the mechanical response of skin are discussed in the context of representing the empirically observed behavior.
The drug-loaded polyvinyl alcohol (PVA)/chitosan (CS) composite nanofibers intended to be used as matrix for transdermal drug delivery were fabricated by electrospinning, and then crosslinked through glulataraldehyde (GA). The morphology, chemical structure, thermal behavior, mechanical properties, hydrophilicity and drug release properties of drug-loaded PVA/CS composite nanofibers before and after crosslinking were characterized. The results showed that the morphology of PVA/CS composite nanofibers was not been destroyed in both crosslinking and in vitro drug release process. The Young's modulus, tensile strength, thermal properties and hydrophobicity of crosslinked PVA/CS composite nanofibers significantly increased in comparison with those of PVA/CS (without crosslinking) due to the formation of crosslinking network structure. In vitro release studies showed that crosslinked PVA/CS composite nanofibers had lower drug release rate and smaller amount of drug burst release than that of PVA/CS. According to release exponent “n”, the release of ampicillin sodium from crosslinked PVA/CS composite nanofibers fit to the Fickian diffusion mechanism. Those results demonstrate the potential utilization of crosslinked PVA/CS composite nanofibers as a transdermal drug delivery system.
Background:
Chronic non-healing wounds present a substantial economic burden to healthcare system; significant reductions in quality of life for those affected, and precede often serious events such as limp amputations or even premature deaths. This burden is also likely to increase with a larger proportion of elderly and increasing prevalence of life-style diseases such as obesity and diabetes. Reviews of the evidence on the burden of illness associated with chronic wounds have not been comprehensive in scope and have not provided an assessment of the distribution of the health care costs across categories of resource use.
Methods/design:
This study is a systematic review of multiple databases for studies on adult patients with chronic wounds and with the primary objective to assess the impact on health-related quality of life by category of ulcers, and associated direct and indirect costs. Eligible studies will primary be empirical studies evaluating, describing or comparing measurement of quality of life and economic impact. Two reviewers will independently screen titles and abstracts and select studies involving adults with chronic wounds. These investigators will also independently extract data using a pre-designed data extraction form. Differences in applied methodologies and uncertainties will clearly be accounted for. Conservative valuations of costs and impact on health-related quality of life will be prioritised. Variations that may depend on age distribution, the categorisation of ulcer, healthcare system etc. will be described clearly.
Discussion:
The proposed systematic review will yield a comprehensive assessment of the humanistic and economic burden of chronic wounds in an adult population. A better understanding of the humanistic and economic burden of chronic wounds is essential for policy and planning purposes, to monitor trends in disease burden and not at least in order to estimate the real-world cost-effectiveness of new treatments and therapies.
Systematic review registration:
PROSPERO CRD42016037496.
The surface charge density of nanoparticles plays an important role in the way they interact with biological systems. The ability to measure the surface charge density of nanoparticles in biological media is therefore of importance in understanding the magnitude of such interactions. There are a number of methods which may be used to assess surface charge density through the measurement of electrophoretic mobility. In order to better understand the comparability of these methods, the ζ-potential of silica nanoparticles in water, buffer and serum-based biological medium was measured by one ensemble and two particle-by-particle techniques: electrophoretic light scattering (ELS), tunable resistive pulse sensing (TRPS) and zeta particle tracking analysis (z-PTA). To allow the comparability of results from different techniques, test samples were prepared according to an established protocol, although some variations were necessary to meet specific instrument requirements. Here we compare, for the first time, measurement results from the different techniques and discuss how modifications related to parameters such as environmental pH, dilution factor and presence of biomolecules influence the charge measurements.
Zeta potential is a scientific term for electrokinetic potential in colloidal systems which has a major effect on the various properties of nano-drug delivery systems. Presently, colloidal nano-carriers are growing at a remarkable rate owing to their strong potential for overcoming old challenges such as poor drug solubility and bioavailability. Furthermore, they show an unlimited capacity in the field of drug targeting. The properties of nano-medicines such as release from dosage forms at specific sites as well as drug circulation and absorption into body membranes are dramatically affected by some physical and chemical characteristics of nano-drugs. Particle size and charge are two major factors which could play key roles in this regard. In this paper, the effect of zeta potential on different properties of nano-drug delivery systems is reviewed.
Impaired wound healing is a severe complication of sufferers, related to prolonged wound closure, a high infection rate, and eventually disabilities of organs. To aid resolve this issue, we developed the electrospun polyvinyl alcohol and chitosan (PVA/CS) nanofibrous scaffold-loaded flaxseed extract. The scaffold containing 10 wt% of the extract indicated a three-dimensional cross-network with a nano-scale diameter (257 ± 37 nm) and smooth surface. Also, the relevant analyses confirmed high water absorption, porosity, and wettability of the scaffold. Fourier-transform infrared (FTIR), degradation, and mechanical studies revealed the intact presence and loading of the extract into the scaffold, the complete degradation over 48 h, and a high tensile elastic modulus. Besides, the advanced scaffold displayed remarkable anti-oxidant and could inhibit the growth of both Gram-positive and negative bacteria compared to the free PVA/CS scaffold. Desired fibroblast viability and blood compatibility of flaxseed-loaded scaffold endorsed the biocompatibility for wound zones. The in vitro studies showed that the flaxseed-loaded scaffold resulted in an accelerated wound healing process and 100 % closure of the scratched area within 48 h. The results obtained reveal that the flaxseed-loaded PVA/CS electrospun scaffold could be effectively applied for wound healing promotion.
Wound healing is a complex process requiring multiple biological pathways and chemical responses to be activated and synchronized to recover tissue integrity. In normal physiological circumstances, the epidermal barrier restoration process through new tissue formation is highly efficient. However, increased production of reactive oxygen species, attack of pathogenic microorganisms, and high glucose level delay the normal healing process in diabetic patients. The successful treatment of diabetic wounds requires efficient strategies to control oxidative stress, promoting angiogenesis, re‐epithelialization, and collagen deposition. In this study, we developed a composite hydrogel for rapid wound healing in diabetic condition by the amalgamation of hypolipidemic property of silk fibroin (SF), antioxidant property of melanin and therapeutic effect of berberine. Studies have revealed that cross‐linked mesoporous morphology of hydrogel matrix facilitates slow release of berberine to impart long‐term therapeutic effects at wound site. The composite hydrogel formulation is biocompatible, stimulates effective migration of fibroblast cells, and control oxidative stress under in vitro conditions. The hydrogel served as scaffold for tissue re‐epithelialization and promotes wound repair in diabetic type I Wistar rat model. This study demonstrates the ability of berberine‐ loaded SF‐melanin composite hydrogel (SFCH) as a potential dressing formulation for wound healing in diabetic conditions. This article is protected by copyright. All rights reserved
In modern clinical applications, wound healing remains a considerable challenge. Excessive inflammatory response is associated with delayed wound healing. In this study, we prepared composite nanofibrous membranes by mixing the Chinese herbal extract puerarin (PUE) with natural silk protein (SF) and synthetic polymer polyvinylpyrrolidone (PVP) using electrostatic spinning technique, and conducted a series of studies on the structural and biological properties of the fibrous membranes. The results showed that the loading of PUE increased the diameter, porosity and hydrophilicity of nanofibers, which were more favorable for cell adhesion and proliferation. ABTS radical scavenging assay also showed that the loading of PUE enhanced the antioxidant properties of the fibrous membranes. In addition, SF/PVP/PUE nanofibers are non-toxic and can be used as wound dressings. In vitro experiments showed that SF/PVP/PUE nanofibers could effectively alleviate lipopolysaccharide (LPS)-induced inflammation in Immortalized human keratinocytes (HaCaT) cells and down-regulate pro-inflammatory cytokine expression in cells. In vivo studies further showed that the SF/PVP/PUE nanofibers could effectively accelerate wound repair. The mechanism is that SF/PVP/PUE nanofibers can inhibit the activation and transduction of toll-like receptor 4/myeloid differentiation factor88/nuclear factor kappa B (TLR4/MyD88/NF-κB) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathways, thereby reducing the inflammatory response and achieving wound healing.
Impaired diabetic wounds are serious pathophysiological complications associated with persistent microbial infections including failure in the closure of wounds, and the cause of a high frequency of lower limb amputations. The healing of diabetic wounds is attenuated due to the lack of secretion of growth factors, prolonged inflammation, and/or inhibition of angiogenic activity. Diabetic wound healing can be enhanced by supplying nitric oxide (NO) endogenously or exogenously. NO produced inside the cells by endothelial nitric oxide synthase (eNOS) naturally aids wound healing through its beneficial vasculogenic effects. However, during hyperglycemia, the activity of eNOS is affected, and thus there becomes an utmost need for the topical supply of NO from exogenous sources. Thus, NO-donors that can release NO are loaded into wound healing patches or wound coverage matrices to treat diabetic wounds. The burst release of NO from its donors is prevented by encapsulating them in polymeric hydrogels or nanoparticles for supplying NO for an extended duration of time to the diabetic wounds. In this article, we review the etiology of diabetic wounds, wound healing strategies, and the role of NO in the wound healing process. We further discuss the challenges faced in translating NO-donors as a clinically viable nanomedicine strategy for the treatment of diabetic wounds with a focus on the use of biomaterials for the encapsulation and in vivo controlled delivery of NO-donors.
Background
The emergence of antibiotic resistance over the past decade has made the treatment of Staphylococcus aureus infection difficult. Burn wounds infected with methicillin-resistant S. aureus (MRSA) can cause mortality in animals. Shikonin (SH) has been reported to possess antimicrobial and anti-inflammatory properties, and is also responsible for the process of wound healing. However, the pharmacological mechanism of its wound healing process remains poorly comprehended, hence the probable mechanism deserves further investigation.
Purpose
The current study was designed to develop a novel SH-liposome with improved anti-MRSA effect and to detect its beneficial wound healing effects.
Study Design
In vitro antibacterial tests and in vivo infected wound healing test were conducted.
Methods
SH-liposome was produced by the film formation method, and the characteristics were measured using a laser particle size analyzer, transmission electron microscopy, and the dialysis method. Additionally, in vitro antibacterial tests were conducted to investigate the antibacterial effects and the relative mechanism of SH-liposome. Furthermore, the therapeutic effects and bioactivity of SH-liposome in MRSA infected burn wounds were investigated in rats. Sixty-four male Sprague Dawley rats (250 ± 10 g) were randomly divided into four groups, including Group I (control group); Group II (model group); Group III (SH-liposome group) and Group IV (Arnebia oil® group), and the drug treatments were applied topically twice daily for 21 days. Further, full thickness skin biopsies at different periods were collected aseptically to evaluate tissue cytokines, recognize flora, observe histopathological changes, and determine the mechanism underlying the wound healing effects of SH-liposome. The data were analyzed via one-way analysis of variance (ANOVA) and Duncan's multiple range test.
Results
The results showed that SH-liposome was successful with a drug load of 4.6 ± 0.17%. Moreover, SH-liposome showed a sustained-release behavior and improved antibacterial ability in a dose-dependent manner. For the possible antibacterial mechanism, we observed that SH-liposome achieved antibacterial activity by damaging the integrity of bacterial cell wall and membrane to further disturb the physiological activities of S. aureus. In addition, SH-liposome facilitated wound healing by inhibiting bacterial activities to control infection, regulating the I-κBα/NFκB-p65 pathway to alleviate inflammation, and directly promoting repair in burn wounds.
Conclusion
In conclusion, SH-liposome showed an antibacterial effect against S. aureus, promoted effective healing of infected burn wounds; hence, it could be used as an alternative therapy for drug-resistant infections.
Drug delivery technology can prevent wound infection and inflammatory reactions and accelerate wound healing and quality. In this paper, we propose preparing a multifunctional medical dressing to meet the various needs of people for dressing. A multi-layered composite nanofiber membrane was constructed using silk fibroin as the substrate, and mesoporous silica nanoparticles (MSN) with high adsorption properties were first prepared and then electrosprayed on silk fibroin (SF)/chitosan (CS) microspheres to form MSN-SF/CS microspheres with uniform distribution. Then the MSN-SF/CS microspheres were sprayed on the silk fibroin (SF)/polycaprolactone (PCL)-polyvinyl alcohol (PVA) unidirectional water-conducting composite nanofiber membrane. The test results showed that the encapsulation rate of bovine serum albumin (BSA) by MSN-SF/CS drug-loaded microspheres was 65.53% and the cumulative release rate in vitro was 54.46%. The results of in vitro experiments also showed its good antibacterial effect and good biocompatibility. To eliminate excess wound exudate and reduce inflammation, the cumulative unidirectional transport capacity (AOTC) of 651.75% was achieved by spraying the microspheres on an SF/PCL- PVA unidirectional water conductive composite membrane. This study could stimulate and promote the use of additional wound healing biomaterials in clinical medicine.
The high cost of wound healing treatment, the slow recovery of wounds, and the uncertainty of being affected by the body's physiological activities constitute a serious burden on public health. In this work, we report the preparation and characterization of chitosan (CS), PVP, and dihydroquercetin (DHQ) nanofiber film used as wound excipients, as well as in vivo and in vitro evaluations, and verify that the film is effective in wounds. The results show that the prepared film has good morphology, thermal stability and hydrophilicity. In vitro studies have shown that it has antibacterial activity against S.aureus and E.coli, and the DPPH free radical scavenging rate proves that the fiber film has antioxidant activity. MTT cytotoxicity test proved that the film is non-toxic to Hacat cells. Animal experiments have proved that wounds treated with CS-PVP-DHQ nanofiber film heal faster. This article also studied the composite nanofiber film by inducing autophagy pathway and increasing the expression of pan-keratin, vascular endothelial growth factor VEGF and CD31 to promote wound healing. Therefore, the nanofiber film herein show great potential in wound healing applications.
To investigate antibacterial properties and application in food preservation of nanofibrous films (NFs), baicalin-liposomes (BCL-LPs) were loaded into polyvinyl alcohol-chitosan (PVA-CS) substrates to form NFs using electrospinning technology. The microstructure and phase identification of the NFs were characterized. The antibacterial properties and cytotoxicity of NFs were determined. The preservation of the NFs to mushrooms was evaluated. The results showed that smooth and uniform NFs were formed through molecular interaction between BCL-LPs and PVA-CS matrix. The NFs exhibited good antibacterial effects on Escherichia coli and Staphylococcus aureus due to the bacterial destruction resulting from the BCL delivery to bacterial cells by liposomes. In addition, the NFs were compatible with L929 fibroblasts. The BCL-LPs/PVA-CS NFs inhibited weight loss, browning, rancidity and bacterial growth as well as maintained the nutrients of mushrooms. The results show BCL-LPs/PVA-CS NFs possessed effective antibacterial properties, non-cytotoxicity and preservation performance, indicating the potential utilization as food-active packing.
Combining biodegradable materials with natural plant components for wound dressing has been receiving significant attention. ART is a sesquiterpene lactone compound extracted from Artemisia annua L., possessing multiple pharmacological effects including antibacterial activity and anti-inflammatory property. Herein, the blended polylactic acid glycolic acid (PLGA)/silk fibroin (SF) membranes loaded with artemisinin (ART) are fabricated through electrospinning. With aid of SF, the fabricated membranes have a good sustained-release effect, and the accumulated ART release can reach 69% after three weeks. PLGA/SF/ART membranes exhibit favorable anti-inflammatory and cell compatibility in vitro evaluations. The in vivo experiment indicates that PLGA/SF/ART2 membranes can shorten the inflammation period and enhance skin regeneration in a full-thickness wound model through down-regulating the expressions of pro-inflammatory cytokines IL-1β and TNF-α. To sum up, the fabricated PLGA/SF/ART2 composite membranes with anti-inflammatory properties can be a proposal wound dressing for chronic wound healing.
Wounds can take longer to heal in diabetic patients, increasing the risk of infections and other complications. The most common wounds in diabetic patients are diabetic foot ulcers, a severe complication associated with diabetes mellitus. The United States alone spends $18.7 billion annually on care for these wounds including pain and infection management. If improperly managed, infected lesions may require amputation. The enormous cost associated with wound care and the dire consequences if not cared for properly, emphasize the need to develop strategies to accelerate the healing of diabetic foot wounds. Natural rubber latex (NRL), extracted from Hevea brasiliensis (the rubber tree), has been widely applied as a carrier system for several pharmacologically active compounds. Furthermore, it has been shown to encourage angiogenesis, facilitate cell adhesion, and accelerate wound healing. When NRL dressings are applied to wounds of diabetic patients, exudate release is upregulated. The production of exudate is essential to wound healing as it provides the nutrients, proteins, cells, and environment required for regeneration. Despite its benefits, it is necessary to control excess exudate to avoid prolonged healing resulting from dermatitis, maceration of the wound edges, and lesion growth. In order to solve the problem of excessive exudate release induced by NRL membrane application, we aimed to regulate humidity by absorbing excess exudate and increase water vapor transmission. We developed a highly absorptive, permeable, alginate loaded NRL dressing. Adding alginate to NRL membranes, swelling was increased up to 80-fold, absorbing 4.80 g of water per gram of dry membrane. Moreover, water vapor transmission was improved drastically as the material transmitted 480% more water vapor than pure NRL membranes. Furthermore, in vitro tests demonstrated not only that the membranes are biocompatible, but that they also enhance cell proliferation. Through a cell proliferation assay, we observed that fibroblast proliferation was improved by the presence of NRL while the keratinocytes benefit from the presence of alginate. The NRL-alginate dressings have great potential to improve diabetic wound care by accelerating the healing process.
PurposeThe study aimed to formulate hydrocolloid dressings incorporated with nano calcium oxide for effective wound healing. Hydrocolloid dressings create an insulated, moist environment in the wound bed for controlling the exudate and promoting autolytic debridement. Calcium ions play an important role in wound response and are considered to be an initial trigger in our immune response to healing, and research has shown that Ca2+ in the external medium is essential for wound repair.Methods
Seventy five parts per million of nano calcium oxide (NCO) obtained by thermal decomposition of calcium nitrate at 450 °C was used in the preparation of hydrocolloid dressings along with varying concentrations of micronized xanthan gum and HPMC. The dressings were evaluated for their surface characteristics, thickness, mechanical properties, folding endurance, pH, viscosity, swelling studies, water vapor transmission, and in vivo wound healing activity.ResultsThe average particle size of NCO was found to be 307.8 nm. The SEM (scanning electron microscopy) analysis of the dressing revealed a porous surface and EDX (energy dispersive X-ray spectroscopy) characterization showed intense peaks of calcium and oxygen. The formulated dressings possessed uniform thickness, flexibility, and mechanical strength. The percentage of wound contraction was higher in wounds treated with formulated hydrocolloid dressings in comparison to standard commercial product (DuoDERM® hydrocolloid dressing) and control (untreated) group. The wound healing properties of hydrocolloid dressings were confirmed by histopathological analysis.Conclusion
Nano calcium incorporated hydrocolloid dressings with enhanced wound healing activity were developed successfully.
Herein, the natural extract of garlic, allicin (Alli), was added into chitosan (CS)/polyvinyl alcohol (PVA)/graphene oxide (GO) composites to develop the nanofibrous membranes with strong antibacterial activity and sustained-release properties by electrospinning technology. Vitro Alli release test showed that the release rate and amount of Alli could be regulated by the content of GO in the nanofibrous membrane. The antibacterial activity test against Staphylococcus aureus was performed and revealed the antibacterial activity of nanofibrous membranes loading with Alli. Compared with the nanofibrous membrane without GO, the CS/PVA/Alli nanofibrous membrane with 0.1 wt% GO still had nice antibacterial activity after 48 h. The water contact angle of nanofibrous membranes dropped significantly with the addition of GO and Alli, which showed the nanofibrous membrane had highly hydrophobic. The CS/PVA/GO nanofibrous membrane loading with Alli had great hygroscopicity and moisture-retention capacity. The essential characteristics of nanofibrous membranes were evaluated by SEM, FTIR, XRD. The above results indicate that the membrane has a strong antimicrobial activity and long-lasting efficacy, so the developed natural nanofibrous membranes hold potential as promising antibacterial wound dressing and tissue engineering.
Easy and rapid continuous large-scale industrial production of transparent visualized cutaneous wound healing dressing from normal nature polymers is very worth studying in medical natural polymer materials and multifunction gauze dressing design fields. In this work, a super clear, porous cellulose membranes with chitosan-coated nanofiber were fabricated by using a simple, one-step electrostatic spinning (ES) technology and evaluated as potential wound dressings. Firstly, the pure cellulose membranes (CM) were dissolved by a simple physical method, and then the membranes were regenerated in the acidic coagulation bath by the casting method. The chitosan solution was polarized into nanofiber and formed a continuous fiber mat on cellulose membranes due to the charge repulsion between molecules. The prepared chitosan-coated cellulose membranes (CM-CS) were characterized by SEM, FT-IR, XRD, DSC and Tensile tests, etc. The results indicated that CM-CS showed high wettability, hydrophilicity, and gas permeability, in addition to excellent light transmittance and mechanical compliance. Cell cytotoxicity and morphology assay, and antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were also studied. It exhibited a good biocompatibility and antibacterial activity of CM-CS. Moreover, evaluation of an in vivo wound healing model in mice revealed that CM-CS had a good effect in promoting wound healing. This work provided an easy and rapid continuous large-scale industrial design strategy for nature bioresource-based wound dressing materials, which could act the potential wound dressings for clinical use. Keywords: Cellulose/chitosan membrane; electrostatic spinning technology; visualization; antibacterial activity; wound dressing.
In this study, nanovesicles such as transfersomes, niosomes and liposomes prepared by Ethanol Injection Method (EIM) and formulated with soybean lecithin, Tween 80, Span 60 and cholesterol, were used to improve the bioavailability of taxifolin, a natural antioxidant with beneficial properties for health and food preservation. Morphology, stability and the in‐vitro release of the optimal formulations were fully examined. The obtained results indicated that taxifolin‐loaded nanovesicles presented sizes ranging between 98 to 215 nm along with a narrow size distribution (polydispersity index (PDI) less than 0.250). The zeta potential of nanovesicles was negative and in the range of ‐20.40 to ‐32.20 mV. The optimal formulations with the maximum encapsulation efficiency (72‐75%) were the transfersomes formulated with lecithin and Tween 80 in the presence and absence of cholesterol. Additionally, in vitro release behavior of nanovesicles showed low taxifolin released (3.68‐10.13%) at intestinal conditions, whereas more than 90% of taxifolin released at gastrointestinal conditions. The compatibility between taxifolin and nanovesicles components was confirmed by FTIR. Transmission Electron microscopy (TEM) demonstrated spherical shaped particles around 200 nm. Backscattering (BS) profiles variations showed the potential application of taxifolin nanovesicles for producing fortified apple juice with excellent physical stability. Practical applications: Taxifolin is a flavanonol, which fulfills a particular task in preserving stable functions of circulatory system owing to its special antioxidant ability and biological activity. Nevertheless, its low bioavailability is a salient drawback for biomedical and food applications. Thus, the current study has been conducted to encapsulate taxifolin in nanovesicles (such as liposome, niosome, transfersome) by Ethanol Injection Method (EIM) to improve its bioavailability. Nanocarriers with relatively decent physical stability and high encapsulation efficiency could be brought about through Tween 80, soybean lecithin and in the presence and absence of cholesterol as stabilizer which ensures the successful delivery of taxifolin to food format such as beverages. This article is protected by copyright. All rights reserved
Potential usage of biodegradable and biocompatible polymeric nanofibers is the most attention grabbing topic for the drug delivery system. In order to fabricate ultrafine fibers, electrospinning, one of the well-known techniques, has been extensively studied in the literature. In the present study, the objective is to achieve the optimum blend of hydrophobic and hydrophilic polymers to be used as a drug delivery vehicle and also to obtain the optimum amount of doxycycline (DOXH)to reach the optimum release. In this case, the biodegradable and biocompatible synthetic polymers, poly(ε-caprolactone)(PCL)and poly(ethylene oxide)(PEO), were blended with different ratios for the production of DOXH-loaded electrospun PCL/PEO membranes using electrospinning technique, which is a novel attempt. The fabricated membranes were subsequently characterized to optimize the blending ratio of polymers by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD)and water contact angle analysis. After the characterization studies, different amounts of DOXH were loaded to the optimized blend of PCL and PEO to investigate the release of DOXH from the membrane used as a drug delivery vehicle. In vitro drug release studies were performed, and in vitro drug release kinetics were assessed to confirm the usage of these nanofiber materials as efficient drug delivery vehicles. The results indicated that 3.5% DOXH-loaded (75:25 w/w)PCL/PEO is the most acceptable membrane to provide prolonged release rather than immediate release of DOXH.
Propolis, a natural bee product, has both antimicrobial/antifungal and antioxidant characteristics. Active substances having antimicrobial and antifungal effects are used to avoid infections, which develop during long treatment process of chronic wounds. Antioxidant substances protect wound areas against the effect of free radicals and accelerate the healing process. For this purpose, propolis was used to develop topical liposome formulations for wound treatment. Characterization studies (particle size distribution, polydispersity index, Zeta Potential, morphology pH, loading capacity, encapsulation efficiency, in-vitro release behavior) as well as stability studies were performed. Then in-vitro antioxidant (free radical scavenging capacity and trolox equivalent antioxidant capacity) and antimicrobial/antifungal activities of formulations have been evaluated. The particle size of formulations was found within the range of 300-750 nm depending on the concentration of lipid and water phase in the formulation. The Zeta Potential and pH values of optimum formulation were -23.0 ± 0.666 and 6.34, respectively. Loading capacity and encapsulation efficiency were 66.535 ± 2.705% and 57.321 ± 2.448%. At the end of 8 hours, 48.16% of propolis was released and the formulations were found stable during 3 months at +4 °C. Drug loaded liposome formulations significantly scavenged the ABTS⁺ radical in a dose-dependent manner of propolis when compared with unloaded liposome formulations (p < 0.05). The minimum inhibitory concentration (MIC) values of liposomes ranged from 512-128 μg/mL for bacteria and 256-128 μg/mL for fungi. Overall results showed that effective and innovative alternative was developed for topical application in wound treatment with propolis loaded liposomal formulations having antioxidant and antimicrobial effects.
Aloin is the major anthraquinone glycoside obtained from the Aloe species and exhibits anti-inflammatory and anti-oxidative activities. Here, we aimed to determine the effects of aloin on heme oxygenase-1 (HO-1) induction and on the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX) 2 in lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs). To the end, aloin was tested whether aloin reduces iNOS protein expression and inflammatory markers (interleukin (IL)-1β and tumor necrosis factor (TNF)-α) in LPS-treated mice lung tissue. The results indicated that aloin affected HO-1 induction and reduced LPS-activated NF-κB-luciferase activity showed to preferential inhibition of iNOS/NO and COX-2/PGE2 that was partly related to inhibition of STAT-1 phosphorylation. In particular, aloin induced translocation of Nrf2 from cytosol into the nucleus by an increased Nrf2-ARE binding activity, and reduced IL-1β production in LPS-activated HUVECs. The reduced expression of iNOS/NO by aloin was reversed by siHO-1RNA-transfection. In LPS-treated mice, aloin significantly reduced iNOS protein in lung tissues, and TNF-α levels in the BALF. We concluded that aloin may be beneficial for treatment of lung injury.
Electrospun nanofibrous mats based on biopolymers have been widely investigated for tissue engineering in recent years, primarily due to remarkable morphological similarity to the natural extracellular matrix (ECM). In this research, electrospun PVA/Chitosan/Starch nanofibrous mats were fabricated using electrospinning method for wound dressing application. The prepared nanofibrous mats were then cross-linked to enhanced the water resistance and also optimize the biodegradation rate followed by characterization and evaluation of their properties as wound dressings. The morphological studies performed by SEM and AFM showed that uniform bead-free electrospun nanofibrous mats were formed. The structural properties of the fabricated mats were characterized by FTIR. The proper porosity and balanced water absorption and water vapor transmission rate (WVTR) of obtained dressings, demonstrate their ability in providing suitable moist environment for wound, result in the appropriate wound breathing and simultaneously efficient handling of wound exudates. Suitable mechanical properties of nanofibrous dressing in both dry and wet states confirm the capability of fabricated wound dressing to protect wound area against the external forces during the healing process. Antibacterial test revealed excellent antibacterial activity of nanofibrous mats against both gram negative and gram positive bacteria. Furthermore, the in vitro cytotoxicity evaluated by MTT assay, proved appropriate cytocompatibility and cell viability of the developed nanofibrous mats which were also verified with in vitro wound healing analysis performed by scratch assay, confirming the remarkable potential of the investigated nanofibrous mats for wound dressing application.
The increased prevalence of chronic wounds requires novel treatment options. The aim of this study was to develop a beta-glucan (βG)-loaded nanofiber wound dressing. Nanofibers were prepared using the needle-free Nanospider™ technology, an electrospinning method which enables the production of nanofibers at an industrial scale. The βG was selected as active ingredient based on its confirmed wound healing potential in both animals and humans. Hydroxypropyl methylcellulose (HPMC) and polyethylene oxide (PEO) were included as copolymers. Rheological profiles of spinning solutions containing HPMC, PEO, βG, ethanol and water, were optimized. The nanofiber formation was confirmed by Field Emission Scanning Electron Microscopy (FE-SEM), and both nanofibers with (βG-nanofibers) or without βG (NoβG-nanofibers) were evaluated by their swelling index and FT-IR spectroscopy. The formulations, active ingredient and excipients were tested for their possible in vitro toxicity in keratinocytes. Finally, the wound healing potential of the nanofibers was tested in externally induced excisional wounds in male diabetic db/db mice. Three different doses of βG-nanofibers and the βG-free, NoβG-nanofibers, were evaluated for their in vivo wound healing efficacy. All nanofiber-treatments provided improved wound healing as compared to the negative control (water). All βG-nanofiber treated groups exhibited significantly improved wound healing as compared to the NoβG-nanofiber treated group, indicating the potential of βG-nanofibers as wound dressing.
The present study aimed to evaluate the efficacy of cellulose acetate/gelatin/nanohydroxyapatite (CA/Gel/nHA) nanocomposite mats as the wound dressing. The dressings were prepared with electrospinning of CA/Gel solutions containing 12.5, 25 and 50 mg nHA. The dressings were evaluated regarding their water uptake capacity, morphology, tensile strength, water vapour transmission rate, wettability and cellular response with L929 cell line. The results showed that the concentration of nHA had a direct correlation with porosity, water contact angle, water uptake, water vapor transmission rate and proliferation. In vivo studies showed that all dressings had higher wound closure percent than the sterile gauze, as the control. The highest wound closure value was achieved in the CA/Gel +25 mg nHA group, which showed 93.5 ± 1.6%. The histological and the histomorphometric examinations of the wounds revealed that the CA/Gel +25 mg nHA dressing had the greatest collagen synthesis, re-epithelialization, neovascularization and also the best cosmetic appearance. Based on our finding, it could be concluded the applicability of electrospun nanofibrous CA/Gel/nHA dressings for successful wound treatment.
How to maintain the stability of basic fibroblast growth factor (bFGF) in wounds with massive wound fluids is important to accelerate wound healing. Here, a novel liposome with hydrogel core of silk fibroin (SF-LIP) is successfully developed by the common liposomal template, followed by gelation of liquid SF inside vesicle under sonication. SF-LIP is capable of encapsulating bFGF (SF-bFGF-LIP) with high efficiency, having a diameter of 99.8 ± 0.5 nm and zeta potential of -9.41 ± 0.10 mV. SF-LIP effectively improves the stability of bFGF in wound fluids. After 8 h of incubation with wound fluids at 37 °C, more than 50% of free bFGF are degraded, while only 18.6% of the encapsulated bFGF in SF-LIP are destroyed. Even after 3 d of preincubation with wound fluids, the cell proliferation activity and wound healing ability of SF-bFGF-LIP are still preserved but these are severely compromised for the conventional bFGF-liposome (bFGF-LIP). In vivo experiments reveal that SF-bFGF-LIP accelerates the wound closure of mice with deep second-degree scald. Moreover, due to the protective effect and enhanced penetration ability, SF-bFGF-LIP is very helpful to induce regeneration of vascular vessel in comparison with free bFGF or bFGF-LIP. The liposome with SF hydrogel core may be a potential carrier as growth factors for wound healing.
Lower-extremity complications of diabetes such as foot ulcers constitute a substantial burden for people with diabetes. Once healed, foot ulcers frequently recur. This fact, coupled with demographic trends, requires a collective refocusing on prevention and a reallocation of resources from simply healing active ulcers to maximizing ulcer-free days for all patients with a history of diabetic foot ulceration. Aggressive therapy during active disease combined with a focus on improving care during remission can lead to more ulcer-free days, fewer inpatient and outpatient visits, and an improved quality of life.
This study is aimed to develop curcumin (Cur) incorporated electrospun nanofibers of a blend of poly (lactic acid) (PLA) and hyperbranched polyglycerol (HPG) for wound healing applications. Both the polymers are synthesized and fabricated by electrospinning technique. The produced nanofibers were characterized by Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), Differential Scanning Colorimetry (DSC) and Thermogravimetric Analysis (TGA). Electrospun scaffolds (PLA/HPG/Cur) exhibits very high hydrophilicity, high swelling and drug uptake and promotes better cell viability, adhesion and proliferation when compared to PLA/Cur electrospun nanofibers. Biodegradation study revealed that the morphology of the nanofibers were unaffected even after 14 days immersion in Phosphate Buffered Saline. In vitro scratch assay indicates that migration of the cells in the scratch treated with PLA/HPG/Cur is complete within 36 h. These results suggest that PLA/HPG/Cur nanofibers can be a potential wound patch dressing for acute and chronic wound applications.
In consideration of the strong volatility and chemical instability of eugenol, liposomes were introduced to remain the activity of eugenol during processing and storage. Silica nanoparticle (SiO2) was used to adsorb eugenol before liposome encapsulation for getting better physicochemical properties and physical stability. The results of particle size, zeta potential and encapsulation efficiency of liposomes containing SiO2-eugenol were 315.7 ± 0.7 nm, −47.7 ± 0.3 mV, and 89.91 ± 0.43%, respectively. The experiments testing the physical stability of liposomes containing SiO2-eugenol showed that SiO2 could significantly promote its stability. For the application in food antioxidant, electrospun nanofibrous membranes were introduced to immobilize the SiO2-eugenol liposomes. In this study, the antioxidant assay of SiO2-eugenol liposome loaded nanofibrous membranes exhibited antioxidant activity on beef.
Background:
Negative pressure wound therapy (NPWT) was one of the most important treatments of diabetic foot, but the underlying mechanisms still remain elusive. This study aimed to evaluate the inflammatory signals involved in the effects of NPWT on diabetic foot ulcers.
Methods:
We enrolled 22 patients with diabetic foot ulceration, eleven treated with NPWT and others treated with traditional debridement. All the patients were treated and observed for 1 week. Granulation tissue harvested and analyzed in both groups, and was histologically and immunohistochemical analyzed. Enzyme-Linked Immunosorbent Assay (ELISA), Western blot analysis and real-time PCR were performed to evaluate expression of IL-6, TNF-α, iNOS, Nuclear Factor-κB P65, Ik B-α and activating transcription factor-3 (ATF-3).
Results:
After 7 days treatment, NPWT could obviously promote diabetic wound healing because of the mild inflammation and densely cell deposited matrix. Meanwhile, NPWT significantly decreased the expression of TNF-α, IL-6 and iNOS (all P < 0.05). The result of Western blotting and real-time PCR indicated that NPWT obviously decreased the level of Ik B-α and NF-κB P65 and increased the level of ATF-3 (all P < 0.05).
Conclusion:
NPWT exerts an anti-inflammatory effect possibly through the suppression of pro-inflammatory enzymes and cytokines resulting from Ik B-α inhibition and ATF-3 activation, which may prevented the activation of NF-κB pathway in human diabetic foot wounds.
A novel rapid hemostatic and mild polyurethane-urea foam (PUUF) wound dressing was prepared by the particle leaching method and vacuum freeze-drying method using 4, 4-Methylenebis(cyclohexyl isocyanate), 4,4-diaminodicyclohexylmethane and poly (ethylene glycol) as raw materials. And X-ray diffraction (XRD), tensile test, differential scanning calorimetry (DSC) and thermogravimetry (TG) were used to its crystallinity, stress and strain behavior, and thermal properties, respectively. Platelet adhesion, fibrinogen adhesion and blood clotting were performed to evaluate its hemostatic effect. And H&E staining and Masson Trichrome staining were used to its wound healing efficacy. The results revealed the pore size of PUUF is 50–130 μm, and its porosity is 71.01%. Porous PUUF exhibited good water uptake that was benefit to adsorb abundant wound exudates to build a regional moist environment beneficial for wound healing. The PUUF wound dressing exhibit better blood coagulation effect than commercial polyurethane dressing (CaduMedi). Though both PUUF and CaduMedi facilitated wound healing generating full re-epithelialization within 13 days, PUUF was milder and lead to more slight inflammatory response than CaduMedi. In addition, PUUF wound dressing exhibited lower cytotoxicity than CaduMedi against NIH3T3 cells. Overall, porous PUUF represents a novel mild wound dressing with excellent water uptake, hemostatic effect and low toxicity, and it can promote wound healing and enhance re-epithelialization.
OBJECTIVE: This study aimed to use glycerin to improve physical and wound adhesion properties of a wound dressing made of silk sericin and polyvinyl alcohol (PVA).
DESIGN: Glycerin of a natural-derived plasticizer was used to modify the properties of silk sericin/PVA scaffolds. Various concentrations of glycerin were mixed with silk sericin and PVA and then fabricated into the scaffolds by a freeze-drying technique. The control study was performed to examine the properties of the silk sericin/PVA scaffolds with and without glycerin.
MAIN OUTCOME MEASURES: Physical, mechanical, wound adhesion properties, the release profile of silk sericin, and in vivo safety of the silk sericin/PVA scaffolds with and without glycerin were investigated.
MAIN RESULTS: The silk sericin/PVA scaffolds with glycerin exhibited more homogenous structure, less compressive modulus, higher Young modulus and elongation percentage, and a higher degree of crosslinking compared with the scaffold without glycerin. The silk sericin/PVA scaffold with 2% wt/vol glycerin showed more controlled release of silk sericin than the other scaffolds. The sustained release of silk sericin from the scaffold with glycerin would be advantageous for long-term healing of wounds. The silk sericin/PVA scaffold with 2% (wt/vol) glycerin was less adhesive to the wound compared with the scaffold without glycerin. Furthermore, the implantation of silk sericin/PVA scaffolds with 2% (wt/vol) glycerin did not cause any irritation to the tissue.
CONCLUSION: The silk sericin/PVA scaffolds with glycerin were introduced as a biocompatible, more flexible, and less adhesive wound dressing than the scaffold without glycerin.
The aim of this study was to develop novel biomedical electrospun nanofiber mats for controlled drug release, in particular to release a drug directly to an injury site to accelerate wound healing. Here, nanofibers of chitosan (CS), poly(ethylene oxide) (PEO), and a 90 : 10 composite blend, loaded with a fluoroquinolone antibiotic, such as ciprofloxacin hydrochloride (CipHCl) or moxifloxacin hydrochloride (Moxi), were successfully prepared by an electrospinning technique. The morphology of the electrospun nanofibers was investigated by scanning electron microscopy. The functional groups of the electrospun nanofibers before and after crosslinking were characterized by Fourier transform infrared spectroscopy. X-ray diffraction results indicated an amorphous distribution of the drug inside the nanofiber blend. In vitro drug-release evaluations showed that the crosslinking could control the rate and period of drug release in wound-healing applications. The inhibition of bacterial growth for both Escherichia coli and Staphylococcus aureus were achieved on the CipHCl- and Moxi-loaded nanofibers. In addition, both types of CS/PEO and drug-containing CS/PEO nanofibers showed excellent cytocompatibility in the cytotoxicity assays. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42060.
Taxifolin is a kind of flavanonol, whose antioxidant ability is superior to that of ordinary flavonoids compounds owing to its special structure. However, its low bioavailability is a major obstacle for biomedical applications, so the experiment is designed to prepare taxifolin nanoparticles by liquid antisolvent precipitation (LAP) to improve its bioavailability. We selected ethanol as solvent, deionized water as antisolvent, and investigated primarily the type of surfactant and adding amount, drug concentration, volume ratio of antisolvent to solvent, precipitation temperature, dropping speed, stirring speed, stirring time factors affecting drug particles size. Results showed that the poloxamer 188 was selected as the surfactant and the particle size of taxifolin obviously reduced with the increase of the poloxamer 188 concentration, the drug concentration and the dropping speed from 0.08% to 0.45%, from 0.04g/ml to 0.12g/ml, from 1ml/min to 5ml/min, respectively, when the volume ratio of antisolvent to solvent increased from 2.5 to 20, the particle size of taxifolin first increased and then decreased, the influence of precipitation temperature, stirring speed, stirring time on particle size were not obvious, but along with the increase of mixing time, the drug solution would separate out crystallization. The optimum conditions were: the poloxamer 188 concentration was 0.25%, the drug concentration was 0.08g/ml, the volume ratio of antisolvent to solvent was 10, the precipitation temperature was 25°C, the dropping speed was 4ml/min, the stirring speed was 800r/min, the stirring time was 5min. Taxifolin nanosuspension with a MPS of 24.6nm were obtained under the optimum conditions. For getting taxifolin nanoparticles, the lyophilization method was chosen and correspondingly γ-cyclodextrin was selected as cryoprotectant from γ-cyclodextrin, mannitol, lactose, glucose. Then the properties of raw taxifolin and taxifolin nanoparticles were characterized by scanning electron microscopy (SEM), fourier-transform infrared spectroscopy (FTIR), high performance liquid chromatography-mass spectrometry (LC-MS), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermo gravimetric (TG), and the conclusion was drawn that taxifolin nanoparticles can be converted into an amorphous form but its chemical construction cannot been changed. Furthermore, dissolving capability test, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity and reducing power assay, solvent residue test were also carried out. The experimental data showed that the solubility and the dissolution rate of taxifolin nanoparticles were about 1.72 times and 3 times of raw taxifolin, the bioavailability of taxifolin nanoparticles increased 7 times compared with raw taxifolin, and the antioxidant capacity of taxifolin nanoparticles was also superior to raw taxifolin. Furthermore, the residual ethanol of the taxifolin nanoparticles was less than the ICH limit for class 3 solvents of 5000ppm or 0.5% for solvents and could be used for pharmaceutical. These results suggested that taxifolin nanoparticles may have potential value to become a new oral taxifolin formulation with high bioavailability.
The objective of this research is to develop a dual-growth factor releasing nanoparticle-innanofiber system for wound healing applications. In order to mimic and promote the natural healing procedure, chitosan and poly(ethylene oxide) were electrospun into nanofibrous meshes as mimics of extracellular matrix. Vascular endothelial growth factor (VEGF) was loaded within nanofibers to promote angiogenesis in short term. In addition, platelet-derived growth factor-BB (PDGF-BB) encapsulated poly(lactic-co-glycolic acid) nanoparticles were embedded inside nanofibers to generate a sustained release of PDGF-BB for accelerated tissue regeneration and remodeling. In vitro studies revealed that our nanofibrous composites delivered VEGF quickly and PDGF-BB in a relayed manner, supported fibroblast growth, and exhibited anti-bacterial activities. Preliminary in vivo study performed on normal full thickness rat skin wound models demonstrated that nanofiber/nanoparticle scaffolds significantly accelerated the wound healing process through promoting angiogenesis, increasing re-epithelialization, and controlling granulation tissue formation. For later stages of healing, evidence also showed quicker collagen deposition and earlier remodeling of the injured site to achieve a faster full regeneration of skin compared to the commercial Hydrofera Blue® wound dressing. These results suggest that our nanoparticle-in-nanofiber system could provide a promising treatment for normal and chronic wound healing.
Skin cancer is one of the most commonly diagnosed cancers in the United States. Taxifolin reportedly exerts multiple biologic effects, but the molecular mechanisms and direct target(s) of taxifolin in skin cancer chemoprevention are still unknown. In silico computer screening and kinase profiling results suggest that the EGF receptor (EGFR), phosphoinositide 3-kinase (PI3K), and Src are potential targets for taxifolin. Pull-down assay results showed that EGFR, PI3K, and Src directly interacted with taxifolin in vitro, whereas taxifolin bound to EGFR and PI3K, but not to Src in cells. ATP competition and in vitro kinase assay data revealed that taxifolin interacted with EGFR and PI3K at the ATP-binding pocket and inhibited their kinase activities. Western blot analysis showed that taxifolin suppressed UVB-induced phosphorylation of EGFR and Akt, and subsequently suppressed their signaling pathways in JB6 P+ mouse skin epidermal cells. Expression levels and promoter activity of COX-2 and prostaglandin E(2) (PGE(2)) generation induced by UVB were also attenuated by taxifolin. The effect of taxifolin on UVB-induced signaling pathways and PGE(2) generation was reduced in EGFR knockout murine embryonic fibroblasts (MEF) compared with EGFR wild-type MEFs. Taxifolin also inhibited EGF-induced cell transformation. Importantly, topical treatment of taxifolin to the dorsal skin significantly suppressed tumor incidence, volume, and multiplicity in a solar UV (SUV)-induced skin carcinogenesis mouse model. Further analysis showed that the taxifolin-treated group had a substantial reduction in SUV-induced phosphorylation of EGFR and Akt in mouse skin. These results suggest that taxifolin exerts chemopreventive activity against UV-induced skin carcinogenesis by targeting EGFR and PI3K. Cancer Prev Res; 5(9); 1103-14. ©2012 AACR.