Nanomaterials in crossroad of autophagy control in human cancers: Amplification of cell death mechanisms.

Cancer is the result of genetic abnormalities that cause normal cells to grow into neoplastic cells. Cancer is characterized by several distinct features, such as uncontrolled cell growth, extensive spreading to other parts of the body, and the ability to resist treatment. The scientists have stressed the development of nanostructures as novel therapeutic options in suppressing cancer, in response to the emergence of resistance to standard medicines. One of the specific mechanisms with dysregulation during cancer is autophagy. Nanomaterials have the ability to specifically carry medications and genes, and they can also enhance the responsiveness of tumor cells to standard therapy while promoting drug sensitivity. The primary mechanism in this process relies on autophagosomes and their fusion with lysosomes to break down the components of the cytoplasm. While autophagy was initially described as a form of cellular demise, it has been demonstrated to play a crucial role in controlling metastasis, proliferation, and treatment resistance in human malignancies. The pharmacokinetic profile of autophagy modulators is poor, despite their development for use in cancer therapy. Consequently, nanoparticles have been developed for the purpose of delivering medications and autophagy modulators selectively and specifically to the cancer process. Furthermore, several categories of nanoparticles have demonstrated the ability to regulate autophagy, which plays a crucial role in defining the biological characteristics and response to therapy of tumor cells.

Diagnostic, Therapeutic, and Theranostic Multifunctional Microneedles.

Microneedles (MNs) have maintained their popularity in therapeutic and diagnostic medical applications throughout the past decade. MNs are originally designed to gently puncture the stratum corneum layer of the skin and have lately evolved into intelligent devices with functions including bodily fluid extraction, biosensing, and drug administration. MNs offer limited invasiveness, ease of application, and minimal discomfort. Initially manufactured solely from metals, MNs are now available in polymer-based varieties. MNs can be used to create systems that deliver drugs and chemicals uniformly, collect bodily fluids, and are stimulus-sensitive. Although these advancements are favorable in terms of biocompatibility and production costs, they are insufficient for the therapeutic use of MNs. This is the first comprehensive review that discusses individual MN functions toward the evolution and development of smart and multifunctional MNs for a variety of novel and impactful future applications. The study examines fabrication techniques, application purposes, and experimental details of MN constructs that perform multiple functions concurrently, including sensing, drug-molecule release, sampling, and remote communication capabilities. It is highly likely that in the near future, MN-based smart devices will be a useful and important component of standard medical practice for different applications.

From animal testing to in vitro systems: advancing standardization in microphysiological systems.

Limitations with cell cultures and experimental animal-based studies have had the scientific and industrial communities searching for new approaches that can provide reliable human models for applications such as drug development, toxicological assessment, and in vitro pre-clinical evaluation. This has resulted in the development of microfluidic-based cultures that may better represent organs and organ systems in vivo than conventional monolayer cell cultures. Although there is considerable interest from industry and regulatory bodies in this technology, several challenges need to be addressed for it to reach its full potential. Among those is a lack of guidelines and standards. Therefore, a multidisciplinary team of stakeholders was formed, with members from the US Food and Drug Administration (FDA), the National Institute of Standards and Technology (NIST), European Union, academia, and industry, to provide a framework for future development of guidelines/standards governing engineering concepts of organ-on-a-chip models. The result of this work is presented here for interested parties, stakeholders, and other standards development organizations (SDOs) to foster further discussion and enhance the impact and benefits of these efforts.

Fundamental properties of smart hydrogels for tissue engineering applications: A review.

Tissue engineering is an advanced and potential biomedical approach to treat patients suffering from lost or failed an organ or tissue to repair and regenerate damaged tissues that increase life expectancy. The biopolymers have been used to fabricate smart hydrogels to repair damaged tissue as they imitate the extracellular matrix (ECM) with intricate structural and functional characteristics. These hydrogels offer desired and controllable qualities, such as tunable mechanical stiffness and strength, inherent adaptability and biocompatibility, swellability, and biodegradability, all crucial for tissue engineering. Smart hydrogels provide a superior cellular environment for tissue engineering, enabling the generation of cutting-edge synthetic tissues due to their special qualities, such as stimuli sensitivity and reactivity. Numerous review articles have presented the exceptional potential of hydrogels for various biomedical applications, including drug delivery, regenerative medicine, and tissue engineering. Still, it is essential to write a comprehensive review article on smart hydrogels that successfully addresses the essential challenging issues in tissue engineering. Hence, the recent development on smart hydrogel for state-of-the-art tissue engineering conferred progress, highlighting significant challenges and future perspectives. This review discusses recent advances in smart hydrogels fabricated from biological macromolecules and their use for advanced tissue engineering. It also provides critical insight, emphasizing future research directions and progress in tissue engineering.

Graphene Oxide-Functionalized Bacterial Cellulose-Gelatin Hydrogel with Curcumin Release and Kinetics: In Vitro Biological Evaluation.

Biopolymer-based bioactive hydrogels are excellent wound dressing materials for wound healing applications. They have excellent properties, including hydrophilicity, tunable mechanical and morphological properties, controllable functionality, biodegradability, and desirable biocompatibility. The bioactive hydrogels were fabricated from bacterial cellulose (BC), gelatin, and graphene oxide (GO). The GO-functionalized-BC (GO-f-BC) was synthesized by a hydrothermal method and chemically crosslinked with bacterial cellulose and gelatin using tetraethyl orthosilicate (TEOS) as a crosslinker. The structural, morphological, and wettability properties were studied using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and a universal testing machine (UTM), respectively. The swelling analysis was conducted in different media, and aqueous medium exhibited maximum hydrogel swelling compared to other media. The Franz diffusion method was used to study curcumin (Cur) release (Max = 69.32%, Min = 49.32%), and Cur release kinetics followed the Hixson-Crowell model. Fibroblast (3T3) cell lines were employed to determine the cell viability and proliferation to bioactive hydrogels. Antibacterial activities of bioactive hydrogels were evaluated against infection-causing bacterial strains. Bioactive hydrogels are hemocompatible due to their less than 0.5% hemolysis against fresh human blood. The results show that bioactive hydrogels can be potential wound dressing materials for wound healing applications.

High Boron Content Enhances Bioactive Glass Biodegradation.

Derived Hench bioactive glass (BaG) containing boron (B) is explored in this work as it plays an important role in bone development and regeneration. B was also found to enhance BaG dissociation. However, it is only possible to incorporate a limited amount of B. To increase the amount of B in BaG, bioactive borosilicate glasses (BaG-Bx) were fabricated based on the use of the solution-gelation process (sol-gel). In this work, a high B content (20 wt.%) in BaG, respecting the conditions of bioactivity and biodegradability required by Hench, was achieved for the first time. The capability of BaG-Bx to form an apatite phase was assessed in vitro by immersion in simulated body fluid (SBF). Then, the chemical structure and the morphological changes in the fabricated BaG-Bx (x = 0, 5, 10 and 20) were studied. The formation of hydroxyapatite (HAp) layer was observed with X-ray diffraction (XRD) and infrared (IR) spectroscopy. The presence of HAp layer was confirmed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Enhanced bioactivity and chemical stability of BaG-Bx were evaluated with an ion exchange study based on Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) and energy dispersive spectroscopy (EDS). Results indicate that by increasing the concentration of B in BaG-Bx, the crystallization rate and the quality of the newly formed HAp layer on BaG-Bx surfaces can be improved. The presence of B also leads to enhanced degradation of BaGs in SBF. Accordingly, BAG-Bx can be used for bone regeneration, especially in children, because of its faster degradation as compared to B-free glass.

Bioadhesives with Antimicrobial Properties.

Bioadhesives with antimicrobial properties enable easier and safer treatment of wounds as compared to the traditional methods such as suturing and stapling. Composed of natural or synthetic polymers, these bioadhesives seal wounds and facilitate healing while preventing infections through the activity of locally released antimicrobial drugs, nanocomponents, or inherently antimicrobial polers. Although many different materials and strategies are employed to develop antimicrobial bioadhesives, the design of these biomaterials necessitates a prudent approach as achieving all the required properties including optimal adhesive and cohesive properties, biocompatibility, and antimicrobial activity can be challenging. Designing antimicrobial bioadhesives with tunable physical, chemical, and biological properties will shed light on the path for future advancement of bioadhesives with antimicrobial properties. In this review, the requirements and commonly used strategies for developing bioadhesives with antimicrobial properties are discussed. In particular, different methods for their synthesis and their experimental and clinical applications on a variety of organs are reviewed. Advances in the design of bioadhesives with antimicrobial properties will pave the way for a better management of wounds to increase positive clinical outcomes.

Translational Research Techniques for the Facial Plastic Surgeon: An Overview.

The field of facial plastic and reconstructive surgery (FPRS) is an incredibly diverse, multispecialty field that seeks innovative and novel solutions for the management of physical defects on the head and neck. To aid in the advancement of medical and surgical treatments for these defects, there has been a recent emphasis on the importance of translational research. With recent technological advancements, there are now a myriad of research techniques that are widely accessible for physician and scientist use in translational research. Such techniques include integrated multiomics, advanced cell culture and microfluidic tissue models, established animal models, and emerging computer models generated using bioinformatics. This study discusses these various research techniques and how they have and can be used for research in the context of various important diseases within the field of FPRS.

Biomimetic cell membrane-coated poly(lactic-co-glycolic acid) nanoparticles for biomedical applications.

Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are commonly used for drug delivery because of their favored biocompatibility and suitability for sustained and controlled drug release. To prolong NP circulation time, enable target-specific drug delivery and overcome physiological barriers, NPs camouflaged in cell membranes have been developed and evaluated to improve drug delivery. Here, we discuss recent advances in cell membrane-coated PLGA NPs, their preparation methods, and their application to cancer therapy, management of inflammation, treatment of cardiovascular disease and control of infection. We address the current challenges and highlight future research directions needed for effective use of cell membrane-camouflaged NPs.

A Biodegradable Bioactive Glass-Based Hydration Sensor for Biomedical Applications.

Monitoring changes in edema-associated intracranial pressure that complicates trauma or surgery would lead to improved outcomes. Implantable pressure sensors have been explored, but these sensors require post-surgical removal, leading to the risk of injury to brain tissue. The use of biodegradable implantable sensors would help to eliminate this risk. Here, we demonstrate a bioactive glass (BaG)-based hydration sensor. Fluorine (CaF2) containing BaG (BaG-F) was produced by adding 5, 10 or 20 wt.% of CaF2 to a BaG matrix using a melting manufacturing technique. The structure, morphology and electrical properties of the resulting constructs were evaluated to understand the physical and electrical behaviors of this BaG-based sensor. Synthesis process for the production of the BaG-F-based sensor was validated by assessing the structural and electrical properties. The structure was observed to be amorphous and dense, the porosity decreased and grain size increased with increasing CaF2 content in the BaG matrix. We demonstrated that this BaG-F chemical composition is highly sensitive to hydration, and that the electrical sensitivity (resistive-capacitive) is induced by hydration and reversed by dehydration. These properties make BaG-F suitable for use as a humidity sensor to monitor brain edema and, consequently, provide an alert for increased intracranial pressure.

Engineering organ-on-a-chip systems to model viral infections.

Infectious diseases remain a public healthcare concern worldwide. Amidst the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infection, increasing resources have been diverted to investigate therapeutics targeting the COVID-19 spike glycoprotein and to develop various classes of vaccines. Most of the current investigations employ two-dimensional (2D) cell culture and animal models. However, 2D culture negates the multicellular interactions and three-dimensional (3D) microenvironment, and animal models cannot mimic human physiology because of interspecies differences. On the other hand, organ-on-a-chip (OoC) devices introduce a game-changer to model viral infections in human tissues, facilitating high-throughput screening of antiviral therapeutics. In this context, this review provides an overview of thein vitroOoC-based modeling of viral infection, highlighting the strengths and challenges for the future.

Multifunctional Bioactive Scaffolds from ARX-g-(Zn@rGO)-HAp for Bone Tissue Engineering: In Vitro Antibacterial, Antitumor, and Biocompatibility Evaluations.

Advanced biomaterials are required with enhanced antibacterial and anticancer activities to obtain desirable biocompatibility during and after scaffold implantation in tissue engineering. Here, we report the development of a nanosystem by the hydrothermal method using different zinc (Zn) amounts and reduced graphene oxide (GO). Arabinoxylan, the nanosystem (Zn@rGO), and nanohydroxyapatite polymeric nanocomposites ARX-g-(Zn@rGO)/HAp were prepared by the free radical polymerization method, and porous bioactive scaffolds were fabricated via the freeze-drying technique. The structural, morphological, and elemental analyses of the bioactive scaffolds were conducted using Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray analysis. The wetting behavior was studied by a water contact meter and swelling in aqueous and phosphate-buffered saline solutions at 37 °C. The degradation was also studied in the phosphate-buffered saline solution at 37 °C. The increase in Zn content increased the pore size, and hydrophobic behavior shifted to hydrophilic (AGZ-1 = 131.40° at 0 s and 120.60° at 10 s to AGZ-1 = 81.30° at 0 s and 69.20° at 10 s) with the increase in contact time. Maximum swelling was observed in deionized water (AGZ-1 = 52.87%, AGZ-4 = 90.20%), followed by phosphate-buffered saline (PBS; AGZ-1 = 44.80%, AGZ-4 = 67.90%) and electrolyte (AGZ-1 = 32.40%, AGZ-4 = 63.47%), and biodegradation in PBS media increased (AGZ-1 = 36.80%, AGZ-4 = 55.92%). Antimicrobial activities against severe infection-causing pathogens and antitumor activity against U87 cell lines showed exceptional results. Cell viability and cell proliferation studies were conducted against preosteoblast cell lines, and increased cell viability and proliferation were observed from AGZ-1 to AGZ-4. Antimicrobial and anticancer activities were enhanced with the increase of Zn content in the Zn@rGO system. The bioactive scaffolds with different formulations could be potential biomaterials to treat and regenerate defected bone tissue.

Implants with Sensing Capabilities.

Because of the aging human population and increased numbers of surgical procedures being performed, there is a growing number of biomedical devices being implanted each year. Although the benefits of implants are significant, there are risks to having foreign materials in the body that may lead to complications that may remain undetectable until a time at which the damage done becomes irreversible. To address this challenge, advances in implantable sensors may enable early detection of even minor changes in the implants or the surrounding tissues and provide early cues for intervention. Therefore, integrating sensors with implants will enable real-time monitoring and lead to improvements in implant function. Sensor integration has been mostly applied to cardiovascular, neural, and orthopedic implants, and advances in combined implant-sensor devices have been significant, yet there are needs still to be addressed. Sensor-integrating implants are still in their infancy; however, some have already made it to the clinic. With an interdisciplinary approach, these sensor-integrating devices will become more efficient, providing clear paths to clinical translation in the future.

Recent Advances in Cochlear Implant Electrode Array Design Parameters.

Cochlear implants are neural implant devices that aim to restore hearing in patients with severe sensorineural hearing impairment. Here, the main goal is to successfully place the electrode array in the cochlea to stimulate the auditory nerves through bypassing damaged hair cells. Several electrode and electrode array parameters affect the success of this technique, but, undoubtedly, the most important one is related to electrodes, which are used for nerve stimulation. In this paper, we provide a comprehensive resource on the electrodes currently being used in cochlear implant devices. Electrode materials, shape, and the effect of spacing between electrodes on the stimulation, stiffness, and flexibility of electrode-carrying arrays are discussed. The use of sensors and the electrical, mechanical, and electrochemical properties of electrode arrays are examined. A large library of preferred electrodes is reviewed, and recent progress in electrode design parameters is analyzed. Finally, the limitations and challenges of the current technology are discussed along with a proposal of future directions in the field.

Engineering viral genomics and nano-liposomes in microfluidic platforms for patient-specific analysis of SARS-CoV-2 variants.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuing to spread globally, contributing to the persistence of the COVID-19 pandemic. Increasing resources have been focused on developing vaccines and therapeutics that target the Spike glycoprotein of SARS-CoV-2. Recent advances in microfluidics have the potential to recapitulate viral infection in the organ-specific platforms, known as organ-on-a-chip (OoC), in which binding of SARS-CoV-2 Spike protein to the angiotensin-converting enzyme 2 (ACE2) of the host cells occurs. As the COVID-19 pandemic lingers, there remains an unmet need to screen emerging mutations, to predict viral transmissibility and pathogenicity, and to assess the strength of neutralizing antibodies following vaccination or reinfection. Conventional detection of SARS-CoV-2 variants relies on two-dimensional (2-D) cell culture methods, whereas simulating the micro-environment requires three-dimensional (3-D) systems. To this end, analyzing SARS-CoV-2-mediated pathogenicity via microfluidic platforms minimizes the experimental cost, duration, and optimization needed for animal studies, and obviates the ethical concerns associated with the use of primates. In this context, this review highlights the state-of-the-art strategy to engineer the nano-liposomes that can be conjugated with SARS-CoV-2 Spike mutations or genomic sequences in the microfluidic platforms; thereby, allowing for screening the rising SARS-CoV-2 variants and predicting COVID-19-associated coagulation. Furthermore, introducing viral genomics to the patient-specific blood accelerates the discovery of therapeutic targets in the face of evolving viral variants, including B1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), c.37 (Lambda), and B.1.1.529 (Omicron). Thus, engineering nano-liposomes to encapsulate SARS-CoV-2 viral genomic sequences enables rapid detection of SARS-CoV-2 variants in the long COVID-19 era.

Brain-on-a-chip: Recent advances in design and techniques for microfluidic models of the brain in health and disease.

Recent advances in biomaterials, microfabrication, microfluidics, and cell biology have led to the development of organ-on-a-chip devices that can reproduce key functions of various organs. Such platforms promise to provide novel insights into various physiological events, including mechanisms of disease, and evaluate the effects of external interventions, such as drug administration. The neuroscience field is expected to benefit greatly from these innovative tools. Conventional ex vivo studies of the nervous system have been limited by the inability of cell culture to adequately mimic in vivo physiology. While animal models can be used, their relevance to human physiology is uncertain and their use is laborious and associated with ethical issues. To date, organ-on-a-chip systems have been developed to model different tissue components of the brain, including brain regions with specific functions and the blood brain barrier, both in normal and pathophysiological conditions. While the field is still in its infancy, it is expected to have major impact on studies of neurophysiology, pathology and neuropharmacology in future. Here, we review advances made and limitations faced in an effort to stimulate development of the next generation of brain-on-a-chip devices.

Methods for fabricating oxygen releasing biomaterials.

Sustained external supply of oxygen (O2) to engineered tissue constructs is important for their survival in the body while angiogenesis is taking place. In the recent years, the trend towards the fabrication of various O2-generating materials that can provide prolonged and controlled O2 source to the large volume tissue constructs resulted in preventing necrosis associated with the lack of O2 supply. In this review, we explain different methods employed in the fabrication of O2-generating materials such as emulsion, microfluidics, solvent casting, freeze drying, electrospraying, gelation, microfluidic and three-dimensional (3D) bioprinting methods. After discussing pros and cons of each method, we review physical, chemical, and biological characterisation techniques used to analyse the resulting product. Finally, the challenges and future directions in the field are discussed.