Hierarchical Chitin Nanocrystal-Based 3D Printed Dual-Layer Membranes Hydrogels: A Dual Drug Delivery Nano-Platform for Periodontal Tissue Regeneration.

Periodontitis, a prevalent chronic inflammatory disease caused by bacteria, poses a significant challenge to current treatments by merely slowing their progression. Herein, we propose an innovative solution in the form of hierarchical nanostructured 3D printed bilayer membranes that serve as dual-drug delivery nanoplatforms and provide scaffold function for the regeneration of periodontal tissue. Nanocomposite hydrogels were prepared by combining lipid nanoparticle-loaded grape seed extract and simvastatin, as well as chitin nanocrystals, which were then 3D printed into a bilayer membrane that possesses antimicrobial properties and multiscale porosity for periodontal tissue regeneration. The constructs exhibited excellent mechanical properties by adding chitin nanocrystals and provided a sustained release of distinct drugs over 24 days. We demonstrated that the bilayer membranes are cytocompatible and have the ability to induce bone-forming markers in human mesenchymal stem cells, while showing potent antibacterial activity against pathogens associated with periodontitis. In vivo studies further confirmed the efficacy of bilayer membranes in enhancing alveolar bone regeneration and reducing inflammation in a periodontal defect model. This approach suggests promising avenues for the development of implantable constructs that not only combat infections, but also promote the regeneration of periodontal tissue, providing valuable insights into advanced periodontitis treatment strategies.

Acaricidal activity of synthetic spilanthol derivative against ticks of medical and veterinary importance.

The ANESPSAT, a synthetic spilanthol derivative, and its nanoformulation were evaluated against Rhipicephalus microplus and Amblyomma sculptum ticks. ANESPSAT activity was compared with spilanthol and derivatives (ANESPE and others). The compound was synthesized in a gram-scale by a 2-step process, comprising a direct ester amidation and a Horner-Wadsworth- Emmons reaction. The nanoemulsions were produced by coarse homogenization followed by high-energy ultrasonication, in which hydrodynamic diameter, polydispersity index, and zeta potential remained stable. The spilanthol-eugenol hybrid derivatives did not show significant acaricidal activity. ANESPE killed 83% of the R. microplus larvae at 30 mg.mL-1, while ANESPSAT killed 97% at 0.5 mg.mL-1, showing to be the most active compound. Spilanthol and ANESPSAT had similar high mortality rates for tick larvae, with LC50 values of 0.10 and 0.14 mg.mL-1 for R. microplus larvae, and 0.04 and 0.48 mg.mL-1 for A. sculptum larvae, respectively. The efficacy of spilanthol was lower against R. microplus engorged females when compared with ANESPSAT, which was highly effective (>98%) against R. microplus engorged females. The nanoemulsion with ANESPSAT was effective against tick females, preventing egg laying and achieving 100% efficacy at 2.5 mg.mL-1. Spilanthol had only 59% efficacy at 10 mg.mL-1. The results suggest that ANESPSAT, a natural product derivative, could be used in novel formulations for tick management that might be safer and environmentally friendly.

Silk fibroin-derived electrospun materials for biomedical applications: A review.

Electrospinning is a versatile technique for fabricating polymeric fibers with diameters ranging from micro- to nanoscale, exhibiting multiple morphologies and arrangements. By combining silk fibroin (SF) with synthetic and/or natural polymers, electrospun materials with outstanding biological, chemical, electrical, physical, mechanical, and optical properties can be achieved, fulfilling the evolving biomedical demands. This review highlights the remarkable versatility of SF-derived electrospun materials, specifically focusing on their application in tissue regeneration (including cartilage, cornea, nerves, blood vessels, bones, and skin), disease treatment (such as cancer and diabetes), and the development of controlled drug delivery systems. Additionally, we explore the potential future trends in utilizing these nanofibrous materials for creating intelligent biomaterials, incorporating biosensors and wearable sensors for monitoring human health, and also discuss the bottlenecks for its widespread use. This comprehensive overview illuminates the significant impact and exciting prospects of SF-derived electrospun materials in advancing biomedical research and applications.

Fast Fabrication of Multifunctional PCL/Curcumin Nanofibrous Membranes for Wound Dressings.

Therapeutic intervention to skin wounds requires covering the affected area with wound dressings. Interdisciplinary efforts have focused on the development of smart bandages that can perform multiple functions. In this direction, here, we designed a low cost (U$0.012 per cm2) multifunctional therapeutic wound dressing fabricated by loading curcumin (CC) into poly(ϵ-caprolactone) (PCL) nanofibers using solution blow spinning (SBS). The freestanding PCL/CC bandages were characterized by distinct physicochemical approaches and were successful in performing varied functions, including controlled release of CC, colorimetric indication of the wound conditions, barrier against microorganisms, being biocompatible, and providing a photosensitive platform for antimicrobial photodynamic therapy (aPDT). The chemical nature of PCL and CC and the interactions between these components allowed CC to be released for 192 h (ca. 8 days), which could be correlated with the Korsmeyer-Peppas model, with a burst release suitable to treat the inflammatory phase. Due to the CC keto-enol tautomerism, an optical indication of the healing status could be obtained using PCL/CC, which occurred immediately, ranging between red/orange and yellow shades. The effect against pathogenic microorganisms evaluated by agar disc-diffusion, affected skin wound simulation (ex vivo), and microbial penetration tests demonstrated the ability to block and inhibit microbial permeation in different environments. The biocompatibilities of PCL and PCL/CC were verified by in vitro cytotoxicity study, which demonstrated that cell viabilities average above 94 and 96% for human dermal fibroblasts. In addition, the proposed bandage responded to aPDT applied to an in vivo assay, showing that, when irritated, PCL/CC was able to reduce the bacteria present on the real wound of mice. In summary, our findings demonstrate that using PCL and CC to produce nonwovens by the SBS technique offers potential for the rapid fabrication of biocompatible and multifunctional wound dressings, paving the way for large-scale production and utilization of such dressings in the treatment of skin wounds.

Nanoarchitectonic E-Tongue of Electrospun Zein/Curcumin Carbon Dots for Detecting Staphylococcus aureusin Milk.

We report a nanoarchitectonic electronic tongue made with flexible electrodes coated with curcumin carbon dots and zein electrospun nanofibers, which could detect Staphylococcus aureus(S. aureus) in milk using electrical impedance spectroscopy. Electronic tongues are based on the global selectivity concept in which the electrical responses of distinct sensing units are combined to provide a unique pattern, which in this case allowed the detection of S. aureus through non-specific interactions. The electronic tongue used here comprised 3 sensors with electrodes coated with zein nanofibers, carbon dots, and carbon dots with zein nanofibers. The capacitance data obtained with the three sensors were processed with a multidimensional projection technique referred to as interactive document mapping (IDMAP) and analyzed using the machine learning-based concept of multidimensional calibration space (MCS). The concentration of S. aureus could be determined with the sensing units, especially with the one containing zein as the limit of detection was 0.83 CFU/mL (CFU stands for colony-forming unit). This high sensitivity is attributed to molecular-level interactions between the protein zein and C-H groups in S. aureus according to polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS) data. Using machine learning and IDMAP, we demonstrated the selectivity of the electronic tongue in distinguishing milk samples from mastitis-infected cows from milk collected from healthy cows, and from milk spiked with possible interferents. Calibration of the electronic tongue can also be reached with the MCS concept employing decision tree algorithms, with an 80.1% accuracy in the diagnosis of mastitis. The low-cost electronic tongue presented here may be exploited in diagnosing mastitis at early stages, with tests performed in the farms without requiring specialized laboratories or personnel.

SARS-CoV-2 detection enabled by a portable and label-free photoelectrochemical genosensor using graphitic carbon nitride and gold nanoparticles.

Fast, sensitive, simple, and cheap sensors are highly desirable to be applied in the health system because they improve point-of-care diagnostics, which can reduce the number of cases of infection or even deaths. In this context, here we report the development of a label-free genosensor using a screen-printed electrode modified with 2D-carbonylated graphitic carbon nitride (c-g-C3N4), poly(diallyldimethylammonium) chloride (PDDA), and glutathione-protected gold nanoparticles (GSH-AuNPs) for photoelectrochemical (PEC) detection of SARS-CoV-2. We also made use of Arduino and 3D printing to miniaturize the sensor device. The electrode surface was characterized by AFM and SEM techniques, and the gold nanoparticles by UV-Vis spectrophotometry. For SARS-CoV-2 detection, capture probe DNA was immobilized on the electrode surface. The hybridization of the final genosensor was tested with a synthetic single-strand DNA target and with natural saliva samples using the photoelectrochemistry method. The device presented a linear range from 1 to 10,000 fmol L-1 and a limit of detection of 2.2 and 3.4 fmol L-1 using cpDNA 1A and 3A respectively. The sensibility and accuracy found for the genosensor using cpDNA 1A using biological samples were 93.3 and 80% respectively, indicating the potential of the label-free and portable genosensor to detect SARS-CoV-2 RNA in saliva samples.

Smart choices: Mechanisms of intelligent food packaging.

Intelligent food packaging is usually designed to monitor the state of the food itself and/or the environment around it, as well as the interactions between them, providing customers with information on food quality and/or safety through a variety of signals. They involve indicators (which inform by direct visual changes about specific properties related to food quality) and sensors (which detect specific analytes by using receptors, transducers, and signal processing electronics). A third type of intelligent packaging is known as data carriers, which are not typically used for information on food quality, but rather to track the movement of food along the food supply chain. In this graphical review, the basic mechanisms of intelligent food packaging systems are presented, as well as their main applications, with particular emphasis on those focused on food quality monitoring.

Polycaprolactone and polycaprolactone triol blends to obtain a stable liquid nanotechnological formulation: synthesis, characterization and in vitro - in vivo taste masking evaluation.

The use of polymeric blends is a potential strategy to obtain novel nanotechnological formulations aiming at drug delivery systems. Saquinavir, an antiretroviral drug, was chosen as a model drug for the development of new stable liquid formulations with unpleasant taste masking properties. Three formulations containing different polymeric ratios (1:3, 1:1 and 3:1) were prepared and properly characterized by particle size distribution, zeta potential, pH, drug content and encapsulation efficiency measurements. The stability was verified by monitoring the zeta potential, particle size distribution, polydispersity index and drug content by 90 days. The light backscattering analysis was used to early identify possible phenomena of instability in the formulations. The in vitro drug release and saquinavir cytotoxicity were evaluated. The in vitro and in vivo taste masking properties were studied using an electronic tongue and a human sensory panel. All formulations presented nanometric sizes around 200 nm and encapsulation efficiency above 99%. The parameters evaluated for stability remained constant throughout 90 days. The in vitro tests showed a controlled drug release and absence of toxic effects on human T lymphocytes. The electronic tongue experiment showed taste differences for all formulations in comparison to drug solutions, with a more pronounced difference for the formulation with higher polycaprolactone content (3:1). This formulation was chosen for in vivo sensory panel evaluation which results corroborated the electronic tongue experiments. In conclusion, the polymer blend nanoformulation developed herein showed the promising application to incorporate drugs aiming at pharmaceutical taste-masking properties.

Taste-masked nanoparticles containing Saquinavir for pediatric oral administration.

This research has aimed to improve the stability and taste-masking properties by developing nanostructured dosage forms containing Saquinavir. Liquid formulations were developed using Eudragit RS100® and Pullulan as polymers. The physicochemical characteristics, stability, in vitro drug release, morphology, mucoadhesion and taste masking capacity were evaluated. The Saquinavir-nanoparticles had average diameters between 136 and 158 nm, with a Span below 1.4. These formulations presented a drug content above 80%, a high encapsulation efficiency (>97%), slightly acidic pH levels, low dynamic viscosity and controlled drug release. Electron microscopy revealed irregular spherical nanoparticles. The formulations prepared with higher amounts of Eudragit RS100® had greater mucoadhesion. Both polymers were able to improve drug stabilization, taste-masking properties and protection against drug cytotoxicity. The Saquinavir-nanoparticles exhibited stability and control releasing properties, thus making it a promising liquid dosage form with taste-masking properties intended for application in pediatric treatment.

Cantilever Nanobiosensor Functionalized with Tyrosinase for Detection of Estrone and ß-estradiol in Water.

This work aimed to develop cantilever nanobiosensor functionalized with tyrosinase enzyme to detect 17ß-estradiol and estrone hormones. In this system, the tyrosinase enzyme was covalently immobilized by self-assembled monolayer onto the cantilever sensor surface. It was possible to verify that the high hormone concentration investigated resulted in high voltage response. The nanobiosensor presented a distinction between the concentrations evaluated and was verified sensitivities of 0.497 and 0.101 V/µg, limit of detection of 0.1 and 0.4 ng/L for the hormones 17ß-estradiol and estrone, respectively. The device showed good reversibility and during 30 days of storage maintained about 99% of the original signal. The cantilever nanobiosensor applied in different water samples (ultrapure, river, tap, and mineral) showed good performance, so could be readily extended toward the on-site monitoring of the other trace small molecular pollutants in environmental water matrices.

Single-Walled Carbon Nanotubes Functionalized with Carboxylic Acid for Fabricating Polymeric Composite Microstructures.

Carbon nanotube composites are promising materials for mechanical and electrical applications. However, methodologies to incorporate carbon nanotubes in polymeric matrices are on high demand, especially for fabricating devices in the micro-nanoscale. In this paper we show the fabrication of 3D polymeric microstructures with functionalized single-walled carbon nanotubes (SWCNT), by means of two-photon polymerization (2PP). We used a range of SWCNT concentrations (0.01-1 wt%) in the resin to fabricate the composite material. Scanning electron microscopy images show the fabricated microstructures surface quality. Raman spectroscopy was used to confirm the presence and evaluate the distribution of SWCNT in the microstructures. Atomic force microscopy was used to evaluate the mechanical properties of the fabricated microstructures.

Indirect doping of microstructures fabricated by two-photon polymerization with gold nanoparticles.

Nanoplasmonics and metamaterials sciences are rapidly growing due to their contributions to photonic devices fabrication with applications ranging from biomedicine to photovoltaic cells. Noble metal nanoparticles incorporated into polymer matrix have great potential for such applications due to their distinctive optical properties. However, methods to indirectly incorporate metal nanoparticles into polymeric microstructures are still on demand. Here we report on the fabrication of two-photon polymerized microstructures doped with gold nanoparticles through an indirect doping process, so they do not interfere in the two-photon polymerization (2PP) process. Such microstructures present a strong emission, arising from gold nanoparticles fluorescence. The microstructures produced are potential candidates for nanoplasmonics and metamaterials devices applications and the nanoparticles production method can be applied in many samples, heated simultaneously, opening the possibility for large scale processes.