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In recent years, the main quest of science has been the pioneering of the groundbreaking biomedical strategies needed for achieving a personalized medicine. Ribonucleic acids (RNAs) are outstanding bioactive macromolecules identified as pivotal actors in regulating a wide range of biochemical pathways. The ability to intimately control the cell fate and tissue activities makes RNA‐based drugs the most fascinating family of bioactive agents. However, achieving a widespread application of RNA therapeutics in humans is still a challenging feat, due to both the instability of naked RNA and the presence of biological barriers aimed at hindering the entrance of RNA into cells. Recently, material scientists’ enormous efforts have led to the development of various classes of nanostructured carriers customized to overcome these limitations. This work systematically reviews the current advances in developing the next generation of drugs based on nanotechnology‐assisted RNA delivery. The features of the most used RNA molecules are presented, together with the development strategies and properties of nanostructured vehicles. Also provided is an in‐depth overview of various therapeutic applications of the presented systems, including coronavirus disease vaccines and the newest trends in the field. Lastly, emerging challenges and future perspectives for nanotechnology‐mediated RNA therapies are discussed., Nanotechnology‐mediated RNA delivery enables regulating a broad range of cellular processes providing effective strategies for personalized medicine. This review provides a comprehensive overview of the recent evidence in the field, highlighting key RNA molecules and nanostructured carriers. Their innovative applications for vaccine development, wound healing, cancer, and neural system treatments are summarized. Finally, new trends and future applications are discussed.

Surface hydrophilicity and scaffold integrity determine the drug release behavior of drug loaded electrospun fibrous mats. When mixture miscibility is acceptable, blend electrospinning of hydrophobic with hydrophilic polymers can improve scaffold hydrophilicity while the hydrophobic polymer maintains the mechanical strength of scaffold. Polycaprolactone (PCL) and Pluronic P123 (P123) blend electrospinning has been investigated. In routine blend electrospinning, surface enrichment of Pluronic sets a limit for P123 weight ratio in which exceeding from that limit causes the excess P123 to be accumulated within the electrospun fiber core. To overcome this setback, a method named surfactant assisted water exposed (SAWE) electrospinning was introduced which was proven to be effective for increasing the surface enrichment of Pluronic. In order to test the validity of this method, the electrospinning of solution containing PCL which is exposed to aqueous solution of P123 was investigated. This new method was named surfactant aqueous solution exposed (SASE) electrospinning. Myelin formation at the contact interface of aqueous solution and chloroform solution was studied and it was found that this layer can effectively barricade the migration of Pluronic chains between immiscible phases. For SASE, fiber surface coverage by P123 was uneven and loose. Electrospun scaffolds from SAWE and SASE were loaded with drug to investigate the effect of the exposure time during electrospinning on in vitro drug release. By increasing the exposure time, the abnormal two-stage phased release profile of SAWE became normal with moderate initial burst. Longer exposure time increased the initial burst of the drug loaded SASE fibers. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 597-609, 2019.

Modified halloysite nanotubes (HNT-NH2 and HNT-COOH) were synthesized by a coupling reaction with 3-aminopropyltriethoxysilane and maleic anhydride from hydroxyl groups of neat halloysite nanotubes (HNTs). Successful attachment of functional groups onto HNTs was evaluated by Fourier transform infrared and thermogravimetric analysis. X ray diffraction was used to study the crystalline structure of scaffolds and the formation of intercalated structure as a result of improved dispersion and decreased agglomeration of modified nanoparticles. Neat HNT, HNT-NH2 , and HNT-COOH were subsequently introduced into polycaprolactone/Pluronic P123 (PCL/P123) electrospun substrate. Morphology, thermodynamics, mechanics, and biocompatibility of resulted electrospun nanocomposites were evaluated. Nanofibers containing modified HNTs showed excellent mechanical performance and thermal stability in comparison with those containing neat HNTs. homogeneous dispersion of the modified HNTs and strong interfacial adhesion between nanotubes and polymer matrix can be considered for mentioned improvements. Ultraviolet-visible spectrophotometer was used to study diphenhydramine hydrochloride and diclofenac sodium release from nanocomposites containing drug loaded modified and neat HNTs. Nanocomposites containing drug loaded HNT-COOH exhibited prolonged release of drug molecules in comparison with that of neat HNTs. MTT assay reveled that PCL/P123/modified HNTs nanocomposites provide a suitable platform for cell growth where PCL/P123/HNT-NH2 can facilitate cell attachment through electrostatic interactions between negatively charged phospholipids bilayer membrane of cells and positively charged HNT-NH2 embedded in PCL/P123 substrate. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1276-1287, 2018.

Curcumin has been proven to be an effective herbal derived anti-inflammatory and antioxidant biocompatible agent. In this research, poly(lactic-co-glycolic acid) (PLGA) (as a biocompatible and generally recognized as safe (GRAS) polymer) nanoparticles containing Curcumin were electrosprayed from different polymeric solutions with different concentrations for the first time. Morphology of these nanoparticles in the absence/presence of Curcumin was evaluated by scanning electron microscope, transmission electron microscope, and X-ray photoelectron spectroscopy analyses. Perfectly shaped nanoparticles with an average size of 300 and 320 nm were observed for neat and Curcumin-loaded PLGA, respectively. Curcumin-loaded electrosprayed nanoparticles showed a normal moderate initial burst and then a prolonged release period. Weibull, Peppas, and modified Korsmeyer-Peppas models were applied to study the kinetic and mechanism of Curcumin release from PLGA nanoparticles. Results showed high specific surface area and spherical geometry of the nanoparticles. Effectiveness of the electrospray method as a promising technique for preparing Curcumin-loaded nanoparticles was confirmed in this study. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 285-292, 2018.

In order to improve surface hydrophilicity, blood compatibility and cell-antiadhesion of polypropylene (PP) film, polypropylene oxide (PPO)-polyethylene oxide-PPO used as macromolecular surface modifier through physical blending. Surface properties of blended PP/Pluronic F127 (PF127) samples were investigated by attenuated total reflection infrared spectroscopy and water contact angle measurements. Results demonstrated that PF127 migrated to the surface. Thus, mechanical properties of blended PP/PF127 samples with the aim of the revealing the effects of the presence of modifier in the bulk were investigated through differential scanning calorimetry, X-ray diffraction, and tensile tests. The biocompatibility and hemocompatibility of modified PP films were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, platelet-rich plasma, and hemolysis tests. These results showed excellent anticell and antiplatelet adhesion which deems the prepared blended films proper biomaterials. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 652-662, 2018.

Molecular dynamics simulations are performed to study the design and optimization of nanocarriers with high drug loading capacity. Functionalized graphene is considered as the nominated high capacity drug carrier and Dox as the drug model. The graphene surface functionalized with hydroxyl (– O H ), carboxyl (– C O O H ), methyl (– C H 3 ) and amine (– N H 2 ) groups and their associated properties are investigated. The simulation results are illustrated that G − C O O H surface absorbs Dox more effectively in comparison to other functionalized graphene surfaces due to the higher binding energy of carboxylic groups and the model drug. The effect of hydrogen bonding, temperature and surface porosity are also evaluated. The results show that binding energy and the solubility parameter are temperature-dependent. The simulation results in this present work reveal the underlying mechanisms of Dox loading on neat and functionalized graphene surfaces may be employed to design better graphene-based nanocarriers for the Dox delivery applications.

Blend electrospun scaffolds composed of Polycaprolactone and Pluronic are suitable for bone tissue engineering due to their excellent biocompatibility and hydrophilicity. However, exceeding from certain amounts of Pluronic, surface enrichment of this polymer leads to segregation of Pluronic chains within the fiber, endangering the integrity and mechanical properties of the scaffold. In this article, a novel method of blend electrospinning has been employed using a parallel water supply, positioning the Pluronic chains on the surface, thus enhancing the miscibility within the fibers. Water uptake test revealed the super hydrophilicity of obtained scaffolds. Atr-FTIR and X-ray photoelectron spectroscopy verified a higher percentage of Pluronics on the surface in comparison with conventional blend electrospinning. Tensile test demonstrated improved mechanical properties of the modified scaffolds. The results of cytocompatibility tests have also revealed enhanced viability of cells on these scaffolds confirming their great promise for clinical applications. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1204-1212, 2019.

To overcome the problems related to the low surface enrichment of blended fibers from hydrophilic polymer, routine blend electrospinning setup was modified by exposing the polycaprolactone (PCL)–Pluronic P123 solution to water in order to attract the hydrophilic chains toward the fiber surface. Analysis of the modified fibers revealed a drastic surge of hydrophilic polymer surface enrichment value in comparison with that of the routine method which suggested homogenously positioned Pluronic on the surface and the subsequent reduction of its accumulations within fibers. The thermogram of the proposed method showed induced crystallization in the Pluronic section. Furthermore, the intensity of PCL characteristic peaks decreased for this method.

Functionalized hydroxyapatite nanoparticles (HA-F127) were synthesized by immobilizing pluronic F127 onto hydroxyapatite nanoparticles (HA). Successful grafting of F127 was evaluated by FTIR, TGA and TEM. XRD was used to study the crystalline structure of neat and functionalized nanoparticles. Grafted F127 chains on the surface of HA formed a core–shell structure. Furthermore, immobilization of F127 chains on the HA surface decreased the agglomeration of modified nanoparticles and improved their dispersion. In the next step, the HA-F127 and unmodified HA were introduced into a PCL/P123 electrospun substrate, and nanocomposites containing 4 wt% nano-filler were obtained. The corresponding properties of these polymer/ceramic nanocomposites, including morphology, thermodynamics, mechanics and biocompatibility, were evaluated. HA-F127/PCL/P123 showed superior mechanical performance, crystallinity percentage and thermal stability. The aforementioned improvements were primarily ascribed to a uniform dispersion of HA-F127 and strong interfacial adhesion between filler and matrix, which resulted from superior chain entanglements and interfacial crystallization of modified HA in the polymer substrate. Nanocomposites containing modified HA organized into a reliable platform for adhesion and proliferation of mouse L929 fibroblast cells. Finally, to analyze the interfacial interactions between phases, molecular dynamics simulation was applied. It was found that strong interfacial interactions exist between HA-F127 and PCL/P123. Consequently, HA-F127/PCL/P123 nanofibrous scaffolds can be considered as a promising candidate for tissue engineering applications.

Surface hydrophilicity and scaffold integrity determine the drug release behavior of drug loaded electrospun fibrous mats. When mixture miscibility is acceptable, blend electrospinning of hydrophobic with hydrophilic polymers can improve scaffold hydrophilicity while the hydrophobic polymer maintains the mechanical strength of scaffold. Polycaprolactone (PCL) and Pluronic P123 (P123) blend electrospinning has been investigated. In routine blend electrospinning, surface enrichment of Pluronic sets a limit for P123 weight ratio in which exceeding from that limit causes the excess P123 to be accumulated within the electrospun fiber core. To overcome this setback, a method named surfactant assisted water exposed (SAWE) electrospinning was introduced which was proven to be effective for increasing the surface enrichment of Pluronic. In order to test the validity of this method, the electrospinning of solution containing PCL which is exposed to aqueous solution of P123 was investigated. This new method was named surfactant aqueous solution exposed (SASE) electrospinning. Myelin formation at the contact interface of aqueous solution and chloroform solution was studied and it was found that this layer can effectively barricade the migration of Pluronic chains between immiscible phases. For SASE, fiber surface coverage by P123 was uneven and loose. Electrospun scaffolds from SAWE and SASE were loaded with drug to investigate the effect of the exposure time during electrospinning on in vitro drug release. By increasing the exposure time, the abnormal two-stage phased release profile of SAWE became normal with moderate initial burst. Longer exposure time increased the initial burst of the drug loaded SASE fibers. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 597-609, 2019.

Curcumin has been proven to be an effective herbal derived anti-inflammatory and antioxidant biocompatible agent. In this research, poly(lactic-co-glycolic acid) (PLGA) (as a biocompatible and generally recognized as safe (GRAS) polymer) nanoparticles containing Curcumin were electrosprayed from different polymeric solutions with different concentrations for the first time. Morphology of these nanoparticles in the absence/presence of Curcumin was evaluated by scanning electron microscope, transmission electron microscope, and X-ray photoelectron spectroscopy analyses. Perfectly shaped nanoparticles with an average size of 300 and 320 nm were observed for neat and Curcumin-loaded PLGA, respectively. Curcumin-loaded electrosprayed nanoparticles showed a normal moderate initial burst and then a prolonged release period. Weibull, Peppas, and modified Korsmeyer-Peppas models were applied to study the kinetic and mechanism of Curcumin release from PLGA nanoparticles. Results showed high specific surface area and spherical geometry of the nanoparticles. Effectiveness of the electrospray method as a promising technique for preparing Curcumin-loaded nanoparticles was confirmed in this study. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 285-292, 2018.

Tissue engineering of implantable cellular constructs is an emerging cellular therapy for hepatic disease. In this study, we tested the ability of poly(ε-caprolactone) (PCL) nanofiber scaffold to support and maintain hepatic differentiation of human cord blood-derived unrestricted somatic stem cells (USSCs) in vitro. USSCs, self-renewing pluripotent cells, were isolated from human cord blood. The electrospun PCL nanofiber porous scaffold was constructed of uniform, randomly oriented nanofibers. USSCs were seeded onto PCL nanofiber scaffolds, and were induced to differentiate into hepatogenic lineages by culturing with differentiation factors for 6 weeks. RT-PCR analysis of endoderm and hepatic-specific gene expression, immunohistochemical detection of cytokeratin 18 (CK-18), α-fetoprotein, albumin, glycogen storage and indocyanine green uptake confirmed the differentiation of USSCs into endoderm and hepatocyte-like cells. In the present study, we show that hepatocyte-like cells differentiated from USSCs on the PCL nanofiber scaffold can be candidate for tissue engineering and cell therapy of hepatic tissues.