Confocal laser scanning microscope enables non-invasive ocular Demodex screening but faces field-of-view (FOV) limitations. Although image stitching can theoretically expand FOV, traditional methods only achieve approximately 60% success rate due to low illumination, weak textures and repetitive patterns. To address these challenges, we propose an unsupervised deep learning-based image stitching framework with dual-stage alignment and generative adversarial network (GAN)-based fusion. Our dual-stage alignment network combines homography matrix and Thin Plate Spline (TPS) transformations to accommodate tissue deformation during imaging, supported by a Non-Maximum Suppression Feature Displacement Layer that simultaneously considers both long-range and short-range dependencies, yielding more accurate results with reduced memory consumption. To achieve smooth and seamless image fusion, we employ a GAN framework where the generator is designed to produce fusion probability maps that eliminate noticeable blending seams and fusion artifacts. This is an innovative attempt to apply deep learning for precise image stitching in confocal superficial eyelid image, demonstrating 40% higher success rate than traditional methods. Quantitative evaluations show 13.37% and 3.25% improvements in mPSNR and mSSIM over the state-of-the-art model, with 11.29% and 3.76% reductions in NIQE and PIQE metrics.

Objective: The scleral spur is a key anatomical landmark in the anterior chamber and serves as the reference point for multiple biometric parameters in glaucoma assessment. Accurate and efficient localization of the scleral spur is essential for reliable anterior chamber angle measurements and early glaucoma diagnosis. Methods: A novel AS-U2-Net framework is presented for automated scleral spur localization in AS-OCT images. The model enhances the original U2-Net architecture through reduced downsampling and the integration of anatomical attention mechanisms to emphasize features around the cornea-sclera junction. An adaptive sigma strategy is employed to dynamically adjust Gaussian heatmap dispersion during training, improving convergence stability and localization precision. In addition, Fast Gradient Sign Method (FGSM) adversarial augmentation is incorporated to strengthen robustness against distributional variations. A YOLOv5-based region-of-interest (ROI) extraction module is further utilized to suppress irrelevant structures and focus the network on clinically meaningful regions. Results: The proposed AS-U2-Net achieves a 27.61% improvement in localization accuracy compared with the baseline U2-Net. On external multi-center datasets, models trained with the proposed training strategy demonstrate a 28.6%-33.7% accuracy gain over conventional approaches, indicating superior generalization capability. Conclusion: The AS-U2-Net delivers precise and stable scleral spur localization, outperforming existing deep learning methods in both in-domain and cross-domain evaluations. Significance: By combining anatomical awareness with adaptive training strategies, the proposed framework offers strong potential for integration into clinical workflows, supporting automated anterior chamber analysis and enhancing decision-making in glaucoma screening and surgical planning.

Meniscus injuries are difficult to heal because of the limited vascularization and intrinsic structural heterogeneity of native meniscal tissue. Although 3D bioprinting has emerged as a promising strategy for meniscus tissue engineering, most existing scaffolds remain homogeneous and fail to recapitulate the zonal mechanical and biological characteristics of the native meniscus. In this study, a dual-nozzle 3D bioprinting strategy was developed to fabricate a biomimetic heterogeneous meniscus scaffold with region-specific mechanical and biological properties. Two hydrogel-based bioinks with distinct physicochemical and rheological characteristics were designed to mimic the inner and outer regions of the native meniscus. By integrating region-specific bioinks and cell-laden printing through a dual-nozzle extrusion system, heterogeneous meniscus scaffolds with stable structural fidelity and controllable spatial distribution were successfully fabricated. Rheological analysis demonstrated favorable shear-thinning behavior and printability of both bioinks, enabling continuous extrusion and shape maintenance during the printing process. Mechanical characterization and atomic force microscopy further confirmed the successful establishment of zonal mechanical heterogeneity within the printed constructs. In vitro biological evaluations showed that the bioprinted scaffolds supported high cell viability, sustained proliferation, and favorable cytoskeletal spreading during long-term culture. More importantly, region-specific extracellular matrix expression was observed, with significantly enhanced type I collagen expression in the outer region and elevated type II collagen expression in the inner region, consistent with the native meniscal phenotype. Overall, this study demonstrates that dual-nozzle 3D bioprinting can effectively reconstruct the zonal mechanical and biological heterogeneity of native meniscus tissue. The proposed heterogeneous hydrogel scaffold provides a promising in vitro platform for investigating biomimetic meniscus tissue engineering and may serve as a foundation for future in vivo studies.

Purpose:The purpose of this study was to develop an optimized treatment for pathological myopia: a degradable cell-free suture-free tissue scaffold implant that reverses the excessive axial elongation and induces a therapeutic ridge. Methods:A form-deprivation (FD) myopia model was established in New Zealand White rabbits. Comprised of gelatin methacryloyl and a poly-L-lactide microfiber film, the tissue scaffold was implanted onto the posterior sclera of FD eyes (model + implant group; n =12), compared with model-only (n = 12) and controls eyes (n = 24). Ocular dimensions were monitored via ultrasound. Safety was assessed by electroretinogram, intraocular pressure, and apoptosis assays. The histology structure of regenerated tissue and sclera was shown. Results:The axial length in model + implant eyes was significantly shorter than model-only eyes and the control eyes since 2 weeks after the implantation (13.79 ± 0.23 mm, 15.15 ± 0.33 mm, and 14.70 ± 0.18 mm, P < 0.001) and maintained. The scaffold prompted the in situ regeneration of tissue mimicking the pseudo-lamellar arrangement of collagen fibers and major cell types found in native sclera, which formed an inward therapeutic ridge at the posterior sclera. The simulation indicated the ridge relieved outward macular traction significantly with minimum perturbation to stress distribution outside the central macula. Furthermore, collagen synthesis was prompted within the sclera itself. Conclusions:This innovative strategy, which avoids the long-term complications of foreign body compression, suturing, or tension fixation, effectively reversed myopic eye elongation and induced a therapeutic ridge. Translational Relevance:Demonstration of a degradable scaffold implantation as a treatment for pathological myopia with potential for minimally invasive clinical application was presented.

Objective Optical coherence tomography (OCT) is a powerful imaging modality widely used for ophthalmic diagnosis owing to its high resolution and noninvasive nature. However, the practical deployment of conventional tabletop OCT systems is largely restricted by their bulky size, high cost, and limited flexibility, which hinders their application in primary care, mobile medicine, and home-based screening scenarios. In recent years, various portable and handheld OCT systems have been reported, yet many of them still face challenges in imaging performance, system integration, operational automation, and robustness under real-world conditions. In this study, we develop a compact suitcase-type portable OCT system (OCT-BOX) to balance imaging quality, miniaturization, and ease of use. By integrating a compact optical engine, a miniaturized spectrometer, a micro-electro-mechanical system (MEMS)-based scanning probe, and an automatic alignment strategy, the system is designed to operate under strict constraints of volume and power consumption. This work demonstrates that portable OCT systems can achieve imaging performance comparable to desktop devices while significantly improving accessibility and deployment flexibility. Methods This system is designed to meet the requirements of portable ophthalmic examinations in primary care and mobile screening scenarios and adopts a spectral-domain OCT (SD-OCT) architecture optimized for retinal imaging. The system consists of a light source and optical coupling module, a miniaturized spectrometer, a MEMS-based imaging probe, a data acquisition and processing unit, as well as timing control, human-machine interaction, and data storage modules. In the imaging pathway, the interferometric signal returning from the sample arm is sampled by a line-scan detector after spectral dispersion in the miniaturized spectrometer. Subsequent k-linearization, windowing, and fast Fourier transform (FFT) processing are performed to generate B-scan images or three-dimensional volumetric datasets. In parallel, the control pathway unifies scanning and exposure timing through hardware triggering to ensure stable and synchronized image acquisition. To accommodate the strict constraints on volume and power consumption imposed by the suitcase-type form factor, three key architectural design principles are adopted. 1) Modular optical functions with co-referenced encapsulation: Core optical functions, including the reference arm, optical coupling, and optical path difference (OPD) adjustment, are integrated into a palm-sized "optical engine." Short free-space propagation lengths and a rigid housing are employed to enhance vibration resistance and optical path reproducibility. 2) Customized layout of the miniaturized spectrometer: A single-fold optical configuration is introduced into a conventional collimation-dispersion-imaging spectrometer design, enabling a slender, elongated form factor without compromising imaging quality or k-space sampling uniformity. This layout is well suited to the spatial and mounting constraints of the suitcase enclosure. 3) Co-design of scanning and alignment in a compact probe: The imaging probe combines multi-stage beam folding with dual-axis MEMS scanning, while a two-dimensional micro-travel automatic alignment mechanism is realized by actuating only the front optical element. This design allows stable pupil coverage and consistent visual-axis alignment to be achieved without the need for fine manual adjustments by the operator. Results and Discussions The OCT-BOX system fabricated in small-batch production is shown. To evaluate in vivo imaging performance, macular B-scan images are acquired from three healthy volunteers using both the OCT-BOX system and a commercial tabletop SD-OCT device. For each comparison, images are obtained from the same eye of the same subject, with the scanning range and acquisition parameters kept as consistent as possible to minimize inter-subject variability and operator-dependent effects. The OCT-BOX system clearly resolves major retinal microstructures, including the retinal nerve fiber layer (RNFL), the boundaries between the inner and outer plexiform layers, and the continuity of the ellipsoid zone (EZ) and retinal pigment epithelium (RPE) complex. The overall layer contrast and structural delineation are comparable to those of the tabletop system. A closer inspection indicates that near the maximum imaging depth, the commercial system exhibits slightly better sensitivity roll-off and local contrast; however, under the constraints of compact size and limited power consumption, the in vivo image quality achieved by OCT-BOX is sufficient for structural assessment in primary screening and follow-up applications. To reduce the uncertainty associated with purely subjective visual comparison, the image entropy and local signal-to-noise ratio (SNR) are further employed for objective quantitative evaluation of the images. Image entropy characterizes the effective information content and structural complexity of tomographic images, while local SNR reflects the distinguishability of intra-layer details from the noise background. Both systems exhibit comparable values for these metrics, indicating that OCT-BOX achieves a noise level and structural fidelity similar to those of the tabletop SD-OCT system, thereby providing quantitative support for the visual observations. In terms of real-time performance and automation, the OCT-BOX system enables continuous B-scan refresh in preview mode, allowing operators to monitor cross-sectional changes during alignment. In volumetric acquisition mode, a typical 6 mm & times; 6 mm dataset is acquired within 3 s, with reconstruction and display completed shortly after acquisition. Combined with iris-based centering and automatic interferometric signal searching, the automated workflow achieves an interferometric signal detection rate of approximately 98.7% across representative subjects, with average alignment time of approximately 1.8 s. These results demonstrate that, despite stringent constraints on system size and power consumption, the proposed system provides interaction efficiency and one-click operation comparable to those of tabletop SD-OCT devices, making it well suited for mobile screening and home-visit examinations. Conclusions In this work, a compact suitcase-type ophthalmic OCT system with full opto-mechatronic-computational integration is developed. By incorporating an optical engine with an encapsulated reference arm, a single-fold miniaturized spectrometer, a MEMS-based scanning probe operating at small incidence angles, and an automated alignment strategy, the proposed system achieves imaging quality and user experience comparable to those of conventional tabletop SD-OCT devices under strict constraints of size, power consumption, and mechanical stability. Comparative experiments show that the system provides similar imaging depth, layer resolution, and visualization of key retinal microstructures, indicating that it is suitable for primary screening and mobile ophthalmic applications. Future work focuses on further miniaturization and customization of the spectrometer to reduce the overall system volume and enhance environmental robustness. Meanwhile, the computing platform is transitioned from a computer to a more highly integrated, low-power embedded architecture to improve portability and deployment flexibility. In addition, faster scanning modes, OCT angiography (OCTA) capability, and artificial intelligence (AI)-based image enhancement and disease screening algorithms are explored to further expand the potential applications of the system in primary healthcare and public health settings.

Untethered magnetic actuators offer a promising platform for minimally invasive surgery due to their compact size, mechanical compliance, multifunctionality, and remote controllability. However, the structural simplicity imposed by current construction strategies limits their operational versatility to leverage established surgical paradigms, and systematic studies of locomotion across the variable viscosities of bodily fluids remain scarce. Herein, we introduce an interference-fit assembly strategy that couples stereolithographic 3D-printed microstructures with customized magnetic pixels to fabricate submillimeter-scale untethered magnetic actuators. Theoretical and experimental analyses in model-fluid environments spanning physiologically relevant viscosity ranges demonstrate that, once above the critical magnetic flux density required for stable motion, the locomotion velocity scales linearly with the driving frequency. The velocity-frequency slope exhibits a hyperbolic dependence on ambient viscosity, enabling semi-quantitative viscosity sensing concurrently with motion and functional execution. Furthermore, we showcase multifunctional on-demand manipulation capabilities: enhanced diffusion and directional transport with qualitative viscosity sensing; in situ quantitative viscosity measurement inspired by a rotational viscometer; mechanical fragmentation via continuous rotation; and a rigid-soft synergistic magnetic gripper for targeted cargo capture and delivery. Collectively, this strategy establishes a versatile and scalable paradigm for designing multifunctional, untethered, submillimeter‑scale magnetic actuators with prospective potential for biomedical applications.

Continuous and non-invasive intraocular pressure (IOP) monitoring is crucial for managing glaucoma, a leading cause of irreversible blindness worldwide. However, existing tonometry methods are intermittent and lack the capability to capture dynamic IOP fluctuations. Herein, we present a highly sensitive, wireless contact lens (WCL) sensor based on a dual-spiral inductor-capacitor-resistor (LCR) resonator for real-time IOP monitoring. The sensor features an axisymmetric anti-parallel spiral architecture that synergistically enhances capacitive coupling and suppresses inductive mutual coupling, thereby amplifying the resonant frequency shift in response to corneal biomechanical deformation. Furthermore, a gradient line-width strategy is implemented to minimize resistive loss, concentrate charge density, and improve mechanical robustness. Systematic evaluations on a biomimetic eyeball platform and ex vivo porcine eyes demonstrate high sensitivity, with values of -1.839 MHz mmHg(-1) and -0.69 MHz mmHg(-1), respectively. These results highlight the potential of the WCL as a robust and scalable platform for continuous, non-invasive IOP monitoring in glaucoma management.

Untethered magnetic actuators hold great promise for minimally invasive medicine, yet reconciling functional versatility with simple, reliable control remains a critical challenge. To address this, we introduce a modular design paradigm that employs revolute joints to interconnect discrete rigid modules. This strategy synergizes the mechanical robustness of rigid systems with the reconfigurability of soft robots, imparting additional degrees of freedom that enable complex, on-demand deformations. We demonstrate this approach through articulated prototypes capable of executing diverse locomotion strategies, including crawling and rolling, while leveraging on-demand mode switching to perform functional tasks such as cargo transportation, stirring and release. A critical advantage is that all locomotion and mode transitions are driven by a single, uniform magnetic field, thereby decoupling control from function and simplifying the system architecture. The robustness of the mechanism is confirmed through mathematical simulations and a dimensionless analysis that validates its feasibility across scales. The platform’s versatility is ultimately demonstrated by its high-dexterity navigation through a tortuous vascular phantom and its successful execution of targeted cargo delivery within an ex vivo porcine stomach model. This work establishes a readily controllable and scalable framework for designing multifunctional magnetic robots, paving the way for high-precision operations within complex biological environments.

OBJECTIVE:To evaluate the efficacy and safety of portable, cost-effective manual thermal pulsation as a single therapy for meibomian gland dysfunction (MGD) and to compare the microbiota and lipid composition in subjects with different therapeutic efficacy. METHODS AND ANALYSIS:In this single-centre, randomised, positive-controlled clinical trial, 84 subjects were randomly assigned (1:1) to receive a single treatment of manual (self-developed device) or automatic (Lipiflow) thermal pulsation and followed up for 4 weeks, 76 of which were finally analysed. Efficacy was evaluated by Δ Meibomian Gland Score (MGS) (Δ variable=parameter at follow-up-parameter at baseline), Δ non-invasive break-up time (NIBUT), Δ standard patient evaluation of eye dryness (SPEED), Δ Meibomian Gland Expressibility Score (MES) and Δ corneal fluorescein staining (CFS), with safety investigated. Subjects who underwent manual thermal pulsation were further divided into two subgroups based on whether ΔMGS ≥-2, meibum microbiome and lipid metabolomics in the subgroups were analysed. RESULTS:ΔMGS, ΔNIBUT, ΔSPEED, ΔMES and ΔCFS were not significantly different between manual and automatic thermal pulsation groups in 4 weeks (both p>0.05), indicating non-inferior efficacy of manual thermal pulsation. No serious ocular or device-related adverse events were reported. A more complex meibum microorganism diversity and 46 differentially expressed lipids (such as triglycerides, diglycerides, ceramides and oxidised species) were identified in those with a relatively weak therapeutic efficacy. CONCLUSIONS:Portable, cost-effective manual thermal pulsation demonstrated non-inferiority to automatic thermal pulsation for MGD during the 4-week follow-up period, with therapeutic efficacy associated with meibum micro-organism and lipid components.

Dysthyroid optic neuropathy (DON) represents a severe ocular complication in thyroid eye disease (TED) that can lead to vision loss. Although surgical decompression is a well-established treatment modality, the optimal decompression area remains controversial in orbital decompression surgery. Purpose: This study aims to develop and validate a finite element analysis (FEA) model of DON to compare the biomechanical behavior between patients undergoing conventional or augmented orbital decompression surgery, with potential clinical implications for surgical planning. Methods: FEA models were established using magnetic resonance imaging data from patients with myopathic TED. Pre-disease, preoperative, and postoperative FEA models were developed for both the conventional orbital decompression group and the augmented group, in which the posteromedial floor and the orbital process of the palatine bone were additionally removed to analyze the stress distribution and displacement of the optic nerve, eyeball, and orbital wall. A retrospective analysis was performed to validate the biomechanical analysis results. Results: The FEA results reveal that DON patients experience higher stress on the optic nerve, eyeball, and orbital wall than healthy individuals, mainly concentrated at the orbital apex. Postoperatively, the stress on the optic nerve was significantly reduced in both groups. In addition, postoperative stress on the optic nerve was significantly lower in the augmented group than in the conventional group. The clinical results demonstrate that patients in the augmented group experienced significantly faster and more pronounced improvements in visual acuity and visual field. Conclusions: FEA shows that augmented orbital decompression surgery can alleviate stress more effectively, especially for the optic nerve, which was validated by clinical analysis. This developed FEA model of DON may facilitate determining the appropriate surgical procedure for orbital decompression.

To propose and evaluate a novel, non-invasive approach for enduring corneal astigmatism correction based on topography-guided, patterned, customized riboflavin-ultraviolet A corneal collagen crosslinking (CXL). Astigmatism was modelled on both eyes of rabbits. A randomly selected eye of each rabbit was treated by the proposed CXL procedure with another eye as control. The proposed procedure was performed by a self-built intelligent platform through delivering ultraviolet A lattice in a refined and patterned manner, based on pre-operative corneal topography. The long-term effectiveness, stability, and safety were investigated for 180 days, with topographic measurements, anterior segment optical coherence tomography (AS-OCT), and in vivo corneal confocal microscopy (IVCM). Spatially selective demarcation lines in AS-OCT images and trabecular patterned hyperdense structure with abundant needle-like processes in IVCM images were detected in the CXL eyes, revealing spatially selective crosslinking. Reductions of astigmatic magnitude (in the steep axis: 0.46 ± 0.28 vs. 2.15 ± 0.58 dioptres, P < 0.001) and high order aberration (0.38 ± 0.18 vs. 0.59 ± 0.19, P = 0.009) with increase of visual strehl ratio (0.21 ± 0.06 vs. 0.13 ± 0.03, P < 0.001) were found in the CXL eyes after CXL and maintained for 180 days, compared to inconspicuous changes in the control eyes. No obvious opacity and inflammation were observed in the CXL eyes, and transient loss of endothelial cells in the treated area was recovered in the subsequent visit. The proposed novel, non-invasive approach safely fulfilled corneal astigmatism correction with visual quality improvement as well as a decrease in high-order aberration.

Gouty arthritis may cause meniscal damage, necessitating surgery for meniscus replacement. However, the meniscus remains at risk of urate crystal accumulation and oxidative stress post-surgery. To tackle this challenge, we developed tri-level bionic menisci that achieve an integrated material-structure-functionality design. Its gradient network mimics natural structures, providing biomechanical adaptation and functioning as a porous catalyst carrier to load multifunctional nanozymes to eliminate excess uric acid and oxyradicals. Specifically, we utilized 3D printing to incorporate Pt-CeO2 nanozymes within the meniscus scaffold and designed a bionic structure driven by biomechanical data of the articular cavity. The Pt-CeO2 demonstrated significant catalytic efficacy in promoting the oxidation of uric acid while concurrently scavenging reactive oxygen and nitrogen species. DFT+U calculations revealed the synergistic catalytic mechanism at Pt-Ov-Ce sites. We elucidated the catalytic therapeutic mechanism of the bionic menisci. Furthermore, we developed a regulatory model capable of modulating intra-articular uric acid concentration to accommodate the varied requirements of different patients. These findings underscore the potential of the bionic menisci in personalized treatment for gouty arthritis.

Nucleic acid detection is an important tool for clinical diagnosis. The purification of the sample is the most time-consuming step in the nucleic acid testing process and will affect the results of the assay. Here, we developed a surface modification-based nucleic acid purification method and designed an accompanying set of centrifugation equipment and chips to integrate the steps of nucleic acid purification on a single platform. The results of experiments with HeLa cells and HPV type 16 as samples showed that the mentioned method had good nucleic acid purification capability and the accompanying equipment greatly simplified the operation of the experimenters in the whole process. Overall, our equipment can improve the efficiency of nucleic acid purification and is suitable for application in larger-scale clinical assays.

Magnetic soft actuators and robots have attracted considerable attention in biomedical applications due to their speedy response, programmability, and biocompatibility. Despite recent advancements, the fabrication process of magnetic actuators and the reprogramming approach of their magnetization profiles continue to pose challenges. Here, a facile fabrication strategy is reported based on arrangements and distributions of reusable magnetic pixels on silicone substrates, allowing for various magnetic actuators with customizable architectures, arbitrary magnetization profiles, and integration of microfluidic technology. This approach enables intricate configurations with decent deformability and programmability, as well as biomimetic movements involving grasping, swimming, and wriggling in response to magnetic actuation. Moreover, microfluidic functional modules are integrated for various purposes, such as on/off valve control, curvature adjustment, fluid mixing, dynamic microfluidic architecture, and liquid delivery robot. The proposed method fulfills the requirements of low-cost, rapid, and simplified preparation of magnetic actuators, since it eliminates the need to sustain pre-defined deformations during the magnetization process or to employ laser heating or other stimulation for reprogramming the magnetization profile. Consequently, it is envisioned that magnetic actuators fabricated via pixel-assembly will have broad prospects in microfluidics and biomedical applications. This study proposes a fabrication strategy called "pixel-assembly" to construct magnetic actuators with reprogrammable magnetic configurations and integrated microfluidic functional modules. The pixel-assembled magnetic actuators implement various structures with reasonable deformability, biomimetic movements with high maneuverability, and multiple microfluidic applications such as fluid manipulation, dynamic microfluidic architectures, and the liquid-delivery robot. image

A multi-step PDMS curing method and a local PDMS separation strategy were proposed to achieve mass, standardized, and low-cost manufacturing of valved micropumps, satisfying a wider range of fluid-driven applications.

Recently, significant progress has been made in the field of flexible bulk metamaterials composed of soft and elastic materials, unlocking the potential for achieving programmable non-linear mechanical responses, such as shape morphing, energy absorption, and information processing. However, the majority of these metamaterials utilize expensive hyperelastic materials and require complex fabrication processes. Additionally, constructing eco-friendly stiff constituents for these metamaterials remains challenging due to their limited elastic limit strains (<0.1). Here, we propose a systematic design strategy by combining curved beams with chiral metastructures to generate a family of three-dimensional programmable resilient mechanical metamaterials without relying on flexible or hyperelastic constituents. These tiled metamaterials demonstrate robust, anisotropic and non-linear resilience under large elastic compression strains (>0.75), while exhibiting a programmable effective modulus reduction of nearly 6 orders of magnitude compared to the native stiff components. Furthermore, leveraging their stable resilience under high-frequency stimuli, we successfully developed a meter-scale soft robot capable of traversing complex narrow scenarios on demand without the need for flexible materials or sophisticated pipelines. We anticipate that these mechanical metamaterials could serve as a universal platform for programmable active dampers, modular flexible robots, and medical rehabilitation equipment at various scales.

Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries. Corneal scars such as leukoplakia are formed due to inflammation, oxidative stress and non-directed repair, which seriously affect the patients' subsequent visual and life quality. In this study, drawing inspiration from the oriented structure of collagen fibers within the corneal stroma, we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning. It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer. The results showed that it effectively inhibited Candida albicans, Aspergillus Niger, Fusarium sapropelum, which mainly affects TNF, NF-kappa B, and HIF-1 signaling pathways, achieving effective antifungal functions. More importantly, the fibroblasts interacted with extracellular matrix (ECM) of corneal stroma through formation of focal adhesions, promoted the proliferation and directional migration of cells in vitro, induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo. This process is mainly associated with MYLK, MYL9, and ITGA3 molecules. Furthermore, the downregulation the growth factors TGF-β and PDGF-β inhibits myofibroblast development and reduces scar-type ECM production, thereby reducing corneal leukoplakia. It also activates the PI3K-AKT signaling pathway, promoting corneal healing. In conclusion, the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers, inhibits inflammation, eliminates reactive oxygen species, and reduces corneal leukoplakia, which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.

Embedded bioprinting enables direct deposition of bioinks in three dimensions inside a support bath with shear-thinning and self-healing capabilities, and it has been used to fabricate complex tissues and organs for several biomedical applications. In this study, a support bath comprising gelatin/alginate microparticles and oxidized alginate solution was developed and crosslinked in situ with carbonyl hydrazide-modified gelatin bioink via the Schiff base reaction. The numerical model of embedded printing was established to analyze the extrusion process and disturbance of the support bath. The process window (e.g., extrusion pressure, nozzle moving speed, nozzle size, and support bath composition) was established experimentally to ensure stable fiber formation. In addition, the compressive modulus of the printed construct has been reinforced due to the formation of interpenetrating polymer networks in the microparticles. Based on the process investigation, a zonally stratified artificial cartilage with a three-layered structure was designed: vertically printed fibers in the bottom, oblique fibers in the middle, and horizontally printed fibers in the superficial layer. The bioprinted cartilage supported cell survival, proliferation, and spreading, with the observed deposition of cartilage-specific proteins, offering a new strategy for developing tissue-engineered cartilage constructs with biological and histological relevance.

Objective: Infection by Demodex mites is a significant factor in causing blepharitis. The collected superficial eyelid tissue images currently have low resolution and strong noise. High-quality reconstruction of low-quality images is needed to assist ophthalmologists in accurately and quickly diagnosing mite infestations. Methods: We propose a novel GAN-based super-resolution reconstruction model. We utilize Residual-in Residual Dense Blocks (RRDB) as the fundamental building units and employ high-order degradation to simulate real-world degradation. Additionally, we introduce a new attention mechanism, All Attention Mechanism (AAM), which effectively captures and utilizes crucial image features, expanding the scope of utilized pixels. This significantly enhances the quality of reconstructed images. Results: Compared to existing super-resolution reconstruction models, our model demonstrates the strongest generalization ability and robustness. On the CIDMG and FMD datasets, we achieve the lowest NIQE and the highest SSIM values. Our model outperforms the SOTA SwinIR model, reducing reconstruction time by 76% and improving the image quality by 6.6% for low-noise images and 15.3% for high-noise images. Conclusion: By combining GAN with AAM, we have significantly improved the model's generalization ability, robustness, and real-time performance. Significance: This is the first time that domain generalization has been used for reconstructing superficial eyelid tissue images. The stable and fast reconstruction performance reduces the impact of noise and low resolution on image quality, significantly reducing examination time and improving diagnostic accuracy. This greatly enhances the clinical utility of confocal microscopy for eyelid demodex examination.