Electrospinning Proteins for Wound Healing Purposes: Opportunities and Challenges.

With the growth of the aging population worldwide, chronic wounds represent an increasing burden to healthcare systems. Wound healing is complex and not only affected by the patient's physiological conditions, but also by bacterial infections and inflammation, which delay wound closure and re-epithelialization. In recent years, there has been a growing interest for electrospun polymeric wound dressings with fiber diameters in the nano- and micrometer range. Such wound dressings display a number of properties, which support and accelerate wound healing. For instance, they provide physical and mechanical protection, exhibit a high surface area, allow gas exchange, are cytocompatible and biodegradable, resemble the structure of the native extracellular matrix, and deliver antibacterial agents locally into the wound. This review paper gives an overview on cytocompatible and biodegradable fibrous wound dressings obtained by electrospinning proteins and peptides of animal and plant origin in recent years. Focus is placed on the requirements for the fabrication of such drug delivery systems by electrospinning as well as their wound healing properties and therapeutic potential. Moreover, the incorporation of antimicrobial agents into the fibers or their attachment onto the fiber surface as well as their antimicrobial activity are discussed.

Highly Elastic and Water Stable Zein Microfibers as a Potential Drug Delivery System for Wound Healing.

The development of biomaterials for wound healing applications requires providing a number of properties, such as antimicrobial action, facilitation of cell proliferation, biocompatibility and biodegradability. The aim of the present study was to investigate morphological and mechanical properties of zein-based microfibers, ultimately aimed at creating an environment suitable for wound healing. This was achieved through co-axial electrospinning of core-shell microfibers, with zein protein in the core and polyethylene oxide (PEO) in the shell. Small amounts of PEO or stearic acid were additionally incorporated into the fiber core to modify the morphology and mechanical properties of zein fibers. The presence of PEO in the core was found to be essential for the formation of tubular fibers, whereas PEO in the shell enhanced the stability of the microfibers in water and ensured high elasticity of the microfiber mats. Tetracycline hydrochloride was present in an amorphous form within the fibers, and displayed a burst release as a result of pore-formation in the fibers. The developed systems exhibited antimicrobial activity against Staphylococcus aureus and Escherichia coli, and showed no cytotoxic effect on fibroblasts. Biocompatibility, antimicrobial activity and favorable morphological and mechanical properties make the developed zein-based microfibers a potential biomaterial for wound healing purposes.

Impact of electromagnetic fields on in vitro toxicity of silver and graphene nanoparticles.

The correlation between shape and concentration of silver nanoparticles (AgNPs), their cytotoxicity and formation of reactive oxygen species (ROS) in the presence of electromagnetic fields (EMFs) has been investigated. In addition, the bio-effects caused by the combination of EMFs and graphene nanoparticles (GrNPs) have been also assessed. The AgNPs of three shapes (triangular, spherical and colloidal) and GrNPs were added in high concentrations to the culture of human fibroblasts and exposed to EMF of three different frequencies: 900, 2400 and 7500 MHz. The results demonstrated the dependence of the EMF-induced cytotoxicity on the shape and concentration of AgNPs. The maximal cell killing effect was observed at 900 MHz frequency for NPs of all shapes and concentrations. The highest temperature elevation was observed for GrNPs solution irradiated by EMF of 900 MHz frequency. The exposure to EMF led to significant increase of ROS formation in triangular and colloidal AgNPs solutions. However, no impact of EMF on ROS production was detected for spherical AgNPs. GrNPs demonstrated ROS-protective activity that was dependent on their concentration. Our findings indicate the feasibility to control cytotoxicity of AgNPs by means of EMFs. The effect EMF on the biological activity of AgNPs and GrNPs is reported here for the first time.

A Comprehensive Review of Topical Odor-Controlling Treatment Options for Chronic Wounds.

The process of wound healing is often accompanied by bacterial infection or critical colonization, resulting in protracted inflammation, delayed reepithelization, and production of pungent odors. The malodor produced by these wounds may lower health-related quality of life and produce psychological discomfort and social isolation. Current management focuses on reducing bacterial activity within the wound site and absorbing malodorous gases. For example, charcoal-based materials have been incorporated into dressing for direct adsorption of the responsible gases. In addition, multiple topical agents, including silver, iodine, honey, sugar, and essential oils, have been suggested for incorporation into dressings in an attempt to control the underlying bacterial infection. This review describes options for controlling malodor in chronic wounds, the benefits and drawbacks of each topical agent, and their mode of action. We also discuss the use of subjective odor evaluation techniques to assess the efficacy of odor-controlling therapies. The perspectives of employing novel biomaterials and technologies for wound odor management are also presented.

Therapeutic Potential of Noble Nanoparticles for Wound Repair.

INTRODUCTION: Nanoparticles made of noble metals, such as gold and silver, have a great potential to be effectively employed for wound management. The nano-size of such particles provides an opportunity to enlarge the contacting area, which results in more effective anti-bacterial action and faster wound repair. It must be noted that the shape of noble nanoparticles might play a crucial role in the manifestation of their anti-microbial properties. The modern state of technology allows fabrication of the nanoparticles with the desired shape and physical properties. In order to provide efficacy and close contact with the wound, the noble nanoparticles can be incorporated into a special matrix made of a cryogel (based on polymethyl methacrylate). This combination might serve as a foundation for developing completely new types of wound dressing. MATERIALS AND METHODS: We have developed a few methods for synthesizing gold and silver nanoparticles of different shapes and sizes. After fabrication of metallic nanoparticles, they were characterized by using Tunneling Electron Microscopy (TEM) and Malvern Zetasizer system in order to determine the average population size and consistency. The silver nanoparticles was synthesized using sodium borohydride reduction of silver nitrate. The synthesis of gold nanoparticles was conducted by using the Turkevich method. RESULTS: We have developed a synthetic cryogel based on polyacrylamide (by cryogelation reaction) at several temperatures. At the second step, we developed a method for conjugating fabricated gold and silver nanoparticles to the surface (or pores) of cryogel through covalent bonds so they can provide antibacterial action within the wound. By following the developed protocol, we were able to obtain an approximate cryogel layer (1 cm thickness) with embedded gold and silver nanoparticles. This conjugate was analyzed and confirmed using Scanning Electron Microscopy (SEM) and TEM. DISCUSSION: The obtained results indicate the feasibility of the fabrication of a novel type of wound dressing. At the next step, we are planning to elucidate the bio-compatibility of the combination of cryogel and nanoparticles. Moreover, anti-bacterial properties of this new type of wound dressing will be analyzed.

Genetic Diversity of IFγ, IL1ß, TLR2, and TLR8 Loci in Pulmonary Tuberculosis in Kazakhstan.

INTRODUCTION: Tuberculosis (TB) is caused by bacterium Mycobacterium tuberculosis (MTB), and according to the WHO, up to 30% of world population is infected with latent TB. Pathogenesis of TB is multifactorial, and its development depends on environmental, social, microbial, and genetic factors of both the bacterium and the host. The number of TB cases in Kazakhstan has decreased in the past decade, but multidrug-resistant (MDR) TB cases are dramatically increasing. Polymorphisms in genes responsible for immune response have been associated with TB susceptibility. The objective of this study was to investigate the risk of developing pulmonary TB (PTB) associated with polymorphisms in several inflammatory pathway genes among Kazakhstani population. METHODS: 703 participants from 3 regions of Kazakhstan were recruited for a case-control study. 251 participants had pulmonary TB (PTB), and 452 were healthy controls (HC). Males and females represented 42.39% and 57.61%, respectively. Of all participants, 67.4% were Kazakhs, 22.8% Russians, 3.4% Ukrainians, and 6.4% were of other origins. Clinical and epidemiological data were collected from medical records, interviews, and questionnaires. DNA samples were genotyped using TaqMan assay on 4 polymorphisms: IFNγ (rs2430561) and IL1ß (rs16944), TLR2 (rs5743708) and TLR8 (rs3764880). Statistical data was analyzed using SPSS 19. RESULTS: Genotyping by IFγ, IL1ß, TLR2 showed no significant association with PTB susceptibility (p > 0.05). TLR8 genotype A/G was significantly higher in females (F/M - 41.5%/1.3%) and G/G in males (M/F - 49%/20.7%) (χ2=161.43, p < 0.001). A significantly increased risk of PTB development was observed for TLR A/G with an adjusted OR of 1.48 (95%, CI: 0.96 - 2.28), and a protective feature was revealed for TLR8 G/G genotype (OR: 0.81, 95%, CI: 0.56 - 1.16, p = 0.024). Additional grouping by gender revealed that TLR8 G/G contributes as protective genotype (OR: 1.83, 95%, CI: 1.18 - 2.83, p = 0.036) in males of the control group. CONCLUSION: Results indicate that heterozygous genotype A/G of TLR8 increases the risk of PTB development, while G/G genotype may serve as protection mechanism. A/A genotype is strongly associated with susceptibility to PTB. To clarify the role of other polymorphisms in susceptibility to PTB in Kazakhstani population, further investigations are needed.