Remote-Controlled Sensing and Drug Delivery via 3D-Printed Hollow Microneedles.

Remote health monitoring and treatment serve as critical drivers for advancing health equity, bridging geographical and socioeconomic disparities, ensuring equitable access to quality healthcare for those in underserved or remote regions. By democratizing healthcare, this approach offers timely interventions, continuous monitoring, and personalized care independent of one's location or socioeconomic status, thereby striving for an equitable distribution of health resources and outcomes. Meanwhile, microneedle arrays (MNAs), revolutionize painless and minimally invasive access to interstitial fluid for drug delivery and diagnostics. This paper introduces an integrated theranostic MNA system employing an array of colorimetric sensors to quantitatively measure -pH, glucose, and lactate, alongside a remotely-triggered system enabling on-demand drug delivery. Integration of an ultrasonic atomizer streamlines the drug delivery, facilitating rapid, pumpless, and point-of-care drug delivery, enhancing system portability while reducing complexities. An accompanying smartphone application interfaces the sensing and drug delivery components. Demonstrated capabilities include detecting pH (3 to 8), glucose (up to 16 mm), and lactate (up to 1.6 mm), showcasing on-demand drug delivery, and assessing delivery system performance via a scratch assay. This innovative approach confronts drug delivery challenges, particularly in managing chronic diseases requiring long-term treatment, while also offering avenues for non-invasive health monitoring through microneedle-based sensors.

The Effect of 3D Printing Tilt Angle on the Penetration of 3D-Printed Microneedle Arrays.

Microneedle arrays (MNAs) are emerging devices that are mainly used for drug delivery and diagnostic applications through the skin. Different methods have been used to fabricate MNAs. Recently developed fabrication methods based on 3D printing have many advantages compared to conventional fabrication methods, such as faster fabrication in one step and the ability to fabricate complex structures with precise control over their geometry, form, size, and mechanical and biological properties. Despite the several advantages that 3D printing offers for the fabrication of microneedles, their poor penetration capability into the skin should be improved. MNAs need a sharp needle tip to penetrate the skin barrier layer, the stratum corneum (SC). This article presents a method to improve the penetration of 3D-printed microneedle arrays by investigating the effect of the printing angle on the penetration force of MNAs. The penetration force needed to puncture the skin for MNAs fabricated using a commercial digital light processing (DLP) printer, with different printing tilt angles (0-60°), was measured in this study. The results showed that the minimum puncture force was achieved using a 45° printing tilt angle. Using this angle, the puncture force was reduced by 38% compared to MNAs printed with a tilting angle of 0°. We also identified that a tip angle of 120° resulted in the smallest penetration force needed to puncture the skin. The outcomes of the research show that the presented method can significantly improve the penetration capability of 3D-printed MNAs into the skin.

3D Printed Hydrogel Microneedle Arrays for Interstitial Fluid Biomarker Extraction and Colorimetric Detection.

To treat and manage chronic diseases, it is necessary to continuously monitor relevant biomarkers and modify treatment as the disease state changes. Compared to other bodily fluids, interstitial skin fluid (ISF) is a good choice for identifying biomarkers because it has a molecular composition most similar to blood plasma. Herein, a microneedle array (MNA) is presented to extract ISF painlessly and bloodlessly. The MNA is made of crosslinked poly(ethylene glycol) diacrylate (PEGDA), and an optimal balance of mechanical properties and absorption capability is suggested. Besides, the effect of needles' cross-section shape on skin penetration is studied. The MNA is integrated with a multiplexed sensor that provides a color change in a biomarker concentration-dependent manner based on the relevant reactions for colorimetric detection of pH and glucose biomarkers. The developed device enables diagnosis by visual inspection or quantitative red, green, and blue (RGB) analysis. The outcomes of this study show that MNA can successfully identify biomarkers in interstitial skin fluid in a matter of minutes. The home-based long-term monitoring and management of metabolic diseases will benefit from such practical and self-administrable biomarker detection.

A handheld bioprinter for multi-material printing of complex constructs.

In situbioprinting-the process of depositing bioinks at a defected area, has recently emerged as a versatile technology for tissue repair and restorationviasite-specific delivery of pro-healing constructs. The ability to print multiple materialsin situis an exciting approach that allows simultaneous or sequential dispensing of different materials and cells to achieve tissue biomimicry. Herein, we report a modular handheld bioprinter that deposits a variety of bioinksin situwith exquisite control over their physical and chemical properties. Combined stereolithography 3D printing and microfluidic technologies allowed us to develop a novel low-priced handheld bioprinter. The ergonomic design of the handheld bioprinter facilitate the shape-controlled biofabrication of multi-component fibers with different cross-sectional shapes and material compositions. Furthermore, the capabilities of the produced fibers in the local delivery of therapeutic agents was demonstrated by incorporating drug-loaded microcarriers, extending the application of the printed fibers to on-demand, temporal, and dosage-control drug delivery platforms. Also, the versatility of this platform to produce biosensors and wearable electronics was demonstrated via incorporating conductive materials and integrating pH-responsive dyes. The handheld printer's efficacy in generating cell-laden fibers with high cell viability for site-specific cell delivery was shown by producing single-component and multi-component cell-laden fibers. In particular, the multi-component fibers were able to model the invasion of cancer cells into the adjacent tissue.

A Brief Review on Additive Manufacturing of Polymeric Composites and Nanocomposites.

In this research article, a mini-review study is performed on the additive manufacturing (AM) of the polymeric matrix composites (PMCs) and nanocomposites. In this regard, some methods for manufacturing and important and applied results are briefly introduced and presented. AM of polymeric matrix composites and nanocomposites has attracted great attention and is emerging as it can make extensively customized parts with appreciably modified and improved mechanical properties compared to the unreinforced polymer materials. However, some matters must be addressed containing reduced bonding of reinforcement and matrix, the slip between reinforcement and matrix, lower creep strength, void configurations, high-speed crack propagation, obstruction because of filler inclusion, enhanced curing time, simulation and modeling, and the cost of manufacturing. In this review, some selected and significant results regarding AM or three-dimensional (3D) printing of polymeric matrix composites and nanocomposites are summarized and discuss. In addition, this article discusses the difficulties in preparing composite feedstock filaments and printing issues with nanocomposites and short and continuous fiber composites. It is discussed how to print various thermoplastic composites ranging from amorphous to crystalline polymers. In addition, the analytical and numerical models used for simulating AM, including the Fused deposition modeling (FDM) printing process and estimating the mechanical properties of printed parts, are explained in detail. Particle, fiber, and nanomaterial-reinforced polymer composites are highlighted for their performance. Finally, key limitations are identified in order to stimulate further 3D printing research in the future.

Improved Bacteriostatic and Anticorrosion Effects of Polycaprolactone/Chitosan Coated Magnesium via Incorporation of Zinc Oxide.

Magnesium has been recognized as a groundbreaking biodegradable biomaterial for implant applications, but its use is limited because it degrades too quickly in physiological solutions. This paper describes the research on the influence of polycaprolactone (PCL)/chitosan (CS)/zinc oxide (ZnO) composite coating (PCL/CS/ZnO) on the corrosion resistance and antibacterial activity of magnesium. The PCL/CS film presented a porous structure with thickness of about 40-50 µm, while after incorporation of ZnO into the PCL/CS, a homogenous film without pores and defects was attained. The ZnO embedded in PCL/CS enhanced corrosion resistance by preventing corrosive ions diffusion in the magnesium substrate. The corrosion, antibacterial, and cell interaction mechanism of the PCL/CS/ZnO composite coating is discussed in this study. In vitro cell culture revealed that the PCL/CS coating with low loaded ZnO significantly improved cytocompatibility, but coatings with high loaded ZnO were able to induce some cytotoxicity osteoblastic cells. It was also found that enhanced antibacterial activity of the PCL/CS/ZnO coating against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria, while less significant antibacterial activity was detected for uncoated Mg and PCL/CS coating. Based on the results, the PCL/CS coatings loaded with low ZnO content may be recommended as a candidate material for biodegradable Mg-based orthopedic implant applications.

Carbon Nanotubes (CNTs)-Reinforced Magnesium-Based Matrix Composites: A Comprehensive Review.

In recent years considerable attention has been attracted to magnesium because of its light weight, high specific strength, and ease of recycling. Because of the growing demand for lightweight materials in aerospace, medical and automotive industries, magnesium-based metal matrix nanocomposites (MMNCs) reinforced with ceramic nanometer-sized particles, graphene nanoplatelets (GNPs) or carbon nanotubes (CNTs) were developed. CNTs have excellent material characteristics like low density, high tensile strength, high ratio of surface-to-volume, and high thermal conductivity that makes them attractive to use as reinforcements to fabricate high-performance, and high-strength metal-matrix composites (MMCs). Reinforcing magnesium (Mg) using small amounts of CNTs can improve the mechanical and physical properties in the fabricated lightweight and high-performance nanocomposite. Nevertheless, the incorporation of CNTs into a Mg-based matrix faces some challenges, and a uniform distribution is dependent on the parameters of the fabricating process. The characteristics of a CNTs reinforced composite are related to the uniform distribution, weight percent, and length of the CNTs, as well as the interfacial bonding and alignment between CNTs reinforcement and the Mg-based matrix. In this review article, the recent findings in the fabricating methods, characterization of the composite's properties, and application of Mg-based composites reinforced with CNTs are studied. These include the strategies of fabricating CNT-reinforced Mg-based composites, mechanical responses, and corrosion behaviors. The present review aims to investigate and conclude the most relevant studies conducted in the field of Mg/CNTs composites. Strategies to conquer complicated challenges are suggested and potential fields of Mg/CNTs composites as upcoming structural material regarding functional requirements in aerospace, medical and automotive industries are particularly presented.

Polymethyl Methacrylate-Based Bone Cements Containing Carbon Nanotubes and Graphene Oxide: An Overview of Physical, Mechanical, and Biological Properties.

Every year, millions of people in the world get bone diseases and need orthopedic surgery as one of the most important treatments. Owing to their superior properties, such as acceptable biocompatibility and providing great primary bone fixation with the implant, polymethyl methacrylate (PMMA)-based bone cements (BCs) are among the essential materials as fixation implants in different orthopedic and trauma surgeries. On the other hand, these BCs have some disadvantages, including Lack of bone formation and bioactivity, and low mechanical properties, which can lead to bone cement (BC) failure. Hence, plenty of studies have been concentrating on eliminating BC failures by using different kinds of ceramics and polymers for reinforcement and also by producing composite materials. This review article aims to evaluate mechanical properties, self-setting characteristics, biocompatibility, and bioactivity of the PMMA-based BCs composites containing carbon nanotubes (CNTs), graphene oxide (GO), and carbon-based compounds. In the present study, we compared the effects of CNTs and GO as reinforcement agents in the PMMA-based BCs. Upcoming study on the PMMA-based BCs should concentrate on trialing combinations of these carbon-based reinforcing agents as this might improve beneficial characteristics.

Incidence of incomplete excision in surgically treated cutaneous squamous cell carcinoma and identification of the related risk factors.

Squamous cell carcinoma (SCC) is the second most common type of skin cancer with potential risks for metastasis and recurrence if left untreated or incompletely excised. This case series study was designed to determine the frequency of incompletely excised SCCs and the related risk factors. A total of 273 SCCs (253 patients) excised in Razi dermatology hospital of Tehran from 2006-2008, were evaluated and were analyzed by Chi-square or t-test. The incidence of incomplete excision was 17.58 % and deep margin involvement was observed in 73% of lesions. Risk factors associated with incomplete excision of SCCs were being female, location of the tumors (in particular the lesions on lateral canthus, upper lip, foot, forehead, cheek, neck, nose and ear), large lesions and grafting method of repair. There was no statistically significant difference for the age, degree of histological differentiation, childhood history of radiotherapy for tinea capitis and the type of anesthesia. More care should be taken for high risk SCCs as complete excision avoids potential risk of recurrence and metastasis.

Effect of different epinephrine concentrations on local bleeding and hemodynamics during dermatologic surgery.

In local anesthesia, various epinephrine concentrations are applied for its vasoconstrictive effect. This study was conducted to observe the effect of epinephrine on intraoperative bleeding and also to evaluate hemodynamic changes during skin surgery. Ninety-six patients scheduled for skin surgery under local anesthesia were divided into three groups administered three different concentrations of epinephrine (1:50,000, 1:100,000 and 1:200,000) with 1% lidocaine (an average of 5.7 mL). The rate of bleeding and hemodynamic changes were assessed during surgical procedure. The surgeon's rating of intraoperative bleeding was significantly lower in the group administered epinephrine concentration of 1:50,000 as compared with the group on epinephrine concentration of 1:200,000. However, there was no significant difference between the groups administered epinephrine concentrations of 1:200,000 and 1:100,000. Except for diastolic blood pressure at 1 min after injection of local anesthetics, transient changes of hemodynamic parameters were observed, with no statistically significant difference among the three anesthetic solutions used. It is concluded that, for local anesthesia, the rate of intraoperative bleeding is influenced by epinephrine concentration, and that 1:50,000 epinephrine provides optimal clinical efficacy for the local bleeding control during dermatologic surgery.