Engineered Probiotic Bio-Heterojunction with Robust Antibiofilm Modality via "Eating" Extracellular Polymeric Substances for Wound Regeneration.

The compact three-dimensional (3D) structure of extracellular polymeric substances (EPS) within biofilms significantly hinders the penetration of antimicrobial agents, making biofilm eradication challenging and resulting in persistent biofilm-associated infections. To address this challenge, a solution is proposed: a probiotic bio-heterojunction (P-bioHJ) combining Lactobacillus rhamnosus with MXene (Ti3C2) quantum dots (MQDs)/FeS heterojunction. This innovation aims to break down the saccharides in EPS, enabling effective combat against biofilm-associated infections. Initially, the P-bioHJ targets saccharides through metabolic processes, causing the collapse of EPS and allowing infiltration into bacterial colonies. Simultaneously, upon exposure to near-infrared (NIR) irradiation, the P-bioHJ produces reactive oxygen species (ROS) and thermal energy, deploying physical mechanisms to combat bacterial biofilms effectively. Following antibiofilm treatment, the P-bioHJ adjusts the oxidative environment, reduces wound inflammation by scavenging ROS, boosts antioxidant enzyme activity, and mitigates the NF-κB inflammatory pathway, thereby accelerating wound healing. In vitro and in vivo experiments confirm the exceptional antibiofilm, antioxidant/anti-inflammatory, and wound-regeneration properties of P-bioHJ. In conclusion, this study provides a promising approach for treating biofilm-related infections.

Metal element-fusion peptide heterostructured nanocoatings endow polyetheretherketone implants with robust anti-bacterial activities and in vivo osseointegration.

Polyetheretherketone (PEEK), renowned for its exceptional mechanical properties and bio-stability, is considered a promising alternative to traditional metal-based implants. However, the inferior bactericidal activity and the limited angiogenic and osteogenic properties of PEEK remain the three major obstacles to osseointegration in vivo. To overcome these obstacles, in this work, a versatile heterostructured nanocoating was conceived and equipped on PEEK. This nanocoating was designed to endow PEEK with the ability of photo-activated pathogen disinfection, along with enhanced angiogenesis and osteogenesis, effectively addressing the triple-barrier challenge towards osseointegration. The crafted nanocoating, encompassing diverse nutritional metal elements (Fe3+, Mg2+, and Sr2+) and a fusion peptide adept at promoting angiogenesis and osteogenesis, was seamlessly decorated onto PEEK. The engineered implant exhibited an antibacterial activity of over 94% upon near-infrared illumination by virtue of the photothermal conversion of the polyphenol nanocoating. Simultaneously, the decorated hierarchical nanocoatings synergistically promoted cellular adhesion and proliferation and up-regulated angiogenesis-/osteogenesis-associated cytokine expression in endothelial/osteoblast cells, resulting in superior angiogenic differentiation and osteoinductive capability in vitro. Moreover, an in vivo assay in a rabbit femoral defect model revealed that the decorated implant can achieve ameliorative osseointegrative fixation. Collectively, this work offers a practical and instructive clinical strategy to address the triple-barrier challenge associated with PEEK-based implants.

Achieving Clearance of Drug-Resistant Bacterial Infection and Rapid Cutaneous Wound Regeneration Using an ROS-Balancing-Engineered Heterojunction.

Intractable infected microenvironments caused by drug-resistant bacteria stalls the normal course of wound healing. Sono-piezodynamic therapy (SPT) is harnessed to combat pathogenic bacteria, but the superabundant reactive oxygen species (ROS) generated during SPT inevitably provoke severe inflammatory response, hindering tissue regeneration. Consequently, an intelligent nanocatalytic membrane composed of poly(lactic-co-glycolic acid) (PLGA) and black phosphorus /V2C MXene bio-heterojunctions (2D2-bioHJs) is devised. Under ultrasonication, 2D2-bioHJs effectively eliminate drug-resistant bacteria by disrupting metabolism and electron transport chain (ETC). When ultrasonication ceases, they enable the elimination of SPT-generated ROS. The 2D2-bioHJs act as a "lever" that effectively achieves a balance between ROS generation and annihilation, delivering both antibacterial and anti-inflammatory properties to the engineered membrane. More importantly, in vivo assays corroborate that the nanocatalytic membranes transform the stalled chronic wound environment into a regenerative one by eradicating the bacterial population, dampening the NF-κB inflammatory pathway and promoting angiogenesis. As envisaged, this work demonstrates a novel tactic to arm membranes with programmed antibacterial and anti-inflammatory effects to remedy refractory infected wounds from drug-fast bacteria.

Engineered Bio-Heterojunction Confers Extra- and Intracellular Bacterial Ferroptosis and Hunger-Triggered Cell Protection for Diabetic Wound Repair.

Nanomaterial-mediated ferroptosis has garnered considerable interest in the antibacterial field, as it invokes the disequilibrium of ion homeostasis and boosts lipid peroxidation in extra- and intracellular bacteria. However, current ferroptosis-associated antibacterial strategies indiscriminately pose damage to healthy cells, ultimately compromising their biocompatibility. To address this daunting issue, this work has designed a precise ferroptosis bio-heterojunction (F-bio-HJ) consisting of Fe2 O3 , Ti3 C2 -MXene, and glucose oxidase (GOx) to induce extra-intracellular bacteria-targeted ferroptosis for infected diabetic cutaneous regeneration. Fe2 O3 /Ti3 C2 -MXene@GOx (FMG) catalytically generates a considerable amount of ROS which assaults the membrane of extracellular bacteria, facilitating the permeation of synchronously generated Fe2+ /Fe3+ into bacteria under near-infrared (NIR) irradiation, causing planktonic bacterial death via ferroptosis, Fe2+ overload, and lipid peroxidation. Additionally, FMG facilitates intracellular bacterial ferroptosis by transporting Fe2+ into intracellular bacteria via inward ferroportin (FPN). With GOx consuming glucose, FMG creates hunger protection which helps macrophages escape cell ferroptosis by activating the adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) pathway. In vivo results authenticate that FMG boosts diabetic infectious cutaneous regeneration without triggering ferroptosis in normal cells. As envisaged, the proposed tactic provides a promising approach to combat intractable infections by precisely terminating extra-intracellular infection via steerable ferroptosis, thereby markedly elevating the biocompatibility of therapeutic ferroptosis-mediated strategies.

Emerging treatments for corneal endothelium decompensation - a systematic review.

PURPOSE: Endothelial keratoplasty (EK) is the conventional treatment to improve visual acuity of corneal endothelium decompensation (CED) patients, with other therapies mainly for symptomatic relief. However, the shortage of corneal grafts and other limitations to EK urge the development of novel alternative treatments. In the last decade, novel options have been proposed, yet only a limited number of reviews have systematically reported on outcomes. Therefore, this systematic review evaluates the existing clinical evidence of novel surgical approaches for CED. METHOD: We identified 24 studies that illustrated the clinical observations of the surgical approaches in interest. We included Descemet stripping only (DSO), Descemet membrane transplantation (DMT) where Descement membrane alone instead of corneal endothelium with cells is transplanted, and cell-based therapy. RESULTS: In general, these therapies may provide visual outcomes comparable with EK under specific conditions. DSO and DMT target CED with relatively healthy peripheral corneal endothelium like Fuchs' corneal endothelial dystrophy, while cell-based therapy offers more versatile applications. Side effects of DSO would decrease with modifications to surgical techniques. Moreover, Rho-associated protein kinase inhibitor adjuvant therapy could enhance clinical results in DSO and cell-based therapy. CONCLUSION: Long-term controlled clinical trials with larger sample size on the therapies are needed. The simplicity of DSO and the high translational potential of cell-based therapy to treat CED of most etiologies made these two treatment strategies promising.

Antibacterial and Angiogenic (2A) Bio-Heterojunctions Facilitate Infectious Ischemic Wound Regeneration via an Endogenous-Exogenous Bistimulatory Strategy.

In infectious ischemic wounds, a lack of blood perfusion significantly worsens microbe-associated infection symptoms and frequently complicates healing. To overcome this daunting issue, antibacterial and angiogenic (2A) bio-heterojunctions (bio-HJs) consisting of CuS/MXene heterojunctions and a vascular endothelial growth factor (VEGF)-mimicking peptide (VMP) are devised and developed to accelerate infectious cutaneous regeneration by boosting angiogenesis via an endogenous-exogenous bistimulatory (EEB) strategy. Assisted by near-infrared irradiation, the bio-HJ platform exhibits versatile synergistic photothermal, photodynamic, and chemodynamic effects for robust antibacterial efficacy. In addition, copper ions liberated from 2A bio-HJs elevate VEGF secretion from fibroblasts, which provokes VEGF receptors (VEGFR) activation through an endogenous pathway, whereas VMP itself promotes an exogenous pathway to facilitate endothelial cell multiplication and tube formation by directly activating the VEGFR signaling pathway. Moreover, employing an in vivo model of infectious ischemic wounds, it is confirmed that the EEB strategy can considerably boost cutaneous regeneration through pathogen elimination, angiogenesis promotion, and collagen deposition. As envisaged, this work leads to the development of a powerful 2A bio-HJ platform that can serve as an effective remedy for bacterial invasion-induced ischemic wounds through the EEB strategy.

MXene-Decorated Nanofibrous Membrane with Programmed Antibacterial and Anti-Inflammatory Effects via Steering NF-κB Pathway for Infectious Cutaneous Regeneration.

Although antibiotic is still the main choice for antibacteria both in hospital and community, phototherapy has become a possibly one of the alternative approaches in the treatment of microbe-associated infections nowadays because of its considerable potential in effective eradication of pathogenic bacteria. However, overwhelming reactive oxygen species (ROS) generated from phototherapy inevitably provoke an inflammatory response, complicating the healing process. To address this outstanding issue, a MXene-decorated nanofibrious is devised that not only yield localized heat but also elevate ROS levels under near-infrared laser exposure ascribed to the synergistic photothermal/photodynamic effect, for potent bacterial inactivation. After being further loaded with aspirin, the nanofibrous membranes exhibit benign cytocompatibility, boosting cell growth and suppressing the (nuclear factor kappa-B ( NF-κB) signaling pathways through RNA sequencing analysis, indicating an excellent anti-inflammatory effect. Interestingly, in vivo investigations also corroborate that the nanofibrous membranes accelerate infectious cutaneous regeneration by efficiently killing pathogenic bacteria, promoting collagen deposition, boosting angiogenesis, and dampening inflammatory reaction via steering NF-κB pathway. As envisaged, this work furnishes a decorated nanofibrous membrane with programmed antibacterial and anti-inflammatory effects for remedy of refractory bacteria-invaded wound regeneration.

All-aqueous microfluidic printing of multifunctional bioactive microfibers promote whole-stage wound healing.

Wound healing involves multi-stages of physiological responses, including hemostasis, inflammation, cell proliferation, and tissue remodeling. Satisfying all demands throughout different stages remains a rarely addressed challenge. Here we introduce an innovative all-aqueous microfluidic printing technique for fabricating multifunctional bioactive microfibers, effectively contributing to all four phases of the healing process. The distinctive feature of the developed microfibers lies in their capacity to be printed in a free-form manner in the aqueous-two phase system (ATPS). This is achieved through interfacial coacervation between alkyl-chitosan and alginate, with enhanced structural integrity facilitated by simultaneous crosslinking with calcium ions and alginate. The all-aqueous printed microfibers exhibit exceptional performance in terms of cell recruitment, blood cell coagulation, and hemostasis. The inclusion of a dodecyl carbon chain and amino groups in alkyl-chitosan imparts remarkable antimicrobial properties by anchoring to bacteria, complemented by potent antibacterial effects of encapsulated silver nanoparticles. Moreover, microfibers can load bioactive drugs like epidermal growth factor (EGF), preserving their activity and enhancing therapeutic effects during cell proliferation and tissue remodeling. With these sequential functions to guide the whole-stage wound healing, this work offers a versatile and robust paradigm for comprehensive wound treatment, holding great potential for optimal healing outcomes.

Continuous roller nanoimprinting: next generation lithography.

Nanoimprint lithography (NIL) is a cost-effective and high-throughput technique for replicating nanoscale structures that does not require expensive light sources for advanced photolithography equipment. NIL overcomes the limitations of light diffraction or beam scattering in traditional photolithography and is suitable for replicating nanoscale structures with high resolution. Roller nanoimprint lithography (R-NIL) is the most common NIL technique benefiting large-scale, continuous, and efficient industrial production. In the past two decades, a range of R-NIL equipment has emerged to meet the industrial needs for applications including biomedical devices, semiconductors, flexible electronics, optical films, and interface functional materials. R-NIL equipment has a simple and compact design, which allows multiple units to be clustered together for increased productivity. These units include transmission control, resist coating, resist curing, and imprinting. This critical review summarizes the hitherto R-NIL processes, their typical technical problems, and corresponding solutions and gives guidelines for developing advanced R-NIL equipment.

Current microfluidic platforms for reverse engineering of cornea.

According to the World Health Organization, corneal blindness constitutes 5.1% of global blindness population. Surgical outcomes have been improved significantly in the treatment of corneal blindness. However, corneal transplantation is limited by global shortage of donor tissue, prompting researchers to explore alternative therapies such as novel ocular pharmaceutics to delay corneal disease progression. Animal models are commonly adopted for investigating pharmacokinetics of ocular drugs. However, this approach is limited by physiological differences in the eye between animals and human, ethical issues and poor bench-to-bedside translatability. Cornea-on-a-chip (CoC) microfluidic platforms have gained great attention as one of the advanced in vitro strategies for constructing physiologically representative corneal models. With significant improvements in tissue engineering technology, CoC integrates corneal cells with microfluidics to recapitulate human corneal microenvironment for the study of corneal pathophysiological changes and evaluation of ocular drugs. Such model, in complement to animal studies, can potentially accelerate translational research, in particular the pre-clinical screening of ophthalmic medication, driving clinical treatment advancement for corneal diseases. This review provides an overview of engineered CoC platforms with respect to their merits, applications, and technical challenges. Emerging directions in CoC technology are also proposed for further investigations, to accentuate preclinical obstacles in corneal research.

Multi-Functional Bio-HJzyme: Revolutionizing Diabetic Skin Regeneration with its Glucose-Unlocked Sterilization and Programmed Anti-Inflammatory Effects.

Antibacterial dynamic therapy (ADT) triggered by reactive oxygen species (ROS) is promising for diabetic infectious disease treatment. However, the limited local O2 /H2 O2 production and post-treatment inflammation remain long-standing issues. To address these challenges, a novel H2 -evolving bio-heterojunction enzyme (Bio-HJzyme) consisting of graphite-phase carbon nitride/copper sulfide (CN/Cu2-x S) heterojunction and glucose oxidase (GOx) is created. The Bio-HJzyme offers glutathione peroxidase (GPx), peroxidase (POD), and catalase (CAT) mimetic activities; provides anti-pathogen properties via programmed light activation; and effectively promotes diabetic wound healing. Specifically, its GPx-mimetic activity and the presence of GOx significantly enhance the yield of H2 O2 , which can be catalyzed through POD-mimetic activity to produce highly germicidal •OH. The H2 O2 can also be catalyzed to H2 O and O2 , assisted by the CAT-mimetic activity. The catalyzed products can then be catalyzed into germicidal •OH and •O2 - under NIR light irradiation, giving enhanced ADT. Further, CN can split water to form H2 under solar light, which dramatically suppresses the inflammation caused by excessive ROS. In vivo evaluation confirms that Bio-HJzyme promotes the regeneration of diabetic infectious skin through killing bacteria, enhancing angiogenesis, promoting wound bed epithelialization, and reinforcing anti-inflammatory responses; hence, providing a revolutionary approach for diabetic wounds healing.

Metabolomic analysis of aqueous humor reveals potential metabolite biomarkers for differential detection of macular edema.

BACKGROUND: Macular edema (ME) is a major complication of retinal disease with multiple mechanisms involved in its development. This study aimed to investigate the metabolite profile of aqueous humor (AH) in patients with ME of different etiologies and identify potential metabolite biomarkers for early diagnosis of ME. METHODS: Samples of AH were collected from 60 patients with ME and 20 age- and sex-matched controls and analyzed by liquid chromatography-mass spectrometry (LC/MS)-based metabolomics. A series of univariate and multivariate statistical analyses were performed to identify differential metabolites and enriched metabolite pathways. RESULTS: The metabolic profile of AH differed significantly between ME patients and healthy controls, and differentially expressed metabolites were identified. Pathway analysis revealed that these differentially expressed metabolites are mainly involved in lipid metabolism and amino acid metabolism. Moreover, significant differences were identified in the metabolic composition of AH from patients with ME due to different retinal diseases including age-related macular degeneration (AMD-ME), diabetic retinopathy (DME) and branch retinal vein occlusion (BRVO-ME). In total, 39 and 79 etiology-specific altered metabolites were identified for AMD-ME and DME, respectively. Finally, an AH-derived machine learning-based diagnostic model was developed and successfully validated in the test cohort with an area under the receiver operating characteristic (ROC) curve of 0.79 for AMD-ME, 0.94 for DME and 0.77 for BRVO-ME. CONCLUSIONS: Our study illustrates the potential underlying metabolic basis of AH of different etiologies across ME populations. We also identify AH-derived metabolite biomarkers that may improve the differential diagnosis and treatment stratification of ME patients with different etiologies.

Rapid sterilisation and diabetic cutaneous regeneration using cascade bio-heterojunctions through glucose oxidase-primed therapy.

The cutaneous wound in diabetic patients frequently encounters intractable pathogenic infections due to the hyperglycemia micromilieu which is conducive to bacterial growth and multiplication. Despite the extensive clinical use of antibiotics to treat bacterial infections, the emergence of drug-resistant and super pathogens as well as the potential side effects of antibiotics have elicited alarming challenges to public health. To address this daunting concern, we devise and develop a photo-activated cascade bio-heterojunctions (C-bio-HJs) for rapid sterilization and diabetic cutaneous regeneration. In the designed C-bio-HJs, photo-generated electron-hole pairs of graphite-phase carbon nitride (g-C3N4) are effectively separated with the marriage of molybdenum disulfide (MoS2), which achieves the augmented photodynamic antibacterial effect. Moreover, glucose oxidase (GOx) tethered on the bio-HJs catalyzes glucose into hydrogen peroxide (H2O2) in diabetic wounds for starvation therapy. Furthermore, Mo4+ enables the catalysis of H2O2 into a highly effective hydroxyl radical (·OH) for chemodynamic-photothermal combined antibacterial therapy. Both in vitro and in vivo results authenticate the cascading antibacterial properties and skin regeneration-promoting effects of the C-bio-HJs, which provide a facile strategy to combat diabetic wound healing through the synergistic GOx-primed dynamic therapies.

Photonic double-network hydrogel dressings for antibacterial phototherapy and inflammation regulation in the general management of cutaneous regeneration.

The treatment of festering pathogenic bacteria-induced skin wounds with increased inflammation is an ongoing challenge. The traditional antibacterial photothermal therapy always results in localized hyperthermia (over 50 °C), which inevitably delays tissue recovery. To address this serious issue, we devise a novel photonic hydrogel by integrating urchin-like Bi2S3 nano-heterojunctions (nano-HJs) into double-network hydrogels for infected skin regeneration. The synergy of NIR-triggered heat and ROS enables the hydrogels to achieve a rapid germicidal efficacy against bacteria within 15 min at mild temperature (below 50 °C). In vitro cell analysis results revealed that the photonic hydrogels exhibit superior cytocompatibility even after NIR illumination. More importantly, an in vivo study demonstrated that the photonic hydrogel dressings have a robust ability of accelerating contagious full-thickness wound regeneration through debriding abscesses, eliminating pathogens, improving collagen deposition, promoting angiogenesis, and adjusting the inflammation state. This photonic hydrogel system provides a general management strategy for the remedy of infectious wounds, where the incorporation of nano-HJs endows the hydrogels with the photodisinfection ability; in addition, the multifunctional hydrogels alleviate the damage from overwhelming heat towards surrounding tissues during phototherapy and steer the inflammation during the process of tissue regeneration. Accordingly, this work highlights the promising application of the photonic hydrogels in conquering refractory pathogen-invaded infection.

Lycium barbarum polysaccharide promotes corneal Re-epithelialization after alkaline injury.

Chemical injury of the cornea results in epithelial defect and subsequent stromal scarring and infection. Our study aims to evaluate the effectiveness of pre-treatment of Lycium barbarum polysaccharide (LBP) in promoting corneal re-epithelialization after alkaline burn. The corneas of C57BL/6J mice were pre-treated with topical phosphate-buffered saline or LBP (0.2/2/20 mg/mL) for 7 days, following by 0.1M sodium hydroxide injury for 30 s and washing with distilled water for another 30 s. Area of epithelial defect and thickness of cornea were evaluated. Inflammatory cytokines and water channel expression levels were assessed using immunohistochemistry and Western blot. Compared to the injury group, mice with 2 mg/mL LBP pre-treatment revealed a significant decrease in fluorescein stained area after injury (p = 0.025), with increased epithelial layer thickness (p = 0.004). The corneal opacity was significantly reduced in the group with 2 mg/mL LBP pre-treatment followed by injury (p = 0.02). The expression of matrix metalloproteinase 12 (p = 0.033), platelet derived growth factor-BB (p = 0.031), and aquaporin 5 (p = 0.022) resulted in a decrease in expression level in group with 2 mg/mL LBP pre-treatment. Our results showed that 2 mg/mL LBP, with no apoptotic effect on corneal cells, promoted corneal epithelial growth and minimized disruption of the collagen architecture after injury in vivo. We suggest that LBP, as a natural Traditional Chinese Medicine, may potentially be a novel topical pre-treatment option for patients highly susceptible to ocular injury.

Heterostructured Metal-Organic Frameworks/Polydopamine Coating Endows Polyetheretherketone Implants with Multimodal Osteogenicity and Photoswitchable Disinfection.

Clinically, bacteria-induced contagion and insufficient osseointegrative property inevitably elicit the failure of orthopedic implants. Herein, a heterostructured coating consisting of simvastatin (SIM)-laden metal-organic frameworks and polydopamine nanolayers is created on a porous bioinert polyetheretherketone implant. The heterostructured coating significantly promotes cytocompatibility and osteogenic differentiation through multimodal osteogenicity mechanisms of zinc ion (Zn2+ ) therapy, SIM drug therapy, and surface micro-/nano-topological stimulation. Under the illumination of near-infrared (NIR) light, singlet oxygen (1 O2 ) and local hyperthermia are produced; besides, NIR light dramatically accelerates the release of Zn2+ ions from heterostructured coatings. Gram-positive and -negative bacteria are effectively eradicated by the synergy of photothermal/photodynamic effects and photo-induced accelerated delivery of Zn2+ ions. The superior osteogenicity and osseointegration, as well as photoswitchable disinfection controlled by NIR light are corroborated via in vivo results. This work highlights the great potential of photoresponsive heterostructured orthopedic implants in treatment of the noninvasive bone reconstruction of bacteria-associated infectious tissues through multimodal phototherapy and photoswitchable ion-therapy.

Current and Future Perspectives on Microfluidic Tear Analytic Devices.

Most current invasive analytic devices for disease diagnosis and monitoring require the collection of blood, which causes great discomfort for patients and may potentially cause infection. This explains the great need for noninvasive devices that utilize other bodily fluids like sweat, saliva, tears, or urine. Among them, eye tears are easily accessible, less complex in composition, and less susceptible to dilution. Tears also contain valuable clinical information for the diagnosis of ocular and systemic diseases as the tear analyte level shows great correlation with the blood analyte level. These unique advantages make tears a promising platform for use in clinical settings. As the volume of tear film and the rate of tear flow are only microliters in size, the use of microfluidic technology in analytic devices allows minimal sample consumption. Hence, more and more microfluidic tear analytic devices have been proposed, and their working mechanisms can be broadly categorized into four main types: (a) electrochemical, (b) photonic crystals, (c) fluorescence, and (d) colorimetry. These devices are being developed toward the application of point-of-care tests with rapid yet accurate results. This review aims to provide a general overview of the recent developmental trend of microfluidic devices for tear analysis. Moreover, the fundamental principle behind each type of device along with their strengths and weaknesses will be discussed, especially in terms of their abilities and potential in being used in point-of-care settings.

Scaffold-Free Strategy Using a PEG-Dextran Aqueous Two-Phase-System for Corneal Tissue Repair.

Forming thin tissue constructs with minimal extracellular matrix surrounding them is important for tissue engineering applications. Here, we explore and optimize a strategy that enables rapid fabrication of scaffold-free corneal tissue constructs using the liquid-liquid interface of an aqueous two-phase system (ATPS) that is based on biocompatible polymers, dextran and polyethylene glycol. Intact tissue-like constructs, made of corneal epithelial or endothelial cells, can be formed on the interface between the two liquid phases of ATPS within hours and subsequently collected simply by removing the liquid phases. The formed corneal cell constructs express essential physiological markers and have preserved viability and proliferative ability in vitro. The corneal epithelial cell constructs are also able to re-epithelialize the corneal epithelial wound in vitro. The results suggest the promise of our reported strategy in corneal repair.

Virtual reality and augmented reality- emerging screening and diagnostic techniques in ophthalmology: A systematic review.

In health care, virtual reality (VR) and augmented reality (AR) have been applied extensively for many purposes. Similar to other technologies such as telemedicine and artificial intelligence, VR and AR may improve clinical diagnosis and screening services in ophthalmology by alleviating current problems, including workforce shortage, diagnostic error, and underdiagnosis. In the past decade a number of studies and products have used VR and AR concepts to build clinical tests for ophthalmology, but comprehensive reviews on these studies are limited. Therefore, we conducted a systematic review on the use of VR and AR as a diagnostic and screening tool in ophthalmology. We identified 26 studies that implemented a variety of VR and AR tests on different conditions, including VR cover tests for binocular vision disorder, VR perimetry for glaucoma, and AR slit lamp biomicroscopy for retinal diseases. In general, while VR and AR tools can become standardized, automated, and cost-effective tests with good user experience, several weaknesses, including unsatisfactory accuracy, weak validation, and hardware limitations, have prevented these VR and AR tools from having wider clinical application. Also, a comparison between VR and AR is made to explain why studies have predominantly used VR rather than AR.

A systematic review of multimodal clinical biomarkers in the management of thyroid eye disease.

Thyroid Eye Disease (TED) is an autoimmune disease that affects the extraocular muscles and periorbital fat. It most commonly occurs with Graves' Disease (GD) as an extrathyroidal manifestation, hence, it is also sometimes used interchangeably with Graves' Ophthalmopathy (GO). Well-known autoimmune markers for GD include thyroid stimulating hormone (TSH) receptor antibodies (TSH-R-Ab) which contribute to hyperthyroidism and ocular signs. Currently, apart from radiological investigations, detection of TED is based on clinical signs and symptoms which is largely subjective, with no established biomarkers which could differentiate TED from merely GD. We evaluated a total of 28 studies on potential biomarkers for diagnosis of TED. Articles included were published in English, which investigated clinical markers in tear fluid, orbital adipose-connective tissues, orbital fibroblasts and extraocular muscles, serum, thyroid tissue, as well as imaging biomarkers. Results demonstrated that biomarkers with reported diagnostic power have high sensitivity and specificity for TED, including those using a combination of biomarkers to differentiate between TED and GD, as well as the use of magnetic resonance imaging (MRI). Other biomarkers which were upregulated include cytokines, proinflammatory markers, and acute phase reactants in subjects with TED, which are however, deemed less specific to TED. Further clinical investigations for these biomarkers, scrutinising their specificity and sensitivity on a larger sample of patients, may point towards selection of suitable biomarkers for aiding detection and prognosis of TED in the future.