Preparation and characterization of propolis reinforced eggshell membrane/ GelMA composite hydrogel for biomedical applications.

Gelatin methacrylate-based hydrogels (GelMA) were widely used in tissue engineering and regenerative medicine. However, to manipulate their various chemical and physical properties and create high-efficiency hydrogels, different materials have been used in their structure. Eggshell membrane (ESM) and propolis are two nature-derived materials that could be used to improve the various characteristics of hydrogels, especially structural and biological properties. Hence, the main purpose of this study is the development of a new type of GelMA hydrogel containing ESM and propolis, for use in regenerative medicine. In this regard, in this study, after synthesizing GelMA, the fragmented ESM fibers were added to it and the GM/EMF hydrogel was made using a photoinitiator and visible light irradiation. Finally, GM/EMF/P hydrogels were prepared by incubating GM/EMF hydrogels in the propolis solution for 24 h. After various structural, chemical, and biological characterizations, it was found that the hydrogels obtained in this study offer improved morphological, hydrophilic, thermal, mechanical, and biological properties. The developed GM/EMF/P hydrogel presented more porosity with smaller and interconnected pores compared to the other hydrogels. GM/EMF hydrogels due to possessing EMF showed compressive strength up to 25.95 ± 1.69 KPa, which is more than the compressive strength provided by GM hydrogels (24.550 ± 4.3 KPa). Also, GM/EMF/P hydrogel offered the best compressive strength (44.65 ± 3.48) due to the presence of both EMF and propolis. GM scaffold with a contact angle of about 65.41 ± 2.199 θ showed more hydrophobicity compared to GM/EMF (28.67 ± 1.58 θ), and GM/EMF/P (26.24 ± 0.73 θ) hydrogels. Also, the higher swelling percentage of GM/EMF/P hydrogels (343.197 ± 42.79) indicated the high capacity of this hydrogel to retain more water than other scaffolds. Regarding the biocompatibility of the fabricated structures, MTT assay results showed that GM/EMF/P hydrogel significantly (p-value < 0.05) supported cell viability. Based on the results, it seems that GM/EMF/P hydrogel could be a promising biomaterial candidate for use in various fields of regenerative medicine.

In vitro efficacy of albendazole-loaded ß-cyclodextrin against protoscoleces of Echinococcus granulosus sensu stricto.

BACKGROUND: Cystic echinococcosis (CE), a widespread helminthic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus represents a public health concern in humans. Albendazole (ABZ) is the first-line treatment for CE; however therapeutic failure of ABZ against CE occurs because of size and location of formed cysts as well its low aqueous solubility and consequently its erratic bioavailability in plasma. Serious adverse effects have also been observed following the long-term use of ABZ in vivo. METHODS: We evaluated the apoptotic effects of ABZ-loaded ß-cyclodextrin (ABZ-ß-CD) against protoscoleces (PSCs) versus ABZ alone. After 15 h of exposure, Caspase-3 enzymatic activity was determined by fluorometric assay in PSCs treated with ABZ and ABZ-ß-CD groups. To assess the treatment efficacy of ABZ-ß-CD against PSCs, mRNA expression of Arginase (EgArg) and Thioredoxin peroxidase (EgTPx) were quantified by Real-time PCR. RESULTS: A significant scolicidal activity of ABZ was observed only at a concentration of 800 µg/mL (100% PSCs mortality rate after 4 days of exposure), while the 200 and 400 µg/mL ABZ reached 100% PSCs mortality rate after 9 sequential days. The 400 µg/mL ABZ-ß-CD had 100% scolicidal rate after 5 days of exposure. Morphological alterations using scanning electron microscopy in treated PSCs revealed that 400 µg/mL ABZ-ß-CD induced higher Caspase-3 activity than their controls, indicating a more potent apoptotic outcome on the PSCs. Also, we showed that the 400 µg/mL ABZ-ß-CD can down-regulate the mRNA expression of EgArg and EgTPx, indicating more potent interference with growth and antioxidant properties of PSCs. CONCLUSIONS: In the present study, a significant scolicidal rate, apoptosis intensity and treatment efficacy was observed in PSCs treated with 400 µg/mL ABZ-ß-CD compared to ABZ alone. This provides new insights into the use of nanostructured ß-CD carriers with ABZ as a promising candidate to improve the treatment of CE in in vivo models.

Dietary patterns and relative expression levels of PPAR-γ, VEGF-A and HIF-1α genes in benign breast diseases: case-control and consecutive case-series designs.

We aimed to study dietary patterns in association with the relative expression levels of PPAR-γ, vascular endothelial growth factor-A (VEGF-A) and hypoxia-inducible factor-1α (HIF-1α) in women with benign breast disease (BBD). The study design was combinative, included a case-series and case-control compartments. Initially, eligible BBD patients (n 77, aged 19-52 years old) were recruited at Nour-Nejat hospital, Tabriz, Iran (2012-2014). A hospital-based group of healthy controls was matched for age (n 231, aged 20-63 years old) and sex. Dietary data were collected using a valid 136-item FFQ. Principal component analysis generated two main components (Kaiser-Meyer-Olkin = 0·684), including a Healthy pattern (whole bread, fruits, vegetables, vegetable oils, legumes, spices, seafood, low-fat meat, skinless poultry, low-fat dairy products, nuts and seeds) and a Western pattern (starchy foods, high-fat meat and poultry, high-fat dairy products, hydrogenated fat, fast food, salt and sweets). High adherence to the Western pattern increased the risk of BBD (ORadj 5·59; 95 % CI 2·06, 15·10; P < 0·01), whereas high intake of the Healthy pattern was associated with a 74 % lower risk of BBD (95 % CI 0·08, 0·81; P < 0·05). In the BBD population, the Western pattern was correlated with over-expression of HIF-1α (radj 0·309, P < 0·05). There were inverse correlations between the Healthy pattern and expressions of PPAR-γ (radj -0·338, P < 0·05), HIF-1α (radj -0·340, P < 0·05) and VEGF-A (radj -0·286, P < 0·05). In conclusion, new findings suggested that the Healthy pattern was associated inversely with the risk of BBD, and this could be correlated with down-regulation of PPAR-γ, VEGF-A and HIF-1α genes, which might hold promise to preclude BBD of malignant pathological transformation.

Current progress in hepatic tissue regeneration by tissue engineering.

BACKGROUND: Liver, as a vital organ, is responsible for a wide range of biological functions to maintain homeostasis and any type of damages to hepatic tissue contributes to disease progression and death. Viral infection, trauma, carcinoma, alcohol misuse and inborn errors of metabolism are common causes of liver diseases are a severe known reason for leading to end-stage liver disease or liver failure. In either way, liver transplantation is the only treatment option which is, however, hampered by the increasing scarcity of organ donor. Over the past years, considerable efforts have been directed toward liver regeneration aiming at developing new approaches and methodologies to enhance the transplantation process. These approaches include producing decellularized scaffolds from the liver organ, 3D bio-printing system, and nano-based 3D scaffolds to simulate the native liver microenvironment. The application of small molecules and micro-RNAs and genetic manipulation in favor of hepatic differentiation of distinct stem cells could also be exploited. All of these strategies will help to facilitate the application of stem cells in human medicine. This article reviews the most recent strategies to generate a high amount of mature hepatocyte-like cells and updates current knowledge on liver regenerative medicine.

Recent advances in nano-scaffolds for tissue engineering applications: Toward natural therapeutics.

Among the promising methods for repairing or replacing tissue defects in the human body and the hottest research topics in medical science today are regenerative medicine and tissue engineering. On the other hand, nanotechnology has been expanded into different areas of regenerative medicine and tissue engineering due to its essential benefits in improving performance in various fields. Nanotechnology, a helpful strategy in tissue engineering, offers new solutions to unsolved problems. Especially considering the excellent physicochemical properties of nanoscale structures, their application in regenerative medicine has been gradually developed, and a lot of research has been conducted in this field. In this regard, various nanoscale structures, including nanofibers, nanosheets, nanofilms, nano-clays, hollow spheres, and different nanoparticles, have been developed to advance nanotechnology strategies with tissue repair goals. Here, we comprehensively review the application of the mentioned nanostructures in constructing nanocomposite scaffolds for regenerative medicine and tissue engineering. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Diagnostic Tools > Biosensing.

Multifunctional hydrogels for wound healing: Special focus on biomacromolecular based hydrogels.

Hydrogels are widely used for wound healing applications due to their similarity to the native extracellular matrix (ECM) and ability to provide a moist environment. However, lack of multifunctionality and low mechanical properties of previously developed hydrogels may limit their ability to support skin tissue regeneration. Incorporating various biomaterials and nanostructures into the hydrogels is an emerging approach to develop multifunctional hydrogels with new functions that are beneficial for wound healing. These multifunctional hydrogels can be fabricated with a wide range of functions and properties, including antibacterial, antioxidant, bioadhesive, and appropriate mechanical properties. Two approaches can be used for development of multifunctional hydrogel-based dressings; taking the advantages of the chemical composition of biomaterials and addition of nanomaterials or nanostructures. A large number of synthetic and natural polymers, bioactive molecules, or nanomaterials have been used to obtain hydrogel-based dressings with multifunctionality for wound healing applications. In the present review paper, advances in the development of multifunctional hydrogel-based dressings for wound healing have been highlighted.

A novel multifunctional bilayer scaffold based on chitosan nanofiber/alginate-gelatin methacrylate hydrogel for full-thickness wound healing.

Due to their lack of multifunctionality, the majority of traditional wound dressings do not support all the clinical requirements. Bilayer wound dressings with multifunctional properties can be attractive for effective skin regeneration. In the present study, we designed a multifunctional bilayer scaffold containing Chitosan-Polycaprolactone (PC) nanofiber and tannic acid (TA) reinforced methacrylate gelatin (GM)/alginate (Al) hydrogel (GM/Al/TA). PC nanofibers were coated with GM/Al/TA hydrogel to obtain a bilayer nanocomposite scaffold (Bi-TA). The GM/Al/TA hydrogel layer of Bi-TA showed antibacterial, free radical scavenging, and biocompatibility properties. Also, PC nanofiber acted as a barrier for preventing bacterial invasion and moisture loss of the hydrogel layer. The wound healing performance of the Bi-TA scaffold was investigated via a full-thickness wound model. In addition, the histopathological and immunohistochemical (IHC) stainings of transforming growth factor-ß1(TGF-ß1) and tumor necrosis factor-α (TNF-α) were assessed. The results indicated an enhanced wound closure rate, effective collagen deposition, quick re-epithelialization, more skin appendages, and replacement of defect area with normal skin tissue by Bi-TA scaffold compared to other groups. Additionally, the regulation of TGF-ß1 and TNF-α was observed by Bi-TA dressing. Overall, the Bi-TA with appropriate structural and multifunctional properties can be an excellent candidate for developing effective dressings for wound healing applications.

The Application of Hydrogels Based on Natural Polymers for Tissue Engineering.

Hydrogels are known as polymer-based networks with the ability to absorb water and other body fluids. Because of this, the hydrogels are used to preserve drugs, proteins, nutrients or cells. Hydrogels possess great biocompatibility, and properties like soft tissue, and networks full of water, which allows oxygen, nutrients, and metabolites to pass. Therefore, hydrogels are extensively employed as scaffolds in tissue engineering. Specifically, hydrogels made of natural polymers are efficient structures for tissue regeneration, because they mimic natural environment which improves the expression of cellular behavior. Producing natural polymer-based hydrogels from collagen, hyaluronic acid (HA), fibrin, alginate, and chitosan is a significant tactic for tissue engineering because it is useful to recognize the interaction between scaffold with a tissue or cell, their cellular reactions, and potential for tissue regeneration. The present review article is focused on injectable hydrogels scaffolds made of biocompatible natural polymers with particular features, the methods that can be employed to engineer injectable hydrogels and their latest applications in tissue regeneration.

An overview of various treatment strategies, especially tissue engineering for damaged articular cartilage.

Many traditional procedures, including surgical methods such as microfracture of subchondral bone and soft tissue transplantation, have been widely used to treat damaged cartilage. However, there is still no definitive cure for cartilage defects. In recent decades, tissue engineering has raised hopes for the repair of defective cartilage. Different approaches are used for cartilage engineering, in which cells, scaffolds, and biological signals or growth factors may be used alone or in combination. Additionally, the imitation of the mechanical properties of the natural cartilage tissue by bioreactors is also helpful in this regard. It should be noted that in the transplantation of engineered cartilage tissue, there are challenges such as poor integration, inflammation and phenotypic instability that may lead to failure of neo-cartilage transplantation. Therefore, a comprehensive understanding of the multiple therapeutic approaches, including surgical procedures, cell-based methods and tissue engineering, should be obtained. The present review article provides this information, along with a variety of factors, including cells, materials, and biological/biomechanical factors required for the engineering of cartilage tissue, as well as the challenges ahead and their solutions.

Effect of green GO/Au nanocomposite on in-vitro amplification of human DNA.

Recently nanomaterials have attracted interest for increasing efficiency of polymerase chain reaction (PCR) systems. Here, the authors report on the usefulness of green graphene oxide/gold (GO/Au) nanocomposites for enhancement of PCR reactions. In this study, green GO/Au nanocomposite was prepared with Matricaria chamomilla extract as reducing/capping agent for site-directed nucleation of Auo atoms on surface of GO sheets. The as-prepared green GO/Au nanocomposites were then characterised with UV-VIS spectrophotometer and scanning electron microscopy. Later, the effect of these nanocomposites was studied on end-point and real-time PCR employed for amplification of human glyceraldehyde-3-phosphate dehydrogenase gene. The results indicated that GO/Au nanocomposite can improve both end-point and real-time PCR methods at the optimum concentrations, possibly through interaction between GO/Au nanocomposite and the materials in PCR reaction, and through providing increased thermal convection by the GO surface as well as the Au nanostructures. In conclusion, it can be suggested that green GO/Au nanocomposite is a biocompatible and eco-friendly candidate as enhancer of in-vitro molecular amplification strategies.

Development and characterization of a novel conductive polyaniline-g-polystyrene/Fe3O4 nanocomposite for the treatment of cancer.

The goal of this study is to synthesize, characterize and investigate some physicochemical properties of conductive polyaniline-g-polystyrene/Fe3O4 (Fe3O4/PSt-g-PANi) nanocomposites. For this purpose, initially, Fe3O4 nanoparticles were synthesized by a co-precipitation method. Then, the desired nanocomposite was synthesized in two steps. First, the atom transfer radical polymerization (ATRP) of styrene was performed using an ATRP initiator attached to the surface of Fe3O4 nanoparticles, followed by functionalization of the Fe3O4-PSt with amine groups (-NH2). Second, surface oxidative graft copolymerization of aniline was accomplished using the -NH2 moieties on the Fe3O4/PSt-NH2 as the anchoring sites. The prepared materials were characterized by various instruments, including TEM, SEM, TGA, EDX, FT-IR, XRD and conductivity measurements. The results indicated that the synthesized conductive polymer/Fe3O4 nanocomposites had higher electrical conductivity and thermal resistance than those of the corresponding homopolymers.

An overview of advanced biocompatible and biomimetic materials for creation of replacement structures in the musculoskeletal systems: focusing on cartilage tissue engineering.

Tissue engineering, as an interdisciplinary approach, is seeking to create tissues with optimal performance for clinical applications. Various factors, including cells, biomaterials, cell or tissue culture conditions and signaling molecules such as growth factors, play a vital role in the engineering of tissues. In vivo microenvironment of cells imposes complex and specific stimuli on the cells, and has a direct effect on cellular behavior, including proliferation, differentiation and extracellular matrix (ECM) assembly. Therefore, to create appropriate tissues, the conditions of the natural environment around the cells should be well imitated. Therefore, researchers are trying to develop biomimetic scaffolds that can produce appropriate cellular responses. To achieve this, we need to know enough about biomimetic materials. Scaffolds made of biomaterials in musculoskeletal tissue engineering should also be multifunctional in order to be able to function better in mechanical properties, cell signaling and cell adhesion. Multiple combinations of different biomaterials are used to improve above-mentioned properties of various biomaterials and to better imitate the natural features of musculoskeletal tissue in the culture medium. These improvements ultimately lead to the creation of replacement structures in the musculoskeletal system, which are closer to natural tissues in terms of appearance and function. The present review article is focused on biocompatible and biomimetic materials, which are used in musculoskeletal tissue engineering, in particular, cartilage tissue engineering.

Nanocomposite hydrogels for cartilage tissue engineering: a review.

The loss of cartilaginous tissues is an important challenge to orthopaedic surgeons. Injury to cartilage tissue due to its properties is along with movement difficulties. Tissue engineering is a developing field that can be used for regeneration or replacement of damaged tissues. In this field, an appropriate scaffold that support the recruitment, adhesion, proliferation and differentiation of cells is necessary. Hydrogels recently considered as materials that resemble the extracellular matrix (ECM) and efficiently replace defective tissues, but they have limited mechanical strength. So nanomaterials are embedded in the hydrogel's matrix to improve their properties. Nanoparticles, such as organic/polymeric and inorganic (hydroxyapatite, clay, graphene and metallic nanoparticles), can be used as fillers to reinforce the hydrogel matrix. Utilizing those nanocomposites could help in better performance of hydrogels applicable in cartilage regeneration practices. This review presents some of nanocomposite hydrogel (NCH) systems that used in cartilage tissue engineering.

Synthesis, characterization and in vitro evaluation of magnetic nanoparticles modified with PCL-PEG-PCL for controlled delivery of 5FU.

Magnetic nanoparticles have properties that cause to apply them in cancer therapy and vehicles for the delivery of drugs such as 5FU, especially when they are modified with biocompatible copolymers. The aim of this study is to modify superparamagnetic iron oxide nanoparticles (SPIONPs) with PCL-PEG-PCL copolymers and then utilization of these nanoparticles for encapsulation of anticancer drug 5FU. The ring-opening polymerization (ROP) was used for the synthesis of PCL-PEG-PCL copolymer by ε-caprolactone (PCL) and polyethylene glycol (PEG2000). We used the double emulsion method (water/oil/water) to prepare 5FU-encapsulated Fe3O4 magnetic nanoparticles modified with PCL-PEG-PCL copolymer. Chemical structure and magnetic properties of 5FU-loaded magnetic-polymer nanoparticles were investigated systematically by employing FT-IR, XRD, VSM and SEM techniques. In vitro release profile of 5FU-loaded NPs was also determined. The results showed that the encapsulation efficiency value for nanoparticles were 90%. Moreover, the release of 5FU is significantly higher at pH 5.8 compared to pH 7.4. Therefore, these nanoparticles have sustained release and can apply for cancer therapy.

Fabrication of Three-Dimensional Scaffolds Based on Nano-biomimetic Collagen Hybrid Constructs for Skin Tissue Engineering.

Three-dimensional (3D) biodegradable and biomimetic porous scaffolds are ideal frameworks for skin tissue engineering. In this study, hybrid constructs of 3D scaffolds were successfully fabricated by the freeze-drying method from combinations of the type I collagen (Col) and synthetic poly(lactic acid) (PLLA) or polycaprolactone (PCL). Four different groups of 3D porous scaffolds including PCL, PCL-Col, PCL-PLLA, and PCL-PLLA-Col were fabricated and systematically characterized by hydrogen nuclear magnetic resonance, Fourier transform infrared spectroscopy, and scanning electron microscopy (SEM). Adipose tissue-derived mesenchymal stem cells (AT-MSCs) were seeded in all scaffolds, and the viability, proliferation, and adhesion of the cells were investigated using dimethylthiazol diphenyltetrazolium bromide assay and SEM. The results showed that scaffolds containing Col, particularly PCL-PLLA-Col scaffold, with pore sizes close to 400 nm and being sufficiently interconnected, have significantly greater potential (p < 0.01) for encouraging AT-MSCs adhesion and growth. The PCL-PLLA provided a mechanically stronger mesh support, and the type I Col microsponges encouraged excellent cell adhesion and tissue formation. The scaffold with the best properties could be an appropriate functional candidate for the preparation of artificial skin constructs.

Application of nanostructured drug delivery systems in immunotherapy of cancer: a review.

The cancer immunotherapy method uses the specificity of the immune system to provide a more effective than more conventional treatments, such as chemotherapy and radiotherapy. Immunotherapy has two main strategies (passive or active) to organize the immune system. Passive strategies use advantage of tumor-hyperpermeable cells, which have enhanced permeability and retention effects. Nanoparticles due to their better accumulation within tissues and cells of the immune system are well suitable for delivery of immune therapies such as vaccines or adjuvants. In this review, we explained application of nanotechnology in immunotherapy of cancer.

A Review on Potential Role of Silver Nanoparticles and Possible Mechanisms of their Actions on Bacteria.

The antimicrobial property of silver is associated to the quantity of silver and the grade of silver released. The ionized silver is extremely sensitive, as it binds to tissue proteins and gets operational alterations in the bacterial cell wall and nuclear membrane leading to cell modification and death.Silver nanoparticles have the talent to anchor to the bacterial cell wall and consequently infiltrate it, so causing physical modifications in the cell membrane like the absorptivity of the cell membrane and death of the cell. There are numerous concepts on the act of silver nanoparticle on bacteria to reason the microbicidal influence.

Combined letrozole and clomiphene versus letrozole and clomiphene alone in infertile patients with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age (6.8%-18%), is among the most common causes of infertility due to ovulation factors, and accounts for 55%-70% of infertility cases caused by chronic anovulation. In this study, we used a combination of letrozole and clomiphene in patients resistant to both drugs individually, and studied the effects of this combination in ovulation and pregnancy in resistant PCOS patients. METHODS: The study population included infertile couples diagnosed as PCOS in the wife. The women used clomiphene for at least six cycles in order to ovulate after failure to form the dominant follicle, and were then put on letrozole for four cycles. Patients who were unable to form the dominant follicle were enrolled on letrozole and clomiphene combination therapy. RESULTS: One hundred enrolled patients underwent 257 cycles of a combination of letrozole and clomiphene, in which 213 were able to form the dominant follicle (82.9%) and 44 were unable to do so (17.1%). The number of mature follicles was 2.3±1.1. The mean endometrial thickness in patients on the day of human chorionic gonadotropin administration was 8.17±1.3 mm. The pregnancy rate was 42%. CONCLUSION: According to the results of this study, it can be proposed that in PCOS patients resistant to clomiphene and letrozole used as single agents, a combination of the two drugs can be administered before using more aggressive treatment that may have severe complications or surgery. This combination may also be used as a first-line therapy to induce ovulation in severe cases of PCOS in order to save time and expense.