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.

Electrospun polyurethane/poly (ɛ-caprolactone) nanofibers promoted the attachment and growth of human endothelial cells in static and dynamic culture conditions.

In this study, the angiogenic capacity of human endothelial cells was studied after being plated on the surface of polyurethane-poly caprolactone (PU/PCL) scaffolds for 72 h. In this study, cells were designated into five different groups, including PU, PU/PCL (2:1), PU/PCL (1:1); PU/PCL (1:2); and PCL. Data revealed that the PU/PCL (2:1) composition had a higher modulus and breakpoint in comparison with the other groups (p < 0.05). Compared to the other groups, the PU/PCL scaffold with a molar ratio of 2:1 had lower the contact angle θ and higher tensile stress (p < 0.05). The mean size of the PU nanofibers was reduced after the addition of PCL (p < 0.05). Based on our data, the culture of endothelial cells on the surface of PU/PCL (2:1) did not cause nitrosative stress and cytotoxic effects under static conditions compared to cells plated on a conventional plastic surface (p > 0.05). Based on data from the static condition, we fabricated a tubular PU/PCL (2:1) construct for six-day dynamic cell culture inside loop air-lift bioreactors. Scanning electron microscopy showed the attachment of endothelial cells to the luminal surface of the PU/PCL scaffold. Cells were flattened and aligned under the culture medium flow. Immunofluorescence imaging showed the attachment of cells to the luminal surface indicated by blue nuclei on the luminal surface. These data demonstrated that the application of PU/PCL substrate could stimulate endothelial cells activity under static and dynamic conditions.

An improved method in fabrication of smart dual-responsive nanogels for controlled release of doxorubicin and curcumin in HT-29 colon cancer cells.

The combination therapy which has been proposed as the strategy for the cancer treatment could achieve a synergistic effect for cancer therapies and reduce the dosage of the applied drugs. On account of the the unique properties as the high absorbed water content, biocompatibility, and flexibility, the targeting nanogels have been considred as a suitable platform. Herein, a non-toxic pH/thermo-responsive hydrogel P(NIPAAm-co-DMAEMA) was synthesized and characterized through the free-radical polymerization and expanded upon an easy process for the preparation of the smart responsive nanogels; that is, the nanogels were used for the efficient and controlled delivery of the anti-cancer drug doxorubicin (DOX) and chemosensitizer curcumin (CUR) simultaneously like a promising strategy for the cancer treatment. The size of the nanogels, which were made, was about 70 nm which is relatively optimal for the enhanced permeability and retention (EPR) effects. The DOX and CUR co-loaded nanocarriers were prepared by the high encapsulation efficiency (EE). It is important to mention that the controlled drug release behavior of the nanocarriers was also investigated. An enhanced ability of DOX and CUR-loaded nanoformulation to induce the cell apoptosis in the HT-29 colon cancer cells which represented the greater antitumor efficacy than the single-drug formulations or free drugs was resulted through the In vitro cytotoxicity. Overall, according to the data, the simultaneous delivery of the dual drugs through the fabricated nanogels could synergistically potentiate the antitumor effects on the colon cancer (CC).

Reversion of Multidrug Resistance by Co-Encapsulation of Doxorubicin and Metformin in Poly(lactide-co-glycolide)-d-α-tocopheryl Polyethylene Glycol 1000 Succinate Nanoparticles.

PURPOSE: P-glycoprotein (P-gp) mediated multidrug resistance (MDR) has been recognized as the main obstacle against successful cancer treatment. To address this problem, co-encapsulated doxorubicin (DOX) and metformin (Met) in a biodegradable polymer composed of poly(lactide-co-glycolide) (PLGA) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) was prepared. We reported in our previous study that Met inhibits P-gp in DOX resistant breast cancer (MCF-7/DOX) cells. TPGS is a bioactive compound which has also been shown to inhibit P-gp, further to its pharmaceutical advantages. METHODS: The DOX/Met loaded PLGA-TPGS nanoparticles (NPs) were prepared by double emulsion method and characterized for their surface morphology, size and size distribution, and encapsulation efficiencies of drugs in NPs. RESULTS: All NPs were found to be spherical-shaped with the size distribution below 100 nm and encapsulation efficiencies were 42.26 ± 2.14% for DOX and 7.04 ± 0.52% for Met. Dual drug loaded NPs showed higher cytotoxicity and apoptosis in MCF-7/DOX cells in comparison to corresponding free drugs. The higher cytotoxicity of dual drug loaded NPs was attributed to the enhanced intracellular drug accumulation due to enhanced cellular uptake and reduced drug efflux which was obtained by combined effects of Met and TPGS in reducing cellular ATP content and inhibiting P-gp. CONCLUSION: Simultaneous delivery of DOX and Met via PLGA-TPGS NPs would be a promising approach to overcome MDR in breast cancer chemotherapy.

pH- and thermo-sensitive MTX-loaded magnetic nanocomposites: synthesis, characterization, and in vitro studies on A549 lung cancer cell and MR imaging.

In the current study, we proposed a facile method for fabrication of multifunctional pH- and thermo-sensitive magnetic nanocomposites (MNCs) as a theranostic agent for using in targeted drug delivery and magnetic resonance imaging (MRI). To this end, we decorated Fe3O4 magnetic nanoparticles (MNPs) with N,N-dimethylaminoethyl methacrylate (DMAEMA) and N-isopropylacrylamide (NIPAAm), best known for their pH- and thermo-sensitive properties, respectively. We also conjugated mesoporous silica nanoparticles (MSNs) to polymer matrix acting as drug container to enhance the drug encapsulation efficacy. Methotroxate (MTX) as a model drug was successfully loaded in MNCs (M-MNCs) via surface adsorption onto MSNs and electrostatic interaction between drug and carrier. The pH- and temperature-triggered release of MTX was concluded through the evaluation of in vitro release at both physiological and simulated tumor tissue conditions. Based on in vitro cytotoxicity assay results, M-MNCs significantly revealed higher antitumor activity compared to free MTX. In vitro MR susceptibility experiment showed that M-MNCs relatively possessed high transverse relaxivity (r2) of about 0.15 mM-1·ms-1 and a linear relationship between the transverse relaxation rate (R2) and the Fe concentration in the M-MNCs was also demonstrated. Therefore, the designed MNCs can potentially become smart drug carrier, while they also can be promising MRI negative contrast agent.

Fluorescent multi-responsive cross-linked P(N-isopropylacrylamide)-based nanocomposites for cisplatin delivery.

Magnetic, pH and temperature-sensitive, poly(N-isopropylacrylamide) (PNIPAM)-based nanocomposites with fluorescent properties were synthesized by free radical copolymerization-cross linking of NIPAM, N,N-dimethylaminoethyl methacrylate (DMAEMA) and 4-acrylamidofluorescein (AFA). The model anti-cancer drug, cisplatin (CDDP), was loaded into the resulted nanogel. For the production of CDDP-loaded nanocomposite, Fe3O4 magnetic nanoparticles (MNPs) and CDDP were loaded into the nanogel. Field-emission scanning electron microscopy (FE-SEM) indicated that the size of nanogel and CDDP-loaded nanocomposite were about 90 and 160 nm, respectively. The encapsulation efficiency of CCDP was found up to 65%. The loaded CCDP showed sustained thermal and pH-responsive drug release. A high level of drug release was observed under the conditions of low pH and high temperature. The lower critical solution temperature (LCST) of synthesized nanogel was about 40 °C. CDDP-loaded nanocomposite showed a volume phase transition from 282 to 128 nm at its LCST. Accordingly, in this study, the synthesized nanocomposite can be employed as a stimuli-responsive anti-cancer drug delivery system and the pH and temperature of solution have the potential to monitor the drug release.

Nanoliposomes: Synthesis methods and applications in cosmetics.

Nanotechnology is used frequently in marketing skin care goods, and whereas the word sounds as if it belongs in robotics and science fiction, it is rapidly becoming common in medicine and skin care. As few people actually recognize what the technology, benefits, or possible implications of its use are, we determined to outline them. The type of nanotechnology that is most significant in cosmetics, skin care and health products is the use of nanoparticles (or Bucky balls as they are known in manufacturing), and a particular kind of these nanoparticles have been touted as the next generation of liposomes. Nanoliposomes is one of the most recognized names for the nanoparticles used in skin care and cosmetic products, and we are also familiar with the term liposome, so this connection between the two is the perhaps the best way to clarify what nanoliposomes are. In this article, some of the techniques for their production are reviewed. Common methods of nanoliposome preparation are discussed.

Scolicidal and apoptotic activities of albendazole sulfoxide and albendazole sulfoxide-loaded PLGA-PEG as a novel nanopolymeric particle against Echinococcus granulosus protoscoleces.

Treatment failures of human cystic echinococcosis (CE) with albendazole (ABZ) have attributed to its low solubility and poor drug absorption rate, resulting in low drug level in plasma. The scolicidal effects of ABZ-loaded liposome nanoparticles have recently evaluated; however, these particles have several challenges due to their low encapsulated load. This investigation was designed to evaluate and compare in vitro apoptotic activities of ABZ sulfoxide (ABZs) and ABZs-loaded poly(lactic-co-glycolic acid) (PLGA)-PEG against protoscoleces (PSCs). ABZs-loaded PLGA-PEG was prepared by a double-emulsion method (W1/O/W2). Various concentrations of ABZs and ABZs-loaded PLGA-PEG (50, 100, 150, and 200 µg/ml) were experimentally tested against PSC of CE at different exposure times (5, 10, 20, 30, and 60 min). ABZs-loaded PLGA-PEG at concentrations of 150 and 200 µg/ml was able to act at a 100 % scolicidal rate in all exposure times (5 to 60 min), while ABZs at a concentration of 200 µg/ml demonstrated 94, 100, and 100 % mortality rates following 20, 30, and 60 min of exposure times, respectively. The messenger RNA (mRNA) expression of caspase-3 was assessed by semi-quantitative RT-PCR after 15 h of exposure. Caspase-3 mRNA expression was higher in both PSC treated with ABZs and PSC treated with ABZs-loaded PLGA-PEG than that in control groups (P < 0.05). No significant difference was observed between the apoptotic intensity of PSC treated with ABZs and that of PSC treated with ABZs-loaded PLGA-PEG (P > 0.05). DNA fragmentation assay and ultrastructural changes revealed that ABZs and ABZs-loaded PLGA-PEG induced the apoptosis of PSC by activation of caspase-3. The higher permeability and scolicidal rate of ABZs-loaded PLGA-PEG can be addressed as an effectual alternative strategy to improve the treatment of human CE.

Preparation of pH sensitive insulin-loaded nano hydrogels and evaluation of insulin releasing in different pH conditions.

In the recent years, temperature and pH-sensitive hydrogels were developed as suitable carriers for drug delivery. In this study, four different pH-sensitive nanohydrogels were designed for an oral insulin delivery modeling. NIPAAm-MAA-HEM copolymers were synthesized by radical chain reaction with 80:8:12 ratios respectively. Reactions were carried out in four conditions including 1,4-dioxan and water as two distinct solution under nitrogen gas-flow. The copolymers were characterized with FT-IR, SEM and TEM. Copolymers were loaded with regular insulin by modified double emulsion method with ratio of 1:10. Release study carried out in pH 1.2 and pH 6.8 at 37 °C. For pH 6.8 and pH 1.2, 2 mg of the insulin loaded nanohydrogels was float in a beaker containing 100 mL of PBS with pH 6.8 and 100 mL of HCl solution with pH 1.2, respectively. Sample collection was done in different times and HPLC was used for analysis of samples using water/acetonitrile (65/35) as the mobile phase. Nanohydrogels synthesis reaction yield was 95 %, HPLC results showed that loading in 1,4-dioxan without cross-linker nanohydrogels was more than others, also indicated that the insulin release of 1,4-dioxan without cross-linker nanohydrogels at acidic pH is less, but in pH 6.8 is the most. Results showed that by opting suitable polymerization method and selecting the best nanohydrogels, we could obtain a suitable insulin loaded nanohydrogels for oral administration.

Synthesis and in vitro study of cisplatin-loaded Fe3O4 nanoparticles modified with PLGA-PEG6000 copolymers in treatment of lung cancer.

In the field of cancer therapy, magnetic nanoparticles modified with biocompatible copolymers are promising vehicles for the delivery of hydrophobic drugs such as Cisplatin. The major aim of this effort was to evaluate whether Cisplatin-Encapsulated magnetic nanoparticles improved the anti-tumour effect of free Cisplatin in lung cancer cells. The PLGA-PEG triblock copolymer was synthesised by ring-opening polymerisation of d,l-lactide and glycolide with polyethylene glycol (PEG6000) as an initiator. The bulk properties of these copolymers were characterised using Fourier transform infrared spectroscopy. Cisplatin-loaded nanoparticles (NPs) were prepared by double emulsion solvent evaporation technique and were characterised for size, drug entrapment efficiency (%), drug content (% w/w), and surface morphology. In vitro release profile of cisplatin-loaded NP formulations was determined. Cytotoxic assays were evaluated in lung carcinoma (A549)-treated cells by the MTT assay technique. In addition, the particles were characterised by X-ray powder diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. The anti-proliferative effect of Cisplatin appeared much earlier when the drug was encapsulated in magnetic nanoparticles than when it was free. Cisplatin-Encapsulated magnetic nanoparticles significantly enhanced the decrease in IC50 rate. The in vitro cytotoxicity test showed that the Fe3O4-PLGA-PEG6000 magnetic nanoparticles had no cytotoxicity and were biocompatible. The chemotherapeutic effect of free Cisplatin on lung cancer cells is improved by its encapsulation in modified magnetic nanoparticles. This approach has the prospective to overcome some major limitations of conventional chemotherapy and may be a promising strategy for future applications in lung cancer therapy.

Synthesis, characterization and in vitro studies of doxorubicin-loaded magnetic nanoparticles grafted to smart copolymers on A549 lung cancer cell line.

BACKGROUND: The aim of present study was to develop the novel methods for chemical and physical modification of superparamagnetic iron oxide nanoparticles (SPIONs) with polymers via covalent bonding entrapment. These modified SPIONs were used for encapsulation of anticancer drug doxorubicin. METHOD: At first approach silane-grafted magnetic nanoparticles was prepared and used as a template for polymerization of the N-isopropylacrylamide (NIPAAm) and methacrylic acid (MAA) via radical polymerization. This temperature/pH-sensitive copolymer was used for preparation of DOX-loaded magnetic nanocomposites. At second approach Vinyltriethoxysilane-grafted magnetic nanoparticles were used as a template to polymerize PNIPAAm-MAA in 1, 4 dioxan and methylene-bis-acrylamide (BIS) was used as a cross-linking agent. Chemical composition and magnetic properties of Dox-loaded magnetic hydrogel nanocomposites were analyzed by FT-IR, XRD, and VSM. RESULTS: The results demonstrate the feasibility of drug encapsulation of the magnetic nanoparticles with NIPAAm-MAA copolymer via covalent bonding. The key factors for the successful prepardtion of magnetic nanocomposites were the structure of copolymer (linear or cross-linked), concentration of copolymer and concentration of drug. The influence of pH and temperature on the release profile of doxorubicin was examined. The in vitro cytotoxicity test (MTT assay) of both magnetic DOx-loaded nanoparticles was examined. The in vitro tests showed that these systems are no toxicity and are biocompatible. CONCLUSION: IC50 of DOx-loaded Fe3O4 nanoparticles on A549 lung cancer cell line showed that systems could be useful in treatment of lung cancer.

The fabrication of halloysite nanotube-based multicomponent hydrogel scaffolds for bone healing.

Bone tissue engineering, as an alternative for common available therapeutic approaches, has been developed to focus on reconstructing of the missing tissues and restoring their functionality. In this work, three-dimensional (3D) nanocomposite scaffolds of polycaprolactone-polyethylene glycol-polycaprolactone/gelatin (PCEC/Gel) were prepared by freeze-drying method. Biocompatible nanohydroxyapatite (nHA), iron oxide nanoparticle (Fe3O4) and halloysite nanotube (HNT) powders were added to the polymer matrix aiming to combine the osteogenic activity of nHA or Fe3O4 with high mechanical strength of HNT. The scanning electron microscope (SEM) methods was utilized to characterize the nanotube morphology of HNT as well as nanoparticles of Fe3O4 and nHA. Prepared scaffolds were characterized via Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), and SEM methods. In addition, the physical behavior of scaffolds was evaluated to explore the influence of HNT on the physicochemical properties of composites. Cell viability and attachment were investigated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay and SEM on human dental pulp-derived mesenchymal stem cells (h-DPSCs) in-vitro. Cell proliferation was observed without any cytotoxicity effect on h-DPSCs for all examined scaffolds. Alizarin red (ARS) and alkaline phosphatase (ALP) staining were carried out to determine the osteoconductivity of scaffolds. The data demonstrated that all PCEC/Gel/HNT hydrogel scaffolds supported osteoblast differentiation of hDPSCs with moderate effects on cell proliferation. Moreover, PCEC/Gel/HNT/nHA with proper mechanical strength showed better biological activity compared to PCEC/Gel/HNT/Fe3O4 and PCEC/Gel/HNT scaffolds. Therefore, this study suggested that with proper fillers content, PCEC/Gel/HNT nanocomposite hydrogels alone or in a complex with nHA, Fe3O4 could be a suitable candidate for hard tissue regeneration.

Gentamycin-loaded halloysite-based hydrogel nanocomposites for bone tissue regeneration: fabrication, evaluation of the antibacterial activity and cell response.

Biocompatible hydrogels are promising approaches for bone repair and engineering. A novel therapeutic nanocomposite hydrogel was designed based on triblock copolymer poly e-caprolactone (PCL)-polyethylene glycol-PCL and natural gelatin (PCEC/GEL) and reinforced with halloysite nanotube (HNT). Gentamicin (GM) loaded HNT was immobilized in polymeric hydrogel matrix to fabricate scaffolds using the freeze-drying method. Scaffolds were characterized via Fourier transform infrared (FT-IR), x-ray powder diffraction, and scanning electron microscope (SEM) methods. The swelling ratio, density, porosity, degradation, and mechanical behavior were evaluated to investigate the effects of HNT on the physicochemical properties of the composite. Cell viability and cell attachment were investigated by microculture tetrazolium (MTT) assay and SEM. Cell proliferation was observed without any cytotoxicity effect on human dental pulp-derived mesenchymal stem cells (h-DPSCs). Alizarin red staining and real-time reverse transcription polymerase chain reaction (QRT-PCR) assay were carried out to monitor the osteoconductivity of scaffolds on h-DPSCs which were seeded drop wise onto the top of scaffolds. The quantification of the messenger RNA (mRNA) expression of osteogenic marker genes, bone morphogenetic protein 2, SPARK, bone gamma-carboxyglutamate protein and runt-related transcription factor 2 over a period of 21 d of cell seeding, demonstrated that cell-encapsulating PCEC/GEL/HNT-GM hydrogel scaffolds supported osteoblast differentiation of h-DPSCs into osteogenic cells through the up-regulation of related genes along with moderate effects on cell viability. Moreover, the antibiotics loading reduced bacterial growth while maintaining the osteogenic properties of the scaffold. Therefore, the bactericidal PCEC/GEL/HNT-GM hydrogel nanocomposite, with enhanced durability, maintenance the functionality of seeded cellsin vitrothat can be a remarkable dual-functional candidate for hard tissue reconstruction and customized bone implants fabrication via the direct incorporation of bactericidal drug to prevent infection.

Hepatic cell-sheet fabrication of differentiated mesenchymal stem cells using decellularized extracellular matrix and thermoresponsive polymer.

PURPOSE: Liver tissue engineering via cell sheet technology would open new doors for treatment of patients with liver failure. Decellularized tissues could provide sufficient extracellular matrix (ECM) to support development of hepatocytes in in vivo niches. Besides, with the potential of temperature responsive polymer (pNIPAAm) as an intelligent surface for controlling the attachment/detachment of cell, we set out to generate three in vitro microenvironments models including I: pNIPAAm hydrogel (pN hydrogel), II: decellularized ECM incorporated into pNIPAAm hydrogel (dECM + pN hydrogel) and III: decellularized ECM scaffold (dECM scaffold) to investigate the structural and function cues of hepatocyte-like cells after differentiation of adipose tissue-derived mesenchymal stem cells (AT-MSCs) on the surface of these models. METHOD: dECM scaffold was obtained after decellularization of rat liver, and its efficiency was analyzed. pN hydrogel and dECM + pN hydrogel (1:3 and 2:3 ratios) of were fabricated, and scaffold architecture was characterized. Each well of culturing plates was coated separately with these three constructs and AT-MSCs were instructed to differentiate into hepatocyte-like cells (HLCs). After recellularization, patterns of differentiation, and expression of hepatogenic markers were investigated via biochemical assays and qRT-PCR at different time points. RESULTS: Multipotency of AT-MSCs, after their ability for osteogenesis and adipogenesis was documented. Production of dense and intact cell sheets was reported in dECM + pN hydrogel, as opposed to pN hydrogel and dECM scaffold. Also, statistically significant difference of HLCs functionality in dECM + pN hydrogel was confirmed after evaluation of the expression of hepatocyte markers including, alpha-fetoprotein, cytokeratin 18, cytochrome P450-2E1 and phosphoenolpyruvate carboxykinase. CONCLUSION: Our results proved dECM + pN hydrogel were able to preserve hepatocyte function in cell sheets owing to the high level of albumin, urea, hepatogenic markers, and glycogenesis potential of HLCs. Accordingly, dECM incorporated in pN hydrogel could remodel microenvironments to guide the AT-MSCs into conducive differentiation and proliferation to give rise to multilayer sheets of cells in their own ECM.

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.

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.

Design and fabrication of M-SAPO-34/chitosan scaffolds and evaluation of their effects on dental tissue engineering.

This research aimed to design innovative therapeutic bio-composites that enhance odontogenic and osteogenic differentiation of human dental pulp-derived mesenchymal stem cells (h-DPSCs) in-vitro regeneration. Herein, we report the fabrication of scaffolds containing chitosan, Ca-SAPO-34 monometallic and/or Fe-Ca-SAPO-34 bimetallic nanoparticles by freeze-drying technique. The scaffolds and nanoparticles were characterized using ICP-AES, FT-IR, XRD, TGA, TEM, BET, SEM, and EDS methods. The effects of SAPO-34 and nanoparticles were investigated by changes on the physicochemical properties of scaffolds including swelling ratio, density, porosity, bio-degradation, mechanical behavior, and biomineralization. Cell viability, cell adhesion and cytotoxicity of Ca-SAPO-34/CS and Fe-Ca-SAPO-34 scaffolds were investigated by MTT assay and SEM on h-DPSCs which revealed cell proliferation no toxicity on scaffolds. Cell tests demonstrated that Ca-SAPO-34/CS scaffold clearly displayed a positive effect on differentiation of hDPSCs into osteogenic/odontogenic cells and moderate effect on cell proliferation. Moreover, the incorporation of Fe2O3 to Ca-SAPO-34/CS scaffold promoted the proliferation of hDPSCs and osteogenic differentiation. Alizarin red, Alkaline phosphatase and QRT-PCR results showed that Fe-Ca-loaded SAPO-34/CS can lead to osteoblast/odontoblast differentiation in DPSCs through the up-regulation of related genes, thus indicating that Fe-Ca-SAPO-34/CS has remarkable prospects as a biomaterial for hard tissue engineering.

Antibacterial and antifungal impacts of combined silver, zinc oxide, and chitosan nanoparticles within tissue conditioners of complete dentures in vitro.

BACKGROUND: Tissue conditioners are suitable places for colonization of microorganisms. A combination of tissue conditioners with antibacterial and antifungal materials inhibits the growth of microorganisms. AIMS: Here, we aimed to investigate the antibacterial and antifungal effects of silver (Ag), zinc oxide (ZnO), and chitosan nanoparticles on tissue conditioners in complete dentures. METHODS: The growth of four microorganisms in six different concentrations of Ag, ZnO, and chitosan nanoparticles was investigated after 24 and 48 h. Nanoparticles were synthesized using optical sequestration and approved by scanning electron microscope, x-ray diffraction, and infrared (FT-IR) methods. Nanoparticles were combined at 0.5, 0.25, and 0.25 ratios (chitosan, Ag, and ZnO, respectively) with 0.625, 1.25, 2.5, 5, 10, and 20 mass percentages. Tissue conditioners with nanoparticles were entered to test tubes containing microorganisms, and the growth rate was measured using the turbidity method by spectrophotometer after 24 and 48 h of incubation at 37 °C. RESULTS: Growth inhibition of Candida albicans occurred at 2.5% concentration. However, the growth inhibition of Streptococcus mutans, Enterococcus faecalis, and Pseudomonas aeruginosa occurred at 5% after both 24 and 48 h. Also, the optimum nanoparticle concentration for Candida albicans was found to be 1.25% for both timings. On the other hand, the optimum nanoparticle concentration for Streptococcus mutans, Enterococcus faecalis, and Pseudomonas aeruginosa was 2.5% for both time scales. CONCLUSIONS: The combination of Ag, ZnO, and chitosan nanoparticles inhibited the growth of fungi and bacteria in tissue conditioners. These nanoparticles inhibited the growth of fungi more effectively than bacteria.

Lysine-embedded cellulose-based nanosystem for efficient dual-delivery of chemotherapeutics in combination cancer therapy.

Combination therapy by two or multiple drugs with different mechanisms of action is a promising strategy in cancer treatment. In this regard, a wide range of chemotherapeutics has used simultaneously to achieve the synergistic effect and overcome the adverse side effects of single-drug therapy. Herein, we developed a biocompatible nanoparticle-based system composed of nanocrystalline cellulose (NCC) and amino acid l-lysine for efficient co-delivery of model chemotherapeutic methotrexate (MTX) and polyphenol compound curcumin (CUR) to the MCF-7 and MDA-MB-231 cells. The drugs could release in a sustained and acidic-facilitate manner. In vitro cytotoxicity results represented the superior anti-tumor efficacy of the dual-drug-loaded nanocarriers. Possible inhibition of cell growth and induction of apoptosis in the cells treated with different formulations of CUR and MTX were explored by cell cycle analysis and DAPI staining. Overall, the engineered nanosystem can be used as suitable candidates to achieve efficient multi-drug delivery for combination cancer therapy.

Stimuli-responsive polyvinylpyrrolidone-NIPPAm-lysine graphene oxide nano-hybrid as an anticancer drug delivery on MCF7 cell line.

Despite the advances in the development of chemotherapeutic agents, resistance to chemotherapy and adverse side effects are still big challenges against successful cancer treatment. To overcome these problems, one strategy is the application of nanomaterials and drug delivery systems to efficiently deliver the anticancer agents to tumour tissues with minimum toxic effects on healthy organs. In this study a graphene oxide nanohybrid (GO/NHs) was designed and fabricated for the delivery of chemotherapeutic agent fluorouracil (FU) to the breast cancer MCF7 cells. After preparation and characterization of GO/NHs, several biological analysis including haemolysis assay, cytotoxicity assay, cellular uptake, apoptosis assay, and protein expression were performed. The cytotoxic effects of FU, FU loaded GO/NHs (FU-GO/NHs), and blank GO/NHs was determined by MTT assay. The results of MTT assay showed no significant cytotoxicity for blank nano-hybrid on MCF7 cells. Furthermore, FU-GO/NHs were more cytotoxic than free FU. The uptake analysis results showed that developed nanocarrier could completely be internalized into the cells in the first hour. Besides, apoptotic effects and nuclear morphology changes of cells was evaluated by DAPI staining under fluorescent microscopy. Protein expression levels of p53, PARP, cleaved PARP, Bcl-2, and Bax were determined by western blot analysis. Western blot results showed higher levels of p53 and cleaved PARP after treatment with FU-GO/NHs, however, no substantial effect was observed for Bax and Bcl-2 protein concentrations.