Bioprinted, spatially defined breast tumor microenvironment models of intratumoral heterogeneity and drug resistance.

Cellular, extracellular matrix (ECM), and spatial heterogeneity of tumor microenvironments (TMEs) regulate disease progression and treatment efficacy. Developing in vitro models that recapitulate the TME promises to accelerate studies of tumor biology and identify new targets for therapy. Here, we used extrusion-based, multi-nozzle 3D bioprinting to spatially pattern triple-negative MDA-MB-231 breast cancer cells, endothelial cells (ECs), and human mammary cancer-associated fibroblasts (HMCAFs) with biomimetic ECM inks. Bioprinted models captured key features of the spatial architecture of human breast tumors, including varying-sized dense regions of cancer cells and surrounding microvessel-rich stroma. Angiogenesis and ECM stiffening occurred in the stromal area but not the cancer cell-rich (CCR) regions, mimicking pathological changes in patient samples. Transcriptomic analyses revealed upregulation of angiogenesis-related and ECM remodeling-related signatures in the stroma region and identified potential ligand-receptor (LR) mediators of these processes. Breast cancer cells in distinct parts of the bioprinted TME showed differing sensitivities to chemotherapy, highlighting environmentally mediated drug resistance. In summary, our 3D-bioprinted tumor model will act as a platform to discover integrated functions of the TME in cancer biology and therapy.

Oriented cellulose hydrogel: Directed tissue regeneration for reducing corneal leukoplakia and managing fungal corneal ulcers.

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-ß and PDGF-ß 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.

Programmable and resilient metamaterials with anisotropic and non-linear mechanical responses composed exclusively of stiff constituents.

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.

Reprogrammable Magnetic Soft Actuators with Microfluidic Functional Modules via Pixel-Assembly.

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.

Multi-step PDMS curing and a controlled separation method for mass manufacturing of high-performance and user-friendly micro-devices: valved micropumps.

Although valved micropumps have powerful performance, their popularized application is limited by high technical barriers and high costs brought by complex microstructures. Herein, we propose a multi-step PDMS curing method and a local PDMS separation strategy to achieve mass, standardized, and low-cost manufacturing of valved micropumps, solving their popularized problems by promoting role separation between manufacturers and users. The multi-step curing and the centralized structural layout enable a volume 20 times smaller than other valved micropumps. The lithography mold quality is the main reason for only 74% yield, and using metal molds would be a better alternative. Theoretical analysis shows that the thickness and diameter of the pump membrane are the main factors in designing different driving capabilities of the micropump. By driving the micropump through periodic fluid pressure, the results show that the flow rate is positively related to the input pressure and exhibits two flow rate formation mechanisms at high and low frequencies. Its powerful back pressure generating ability also indicates that the micropump has wide application prospects as injection pumps. The micropump also demonstrates tremendous flexibility and convenience in integration, driving, and application. The multi-step PDMS curing and controlled separating ideas show popularization value for other microfluidic components, such as one-way valves, hoping to innovate the microfluidics field.

Integrated nucleic acid purification technology based on amino-modified centrifugal microfluidic chip.

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.

Modular design of curved beam-based recyclable architected materials.

Advances in manufacturing technologies have enabled architected materials with unprecedented properties. These materials are typically irreversibly designed and fabricated with characteristic geometries and specific mechanical properties, thus rendering them suitable for pre-specified requests. However, these materials cannot be recycled or reconstructed into different shapes and functionalities to economically adapt to various environments. Hence, we present a modular design strategy to create a category of recyclable architected materials comprising elastic initially curved beams and rigid cylindrical magnets. Based on numerical analyses and physical prototypes, we introduce an arc-serpentine curved beam (ASCB) and systematically investigate its mechanical properties. Subsequently, we develop two sets of hierarchical modules for the ASCB, thus expanding the constructable shape of architected materials from regular cuboids to complex curved surfaces. Furthermore, we demonstrate that the magnets attached to the centers of specific serpentine patterns of the modules allows the effective in-situ recycling of the designed materials, including sheet materials for non-damage storage, bulk materials for tunable stiffness, and protective package boxes for reshaping into decorative lampshades. We expect our approach to improve the flexibility of architected materials for multifunctional implementation in resource-limited scenarios.

Biofabrication of Composite Tendon Constructs with the Fibrous Arrangement, High Cell Density, and Enhanced Cell Alignment.

Current tissue-engineered tendons are mostly limited to the replication of fibrous organizations of native tendons, which lack the biomimicry of a densely packed cell arrangement. In this study, composite tendon constructs (CTCs) with fibrous arrangement, high cell density, and enhanced cell alignment were developed by integrating the electrohydrodynamic jet 3D printing (e-jetting) technique and the fabrication of tissue strands (TSs). A tubular polycaprolactone (PCL) scaffold was created using e-jetting, followed by coating a thin layer of alginate. Human mesenchymal stem cells were then microinjected into the PCL scaffolds, aggregated into TSs, and formed CTCs with a core-shell structure. Owing to the presence of TSs, CTCs demonstrated the anatomically relevant cell density and morphology, and cells migrated from the TSs onto e-jetted scaffolds. Also, the mechanical strength of CTCs approached that of native tendons due to the existence of e-jetted scaffolds (Young's modulus: ∼21 MPa, ultimate strength: ∼5 MPa). During the entire culture period, CTCs maintained high survival rates and good structural integrity without the observation of necrotic cores and disintegration of two portions. In addition, CTCs that were cultured with uniaxial cyclic stretching revealed not only the increased expression of tendon-related proteins but also the enhanced cellular orientation. The promising results demonstrated the potential of this novel biofabrication strategy for building tissue-engineered tendon constructs with the proper biological, mechanical, and histological relevance..

Collagen-Hyaluronic Acid Composite Hydrogels with Applications for Chronic Diabetic Wound Repair.

Chronic diabetic wounds have become a major healthcare challenge worldwide. Improper treatment may lead to serious complications. Current treatment methods including biological and physical methods and skin grafting have limitations and disadvantages, such as poor efficacy, inconvenience of use, and high cost. Therefore, developing a more effective and feasible treatment is of great significance for the repair of chronic diabetic wounds. Hydrogels can be designed to serve multiple functions to promote the repair of chronic diabetic wounds. Furthermore, 3D bioprinting enables hydrogel customization to fit chronic diabetic wounds, thus facilitating the healing process. This paper reports a study of 3D printing of a collagen-hyaluronic acid composite hydrogels with application for chronic diabetic wound repair. In situ printed hydrogels were developed by a macromolecular crosslinking network using methacrylated recombinant human collagen (RHCMA) and methacrylated hyaluronic acid (HAMA), both of which can respond to ultraviolet (UV) irradiation. The hydrogels were also loaded with silver nanoclusters (AgNCs) with ultra-small-size nanoparticles, which have the advantages of deep penetration ability and broad-spectrum high-efficiency antibacterial properties. The results of this study show that the developed RHCMA, HAMA, and AgNCs (RHAg) composite hydrogels present good UV responsiveness, porosity, mechanical properties, printability, and biocompatibility, all of which are beneficial to wound healing. The results of this study further show that the developed RHAg hydrogels not only effectively inhibited Staphylococcus aureus and Pseudomonas aeruginosa but also promoted the proliferation and migration of fibroblasts in vitro and tissue regeneration and collagen deposition in vivo, thus producing a desirable wound repair effect and can be used as an effective functional biomaterial to promote chronic diabetic wound repair.

Modular design of centrifugal microfluidic system and its application in nucleic acid screening.

Modular integration of functional components on the chip and increasement in control accuracy through real-time alteration in the force direction of droplets is an effective way to optimize centrifugal microfluidic systems and realize passive components, compact modules, and high-throughput control. Conventional centrifugal microfluidic chips are mainly driven and controlled by centrifugal force and Euler force. The control valves are easily affected by machining precision, making the control unstable. In this study, a novel centrifugal microfluidic system is introduced to improve the freedom and accuracy of chip control while facilitating the design and addition of passive functional components. Furthermore, we modularize the centrifugal microfluidic chip to greatly shorten the period of design and optimization cycle and achieve chip reusability and multi-threaded control. Finally, to verify the feasibility of the modular centrifugal microfluidic chip applied to high-throughput nucleic acid screening, we test the nucleic acid purification and detection colorimetric reactions based on the modular centrifugal microfluidic chip. Among them, Chelex-100 is used to realize the purification of nucleic acid in cell lysate, and the purified solution can realize amplification in the PCR instrument, and the nucleic acid detection results are consistent with the off-chip kit by experimental testing. The system has great flexibility and stability under the acceptable purity of nucleic acid, which indicates that the platform has great potential for large-scale rapid screening applications.

Apolipoprotein A-IV of diabetic-foot patients upregulates tumor necrosis factor α expression in microfluidic arterial models.

Diabetic peripheral arterial atherosclerosis is one of the important characteristics of diabetic foot syndrome. Apolipoprotein (Apo A-IV) participates in various physiological processes, and animal studies have shown that it has roles of anti-atherosclerosis, prevention of platelet aggregation and thrombosis. Apo A-IV glycosylation is closely related to the occurrence and development of diabetic peripheral atherosclerosis. This study aimed to explore the mechanism of diabetic peripheral arterial lesions caused by glycosylated Apo A-IV. Type 2 diabetes mellitus (T2DM) and T2DM with diabetic foot patients (T2DM-F; n = 45, 30) were enrolled in this study, and individuals without diabetes (n = 35) served as normal controls (NC). In T2DM group, serum Apo A-IV content was higher than those in NC and T2DM-F group, as carboxymethyl lysine (CML) glycosylation of Apo A-IV in mixed serum from T2DM-F group was identified to be more significant than those in two other groups. Within a microfluidic arterial chip model, Apo A-IV from T2DM and T2DM-F group significantly increased transcription and protein levels of tumor necrosis factor alpha (TNF-α) in chip arteries, and CML expression was observed in T2DM-F group, which were associated with increased nuclear receptor subfamily 4 group A member 3 (NR4A3) expression. Recombinant human Apo A-IV could reverse the stimulating effect of serum Apo A-IV from T2DM-F group on TNF-α expression, and NR4A3 blocking peptide downregulated TNF-α expression by inhibiting NR4A3 expression. In the chip arteries, Apo A-IV from T2DM and T2DM-F increased TNF-α expression and turn them into a pre-atherosclerotic state, which might be one of the important mechanisms of glycosylated Apo A-IV to induce diabetic peripheral arterial lesions and eventually lead to diabetic foot.

Variable-position centrifugal platform achieves droplet manipulation and logic circuitries on-chip.

Taking information as material to realize non-electronic physical computing is a promising idea, which facilitates the integration of technologies in different fields such as chemistry, biology, and mechanical control into a new computing platform. Here, we propose a novel, efficient and robust manipulation platform that drives droplet computing by way of inertial force. Combining this with droplet flow path design, we demonstrated multiple basic functions of droplet manipulation, including storage, dosing, interrupts, controllable release and addressing. These basic functions without external control lay the foundation for the realization of droplet calculation. We developed AND, OR, and XOR logic gates of the "liquid circuit" and combined them into a binary adder, which successfully completed the addition of four-digit binary numbers through droplet movement. Moreover, we attempted to perform algorithmic design for biological information under the control of droplets based on synchronous logical operations, developing the possibility of biological applications. This programmable physical computing system exists independently of electronic computing, aiming to supplement and expand the computing methods outside the field of electronic technology and to open a new method for the algorithmic operation of materials after combining new physical computing technologies such as biological or chemical computing.

Magnetically Driven Modular Mechanical Metamaterials with High Programmability, Reconfigurability, and Multiple Applications.

Shape transformation and motion guidance are emerging research hotspots of mechanical metamaterials. In this case, the key issue is how to improve the programmability and reconfigurability of metamaterials. The magnetically driven method enables materials to accomplish remote, fast, and reversible deformation, so it is desired for improving the programmability and reconfigurability of metamaterials. However, conventional magnetically driven materials are often pure elastomer materials. Their magnetic programming method is single, and their overall shape is unchangeable after fabrication, which limits their programmability and reconfigurability. Herein, this article proposes a kind of magnetically driven, programmable, and reconfigurable modular mechanical metamaterial based on origami and kirigami design mechanisms. The motion and deformation were designed to follow the predefined creases and incisions that could be transformed into each other. This metamaterial enabled more discrete motion and force transmission and integrated the fold of origami, the rotation of kirigami, and the fold guided by cuts. Such designs laid the foundation for complex, three-dimensional structures which could be quickly reassembled and constructed to deal with complex situations. This paper also demonstrated applications of this metamaterial in information storage and manifestation, mechanical logic computing, reconfigurable robotics, deployable mechanisms, and so on. The results indicated that the high programmability and reconfigurability expanded the application potential of the metamaterial for broader needs.

Research of restricted migration evaluation of MDA-MB-231 cells in 2D and 3D co-culture models.

The restricted migration evaluation is conducive to more complex tumor migration research because of the conformity with in vivo tumors. However, the differences between restricted and unrestricted cell migration and the distinction between different evaluation methods have not been systematically studied, hindering related research. In this study, by constructing the restricted environments on chips, the influence of co-culture conditions on the cancer cell migration capacity was studied. The results showed that the restricted channels can discriminate the influence of weak tumor environmental factors on complex tumor migration behaviors by limiting the free growth instinct of tumor cells. Through the comparison of 2D and 3D restricted migration methods, the extracellular matrix (ECM) restriction was also helpful in distinguishing the influence of the weak tumor environmental factor. However, the 3D ECM can better reflect the tortuosity of the cell migration process and the cooperative behavior among cancer cells. In the anticancer drug evaluation, 3D ECM can more accurately reflect the cytotoxicity of drugs and is more consistent with the drug resistance in the human body. In conclusion, the research will help to distinguish different evaluation methods of cancer cell migration, help researchers select appropriate evaluation models, and promote the research of tumor metastasis.

A Study on Dual-Response Composite Hydrogels Based on Oriented Nanocellulose.

In nature, many biological tissues are composed of oriented structures, which endow tissues with special properties and functions. Although traditional hydrogels can achieve a high level of biomimetic composition, the orderly arrangement of internal structures remains a challenge. Therefore, it is of great significance to synthesize hydrogels with oriented structures easily and quickly. In this study, we first proposed and demonstrated a fabrication process for producing a well-ordered and dual-responsive cellulose nanofibers + hyaluronic acid methacrylate (CN+HAMA) hydrogels through an extrusion-based three-dimensional (3D) printing process. CN in the CN+HAMA hydrogels are directionally aligned after extrusion due to shear stress. In addition, the synthesized hydrogels exhibited responsive behaviors to both temperature and ultraviolet light. Since the temperature-responsiveness is reversible, the hydrogels can transit between the gelation and solution states while retaining their original qualities. Furthermore, the developed well-oriented CN+HAMA hydrogels induced directional cell growth, paving the way for potential applications in ordered biological soft-tissue repair.

Full integration of nucleic acid extraction and detection into a centrifugal microfluidic chip employing chitosan-modified microspheres.

Microfluidic devices especially centrifugal ones have attracted great attention in the nucleic acid testing field, due to their automation, high efficiency, and simple operation. In which, nucleic acid extraction is the basic step, laying a foundation for the downstream amplification and detection procedures. Therefore, the integration of nucleic acid extraction on the chip is expected to achieve cost-efficiency, high-speed automation, diagnostic accuracy, and reaction robustness with the respect to real-time detection. In this work, we employ chitosan-modified magnetic microspheres for pH-induced nucleic acid extraction and integrate this approach into a centrifugal microfluidic chip. The microfluidic system comprises cell lysis, nucleic acids capture and release, isothermal amplification, and real-time fluorescence detection, which is manipulated by centrifugal force and magnetic control. The system exhibits comparable extraction and detection performance in respect of acceptable nucleic acid concentration and purity, high detection specificity and stability, as well as fast detection duration. These efforts to improve the integrated microfluidic detection chip could benefit the portable, efficient and simple nucleic acid diagnosis, especially under the resource-limited circumstance.

Long-term cultured microvascular networks on chip for tumor vascularization research and drug testing.

The vascular structure of the tumor microenvironment (TME) plays an essential role in the process of metastasis. In vitro microvascular structures that can be maintained for a long time will greatly promote metastasis research. In this study, we constructed a mimicking breast cancer invasion model based on a microfluidic chip platform, and the maintenance time of the self-assembled microvascular networks significantly improved by culturing with fibroblasts (up to 13 days). Using this model, we quantified the invasion ability of breast cancer cells and angiogenesis sprouts caused by cancer cells, and the intravasation behavior of cancer cells was also observed in sprouts. We found that cancer cells could significantly cause angiogenesis by promoting sprouting behaviors of the self-assembled human umbilical vein endothelial cells, which, in turn, promoted the invasion behavior of cancer cells. The drug test results showed that the drug resistance of the widely used anti-cancer drugs 5-Fluorouracil (5-FU) and Doxorubicin (DOX) in the 3D model was higher than that in the 2D model. Meanwhile, we also proved that 5-FU and DOX had the effect of destroying tumor blood vessels. The anti-angiogenic drug Apatinib (VEGFR inhibitor) enhanced the drug effect of DOX on MDA-MB-231 cells, further proving the promoting effect of angiogenesis on the invasion ability of cancer cells. These results indicate that our model is of great value in reconstructing TME and drug testing in vitro.

Fluid-driven hydrogel actuators with an origami structure.

Owing to the innate good biocompatibility, tissue-like softness and other unique properties, hydrogels are of particular interest as promising compliant materials for biomimetic soft actuators. However, the actuation diversity of hydrogel actuators is always restricted by their structure design and fabrication methods. Herein, origami structures were introduced to the design of fluid-driven hydrogel actuators to achieve diverse actuation movements, and a facile fabrication strategy based on removable templates and inside-out diffusion-induced in situ hydrogel crosslinking was adopted. As a result, three types of modular cuboid actuator units (CAUs) achieved linear motion, bending, and twisting. Moreover, combinations of multiple CAUs achieved different actuation modes, including actuation decoupling, superposition, and reprogramming. The diverse actuation functionality would enable new possibilities in application fields for hydrogel soft actuators. Several simple application demos, such as grippers for grasping tasks and a multi-way circuit switch, demonstrated their potential for further applications.

A methacrylated hyaluronic acid network reinforced Pluronic F-127 gel for treatment of bacterial keratitis.

In this study, we developed a novelin situthermoresponsive gel by introducing crosslinked methacrylated hyaluronic acid (HA-MA) networks into Pluronic F-127 (PF-127) gel (HP gel) to achieve sustained levofloxacin (LFX) delivery in bacterial keratitis treatment. The interactions between PF-127 molecules and HA-MA networks were studied by scanning electron microscopy, rheology, dynamic light scattering, differential scanning calorimetry, and small angle x-ray scattering. The results showed that the HP gel exhibited a higher critical gelling temperature and lower viscosity than the PF-127 gel (P gel), and could form a uniform thin layer on the ocular surface. Moreover, the drug release profile and gel dissolution rate revealed that the HA-MA network could retard the diffusion and dissolution of drug molecules and prolong the drug release time, which corresponded to an enhanced antibacterial ability of the HP-LFX gel. Furthermore, the HP gel exhibited low cytotoxicity to human corneal epithelial cells. Finally, anin vivopharmacodynamic study was conducted with rabbit keratitis models. An improved treatment efficacy was observed after application of the HP-LFX gels. This study highlights the potential of HP gels in ophthalmic drug delivery.

Retinal fundus image superresolution generated by optical coherence tomography based on a realistic mixed attention GAN.

PURPOSE: Optical coherence tomography (OCT) is widely used to diagnose retinal diseases. However, due to the limited resolution of OCT imaging systems, the quality of fundus images displayed is not satisfactory, which hinders the diagnosis of patients by ophthalmologists. This is an inevitable problem of OCT imaging systems, but few people have given attention to it. We attempt to solve this problem through deep learning methods. METHODS: In this paper, we propose a single-image superresolution (SISR) model that is based on a generative adversarial network (GAN) for restoring low-resolution (LR) OCT fundus images to high-resolution (HR) counterparts. To obtain more realistic images, we craft the training data set by obtaining the real blur kernels of the LR images instead of using the bicubic interpolation kernel. The baseline of our generator is similar to that of an enhanced superresolution generative adversarial network (ESRGAN), but we creatively propose a mixed attention block (MAB). In contrast to other superresolution (SR) tasks, to adapt to the characteristics of OCT imaging systems, our network can reconstruct LR images with different upscaling factors in the height and width directions. RESULTS: The results of qualitative and quantitative experiments prove that our model is capable of reconstructing retinal fundus images clearly and accurately. CONCLUSIONS: We propose a new GAN model for enhancing the quality of displayed OCT retinal fundus images and achieve state-of-the-art results.