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Blood cells are the most integral part of the body, which are made up of erythrocytes, platelets and white blood cells. The examination of subcellular structures and proteins within blood cells at the nanoscale can provide valuable insights into the health status of an individual, accurate diagnosis, and efficient treatment strategies for diseases. Super-resolution microscopy (SRM) has recently emerged as a cutting-edge tool for the study of blood cells, providing numerous advantages over traditional methods for examining subcellular structures and proteins. In this paper, we focus on outlining the fundamental principles of various SRM techniques and their applications in both normal and diseased states of blood cells. Furthermore, future prospects of SRM techniques in the analysis of blood cells are also discussed. [ABSTRACT FROM AUTHOR]

A comparative study of the complexing and solubilizing capacity of β-cyclodextrin and its new dimeric diaminocationic derivatives in relation to baricitinib, a new generation immunomodulator, is performed. Isothermal saturation is used to determine the solubility of baricitinib in the presence of the considered β‑cyclodextrins in a phosphate buffer solution (pH 6.8). Thermodynamic parameters of complex formation are calculated, and a binding mode is proposed on the basis of 1H NMR data. The effect of the structure of β-cyclodextrin on the efficiency of complex formation and the solubilization of baricitinib is analyzed. [ABSTRACT FROM AUTHOR]

Infectious bone defects are characterized by the partial loss or destruction of bone tissue resulting from bacterial contaminations subsequent to diseases or external injuries. Traditional bone transplantation and clinical methods are insufficient in meeting the treatment demands for such diseases. As a result, researchers have increasingly focused on the development of more sophisticated biomaterials for improved therapeutic outcomes in recent years. This review endeavors to investigate specific reparative materials utilized for the treatment of infectious bone defects, particularly those present in the maxillofacial region, with a focus on biomaterials capable of releasing therapeutic substances, functional contact biomaterials, and novel physical therapy materials. These biomaterials operate via heightened antibacterial or osteogenic properties in order to eliminate bacteria and/or stimulate bone cells regeneration in the defect, ultimately fostering the reconstitution of maxillofacial bone tissue. Based upon some successful applications of new concept materials in bone repair of other parts, we also explore their future prospects and potential uses in maxillofacial bone repair later in this review. We highlight that the exploration of advanced biomaterials holds promise in establishing a solid foundation for the development of more biocompatible, effective, and personalized treatments for reconstructing infectious maxillofacial defects. [ABSTRACT FROM AUTHOR]

The solubilizing effect of β-cyclodextrin on fingolimod, a new generation immunosuppressant, is studied for the first time. A possible 20× increase in the solubility of fingolimod due to the penetration of the hydrophobic fragment of the drug molecule into the macrocyclic cavity of the cyclodextrin is shown. Data driven 1H NMR spectroscopy and computer modeling suggest the configuration of the resulting inclusion complexes. The constant of the complex's stability and its energy of complexation are calculated, and the formation of hydrogen bonds between fingolimod and β-cyclodextrin is considered. [ABSTRACT FROM AUTHOR]

Guidance of postinfarct myocardial remodeling processes by an epicardial patch system may alleviate the consequences of ischemic heart disease. As macrophages are highly relevant in balancing immune response and regenerative processes their suitable instruction would ensure therapeutic success. A polymeric mesh capable of attracting and instructing monocytes by purely physical cues and accelerating implant degradation at the cell/implant interface is designed. In a murine model for myocardial infarction the meshes are compared to those either coated with extracellular matrix or loaded with induced cardiomyocyte progenitor cells. All implants promote macrophage infiltration and polarization in the epicardium, which is verified by in vitro experiments. 6 weeks post‐MI, especially the implantation of the mesh attenuates left ventricular adverse remodeling processes as shown by reduced infarct size (14.7% vs 28–32%) and increased wall thickness (854 µm vs 400–600 µm), enhanced angiogenesis/arteriogenesis (more than 50% increase compared to controls and other groups), and improved heart function (ejection fraction = 36.8% compared to 12.7–31.3%). Upscaling as well as process controls is comprehensively considered in the presented mesh fabrication scheme to warrant further progression from bench to bedside. [ABSTRACT FROM AUTHOR]

Our previous study shows that the peptide consisting of 29 residues at positions 354–382 of zebrafish AP‐2 complex subunit mu‐A is an antimicrobial peptide (AMP) capable of inhibiting the growth of Escherichia coli and Staphylococcus aureus. Sequence analysis revealed that the N‐terminal 10 amino acids (designated AP10) of the peptide were highly conserved from nematode to humans. On this basis, we designed two AP10 analogs, AP10R and AP10W, by substituting the amino acids at selected positions of AP10 with tryptophan (W), isoleucine (I), and arginine (R). Both AP10 and AP10R as well as AP10W were found to possess the common features of AMPs: a high hydrophobic ratio, a net positive charge, and amphipathicity. Antibacterial activity assay showed that AP10W exhibited the strongest antimicrobial activity against Gram‐negative and Gram‐positive bacteria including MDR bacteria (with MICs ranging from 20 to 25 μg/ml) among the three peptides. In addition, AP10W was able to bind to lipopolysaccharide (LPS), lipoteichoic acid (LTA), and peptidoglycan (PGN), cause depolarization of the bacterial plasma membrane, and stimulate intracellular reactive oxygen species (ROS) production, suggesting it executes antibacterial activity by a combined action of destabilization/destruction of bacterial cell wall through interaction with LPS, LTA, and PGN, disturbance of the usually polarized membrane through depolarization, and apoptosis/necrosis through intracellular ROS production. Importantly, AP10W is not toxic to mammalian cells, and shows tolerance to serum, salt, and pH variation though it is heat labile. These together suggest that AP10W is a promising template for future development of novel peptide antibiotics against MDR bacteria. [ABSTRACT FROM AUTHOR]

In this work, we studied the formation of supramolecular inclusion complexes (pseudopolyrotaxanes) generated by the interactions between L35 Pluronic (PEO–PPO–PEO triblock copolymer) and hydroxyl propyl-modified cyclodextrins (HP-α-CD and HP-β-CD). The structural characteristics of the L35/CD composites were investigated by X-ray diffraction spectroscopy, which highlighted the effective inclusion of the copolymer. The thermodynamic properties of the pseudopolyrotaxanes were determined through density and speed of sound experiments conducted on aqueous mixtures with various L35/CD compositions, while turbidimetric analyses allowed the investigation of the kinetics of the threading process of L35 polymeric chains within the cavity of the cyclodextrins. Both thermodynamic and kinetic features were explored at various temperatures (20, 25, 30 and 35 °C). According to the negative values of the Gibbs free energies, we observed that the formation of the pseudopolyrotaxanes is spontaneous for both cyclodextrins. Specifically, the inclusion process is more favoured for HP-β-CD. This result was supported by the peculiar effects of the cyclodextrins on the interfacial characteristics of the copolymer at the air/water interface. In conclusion, this paper provides an extensive description of L35/HP-α-CD and L35/HP-β-CD complexes that have potential as thermo-sensitive nanocarriers with controlled release properties. [ABSTRACT FROM AUTHOR]

Additive manufacturing, known as 3D printing, has been widely applied in various fields owing to the development of 3D printing materials and 3D printing techniques. Compared with other fabrication approaches, 3D printing possesses the advantages of high resolution, high accuracy, unique customizability, and repeatability. Therefore, 3D printing can be widely used to fabricate various microstructures, including micromotors, which are capable of converting external energies into motion and subsequently accomplishing various functions. To date, five types of 3D printing techniques have been used to fabricate self‐propelled micromotors with different structures, ingredients, and functions. This progress report summarizes 3D printing techniques for the fabrication of micromotors and introduces the potential biomedical applications of 3D printed micromotors. The advantages and disadvantages of each typical 3D printing method are discussed as well. [ABSTRACT FROM AUTHOR]

The use of magnetic separation based on nanoparticles has been an efficient approach in many research fields and different industries. It has shown multiple advantages including high separation efficiency and fast separation speed as well as low cost, comparing to conventional sedimentation or centrifugation methods. The basic contents and modelling principles such as one-way and two-way coupling methods involving magnetic separation have been introduced specifically and comprehensively, which can be used for better understanding the process and optimizing design of magnetic separators. Then typical industry applications of magnetic separation including kaolin beneficiation, water treatment, protein purification, cell separation, and drug delivery have been summarized in detail. [ABSTRACT FROM AUTHOR]

MicroRNAs are small regulatory noncoding RNAs that regulate various biological processes associated with neurological disorders, cardiovascular diseases, cancer and viral infection. MiRNA-based therapeutics have broad applications including cancer immunotherapy, genomic engineering and protein replacement therapy. Until now, a variety of materials have been proved to be promising as non-viral nanocarriers for intracellular delivery of miRNAs, such as polymeric nanoparticles, lipid nanocapsules, and inorganic nanoparticles, etc. In this review, we will present the strategies for intracellular miRNA delivery, and specially focus on rationally designed routes, their mechanisms of action, and potential therapeutics used in the host cells or in vivo studies. Futhermore, we will also make a conclusion based on the current development. The perspective on the new generation of delivery systems toward the emerging area of miRNA-based therapeutics will be discussed as well. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are targeted as vehicles for cell mediated gene therapy. Here we report on a macromolecular carrier, which was designed aiming at successful targeted gene delivery into MSCs through the mediation of folate receptor and reduced cytotoxicity compared to established cationic polymer vector -- polyethylenimine with a weight average molecular weight (Mw) of 25,000 Dalton (PEI25K). The carrier PHPA-PEI1800-FA was synthesized in a two-step procedure. PHPA-PEI1800 was prepared by grafting polyethylenimine with a Mw of 1800 Dalton (PEI1800) onto the α,β poly(N-3-hydroxypropyl)-D,L-aspartamide (PHPA) backbone. PHPA-PEI1800-FA was obtained by chemically conjugating folic acid onto PHPA-PEI1800. The grafting degree of PEI1800 was 3.9±0.2% in relation to the CH groups of PHPA and the molar ratio of folic acid conjugated to PEI1800 (ΧFA) was 1.8±0.1 as calculated by NMR spectroscopy. The copolymers were biodegradable and exhibited lower cytotoxicity than PEI25K. Compared to PHPA-PEI1800, PHPA-PEI1800-FA led to a significantly higher transfection efficiency in human MSCs, which could be attributed to the mediation of folate receptor during the transfection process as confirmed by folic acid competition assay. Both marker gene (GFP) and therapeutic gene (VEGF) were delivered into human MSCs from multi-donors using PHPA-PEI1800-FA. The percentage of GFP+ MSCs showed an average value of 2.85±1.60% but a large variation for different samples. The VEGF expression level of the PHPA-PEI1800-FA transfected cells was significantly higher than that of either untransfected or naked DNA transfected cells. Conclusively, PHPA-PEI1800-FA is a suitable vector to deliver genes into human MSCs through the interaction with folate receptor. [ABSTRACT FROM AUTHOR]

Non-viral gene carriers for gene therapy have been developed for many years. But the gene transfection is generally limited by deficient cellular uptake, low endo/lysosome escape, and weak nuclear translocation. Some targeting peptides have been conjugated onto gene carriers for highly efficient gene delivery. These targeting carriers can overcome some of these limitations to efficiently deliver therapeutic genes into desired cells. In this review, we will summarize the recent development of multi-targeting peptide immobilized non-viral gene carriers for efficient gene therapy, especially for the targeting and suppression of tumor cells, and the transfection and proliferation of endothelial cells. The peptide functionalization of gene carriers is a promising strategy to promote the elimination of solid tumors and the rapid endothelialization of artificial blood vessels. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) has been identified as an important cell-signaling mediator and has a number of biological functions, such as vascular smooth muscle relaxation, neurotransmission, and regulation of inflammation. A facile and versatile approach for H2S production initiated by light irradiation and controlled by reaction with an amine or an amino acid was developed. The donor was synthesized in a one-pot reaction, and simple crystallization led to a yield of approximately 90 %. The synthetic strategy is scalable and versatile, and the H2S donors can be expressed ina number of different molecular and macromolecular forms, including crystalline small-molecule compounds, water-soluble polymers, polystyrene films, and hydrogels. The H2S donors based on polystyrene film and hydrogel were used as cell-culture scaffolds. The H2S donor based on water-soluble polymer was applied in photocontrolled inhibition of P-selectin expression on human platelets and subsequent regulation of platelet aggregation. This study provides the simplest controllable H2S source to study its biological functions. The developed materials are also new therapeutic platforms to deliver H2S, as there is no accumulation of toxic byproducts, and the donor materials from polystyrene films and hydrogels can be readily removed after releasing H2S. [ABSTRACT FROM AUTHOR]

Superparamagnetic iron oxide nanoparticles (SPIONs) are versatile and easily functionalized agents with high potential for diagnostic and therapeutic intravascular applications. In this study,we analyzed the responses of endothelial (ECs) and monocytic cells to three different types of SPIONs, in order to assess the influence of physico-chemical properties on the biological reactions to SPIONs. The following formulations were used: (1) Lauric acid-coated and BSA-stabilized SPION-1,(2) Lauric acid/BSAcoated SPION-2 and (3) dextran-coated SPION-3. SPION-1 were strongly internalized by ECs and reduced their viability in static conditions. Additionally, they had a dose-dependent inhibitory effect on monocytic cell chemotaxis to MCP-1, but did not affect monocytic cell recruitment by ECs. SPION-2 uptake was less pronounced, both in ECs and monocytic cells, and these particles were better tolerated by the vascular cells. Not being internalized by endothelial or monocytic cells, SPION-3 did not induce relevant effects on cell viability, motility or endothelial-monocytic cell interactions. Taken together, localized accumulation of circulating SPION under physiologic-like flow conditions and their cellular uptake depends on the physicochemical characteristics. Our findings suggest that SPION-2 are suitable for magnetic targeting of atherosclerotic plaques. Due to their excellent biocompatibility and low internalization, SPION-3 may represent a suitable imaging agent for intravascular applications. [ABSTRACT FROM AUTHOR]

Surface modification and endothelialization of vascular biomaterials are common approaches that are used to both resist the nonspecific adhesion of proteins and improve the hemocompatibility and long-term patency of artificial vascular grafts. Surface modification of vascular grafts using hydrophilic poly(ethylene glycol), zwitterionic polymers, heparin or other bioactive molecules can efficiently enhance hemocompatibility, and consequently prevent thrombosis on artificial vascular grafts. However, these modified surfaces may be excessively hydrophilic, which limits initial vascular endothelial cell adhesion and formation of a confluent endothelial lining. Therefore, the improvement of endothelialization on these grafts by chemical modification with specific peptides and genes is now arousing more and more interest. Several active peptides, such as RGD, CAG, REDV and YIGSR, can be specifically recognized by endothelial cells. Consequently, graft surfaces that are modified by these peptides can exhibit targeting selectivity for the adhesion of endothelial cells, and genes can be delivered by targeting carriers to specific tissues to enhance the promotion and regeneration of blood vessels. These methods could effectively accelerate selective endothelial cell recruitment and functional endothelialization. In this review, recent developments in the surface modification and endothelialization of biomaterials in vascular tissue engineering are summarized. Both gene engineering and targeting ligand immobilization are promising methods to improve the clinical outcome of artificial vascular grafts. [ABSTRACT FROM AUTHOR]

Artificial micro-/nanoswimmers have various potential applications including minimally invasive diagnosis and targeted therapies, environmental sensing and monitoring, cell manipulation and analysis, and lab-on-a-chip devices. Inspired by natural motile bacteria such as E. Coli, artificial bacterial flagella (ABFs) are one kind of magnetic helical microswimmers. ABFs can perform 3D navigation in a controllable fashion with micrometer precision under low-strength rotating magnetic fields (<10 mT) and are promising tools for targeted drug delivery in vitro and in vivo. In this work, the successful wirelessly targeted and single-cell gene delivery to human embryonic kidney (HEK 293) cells using ABFs loaded with plasmid DNA (pDNA) in vitro is demonstrated for the first time. The ABFs are functionalized with lipoplexes containing pDNA to generate functionalized ABFs (f-ABFs). The f-ABFs are steered wirelessly by low-strength rotating magnetic fields and deliver the loaded pDNA into targeted cells. The cells targeted by f-ABFs are successfully transfected by the transported pDNA and expressed the encoding protein. These f-ABFs may also be useful for in vivo gene delivery and other applications such as sensors, actuators, cell biology, and lab-on-a-chip environments. [ABSTRACT FROM AUTHOR]

Various kinds of inorganic nanoparticles have been used as non-viral gene carriers. Two fundamental roles of gene carriers are to bind the DNA molecules and to protect them from enzymatic attack after internalization into the cells. Therefore, all nanoparticles that are used as gene carriers must be functionalized. Lately, magnetic gene carriers incorporating PEI have been adopted to improve DNA transfection efficiency. Researchers have used PEI-coated MNPs for DNA entrapment, and they have found that this complex was not able to achieve an efficient DNA transfection, but needed an extra free PEI to deliver the DNA to the cell nucleus. In this study, magnetic gene carriers with small sizes and surface modifications were prepared to explore the magnetofection process. Different methods for PEI immobilization on smaller MNPs were adopted to compare DNA binding abilities, transfection and transient gene expression efficiencies. Finally, the magnetofection process was studied with confocal microscopy and flow cytometry. These results provide details regarding the mechanism of DNA magnetofection, which has not been yet fully understood. [ABSTRACT FROM AUTHOR]

Novel nonviral gene vectors of alkaline amino acids such as arginine- (Arg), histidine- (His), and lysine- (Lys) modified chitosans (AAA-CSs) are developed to simulate the components of viral envelopes to enhance transfection efficiency. The structures of the modified chitosans are characterized using 1H NMR spectroscopy. Acid-base titration results indicate that the modified chitosans exhibit strong buffering capacity. The morphology of the AAA-CSs/pDNA complexes is observed by use of transmission electron microscopy and atomic force microscopy. The complexes are spherical nanoparticles with a mean size around 100 nm. Zeta potential tests reveal that the complexes are positively charged and their zeta potentials vary from +0.1 to +19.5 mV. The MTT assay and agarose gel electrophoresis demonstrate that the AAA-CSs are non-cytotoxic and have excellent DNA condensation and protection abilities. Cellular uptake investigation of the AAA-CSs/pDNA complexes demonstrates that Arg-CS and His-CS have better cellular internalization property than the unmodified chitosan. The in vitro gene transfection is evaluated in HEK293 and NIH3T3 cell lines and in vivo transfection is carried out in tibialis anterior muscles. The results reveal that the arginine-modified chitosan could significantly enhance gene-transfection efficiency both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Thrombus and restenosis are two main factors that cause the failure of vascular implants. Constructing a functional and confluent layer of endothelial cells (ECs) is considered an ideal method to prevent these problems. However, oxidative stress induced by the disease and implantation can damage ECs and hinder the endothelialization of implants. Thus, developing biomaterials that can protect ECs adhesion and proliferation from oxidative stress is urgently needed for the rapid endothelialization of vascular implants. In this work, a novel polyurethane (PU-TBN) is synthesized by employing tetramethylpyrazine-nitrone (TBN) as end-group to endow polymers with dual functions of antioxidant activity and promoting endothelialization. Common PU without TBN is also prepared to be control. Compared to PU, PU-TBN significantly promotes human umbilical vein endothelial cells (HUVECs) adhesion and proliferation, where cells spread well and a confluent endothelial layer is formed. PU-TBN also shows obvious free radical scavenging activity, and thus effectively attenuates oxidative stress to protect HUVECs from oxidative apoptosis. Moreover, PU-TBN exhibits enhanced antiplatelets effect, excellent biocompatibility, and similar mechanical properties to PU. These characteristics can endow PU-TBN with great potential to be used as vascular implants or coatings of other materials for rapid endothelialization under complex oxidative stress environment., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Unsatisfactory post‐stroke recovery has long been a negative factor in the prognosis of ischemic stroke due to the lack of pharmacological treatments. Mesenchymal stem cells (MSCs)‐based therapy has recently emerged as a promising strategy redefining stroke treatment; however, its effectiveness has been largely restricted by insufficient therapeutic gene expression and inadequate cell numbers in the ischemic cerebrum. Herein, a non‐viral and magnetic field‐independent gene transfection approach is reported, using magnetosome‐like ferrimagnetic iron oxide nanochains (MFIONs), to genetically engineer MSCs for highly efficient post‐stroke recovery. The 1D MFIONs show efficient cellular uptake by MSCs, which results in highly efficient genetic engineering of MSCs to overexpress brain‐derived neurotrophic factor for treating ischemic cerebrum. Moreover, the internalized MFIONs promote the homing of MSCs to the ischemic cerebrum by upregulating CXCR4. Consequently, a pronounced recovery from ischemic stroke is achieved using MFION‐engineered MSCs in a mouse model. [ABSTRACT FROM AUTHOR]