Smart Dual-Sensor Wound Dressing for Monitoring Cutaneous Wounds.

Managing slow-healing wounds and associated complications is challenging, time-consuming, and expensive. Systematic collection, analysis, and dissemination of correct wound status data are critical for enhancing healing outcomes and reducing complications. However, traditional data collection approaches are often neither accurate nor user-friendly and require diverse skill levels, resulting in the collection of inconsistent and unreliable data. As an advancement to the authors' previously developed hydrogel-based smart wound dressing, here is reported an enhanced integration of drug delivery and sensing (pH and glucose) modules for accelerated treatment and continuous monitoring of cutaneous wounds. In the current study, growth factor delivery modules and an array of colorimetric glucose sensors are incorporated into the dressing to promote wound healing and extend the dressing's utility for diabetic wound treatment. Furthermore, the efficacy of the wound dressing in monitoring infection and supporting wound healing via antibiotic and growth factor delivery is investigated in mice models. The updated dressing reveals excellent healing benefits on non-infected and infected wounds, as well as real-time monitoring and early detection of wound infection.

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.

Non-destructive mechanical assessment for optimization of 3D bioprinted soft tissue scaffolds.

Characterizing the mechanical properties of engineered tissue constructs provides powerful insight into the function of engineered tissues for their desired application. Current methods of mechanical characterization of soft hydrogels used in tissue engineering are often destructive and ignore the effect of 3D bioprinting on the overall mechanical properties of a whole tissue construct. This work reports on using a non-destructive method of viscoelastic analysis to demonstrate the influence of bioprinting strategy on mechanical properties of hydrogel tissue scaffolds. Structure-function relationships are developed for common 3D bioprinting parameters such as printed fiber size, printed scaffold pattern, and bioink formulation. Further studies include mechanical properties analysis during degradation, real-time monitoring of crosslinking, mechanical characterization of multi-material scaffolds, and monitoring the effect of encapsulated cell growth on the mechanical strength of 3D bioprinted scaffolds. We envision this method of characterization opening a new wave of understanding and strategy in tissue engineering.

Silicate-Based Electro-Conductive Inks for Printing Soft Electronics and Tissue Engineering.

Hydrogel-based bio-inks have been extensively used for developing three-dimensional (3D) printed biomaterials for biomedical applications. However, poor mechanical performance and the inability to conduct electricity limit their application as wearable sensors. In this work, we formulate a novel, 3D printable electro-conductive hydrogel consisting of silicate nanosheets (Laponite), graphene oxide, and alginate. The result generated a stretchable, soft, but durable electro-conductive material suitable for utilization as a novel electro-conductive bio-ink for the extrusion printing of different biomedical platforms, including flexible electronics, tissue engineering, and drug delivery. A series of tensile tests were performed on the material, indicating excellent stability under significant stretching and bending without any conductive or mechanical failures. Rheological characterization revealed that the addition of Laponite enhanced the hydrogel's mechanical properties, including stiffness, shear-thinning, and stretchability. We also illustrate the reproducibility and flexibility of our fabrication process by extrusion printing various patterns with different fiber diameters. Developing an electro-conductive bio-ink with favorable mechanical and electrical properties offers a new platform for advanced tissue engineering.

Electrode-Integrated Textile-Based Sensors for In Situ Temperature and Relative Humidity Monitoring in Electrochemical Cells.

Temperature and humidity measurements in electrochemical energy devices are essential for maximizing their overall performance under different operating conditions and avoiding hazardous consequences that may arise from the malfunction of these systems. Using sensors for in situ measurements of temperature and relative humidity (RH) is a promising approach for continuous monitoring and management of electrochemical power sources. Here, we report on the feasibility of using thread-based sensors for in situ measurements of temperature and RH in proton exchange membrane fuel cells (PEMFCs) as an example of electrochemical energy devices. Commodity threads are low-cost and flexible materials that hold great promise for the creation of complex three-dimensional (3D) circuits using well-established textile methods such as weaving, braiding, and embroidering. Ex situ and in situ characterization show that threads can be introduced in the gas diffusion layer (GDL) structure to inscribe water highways within the GDL with minimal impact on the GDL microstructure and transport properties. Fluorinated ethylene propylene (FEP) is coated on thread-based sensors to decouple the response to temperature and humidity; the resulting threads achieve a linear change of resistance with temperature (-0.31%/°C), while RH is monitored with a second thread coated with poly(dimethylsiloxane) (PDMS). The combination of both threads allows for minimally invasive and dynamically responsive monitoring of local temperature and RH within the electrode of PEMFCs.

Management of Coronavirus Disease 2019 (COVID-19) Pandemic: From Diagnosis to Treatment Strategies.

Following the emergence of severe acute respiratory syndrome (SARS) in 2002 and the Middle East respiratory syndrome (MERS) in 2012, the world is now combating a third large-scale outbreak caused by a coronavirus, the coronavirus disease 2019 (COVID-19). After the rapid spread of SARS-coronavirus (CoV)-2 (the virus causing COVID-19) from its origin in China, the World Health Organization (WHO) declared a Public Health Emergency of International Concern (PHEIC) on January 30, 2020. From the beginning of the COVID-19 pandemic, a significant number of studies have been conducted to better understand the biology and pathogenesis of the novel coronavirus, and to aid in developing effective treatment regimens, therapeutics, and vaccines. This review focuses on the recent advancements in the rapidly evolving areas of clinical care and management of COVID-19. The emerging strategies for the diagnosis and treatment of this disease are explored, and the development of effective vaccines is reviewed.

Co-incorporation of graphene oxide/silver nanoparticle into poly-L-lactic acid fibrous: A route toward the development of cytocompatible and antibacterial coating layer on magnesium implants.

Magnesium (Mg) alloys present great potential for the development of orthopedic implants, whereas, their high degradation rate and poor antibacterial performance have restricted orthopedic applications. In this work, PLLA/GO-AgNP (poly-L-lactic acid/graphene oxide- silver nanoparticle) with different concentration of GO-AgNPs were deposited on Mg alloy via electrospinning method for enhancement of corrosion resistance and antibacterial performance. The result revealed that incorporation of GO into PLLA fibrous considerably slowed down the degradation rate of Mg alloy substrate and reduced the H2 release rate from the substrate. Also, co-incorporation of GO and AgNPs into PLLA fibrous resulted in substantial escalate in compressive strength after immersion in simulated body fluid (SBF). Antibacterial activity test exhibited that Mg alloy and neat PLLA fibrous presented minimal inhibition area toward Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In contrast, using PLLA/GO-AgNPs fibrous improved antibacterial performance against both bacteria. Cytocompatibility results indicated that PLLA/GO-AgNPs fibrous with a low amount of GO-AgNPs enhanced cell proliferation and growth while high co-incorporation of GO-AgNPs showed a negative effect on cell proliferation. Taken together, PLLA/1GO-AgNPs fibrous coating shows suitable corrosion resistance, cytocompatibility, and antibacterial function for use in orthopedic applications.

An Engineered Infected Epidermis Model for In Vitro Study of the Skin's Pro-Inflammatory Response.

Wound infection is a major clinical challenge that can significantly delay the healing process, can create pain, and requires prolonged hospital stays. Pre-clinical research to evaluate new drugs normally involves animals. However, ethical concerns, cost, and the challenges associated with interspecies variation remain major obstacles. Tissue engineering enables the development of in vitro human skin models for drug testing. However, existing engineered skin models are representative of healthy human skin and its normal functions. This paper presents a functional infected epidermis model that consists of a multilayer epidermis structure formed at an air-liquid interface on a hydrogel matrix and a three-dimensionally (3D) printed vascular-like network. The function of the engineered epidermis is evaluated by the expression of the terminal differentiation marker, filaggrin, and the barrier function of the epidermis model using the electrical resistance and permeability across the epidermal layer. The results showed that the multilayer structure enhances the electrical resistance by 40% and decreased the drug permeation by 16.9% in the epidermis model compared to the monolayer cell culture on gelatin. We infect the model with Escherichia coli to study the inflammatory response of keratinocytes by measuring the expression level of pro-inflammatory cytokines (interleukin 1 beta and tumor necrosis factor alpha). After 24 h of exposure to Escherichia coli, the level of IL-1ß and TNF-α in control samples were 125 ± 78 and 920 ± 187 pg/mL respectively, while in infected samples, they were 1429 ± 101 and 2155.5 ± 279 pg/mL respectively. However, in ciprofloxacin-treated samples the levels of IL-1ß and TNF-α without significant difference with respect to the control reached to 246 ± 87 and 1141.5 ± 97 pg/mL respectively. The robust fabrication procedure and functionality of this model suggest that the model has great potential for modeling wound infections and drug testing.

Facile Method for Fabrication of Meter-Long Multifunctional Hydrogel Fibers with Controllable Biophysical and Biochemical Features.

Hydrogel structures with microscale morphological features have extensive application in tissue engineering owing to their capacity to induce desired cellular behavior. Herein, we describe a novel biofabrication method for fabrication of grooved solid and hollow hydrogel fibers with control over their cross-sectional shape, surface morphology, porosity, and material composition. These fibers were further configured into three-dimensional structures using textile technologies such as weaving, braiding, and embroidering methods. Additionally, the capacity of these fibers to integrate various biochemical and biophysical cues was shown via incorporating drug-loaded microspheres, conductive materials, and magnetic particles, extending their application to smart drug delivery, wearable or implantable medical devices, and soft robotics. The efficacy of the grooved fibers to induce cellular alignment was evaluated on various cell types including myoblasts, cardiomyocytes, cardiac fibroblasts, and glioma cells. In particular, these fibers were shown to induce controlled myogenic differentiation and morphological changes, depending on their groove size, in C2C12 myoblasts.

Hyaluronic Acid (HA)-Based Silk Fibroin/Zinc Oxide Core-Shell Electrospun Dressing for Burn Wound Management.

Burn injuries represent a major life-threatening event that impacts the quality of life of patients, and places enormous demands on the global healthcare systems. This study introduces the fabrication and characterization of a novel wound dressing made of core-shell hyaluronic acid-silk fibroin/zinc oxide (ZO) nanofibers for treatment of burn injuries. The core-shell configuration enables loading ZO-an antibacterial agent-in the core of nanofibers, which in return improves the sustained release of the drug and maintains its bioactivity. Successful formation of core-shell nanofibers and loading of zinc oxide are confirmed by transmission electron microscopy, Fourier-transform infrared spectroscopy, and energy dispersive X-ray. The antibacterial activity of the dressings are examined against Escherichia coli and Staphylococcus aureus and it is shown that addition of ZO improves the antibacterial property of the dressing in a dose-dependent fashion. However, in vitro cytotoxicity studies show that high concentration of ZO (>3 wt%) is toxic to the cells. In vivo studies indicate that the wound dressings loaded with ZO (3 wt%) substantially improves the wound healing procedure and significantly reduces the inflammatory response at the wound site. Overall, the dressing introduced herein holds great promise for the management of burn injuries.

A 3D bioprinted hydrogel mesh loaded with all-trans retinoic acid for treatment of glioblastoma.

Treatment of glioblastoma (GBM), as the most lethal type of brain tumor, still remains a major challenge despite the various therapeutic approaches developed over the recent decades. GBM is considered as one of the most therapy-resistant human tumors. Treatment with temozolomide (TMZ) chemotherapy and radiotherapy in GBM patients has led to 30% of two-year survival rate (American Brain Tumor Association), representing a demanding field to develop more effective therapeutic strategies. This study presents a novel method for local delivery of all-trans retinoic acid (ATRA) for targeting GBM cells as a possible adjuvant therapeutic strategy for this disease. We have used 3D bioprinting to fabricate hydrogel meshes laden with ATRA-loaded polymeric particles. The ATRA-loaded meshes have been shown to facilitate a sustained release of ATRA with tunable release rate. Cell viability assay was used to demonstrate the ability of fabricated meshes in reducing cell growth in U-87 MG cell line. We later showed that the developed meshes induced apoptotic cell death in U-87 MG. Furthermore, the use of hydrogel for embedding the ATRA-loaded particles can facilitate the immobilization of the drug next to the tumor site. Our current innovative approach has shown the potential to open up new avenues for treatment of GBM, benefiting patients who suffer from this debilitating disease.

An Advanced Multifunctional Hydrogel-Based Dressing for Wound Monitoring and Drug Delivery.

Wound management is a major global challenge and poses a significant financial burden to the healthcare system due to the rapid growth of chronic diseases such as diabetes, obesity, and aging population. The ability to detect pathogenic infections and release drug at the wound site is of the utmost importance to expedient patient care. Herein, this study presents an advanced multifunctional dressing (GelDerm) capable of colorimetric measurement of pH, an indicator of bacterial infection, and release of antibiotic agents at the wound site. This study demonstrates the ability of GelDerm to detect bacterial infections using in vitro and ex vivo tests with accuracies comparable to the commercially available systems. Wireless interfaces to digital image capture hardware such as smartphones serve as a means for quantitation and enable the patient to record the wound condition at home and relay the information to the healthcare personnel for following treatment strategies. Additionally, the dressing is integrated within commercially available patches and can be placed on the wound without chemical or physical irritation. This study demonstrates the ability of GelDerm to eradicate bacteria by the sustained release of antibiotics. The proposed technology holds great promise in managing chronic and acute injuries caused by trauma, surgery, or diabetes.