PEI-based functional materials: Fabrication techniques, properties, and biomedical applications.

Cationic polymers have recently attracted considerable interest as research breakthroughs for various industrial and biomedical applications. They are particularly interesting due to their highly positive charges, acceptable physicochemical properties, and ability to undergo further modifications, making them attractive candidates for biomedical applications. Polyethyleneimines (PEIs), as the most extensively utilized polymers, are one of the valuable and prominent classes of polycations. Owing to their flexible polymeric chains, broad molecular weight (MW) distribution, and repetitive structural units, their customization for functional composites is more feasible. The specific beneficial attributes of PEIs could be introduced by purposeful functionalization or modification, long service life, biocompatibility, and distinct geometry. Therefore, PEIs have significant potential in biotechnology, medicine, and bioscience. In this review, we present the advances in PEI-based nanomaterials, their transfection efficiency, and their toxicity over the past few years. Furthermore, the potential and suitability of PEIs for various applications are highlighted and discussed in detail. This review aims to inspire readers to investigate innovative approaches for the design and development of next-generation PEI-based nanomaterials possessing cutting-edge functionalities and appealing characteristics.

A review on inertial microfluidic fabrication methods.

In recent decades, there has been significant interest in inertial microfluidics due to its high throughput, ease of fabrication, and no need for external forces. The focusing efficiency of inertial microfluidic systems relies entirely on the geometrical features of microchannels because hydrodynamic forces (inertial lift forces and Dean drag forces) are the main driving forces in inertial microfluidic devices. In the past few years, novel microchannel structures have been propounded to improve particle manipulation efficiency. However, the fabrication of these unconventional structures has remained a serious challenge. Although researchers have pushed forward the frontiers of microfabrication technologies, the fabrication techniques employed for inertial microfluidics have not been discussed comprehensively. This review introduces the microfabrication approaches used for creating inertial microchannels, including photolithography, xurography, laser cutting, micromachining, microwire technique, etching, hot embossing, 3D printing, and injection molding. The advantages and disadvantages of these methods have also been discussed. Then, the techniques are reviewed regarding resolution, structures, cost, and materials. This review provides a thorough insight into the manufacturing methods of inertial microchannels, which could be helpful for future studies to improve the harvesting yield and resolution by choosing a proper fabrication technique.

Polysaccharide-based hydrogels containing herbal extracts for wound healing applications.

Development of an ideal wound dressing with effective function for healing various types of wounds is the ultimate desire of the researchers. Natural-based compounds such as polysaccharides and phytochemicals offer useful properties making them perfect candidates for wound management. Polysaccharides-based hydrogels with an interconnected three-dimensional network, and desired properties have great potential as a carrier for delivery of different herbal extracts for oral and topical applications. Herbal extracts are extensively used for wound healing purposes, individually or in combination with other active agents. This study summarizes the current knowledge acquired on the preparation, functionalizing, and application of different kinds of polysaccharide-based hydrogels enriched by herbal extracts for different wound healing applications. The structural, biological, and functional impact of the polysaccharides and herbal extracts on the final hydrogel characteristics, as well as their influence on the different phases of the wound healing process have been discussed.

Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing.

Wound healing is one of the most complex biological processes. Studies show that Matrixyl (MTI), known as a cosmetic peptide, can lead to a faster healing process. The contribution of MTI to collagen formation during wound healing also depends on its mode of delivery and its release over time. Here, we investigate two modes of MTI-delivery system, the influence of MTI patch for wound healing application in comparison with MTI cream. In this study, animals were randomly divided into seven groups and studied for 21 days: patches containing two different concentrations of MTI (P-MTI-0.1 mg and P-MTI-1 mg), a cream containing MTI (C-MTI-1 mg), a patch (P-MTI-0), a cream with no MTI (C-MTI-0), a positive control (Comfeel), and a negative control (sham) group. To study the wound healing process, the change in collagen density, angiogenesis, epitheliogenesis, histopathology, immunohistochemical analysis, and wound area through imaging was monitored and measured. The macroscopic results showed that wound healing was improved from 63.5 up to 81.81% in treatment groups compared to that in the negative control group (P < 0.05 and P < 0.001). In addition, C-MTI-1 and P-MTI-1 had a larger impact on wound healing compared to that in the positive control group (Comfeel, P < 0.05). In hematoxylin and eosin (H&E) staining analysis, the rejuvenation of skin appendage was visible in both groups of cream and patches with MTI. According to the obtained results, the re-epithelialization had a higher range for the patch with MTI in comparison with cream containing MTI and positive control.

Mantle Cell Lymphoma Presenting as Diarrhea in a Liver Transplant Recipient.

We present a 63-year-old man with a medical history of hepatocellular carcinoma who underwent orthotopic liver transplant 10 years prior on long-term immunosuppressive therapy. The patient presented to the clinic with diarrhea, and the workup revealed mantle cell lymphoma. Mantle cell lymphoma is an extremely rare finding in transplanted livers. It is essential to include mantle cell lymphoma, along with a broad differential, during the workup of diarrhea in post-transplant patients.

Cigarette smoke-induced toxicity consequences of intracellular iron dysregulation and ferroptosis.

Despite numerous studies on the mechanisms of cigarette smoking toxicity over the past three decades, some aspects remain obscure. Recent developments have drawn attention to some hopeful indicators that allow us to advance our awareness of cigarette-induced cell death. Ferroptosis is considered a type of governed death of cells distinguished by the iron-dependent lipid hydroperoxide deposition to fatal concentrations. Ferroptosis has been linked with pathological settings such as neurodegenerative diseases, cancer, heart attack, hemorrhagic stroke, traumatic brain injury, ischemia-reperfusion injury, and renal dysfunction. This review tries to explain the causal role of ferroptosis cascade in cigarette smoke-mediated toxicity and cell death, highlighting associations on potential action mechanisms and proposing suggestions for its detoxifying and therapeutic interventions.

Restoring Endogenous Repair Mechanisms to Heal Chronic Wounds with a Multifunctional Wound Dressing.

Current treatment of chronic wounds has been critically limited by various factors, including bacterial infection, biofilm formation, impaired angiogenesis, and prolonged inflammation. Addressing these challenges, we developed a multifunctional wound dressing-based three-pronged approach for accelerating wound healing. The multifunctional wound dressing, composed of nanofibers, functional nanoparticles, natural biopolymers, and selected protein and peptide, can target multiple endogenous repair mechanisms and represents a promising alternative to current wound healing products.

Enzyme-Responsive Biopolymeric Nanogel Fibers by Extrusion: Engineering of High-Surface-Area Hydrogels and Application in Bacterial Enzyme Detection.

The fabrication of covalently cross-linked high-surface-area biopolymeric nanogel fibers by nanopore extrusion is reported for the first time. The biopolymer pullulan was functionalized with tert-butyl acetoacetate via a transesterification reaction to synthesize the water-soluble ketone-rich precursor pullulan acetoacetate (PUAA). PUAA and carbonic dihydrazide (CDH) as cross-linker were extruded through anodic aluminum oxide (AAO) nanoporous membranes, which possessed an average pore diameter of 61 ± 2 nm. By changing the concentration of PUAA, the flow rate, and extrusion time, the step polymerization cross-linking reaction was controlled so that the polymer can be extruded gradually during cross-linking through the membrane, avoiding the formation of macroscopic bulk hydrogels and rupture of the AAO membrane. Fibers with diameters on the order of 250 nm were obtained. This approach was also expanded to functionalized PUAA derivatives together with the fluorogenic substrate 4-methylumbelliferyl-ß-d-glucuronide MUGlcU in (PUAA-MUGlcU), which exhibited a mean equilibrium swelling ratio of 5.7 and 9.0 in Milli-Q water and in phosphate-buffered saline, respectively. ß-Glucuronidase was sensitively detected via fluorescence of 4-methylumbelliferone, which was liberated in the enzymatic hydrolysis reaction of PUAA-MUGlcU. Compared to hydrogel slabs, the rate of the hydrolysis was >20% higher in the nanogel fibers, facilitating the rapid detection of ß-glucuronidase-producing Escherichia coli (E. coli Mach1-T1). Nanopore extruded nanogel fibers are therefore considered a viable approach to enhance the functionality of hydrogels in surface-dominated processes.

Targeting non-apoptotic cell death in cancer treatment by nanomaterials: Recent advances and future outlook.

Many tumors develop resistance to most of the apoptosis-based cancer therapies. In this sense targeting non-apoptotic forms of cell death including necroptosis, autophagy and ferroptosis may have therapeutic benefits in apoptosis-defective cancer cells. Nanomaterials have shown great advantages in cancer treatment owing to their unique characteristics. Besides, the capability of nanomaterials to induce different forms of cell death has gained widespread attention in cancer treatment. Reports in this field reflect the therapeutic potential of necroptotic cell death induced by nanomaterials in cancer. Also, autophagic cell death induced by nanomaterials alone and as a part of chemo-, radio- and photothermal therapy holds great promise as anticancer therapeutic option. Besides, ferroptosis induction by iron-based nanomaterials in drug delivery, immunotherapy, hyperthermia and imaging systems shows promising results in malignancies. Hence, this review is devoted to the latest efforts and the challenges in this field of research and its clinical merits.

Controlling evolution of protein corona: a prosperous approach to improve chitosan-based nanoparticle biodistribution and half-life.

Protein corona significantly affects in vivo fate of nanoparticles including biodistribution and half-life. Without manipulating the physicochemical properties of nanoparticles with considering their biointerference, attaining effective treatment protocols is impossible. For this reason, protein corona evolution and biodistribution of different chitosan (Ch)-based nanoparticles including Ch and carboxymethyl dextran (CMD)/thiolated dextran (TD) polyelectrolyte complexes (PECs) were studied using highly precious and sensitive methods such as liquid chromatography-mass/mass (LC-MS/MS) spectroscopy and positron emission tomography/computed tomography (PET/CT) scan. The importance of serum presence/absence in culture medium with different pH and corona effect on cellular uptake of PECs investigated by in vitro study. Designed PECs have low amounts of proteins in corona mostly enriched by Apolipoproteins, protein C, hemoglobin subunits, and inter-alpha- trypsin inhibitor that beside improving uptake of nanoparticles, they have low liver uptake and notable heart blood pool accumulation that confirmed the long circulation time of the nanoparticles which is favorable for delivery of nanoparticles to the site of action and achieving required therapeutic effect.

Neoadjuvant Phase II Trial of Chemoradiotherapy in Patients With Resectable and Borderline Resectable Pancreatic Cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma is a largely incurable cancer. Surgical resection remains the only potential option for cure. Even in surgically resectable patients, only about 10% to 20% are long-term survivors. Emerging data suggest a role for neoadjuvant therapy to target occult micrometastatic disease. AIM: To report our institutional experience with a novel neoadjuvant chemoradiation (CRT) regimen in resectable and borderline resectable pancreatic cancer. MATERIALS AND METHODS: Patients were treated with 2 cycles of induction chemotherapy with FOLFOX and then received CRT with gemcitabine and intensity-modulated radiotherapy (IMRT). RESULTS: From April 2014 to June 2017, 24 patients were enrolled. Eighteen patients were borderline resectable and 6 patients were resectable. All patients received induction chemotherapy with FOLFOX. Thirteen patients underwent pancreatectomy after CRT with a resection rate of 62%. R0 resection achieved in 11 patients (84.6%) and 2 patients had R1 resection (15.4%). For patients who underwent resection, the median progression-free survival (PFS) was 31 months, 1-year PFS rate was 69.2% (95% confidence interval [CI], 0.48-0.99), and 2-year PFS rate was 51.9% (95% CI, 0.3-0.89). Median overall survival (OS) was 34.8 months (95% CI, 1.045 to infinity), 1-year OS rate was 91.7% (95% CI, 0.77-1.0), and 2-year OS rate was 75% (95% CI, 0.54-1.0). Median CA 19-9 at screening for patients who underwent surgery was 659 (range, 18 to 2154), which decreased to 146.9 (range, 18 to 462) after CRT before resection. CONCLUSION: Neoadjuvant therapy for borderline resectable and resectable pancreatic ductal adenocarcinoma with CRT facilitated R0 resection in 84% patients who underwent surgery.

3D Printing of Inertial Microfluidic Devices.

Inertial microfluidics has been broadly investigated, resulting in the development of various applications, mainly for particle or cell separation. Lateral migrations of these particles within a microchannel strictly depend on the channel design and its cross-section. Nonetheless, the fabrication of these microchannels is a continuous challenging issue for the microfluidic community, where the most studied channel cross-sections are limited to only rectangular and more recently trapezoidal microchannels. As a result, a huge amount of potential remains intact for other geometries with cross-sections difficult to fabricate with standard microfabrication techniques. In this study, by leveraging on benefits of additive manufacturing, we have proposed a new method for the fabrication of inertial microfluidic devices. In our proposed workflow, parts are first printed via a high-resolution DLP/SLA 3D printer and then bonded to a transparent PMMA sheet using a double-coated pressure-sensitive adhesive tape. Using this method, we have fabricated and tested a plethora of existing inertial microfluidic devices, whether in a single or multiplexed manner, such as straight, spiral, serpentine, curvilinear, and contraction-expansion arrays. Our characterizations using both particles and cells revealed that the produced chips could withstand a pressure up to 150 psi with minimum interference of the tape to the total functionality of the device and viability of cells. As a showcase of the versatility of our method, we have proposed a new spiral microchannel with right-angled triangular cross-section which is technically impossible to fabricate using the standard lithography. We are of the opinion that the method proposed in this study will open the door for more complex geometries with the bespoke passive internal flow. Furthermore, the proposed fabrication workflow can be adopted at the production level, enabling large-scale manufacturing of inertial microfluidic devices.

Optimization of the interaction of graphene quantum dots with lipase for biological applications.

Graphene quantum dots (GQDs) are known as emerging sub-10 nm nanoparticles (NPs), which are in fact few-layered pieces of graphene, capable of emitting blue fluorescence, when exposed to 360 nm UV light. Understanding the details of the interaction between GQDs and lipase can serve as a critical step for improving the biological outcome of GQD-derived drug-delivery and diagnosis systems. The interaction occurs in the form of surface adsorption, which can subsequently influence the physicochemical properties of both the NP and the protein. Hence, a systematic approach was taken here to optimize the GQDs' synthesis conditions in order to achieve the highest possible quantum yield (QY). Furthermore, to understands the influence of the interaction of GQDs and lipase, on both the activity of lipase and the emission intensity of GQDs, various incubation conditions were tested to achieve optimized conditions over central composite design algorithm by Design-Expert®, using response surface methodology. The results show that the GQDs fabricated by thermal decomposition of citric acid at 160°C, with a heating duration of 55 min, obtain almost three times higher QY than the highest values reported previously. The best enzymatic activity after the formation of the hard corona, as well as the highest fluorescent emission, were achieved at GQD-to-enzyme ratios within the rage of 23-25%, at temperatures between 41 and 42°C, for 6-8 min. In the aforementioned condition, the enzyme retains 91-95% of its activity and the NP preserves about 80-82% of its fluorescence intensity after incubation.

Poly(diethylene glycol methylether methacrylate) Brush-Functionalized Anodic Alumina Nanopores: Curvature-Dependent Polymerization Kinetics and Nanopore Filling.

We report on the synthesis and characterization of poly(diethylene glycol methylether methacrylate) (PDEGMA) brushes by surface-initiated atom transfer radical polymerization inside ordered cylindrical nanopores of anodic aluminum oxide with different pore radii between 20 and 185 nm. In particular, the dependence of polymerization kinetics and the degree of pore filling on the interfacial curvature were analyzed. On the basis of field emission scanning electron microscopy data and thermal gravimetric analysis (TGA), it was concluded that the polymerization rate was faster at the pore orifice compared to the pore interior and also as compared to the analogous reaction carried out on flat aluminum oxide substrates. The apparent steady-state polymerization rate near the orifice increased with decreasing pore size. Likewise, the overall apparent polymerization rate estimated from TGA data indicated stronger confinement for pores with increased curvature as well as increased mass transport limitations due to the blockage of the pore orifice. Only for pores with a diameter to length ratio of ∼1, PDEGMA brushes were concluded to grow uniformly with constant thickness. However, because of mass transport limitations in longer pores, incomplete pore filling was observed, which leads presumably to a PDEGMA gradient brush. This study contributes to a better understanding of polymer brush-functionalized nanopores and the impact of confinement, in which the control of polymer brush thickness together with grafting density along the nanopores is key for applications of PDEGMA brushes confined inside nanopores.

In Situ Study of Layer-by-Layer Polyelectrolyte Deposition in Nanopores of Anodic Aluminum Oxide by Reflectometric Interference Spectroscopy.

The modification of cylindrical anodic aluminum oxide (AAO) nanopores by alternating layer-by-layer (LBL) deposition of poly(sodium-4-styrene sulfonate) (PSS) and poly(allylamine hydrochloride) (PAH) was studied in situ by reflectometric interference spectroscopy (RIfS). In particular, the kinetics of polyelectrolyte deposition inside the pores with a diameter of 37 ± 3 nm and a length of 3.7 ± 0.3 µm were unraveled, and potential differences in the LBL multilayer growth compared to flat silicon substrates as well as the effect of different ionic strengths and different types of ions were investigated. RIfS measures the effective optical thicknesses, which is-for a constant pore length-proportional to the effective refractive index of the AAO sample, from which, in turn, the deposited mass of the polymer or the corresponding layer thickness can be estimated. Compared to the multilayer growth by the LBL deposition on the flat aminosilane-primed silicon wafers, which was assessed by spectroscopic ellipsometry, the thickness increment per deposited bilayer, as well as the dependence of this increment on the ionic strength (0.01-0.15) and the counterion type (Na+ vs Ca2+) inside the aminosilane-primed nanopores, was for the first bilayers to within the experimental error identical. For thicker multilayers, the pore diameter became smaller, which led to reduced thickness increments and eventually virtually completely filled the pores. The observed kinetics is consistent with the mass-transport-limited adsorption of the polyelectrolyte to the charged surface according to a Langmuir isotherm with a negligible desorption rate. In addition to fundamental insights into the buildup of polyelectrolyte multilayers inside the AAO nanopores, our results highlight the sensitivity of RIfS and its use as an analytical tool for probing processes inside the nanopores and for the development of biosensors.

Fabrication of unconventional inertial microfluidic channels using wax 3D printing.

Inertial microfluidics has emerged over the past decade as a powerful tool to accurately control cells and microparticles for diverse biological and medical applications. Many approaches have been proposed to date in order to increase the efficiency and accuracy of inertial microfluidic systems. However, the effects of channel cross-section and solution properties (Newtonian or non-Newtonian) have not been fully explored, primarily due to limitations in current microfabrication methods. In this study, we overcome many of these limitations using wax 3D printing technology and soft lithography through a novel workflow, which eliminates the need for the use of silicon lithography and polydimethylsiloxane (PDMS) bonding. We have shown that by adding dummy structures to reinforce the main channels, optimizing the gap between the dummy and main structures, and dissolving the support wax on a PDMS slab to minimize the additional handling steps, one can make various non-conventional microchannels. These substantially improve upon previous wax printed microfluidic devices where the working area falls into the realm of macrofluidics rather than microfluidics. Results revealed a surface roughness of 1.75 µm for the printed channels, which does not affect the performance of inertial microfluidic devices used in this study. Channels with complex cross-sections were fabricated and then analyzed to investigate the effects of viscoelasticity and superposition on the lateral migration of the particles. Finally, as a proof of concept, microcarriers were separated from human mesenchymal stem cells using an optimized channel with maximum cell-holding capacity, demonstrating the suitability of these microchannels in the bioprocessing industry.

Novel therapeutic strategies for Alzheimer's disease: Implications from cell-based therapy and nanotherapy.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease which leads to progressive dysfunction of cognition, memory and learning in elderly people. Common therapeutic agents are not only inadequate to suppress the progression of AD pathogenesis but also produce deleterious side effects; hence, development of alternative therapies is required to specifically suppress complications of AD. The current review provides a commentary on conventional as well as novel therapeutic approaches with an emphasis on stem cell and nano-based therapies for improvement and management of AD pathogenesis. According to our overview of the current literature, AD is a multi-factorial disorder with various pathogenic trajectories; hence, a multifunctional strategy to create effective neuroprotective agents is required to treat this disorder.

Nonlinear photoresponse of NaYF4:Yb,Er@NaYF4 nanocrystals under green CW excitation: a comprehensive study.

One of the efficient and well-known upconverting nanomaterials is NaYF4:Yb,Er@NaYF4, which emits photoluminescence at 545 nm and 660 nm under an excitation of 980 nm. Here, the nonlinearity of ß-NaYF4:Yb,Er@NaYF4 at 532 nm is investigated using three nonlinear approaches. For the first time, the nonlinear optical conjugation of NaYF4:Yb,Er@NaYF4 nanocrystals is observed using the degenerate four-wave mixing method. In the optical bistability study, the optical hysteresis of NaYF4:Yb,Er@NaYF4 is measured using the Mach-Zehnder interferometer nonlinear ring cavity, and the results of bistability loops show different behaviors at different power regimes. Finally, the Z-scan technique is used for determining the nonlinear absorption and refraction coefficients, which are calculated in the order of 10-4 (cm W-1) and 10-8 (cm2 W-1), respectively. The results indicate that by increasing incident powers, optical behaviour changes in both optical bistability and Z-scan. Therefore, the results exhibit that the ß-NaYF4:Yb,Er@NaYF4 nanocrystals have nonlinear photoresponses at both 980 and 532 nm, which could be promising for photonic devices based on NIR light and visible light.

Graphene aerogel nanoparticles for in-situ loading/pH sensitive releasing anticancer drugs.

Free polymer graphene aerogel nanoparticles (GA NPs) were synthesized by using reduction/aggregation of graphene oxide (GO) sheets in the presence of vitamin C (as a biocompatible reductant agent) at a low temperature (40 °C), followed by an effective sonication. Synthesis of GA NPs in doxorubicin hydrochloride (DOX)-containing solution results in the simultaneous synthesis and drug loading with higher performance (than that of the separately synthesized and loaded samples). To investigate the mechanism of loading and the capability of GA NPs in the loading of other drug structures, two groups of ionized (DOX, Amikacin sulfate and, d-glucosamine hydrochloride) and non-ionized (Paclitaxel (PTX)) drugs were examined. Furthermore, the relationship between the bipolar level of DOX solution (contributing to H-bonding of DOX and GO) and the amount of DOX loading was investigated. The DOX showed higher loading (>3 times) than PTX, as anticancer drugs. Since both DOX and PTX possess aromatic structures, the higher loading of DOX was assigned to its positive partial charge and ionized nature. Accordingly, other drugs (having positive partial charge and ionized nature, but no aromatic structure) such as Amikacin sulfate and d-glucosamine hydrochloride presented higher loading than PTX. These results indicated that although the π-π interactions induced by aromatic structures are important in drug loading, the electrostatic interaction of ionized drugs with GO (especially through H-bonding) is the dominant mechanism. DOX-loaded GANPs showed high pH-sensitive release (equivalent to the carrier weight) after 5 days, which can indicate benefits in tumor cell acidic microenvironments in-vivo.

Nanoscale Technologies for Prevention and Treatment of Heart Failure: Challenges and Opportunities.

The adult myocardium has a limited regenerative capacity following heart injury, and the lost cells are primarily replaced by fibrotic scar tissue. Suboptimal efficiency of current clinical therapies to resurrect the infarcted heart results in injured heart enlargement and remodeling to maintain its physiological functions. These remodeling processes ultimately leads to ischemic cardiomyopathy and heart failure (HF). Recent therapeutic approaches (e.g., regenerative and nanomedicine) have shown promise to prevent HF postmyocardial infarction in animal models. However, these preclinical, clinical, and technological advancements have yet to yield substantial enhancements in the survival rate and quality of life of patients with severe ischemic injuries. This could be attributed largely to the considerable gap in knowledge between clinicians and nanobioengineers. Development of highly effective cardiac regenerative therapies requires connecting and coordinating multiple fields, including cardiology, cellular and molecular biology, biochemistry and chemistry, and mechanical and materials sciences, among others. This review is particularly intended to bridge the knowledge gap between cardiologists and regenerative nanomedicine experts. Establishing this multidisciplinary knowledge base may help pave the way for developing novel, safer, and more effective approaches that will enable the medical community to reduce morbidity and mortality in HF patients.