Recent Advances in the Treatment of Spinal Cord Injury.

Spinal cord injury (SCI) is a complex, multifaceted, progressive, and yet incurable complication that can cause irreversible damage to the individual, family, and society. In recent years strategies for the management and rehabilitation of SCI besides axonal regeneration, remyelination, and neuronal plasticity of the injured spinal cord have significantly improved. Although most of the current research and therapeutic advances have been made in animal models, so far, no specific and complete treatment has been reported for SCI in humans. The failure to treat this complication has been due to the inherent neurological complexity and the structural, cellular, molecular, and biochemical characteristics of spinal cord injury. In this review, in addition to elucidating the causes of spinal cord injury from a molecular and pathophysiological perspective, the complexity and drawbacks of neural regeneration that lead to the failure in SCI treatment are described. Also, recent advances and cutting-edge strategies in most areas of SCI treatment are presented.

Biochemical Aspects of Scaffolds for Cartilage Tissue Engineering; from Basic Science to Regenerative Medicine.

Chondral defects are frequent and important causes of pain and disability. Cartilage has limited self-repair and regeneration capacity. The ideal approach for articular cartilage defects is the regeneration of hyaline cartilage with sustainable symptom-free constructs. Tissue engineering provides new strategies for the regeneration of functional cartilage tissue through optimized scaffolds with architectural, mechanical, and biochemical properties similar to the native cartilage tissue. In this review, the basic science of cartilage structure, interactions between proteins, stem cells, as well as biomaterials, scaffold characteristics and fabrication methods, as well as current and potential therapies in regenerative medicine will be discussed mostly from a biochemical point of view. Furthermore, the recent trends in scaffold-based therapies and supplementary factors in cartilage tissue engineering will be considered.

Improvement of the Wound-Healing Process by Curcumin-Loaded Chitosan/Collagen Blend Electrospun Nanofibers: In Vitro and In Vivo Studies.

Chronic wounds have become a major health problem worldwide. Curcumin (Cur), with strong anti-inflammatory and anti-infective properties, is introduced as a unique molecule for wound dressing applications. In the present study, Cur-loaded chitosan/poly(ethylene oxide)/collagen (Cho/PEO/Col) nanofibers were developed for wound dressing applications by the blend-electrospinning process. Structural, mechanical, and biological properties of nanofibers were evaluated using SEM, FTIR, tensile testing, in vitro release study, Alamar blue cytotoxicity assay, and in vivo study in a rat model. According to the results, Cur was successfully released up to 3 days without any significant cytotoxicity of the above hybrid to human dermal fibroblasts. In vivo studies on full-thickness wounds in the rat model indicated significant improvement in the mean wound area closure by applying Cur-loaded Cho/PEO/Col nanofibers. The electrospun Cho/PEO/Col nanofibers loaded with Cur could be considered as a promising type of wound dressing in the wound-healing process.

Evaluation of wound healing efficiency of vancomycin-loaded electrospun chitosan/poly ethylene oxide nanofibers in full thickness wound model of rat.

Electrospun hybrid nanofibers have been extensively regarded as drug carriers. This study tries to introduce a nano fibrous wound dressing as a new strategy for a topical drug-delivery system. The vancomycin (VCM)-loaded hybrid chitosan/poly ethylene oxide (CH/PEO) nanofibers were fabricated by the blend-electrospinning process. Morphological, mechanical, chemical, and biological properties of nanofibers were examined by SEM, FTIR, release profile study, tensile assay, Alamar Blue cytotoxicity evaluation, and antibacterial activity assay. In vivo wound healing activity of hybrid CH/PEO/VCM nanofibers was evaluated in full-thickness skin wounds of rats. The hybrid CH/PEO/VCM nanofibers were successfully fabricated in a nanometer. The CH/PEO/VCM 2.5% had higher Young's Modulus, better tensile strength, smaller fiber diameter with sustained-release profiles compared to CH/PEO/VCM 5%. All nanofibers did not show any significant cytotoxicity (P < 0.05) on the normal fibroblast cells. Also, VCM-load hybrid CH/PEO nanofibers successfully inhibited bacterial growth. The wound area in the rats treated with CH/PEO/VCM 2.5% was less than CH/PEO/VCM 5% treated group. According to histological evaluation, the CH/PEO/VCM 2.5% group showed the fastest wound healing than other treatment groups. Results of this study proposed that CH/PEO/VCM nanofibers could promote the wound healing process by reducing the side effects of VCM as a topical antimicrobial agent.

Synthesis of nano-fibers containing nano-curcumin in zein corn protein and its physicochemical and biological characteristics.

Curcumin contains many biological activities as a natural bioactive substance, however, its low solubility stands as a huge bioavailability disadvantage. Recently, different methods have been developed for utilizing the tremendous medicinal properties of this material. In this study, an Oil/Water nano-emulsion of curcumin (Nano-CUR) has been woven in zein polymer at three percentages of 5%, 10%, and 15% (v/v). We have investigated the physicochemical properties of nanofibers (NFs) including FESEM, FTIR, tensile strength, encapsulation efficiency, and release profile, as well as biological properties. According to the data, the NFs have been observed to become significantly thinner and more uniformed as the involved percentage of Nano-CUR had been increased from 5 to 15%. It is considerable that the tensile strength can be increased by heightening the existing Nano-CUR from 5% towards 15%. The resultant NFs of zein/Nano-CUR 15% have exhibited higher in vitro release and lower encapsulation efficiency than the other evaluated zein/Nano-CUR NFs. It has been confirmed through the performed viability and antioxidant studies that zein/Nano-CUR 10% NFs are capable of providing the best conditions for cell proliferation. Considering the mentioned facts, this work has suggested that Nano-CUR can be successfully woven in zein NFs and maintain their biological properties.

Saccharomyces cerevisiae as a delivery system of Zataria multiflora Boiss. essential oil as a natural preservative for food applications: Encapsulation of Iranian Zataria multiflora Boiss. essential oil.

BACKGROUND: The following study is an evaluation of the encapsulation, stability and release profile of Iranian Zateria multiflora boiss essential oil (ZEO) in Saccharomyces cerevisiae yeast cells. Encapsulation was performed with different essential oil / yeast weight ratios at different temperatures. The encapsulation efficiency and stability of the loaded yeasts and the release profiles of carvacrol and thymol (as the main active ingredients of ZEO) were also investigated. RESULT: The encapsulation efficiencies of carvacrol and thymol at a ZEO / yeast weight ratio of 1.25 were 30.9% ± 0.01% and 44.5% ± 0.02%, respectively. Loaded yeast cells were stable during the 4-week storage period. Both carvacrol and thymol showed substantial releases of around 60% during the first hour and around 70% during the second hour at two different water temperatures, followed by steady release. CONCLUSION: Zateria multiflora boiss essential oil can be encapsulated effectively in S. cerevisiae yeast cells, refrigerated without degradation, and released efficiently. Zateria multiflora boiss essential oil encapsulated into S. cerevisiae yeast may be used as a potential preservative for the food and drug industry. © 2020 Society of Chemical Industry.

Evaluation of debridement effects of bromelain-loaded sodium alginate nanoparticles incorporated into chitosan hydrogel in animal models.

OBJECTIVES: Bromelain, a mixture of proteolytic enzymes from pineapple (Ananas comosus) is known as a potential debriding agent in burn treatment. In this research, the debridement efficiency of chitosan hydrogel loaded by sodium alginate-chitosan nanoparticles (NPs) containing bromelain (Br 10%-AG-CS NPs) was evaluated in animal models. MATERIALS AND METHODS: The NPs were prepared using the ionic gelation technique and their properties were identified. Then, the debridement effect of bromelain NPs incorporated into chitosan hydrogel was evaluated 4 hr after wound treatment in animal models. RESULTS: The particle size of positively charged Br-AG-Cs NPs was about 390±25 nm. The encapsulation efficiency of bromelain into AG-CS NPs was about 92%. The in vitro release profile showed that the maximum release of bromelain from NPs occurred during the first 4 hr (70%). The hydrogel structure did not significantly affect the profile release of bromelain in the formulation. After 6 months of storage at 4 and 25 °C, the synthesized NPs indicated no significant changes in bromelain activity. It was found that Br 10%-Ag-Cs NPs-CS hydrogel had the most beneficial effects on reducing necrotic tissues and resulted in re-epithelialization compared with other treated groups (negative and positive control, CS hydrogel, and Br 10%-CS hydrogel). CONCLUSION: Therefore, using this novel formulation can be considered a potential debridement agent.

Topical green tea formulation with anti-hemorrhagic and antibacterial effects.

OBJECTIVES: Potentially preventable death from uncontrolled hemorrhage clearly indicates the importance of simple, fast and efficient ways to achieving hemostasis. The aim of this study was to develop a topical formulation of green tea extract for reducing bleeding that can be helpful in hemorrhage control. MATERIALS AND METHODS: Hydroalcoholic extract of green tea was isolated from Camellia sinensis and formulated in polyvinyl alcohol (PVA) to achieve two concentrations of 2% and 4% v/v. Folin-Ciocalteau assay was used to determine the total amount of tannins in extract. Rheological behavior of solutions was investigated by measuring viscosity at shear rates of 0-200 sec-1. Quantitative and qualitative microbial limit tests and minimum inhibitory concentration (MIC) assay were done. The effect of formulations on bleeding time was evaluated in an animal model. RESULTS: The total amount of tannin in green tea extract was 3.8% w/w and addition of green tea significantly increased the viscosity of PVA. The results of MIC assay showed that PVA could not inhibit the growth of bacteria, while, 716 µg/ml of green tea and 2860 µg/ml of green tea/PVA 4% inhibited the growth of Staphylococcus aureus and Pseudomonas aeruginosa. In an animal study both 2% and 4% formulations were able to stop hemorrhage approximately at an equal time compared with tranexamic acid (TXA) 50 mg/ml as a control and the lowest bleeding time was 6.4±0.51 sec for green tea/PVA 4%. CONCLUSION: Based on our results, the topical formulation of green tea extract in PVA has a great potential for anti-hemorrhage applications.

Teicoplanin-loaded chitosan-PEO nanofibers for local antibiotic delivery and wound healing.

Antibiotic-loaded nano-delivery systems offer an advanced approach to overcome several limitations associated with antibiotic therapy. Antibiotic-loaded nanofibers can be applied topically for skin and wound healing, post operation implants for the prevention of abdominal adhesion, and prophylaxis and treatment of infections in orthopedic surgery. Here, the authors report the development of local antibiotic delivery system using chitosan- polyethylene oxide (PEO) nanofibers for delivery of teicoplanin. Successful electrospinning of chitosan-PEO solution containing 2 and 4 w/v% teicoplanin resulted in uniform and bead-less nanofibers. Nanofibers were able to release teicoplanin up to 12 days. Antibacterial test in agar diffusion and time-kill study on Staphylococcus aureus also demonstrate that loading teicoplanin in chitosan-PEO nanofibers not only kept the antibacterial activity of antibiotic but also, enhanced it up to 1.5 to 2 fold. Teicoplanin loaded nanofibers did not show any cytotoxicity to human fibroblast. Moreover, in vivo study on rat full thickness wound model confirmed safety and efficacy of applying teicoplanin loaded nanofibers and significant improve in wound closure was observed especially with nanofibers containing 4% teicoplanin. The sustained release profile, enhanced drug activity, cytocompatibility, and significant wound healing activity affirm the potential applications of teicoplanin-loaded nanofibers in wound healing and local antibiotic delivery.

Wound Healing and Antimicrobial Effects of Chitosan-hydrogel/Honey Compounds in a Rat Full-thickness Wound Model.

INTRODUCTION: Honey and chitosan have shown antimicrobial and wound healing effects. As a biocompatible and biodegradable biomaterial, chitosan has shown antimicrobial capabilities. OBJECTIVE: In this study, the effects of the incorporation of high molecular weight chitosan hydrogel on antibacterial, antifungal, and wound healing properties of honey were investigated. MATERIALS AND METHODS: The minimum inhibitory concentration of chitosan and honey were examined in pure and 3:1, 1:1, and 1:3 (v/v) compound ratios for Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans. In addition, the inflammatory, granulation and fibrotic tissue formation, reepithelialization indices, and wound shrinkage effects of each treatment were evaluated and compared with saline and silver sulfadiazine. RESULTS: Chitosan/honey 1:3 was found to be effective against all 5 aforementioned germs. Honey, chitosan/honey 1:1, and chitosan/honey 1:3 showed faster wound healing and shrinkage effects. CONCLUSIONS: Incorporation of chitosan hydrogel into honey can substantially enhance its antimicrobial and wound healing effects. Chitosan-hydrogel/honey (1:3) is an optimal wound dressing formulation with ample antimicrobial and healing properties.

Bromelain-loaded chitosan nanofibers prepared by electrospinning method for burn wound healing in animal models.

Bromelain is a mixture of proteolytic enzymes present in all tissues of pineapple (Ananas comosus). It is known as an efficient debriding agent in burn treatment. In this study, the efficiency of bromelain-loaded chitosan nanofibers for burn wounds repair was investigated in animal model. Chitosan nanofibers containing bromelain (2% and 4% w/v) were prepared by electrospinning method. The physicochemical characteristics of the synthetized nanofibers were evaluated. The release profile and activity of bromelain loaded in nanofibers were also assayed. Cytotoxicity test was carried out using Alamar blue. The burn healing effect of chitosan-2% w/v bromelain nanofiber was studied in the induced burn wounds in rats for 21 days. The efficacy of treatment was assessed by reduction of burn wound area and histological characteristics at different times. Chitosan-2% w/v bromelain showed the better physicochemical properties and release profile as well as low cytotoxicity than chitosan-4% w/v bromelain. The results also indicated that chitosan-2% w/v bromelain nanofiber was more efficient to heal burn skin compared to chitosan nanofiber alone in the animal model tested. The present study concludes that chitosan-2% w/v bromelain nanofiber possesses great wound healing activity and could be considered as an effective natural topical burn wound healing treatment.

Curcumin nanofibers for the purpose of wound healing.

Poor wound healing is a highly prevalent clinical problem with, as yet, no entirely satisfactory solution. A new technique, termed electrospinning, may provide a solution to improve wound healing. Due to their large surface area to volume ratio and porosity, the nanofibers created by electrospinning are able to deliver sustained drug release and oxygen to the wound. Using different types of polymers with varying properties helps strengthening nanofiber and exudates absorption. The nanofibers appear to have an ideal structure applicable for wound healing and, in combination with curcumin, can blend the anti-inflammatory and antioxidant properties of curcumin into a highly effective wound dressing. The use of suitable curcumin solvents and the slow release of curcumin from the nanofiber help in overcoming the known limitations of curcumin, specifically its low stability and limited bioavailability. Here, we review the studies which have been done on synthesized nanofibers containing curcumin, produced by the electrospinning technique, for the purpose of wound healing.

Expanding the clinical phenotype of IARS2-related mitochondrial disease.

BACKGROUND: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. METHODS: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. RESULTS: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. CONCLUSIONS: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia.

Preparation, characterization, and optimization of auraptene-loaded solid lipid nanoparticles as a natural anti-inflammatory agent: In vivo and in vitro evaluations.

Auraptene (AUR) is a bioactive antioxidant coumarin with valuable pharmacological properties; however, poor water solubility is a substantial issue for the topical application of AUR. Therefore, we sought to prepare solid lipid nanoparticles (SLNs) containing AUR (AUR-SLNs) to enhance its anti-inflammatory effect. The prepared formulations were optimized by applying the response surface method. Furthermore, AUR-SLNs were compared to conventional cream containing AUR regarding both the permeation rate of the nanoparticles and the anti-inflammatory effect through both in vitro and in vivo studies. Particle size and entrapment efficiency of the optimized formulation were 140.9 ±â€¯3.55 nm and 84.11% ±â€¯3.30, respectively. Transmission electron microscopy revealed that the nanoparticles were spherical. Differential scanning calorimetry (DSC) analysis demonstrated no drug-lipid incompatibility in the formulation. Fourier transform-infrared spectroscopy (FTIR) spectra revealed the amorphous state of AUR and the encapsulation of this agent in SLNs. The in vitro permeation studies exhibited that AUR-SLNs could significantly enhance cutaneous uptake of AUR and skin targeting. The anti-inflammatory and histopathological studies exhibited no significant differences between AUR-SLNs and indomethacin. AUR-SLNs did not induce skin sensitization in guinea pigs. The results suggest that SLNs could be appropriate carriers for the topical application of AUR as a natural anti-inflammatory agent.

Encapsulation challenges, the substantial issue in solid lipid nanoparticles characterization.

Solid lipid nanoparticles (SLNs), as alternative colloidal carriers, have been used for the sustained release of lipophilic drugs with poor water solubility. One of the most important parameters in the characterization of SLNs is entrapment efficiency (EE). Despite the importance of this factor in estimating the drug loading capacity, EE does not always represent the exact percentage of the entrapped drug. Several variables such as the stirring speed and duration, and concentration of surfactant, emulsifier, and drug play important roles in determining the final EE. In addition, EE is mainly affected by the type and concentration of the lipid. There are two major methods for the measurement of EE are in which the encapsulated drug in SLNs is either directly measured (direct method) or the amount of unencapsulated drug in the supernatant is measured (indirect method). Accuracy of drug analysis is the main challenge for EE calculation, and is either performed in the separated aqueous medium or the particles. In this review, we aimed to introduce the available methods for EE determination in SLNs and discuss the advantages and shortcomings of each method.