Complex Organ Research Articles

Towards the development of sensation-enabled skin substitutes.

Recent advances in cell and biofabrication technologies have contributed to the development of complex human organs. In particular, several skin substitutes are being generated using tissue engineering and regenerative medicine (TERM) technologies. However, recent studies mainly focus on the restoration of the dermis and epidermis layers rather than the regeneration of a fully functional innervated skin organ. Innervation is a critical step in functional tissue repair which has been overlooked in the current TERM studies. In the current study, we highlight the importance of sensation in the skin as the largest sensory organ in the human body. In large non-healing skin wounds, the skin sensation is severely diminished or completely lost and ultimately lead to chronic pain and wound healing process interruption. Current therapeutics for restoring skin sensation after trauma are limited. Recent regenerative medicine-based studies could successfully induce neural networks in skin substitutes, but the effectiveness of these technologies in enhancing sensory capability needs further investigation.

Lipid nanoparticles as the drug carrier for targeted therapy of hepatic disorders.

The liver, a complex and vital organ in the human body, is susceptible to various diseases, including metabolic disorders, acute hepatitis, cirrhosis, and hepatocellular carcinoma. In recent decades, these diseases have significantly contributed to global morbidity and mortality. Currently, liver transplantation remains the most effective treatment for hepatic disorders. Nucleic acid therapeutics offer a selective approach to disease treatment through diverse mechanisms, enabling the regulation of relevant genes and providing a novel therapeutic avenue for hepatic disorders. It is expected that nucleic acid drugs will emerge as the third generation of pharmaceuticals, succeeding small molecule drugs and antibody drugs. Lipid nanoparticles (LNPs) represent a crucial technology in the field of drug delivery and constitute a significant advancement in gene therapies. Nucleic acids encapsulated in LNPs are shielded from the degradation of enzymes and effectively delivered to cells, where they are released and regulate specific genes. This paper provides a comprehensive review of the structure, composition, and applications of LNPs in the treatment of hepatic disorders and offers insights into prospects and challenges in the future development of LNPs.

Parallel Evolution of Transcription Factors in Basal Metazoans.

Transcription factors (TFs) play a pivotal role as regulators of gene expression, orchestrating the formation and maintenance of diverse animal body plans and innovations. However, the precise contributions of TFs and the underlying mechanisms driving the origin of basal metazoan body plans, particularly in ctenophores, remain elusive. Here, we present a comprehensive catalog of TFs in 2 ctenophore species, Pleurobrachia bachei and Mnemiopsis leidyi, revealing 428 and 418 TFs in their respective genomes. In contrast, morphologically simpler metazoans have a reduced TF representation compared to ctenophores, cnidarians, and bilaterians: the sponge Amphimedon encodes 277 TFs, and the placozoan Trichoplax adhaerens encodes 274 TFs. The emergence of complex ctenophore tissues and organs coincides with significant lineage-specific diversification of the zinc finger C2H2 (ZF-C2H2) and homeobox superfamilies of TFs. Notable, the lineages leading to Amphimedon and Trichoplax exhibit independent expansions of leucine zipper (BZIP) TFs. Some lineage-specific TFs may have evolved through the domestication of mobile elements, thereby supporting alternative mechanisms of parallel TF evolution and body plan diversification across the Metazoa.

A skin secretion metabolome analysis of the Greek Dodecanese Lycian salamanders: Preliminary evidence of dietary alkaloid sequestration in urodeles.

Lyciasalamandra species, like most amphibians, secrete a wide array of compounds from their granular and mucous skin glands, including the internally synthesized samandarine alkaloids, making their skin a complex organ performing a variety of functions. Lyciasalamandra helverseni and L. luschani basoglui are insular endemics of the Dodecanese islands of SE Greece, bearing distinct isolated populations, with well-documented phylogenetic profiles. Here, we employ a metabolomics approach, utilizing UPLC-ESI-HRMS/MS data of the skin secretions sampled from a number of specimens found in the islands of Karpathos, Kasos and Kastellorizo, in an effort to reveal aspects of their chemistry and diversity across populations. The results indicated statistically significant variation between all taxa examined, based on various secreted compounds. The underlying factors of variation highlighted by the multivariate analysis were differences in samandarine and other alkaloid content as well as in animal size. Metabolite annotation, based on dereplication tools and most importantly HRMS and HRMS/MS spectra, yielded a number of known samandarine alkaloids, reported for the first time in the currently studied Lyciasalamandra species. We also present documentation for novel members of the samandarine alkaloid family, as well as preliminary evidence for a possible dietary alkaloid sequestration. This work can set the basis for further research of this often-neglected endemic species of the Salamandridae, as well as the structural investigation of the samandarine alkaloid group.

Single-Nucleus ATAC-seq for Mapping Chromatin Accessibility in Individual Cells of Murine Hearts.

During the last decade a wide range of single-cell and single-nucleus next-generation sequencing techniques have been developed, which revolutionized detection of rare cell populations, enabling creation of comprehensive cell atlases of complex organs and tissues. State-of-the-art methods do not only allow classical transcriptomics of individual cells but also comprise a number of epigenetic approaches, including assessment of chromatin accessibility by single-nucleus Assay for Transposase Accessible Chromatin ATAC-seq (snATAC-seq). The snATAC-seq assay detects "open chromatin," a term for low nucleosome occupancy of genomic regions, which is a prerequisite for effective transcription factor binding. Information about open chromatin at the single-nucleus level helps to recognize epigenetic changes, sometimes before transcription of respective genes occurs. snATAC-seq detects cellular heterogeneity in otherwise still transcriptionally and/or morphologically homogeneous cell populations. Chromatin accessibility assays may be used to detect epigenetic changes in cardiac lineages during heart development, chromatin landscape changes during aging, and epigenetic alterations in heart diseases. Here, we provide an optimized protocol for snATAC-seq of murine hearts. We describe isolation of single nuclei from snap-frozen hearts, provide hints for preparation of libraries suitable for snATAC-seq next-generation sequencing (NGS) using the Chromium 10× platform, and give general recommendations for downstream analysis using conventional bioinformatic pipelines and packages. The protocol should serve as a beginner's guide to generate high-quality snATAC-seq datasets and to perform chromatin accessibility analysis of individual heart-derived cell nuclei.

Feto-Maternal Interface Organ-on-Chip: A New Technology to Study Ascending Infection.

Modeling human pregnancy is challenging as two subjects, the mother and fetus, must be evaluated in tandem. To understand pregnancy, parturition, and adverse pregnancy outcomes, the two feto-maternal interfaces (FMi) that form during gestation (i.e., the placenta and fetal membrane) need to be investigated to understand their biological roles, and organ dysfunction can lead to adverse outcomes. Adverse pregnancy outcomes such as preterm rupture of the membranes, spontaneous preterm birth, preeclampsia, intra-uterine growth restriction, and gestational diabetes rates are on the rise worldwide, highlighting the need for future studies and a better understanding of molecular and cellular pathways that contribute to disease onset. Current in vivo animal models nor in vitro cell culture systems can answer these questions as they do not model the function or structure of human FMis. Utilizing microfabrication and soft-lithography techniques, microfluidic organ-on-chip (OOC) devices have been adapted by many fields to model the anatomy and biological function of complex organs and organ systems within small in vitro platforms.These techniques have been adapted to recreate the fetal membrane FMi (FMi-OOC) using immortalized cells and collagen derived from patient samples. The FMi-OOC is a four-cell culture chamber, concentric circle system, that contains both fetal (amniochorion) and maternal (decidua) cellular layers and has been validated to model physiological and pathological states of pregnancy (i.e., ascending infection, systemic oxidative stress, and maternal toxicant exposure). This platform is fully compatible with various analytical methods such as microscopy and biochemical analysis. This protocol will outline this device's fabrication, cell loading, and utility to model ascending infection-related adverse pregnancy outcomes.

Epigenetic Regulation of Pancreas Development and Function.

The field of epigenetics broadly seeks to define heritable phenotypic modifications that occur within cells without changes to the underlying DNA sequence. These modifications allow for precise control and specificity of function between cell types-ultimately creating complex organ systems that all contain the same DNA but only have access to the genes and sequences necessary for their cell-type-specific functions. The pancreas is an organ that contains varied cellular compartments with functions ranging from highly regulated glucose-stimulated insulin secretion in the β-cell to the pancreatic ductal cells that form a tight epithelial lining for the delivery of digestive enzymes. With diabetes cases on the rise worldwide, understanding the epigenetic mechanisms driving β-cell identity, function, and even disease is particularly valuable. In this chapter, we will discuss the known epigenetic modifications in pancreatic islet cells, how they are deposited, and the environmental and metabolic contributions to epigenetic mechanisms. We will also explore how a deeper understanding of epigenetic effectors can be used as a tool for diabetes therapeutic strategies.

Generation of rat-derived lung epithelial cells in Fgfr2b-deficient mice retains species-specific development.

Regenerative medicine is a tool to compensate for the shortage of lungs for transplantation, but it remains difficult to construct a lung in vitro due to the complex three-dimensional structures and multiple cell types required. A blastocyst complementation method using interspecies chimeric animals has been attracting attention as a way to create complex organs in animals, although successful lung formation using interspecies chimeric animals has not yet been achieved. Here, we applied a reverse-blastocyst complementation method to clarify the conditions required to form lungs in an Fgfr2b-deficient mouse model. We then successfully formed a rat-derived lung in the mouse model by applying a tetraploid-based organ-complementation method. Importantly, rat lung epithelial cells retained their developmental timing even in the mouse body. These findings provide useful insights to overcome the barrier of species-specific developmental timing to generate functional lungs in interspecies chimeras.

Decellularised extracellular matrix-based injectable hydrogels for tissue engineering applications.

Decellularised extracellular matrix (dECM) is a biomaterial derived from natural tissues that has attracted considerable attention from tissue engineering researchers due to its exceptional biocompatibility and malleability attributes. These advantageous properties often facilitate natural cell infiltration and tissue reconstruction for regenerative medicine. Due to their excellent fluidity, the injectable hydrogels can be administered in a liquid state and subsequently formed into a gel state in vivo, stabilising the target area and serving in a variety of ways, such as support, repair, and drug release functions. Thus, dECM-based injectable hydrogels have broad prospects for application in complex organ structures and various tissue injury models. This review focuses on exploring research advances in dECM-based injectable hydrogels, primarily focusing on the applications and prospects of dECM hydrogels in tissue engineering. Initially, the recent developments of the dECM-based injectable hydrogels are explained, summarising the different preparation methods with the evaluation of injectable hydrogel properties. Furthermore, some specific examples of the applicability of dECM-based injectable hydrogels are presented. Finally, we summarise the article with interesting prospects and challenges of dECM-based injectable hydrogels, providing insights into the development of these composites in tissue engineering and regenerative medicine.

A Standardized Protocol for Extraction and Homogenization of Ocular Tissues.

The eye is a complex organ composed of multiple tissues in anterior and posterior eye segments. Malfunctions of any of these tissues can lead to ocular diseases and loss of vision. A detailed understanding of the ocular anatomy and physiology in animal models and humans contributes to the development of ocular drugs by enabling studies on drug delivery and clearance routes, pharmacokinetics, and toxicity. This protocol provides step-by-step instructions for the extraction and homogenization of ocular tissues for enzymatic and proteomics analyses. Key features • Suitable protocol for the extraction and isolation of ocular tissue from humans and laboratory animals (rabbit, pig, rat, mouse) while minimizing cross-contamination. • Hard or soft tissue homogenates can be prepared efficiently using a Bead Ruptor homogenizer. • Allows to determine the protein contents in prepared homogenates.

Research Status and Development Trend of EEG Technology for Deep Learning in Emotion Recognition

EEG technology has made significant progress as people's attention to their emotions increases. This has also led to significant progress in various brain sciences, as well as their correlation with emotions. Nevertheless, based on the development of contemporary brain science, it is not possible to provide detailed cause analysis or draw accurate conclusions based on EEG information for a certain symptom or representation. The brain, as a complex organ of multiple entities, processes complex information by connecting multiple brain regions and clarifying the division of labor for each region. This creates a significant obstacle for the research method of brain computer interface, which uses computer algorithms to read information in the brain. Recently, many solutions and research methods have emerged to address this issue, such as electroencephalography (EEG), Positive Positron Emission Computed Tomography (PET) and Functional Magnetic Resolution Imaging (fMRI), etc. However, with such a large number of technologies, a method that can provide precise data from both temporal and spatial angles has not yet been derived. So in-depth research in biology, continuous exploration of computer algorithms can make outstanding contributions to the refinement of brain computer data. In summary, this article aims to provide an overview of the relationship between emotions and EEG analysis, as well as the principles of machine recognition and other applied technologies.

Expression of prolyl hydroxylase domains, the upstream regulators of HIF, in the brain of the anoxia-tolerant crucian carp during anoxia-reoxygenation.

The hypoxia-inducible factor (HIF) is considered key in the transcriptional response to low oxygen. Yet, the role of HIF in the absence of oxygen (anoxia) and in preparation for reoxygenation remains unclear. Recent studies suggest that mounting a HIF response may be counterproductive for anoxia survival. We here studied one of the champions of anoxia survival, the crucian carp (Carassius carassius), and hypothesized that expression of prolyl hydroxylase domains (PHDs; the upstream regulators of HIF) are upregulated to circumvent an energy-costly activation of HIF in anoxia and to prepare for reoxygenation. We measured whole brain mRNA and protein levels of the three isoforms PHD1, PHD2, and PHD3, coded for by multiple paralogs of the genes egln2, egln1, and egln3, using quantitative PCR and Western blotting in the brain of crucian carps exposed to 5 days normoxia or anoxia, and 5 days anoxia followed by 3 or 24 h of reoxygenation. The mRNA levels of most egln paralogs were increased in anoxia and upon reoxygenation, with egln3 showing the largest increase in mRNA level (up to 17-fold) and highest relative mRNA abundance (up to 75% of expressed egln). The protein level of all PHDs was maintained in anoxia and increased upon reoxygenation. We then explored PHD distribution in different brain regions and found PHD immunoreactivity to be associated with axonal branches and showing region-specific changes during anoxia-reoxygenation. Our results support an overall upregulation of egln under prolonged anoxia and PHDs upon reoxygenation in crucian carp, likely aimed at suppressing HIF responses, although regional differences are apparent in such a complex organ as the brain.NEW & NOTEWORTHY We report a profound upregulation of most egln paralog mRNA levels in anoxia and upon reoxygenation, with egln3ii showing the largest, a 17-fold increase, and highest relative mRNA abundance. The relative abundance of prolyl hydroxylase domain (PHD) proteins was maintained during anoxia and increased at reoxygenation. PHD immunoreactivity was localized to axonal branches with region-specific changes during anoxia-reoxygenation. These dynamic and regional changes in crucian carp, champion of anoxia tolerance, are most likely adaptive and call for further mechanistic studies.

Techniques and applications of 3D bioprinting

3D bioprinting is an emerging technology that uses computer printing technology and unique bio-ink components to create artificial organs and biomedical objects. It is an interdisciplinary development technology integrating biology, chemistry, materials science, life science and other disciplines, and the technology behind biological 3D printing has improved in its development over the past few decades. Precisely printed biomaterials could benefit both tissue engineering and regenerative medicine. 3D bioprinting technology makes it possible to print tissues and organs, providing favorable conditions for organ transplantation and medical experiments. This paper mainly reviews the development of bioprinting technology and related concepts. According to the morphological change and chemical composition, the commonly used bioprinting materials (bio-inks) and their characteristics are described. The main methods of bioprinting are summarized, including traditional inkjet 3D bioprinting, extrusion 3D bioprinting, laser-assisted 3D bioprinting, photocuring 3D bioprinting and emerging 4D bioprinting and in situ bioprinting technologies. Finally, the paper introduces the development trend of bioprinting in the transplantation of skin, blood vessels and complex organs, as well as the precision research of tumors. In addition, current research challenges and prospects for future bioprinted 3D printing materials are discussed.

Lectin-mediated, time-efficient, and high-yield sorting of different morphologically intact nephron segments

The kidney is a highly complex organ equipped with a multitude of miniscule filter-tubule units called nephrons. Each nephron can be subdivided into multiple segments, each with its own morphology and physiological function. To date, conventional manual approaches to isolate specific nephron segments are very laborious, time-consuming, often limited to only a specific segment, and typically have low yield. Here, we describe a novel, unconventional method that is superior in many aspects to previous protocols by combining low-cost fluorophore-conjugated lectins or agglutinins (Flaggs) with flow sorting. This allows the simultaneous separation of different nephron segments with preserved 3D morphology from mouse or human samples in under 3 h. Using a 200-µm nozzle and 5 psi, glomeruli, proximal, or distal convoluted tubules are sorted with Cy3-labeled Sambucus Nigra agglutinin (SNA-Cy3), Fluorescein-labeled Lotus Tetragonolobus lectin (LTL-FITC), or Pacific Blue-labeled soybean agglutinin (SBA-PB), respectively. Connecting tubules and collecting ducts are sorted by double-positive SBA-PB and SNA-Cy3 signals, while thick ascending limb segments are characterized by the absence of any Flaggs labeling. From two mouse kidneys, this yields 37–521 ng protein/s or 0.71–16.71 ng RNA/s, depending on the specific nephron segment. The purity of sorted segments, as assessed by mRNA expression level profiling of 15 genes, is very high with a 96.1-fold median enrichment across all genes and sorted segments. In summary, our method represents a simple, straightforward, cost-effective, and widely applicable tool yielding high amounts of pure and morphologically largely intact renal tubule materials with the potential to propel nephron segment-specific research.

The Current Status and Use of Microphysiological Systems by the Pharmaceutical Industry: The International Consortium for Innovation and Quality Microphysiological Systems Affiliate Survey and Commentary.

Microphysiological systems (MPS) are comprised of one or multiple cell types of human or animal origins that mimic the biochemical/electrical/mechanical responses and blood-tissue barrier properties of the cells observed within a complex organ. The goal of incorporating these in vitro systems is to expedite and advance the drug discovery and development paradigm with improved predictive and translational capabilities. Considering the industry need for improved efficiency and the broad challenges of model qualification and acceptance, the International Consortium for Innovation and Quality (IQ) founded an IQ MPS working group in 2014 and Affiliate in 2018. This group connects thought leaders and end users, provides a forum for crosspharma collaboration, and engages with regulators to qualify translationally relevant MPS models. To understand how pharmaceutical companies are using MPS, the IQ MPS Affiliate conducted two surveys in 2019, survey 1, and 2021, survey 2, which differed slightly in the scope of definition of the complex in vitro models under question. The surveys captured demographics, resourcing, rank order for organs of interest, compound modalities tested, and MPS organ-specific questions, including nonclinical species needs and cell types. The major focus of this manuscript is on results from survey 2, where we specifically highlight the context of use for MPS within safety, pharmacology, or absorption, disposition, metabolism, and excretion and discuss considerations for including MPS data in regulatory submissions. In summary, these data provide valuable insights for developers, regulators, and pharma, offering a view into current industry practices and future considerations while highlighting key challenges impacting MPS adoption. SIGNIFICANCE STATEMENT: The application of microphysiological systems (MPS) represents a growing area of interest in the drug discovery and development framework. This study surveyed 20+ pharma companies to understand resourcing, current areas of application, and the key challenges and barriers to internal MPS adoption. These results will provide regulators, tech providers, and pharma industry leaders a starting point to assess the current state of MPS applications along with key learnings to effectively realize the potential of MPS as an emerging technology.

Serum S100A8/A9 and RNA-binding protein, tristetraprolin as prognostic markers of renal damage

Background & objective: The kidneys are vital and complex organs responsible for maintaining normal body functions. Kidney disease or a loss of kidney function and, in severe cases, complete kidney failure disrupt whole of the body systems. Tristetraprolin (TTP ZFP36) is an RNA-binding proteins (RBP), that regulates cytokine mRNAs by specific binding of its two conserved ZF domains to adenylate-uridylate-rich elements (AREs) at the untranslated region (UTR), leading to degradation of the RNA. Recently, it was suggested that S100 A8/A9 and TTP were involved in pathogenesis of renal diseases. However, the protective roles of S100 A8/A9 and TTP in renal disease is still unclear. The primary objective of this study was to explore the involvement of S100 A8/A9 and TTP in the inflammatory response among different groups of kidney diseases. These factors may hold therapeutic value in the treatment of these diseases by targeting and modulating the inflammatory response. Methodology: The study was performed between October 2022 to April 2023. We included 150 subjects, including 30 patients with chronic kidney disease (CKD), (Female = 16, Male = 14) with mean age (58.33 ± 18.33 y), 30 patients with acute kidney injury (AKI), (Female = 15, Male = 15), with mean age (54.48 ± 18.10 y), 30 patients with diabetic nephropathy (DN), (Female = 18, Male = 12), with mean age (60.84 ± 12.38 y), 30 patients with nephrotic syndrome (NS), (Female = 13, Male = 17), with mean age (52.54 ± 14.02 y), and 30 healthy persons as a control group. NLR analysis was performed directly using the hematology analyzer CBC (Sysmex, Japan) technique, serum S100 A8/A9 were measured by ELISA, and TTP gene expression was measured by Quantitative Real Time-Polymerase Chain Reaction (RT-qPCR). Results: In comparison to the healthy control group, all patient groups exhibited a significant increase in the NLR (P < 0.05). Furthermore, the findings clearly demonstrated elevated levels of S100 A8/A9 in all patient groups when compared to the control group (P ≤ 0.05). The results also demonstrated a significant down regulation in the expression of TTP in DN and nephrotic syndrome (NS) groups compared to the control (P ≤ 0.01). AKI showed highly significant increase in TTP expression in comparison to control and other patient groups (P ≤ 0.01). Non-significant decrease in TTP gene expression was indicated in CKD compared to healthy group (P ≥ 0.05). Conclusions: The activation of Ca2+-binding protein S100A8/A9 is involved in the renal damage; thus, targeting it could have a therapeutic value in the treatment of kidney diseases. Tristetraprolin is contributed to the regulation of inflammatory events in kidney diseases especially in AKI group due to a rapid and robust inflammatory response that contributes to the pathogenesis of this disease. Abbreviations: AKI- acute kidney injury ARE- Adenylate-Uridylate-Rich Element; DN- diabetic nephropathy; NS- Nephrotic Syndrome; NLR- Neutrophil-to-Lymphocyte Ratio; RT-qPCR= Quantitative Real Time-Polymerase Chain Reaction; RBP- RNA-Binding Proteins; TTP- Tristetraprolin; UTR- Untranslated Region; Key words: Kidney diseases; S100 A8/A9, Anti-inflammatory RNA binding protein; Tristetraprolin; Neutrophil/Lymphocyte Ration Citation: Mohammed Radhi FZ, Almzaie AJ, Majeed MM. Serum S100A8/A9 and RNA-binding protein, tristetraprolin as prognostic markers of renal damage. Anaesth. pain intensive care 2023;27(6):706−714; DOI: 10.35975/apic.v27i6.2342 Received: August 12, 2023; Revised: September 05, 2023; Accepted: September 07, 2023

Stress-free cell aggregation by using the CEPT cocktail enhances embryoid body and organoid fitness

Embryoid bodies (EBs) and self-organizing organoids derived from human pluripotent stem cells (hPSCs) recapitulate tissue development in a dish and hold great promise for disease modeling and drug development. However, current protocols are hampered by cellular stress and apoptosis during cell aggregation, resulting in variability and impaired cell differentiation. Here, we demonstrate that EBs and various organoid models (e.g., brain, gut, kidney) can be optimized by using the small molecule cocktail named CEPT (chroman 1, emricasan, polyamines, trans-ISRIB), a polypharmacological approach that ensures cytoprotection and cell survival. Application of CEPT for just 24 h during cell aggregation has long-lasting consequences affecting morphogenesis, gene expression, cellular differentiation, and organoid function. Various qualification methods confirmed that CEPT treatment enhanced experimental reproducibility and consistently improved EB and organoid fitness as compared to the widely used ROCK inhibitor Y-27632. Collectively, we discovered that stress-free cell aggregation and superior cell survival in the presence of CEPT are critical quality control determinants that establish a robust foundation for bioengineering complex tissue and organ models.

Modeling.

Modeling is coming to the fore as it is now widely accepted and indeed expected during drug discovery and development. Modeling integrates knowledge, increases understanding and provides the ability to predict an outcome either before it occurs or when it is not possible to measure. This makes modeling an attractive option for inhaled drugs as it is not possible to routinely measure what is occurring to the drug (pharmacokinetics) and what effect the drug is having (pharmacodynamics) at local microscopic sites of such a diverse and complex organ as the lung. Many pieces of information (data and knowledge) exist like the pieces of a jigsaw puzzle and modeling brings the pieces together in a scientific and mechanistically coherent manner to increase understanding of both the efficacy and safety of inhaled drugs.

Nanotechnology in Retinal Disease: Current Concepts and Future Directions.

The retina is one of the most complex and extraordinary human organs affected by genetic, metabolic, and degenerative diseases, resulting in blindness for ∼1.3 million people in the United States and over 40 million people worldwide. This translates into a huge loss of productivity, especially among younger patients with inherited retinal diseases (IRDs) and diabetic retinopathy. Age-related macular degeneration accounts for 90% of all blindness cases worldwide. The prevalence of this condition is projected to reach over 5 million individuals over the next 3 decades. There are also >20 IRD phenotypes, affecting >2 million people worldwide. Nanobiotechnology uses nanotechnology for biological applications, making use of biological materials either conceptually or directly in the fabrication of new materials. Bionanotechnology, on the other hand, uses molecular biology for the purpose of creating nanostructures (ie, structures with at least 1 dimension <100 nm). Retinal applications of these technologies are developing at a rapid pace. This review includes the most current nanotechnological applications in retinal diagnostics, theranostics, drug delivery, and targeting, including the potential for nonviral vehicles such as liposomes, micelles, and dendrimers, which pose advantages over viral vectors in retinal drug delivery. Furthermore, we discuss current and future applications as surgical adjuncts and in regenerative medicine as they pertain to retinal disease. Structure and function of nanoparticles such as carbon nanotubules, quantum dots, and magnetic nanoparticles, as well as diagnostic technologies such as next-generation DNA sequencing and single-molecule bionanosensing, will also be discussed.

Nanotechnology in Smart Contact Lenses: Highlights on Sensor Technologies and Future Prospects

Abstract: The eye is a complex organ in the body containing a repertoire of metabolite indicators such as glucose, peptides, specialized ions, and many critical biological data such as intraocular pressure (IOP), corneal temperature, and pH. Contact lens research and patient care have progressed substantially throughout the last three decades; hence smart contact lenses were developed with significant advancements in material biocompatibility, better lens layouts, the healthcare system, and more flexible and efficient modalities. Smart contact lenses are adjustable sophisticated visual prosthesis devices that monitor various significant physical and biochemical changes in ocular disorders, which are noninvasive and continuous. Wearable systems that utilize bodily fluids like sweat tears, saliva, and electrochemical interactions with steady physiological state and illness monitoring are currently developing. Because of its ease of access, fabrication, and noninvasiveness, tear fluid is commonly used to assess ocular disorders, blood glucose, and even cancers. Furthermore, the integration of nanotechnology into contact lenses has emerged as a promising platform for noninvasive point-of-care diagnostics. Utilizing nano-based contact lenses for ocular drug delivery is a new study area in bioengineering and innovative medical techniques. Despite all of the research done in this area, new technologies are still in their early stages of development, and more work in terms of clinical trials is required to commercialize nanotechnology-based contact lenses. This article encompasses nanotechnology-based smart contact lens technology, including materials, advancements, applications, sensor technologies, and prospects.