Endothelial progenitor cells (EPCs) are a promising cell source for the treatment of several ischemic diseases for their potentials in neovascularization. However, the application of EPCs in ...cell‐based therapy has shown low therapeutic efficacy due to hostile tissue conditions after ischemia. In this study, a bio‐blood‐vessel (BBV) is developed, which is produced using a novel hybrid bioink (a mixture of vascular‐tissue‐derived decellularized extracellular matrix (VdECM) and alginate) and a versatile 3D coaxial cell printing method for delivering EPC and proangiogenic drugs (atorvastatin) to the ischemic injury sites. The hybrid bioink not only provides a favorable environment to promote the proliferation, differentiation, and neovascularization of EPCs but also enables a direct fabrication of tubular BBV. By controlling the printing parameters, the printing method allows to construct BBVs in desired dimensions, carrying both EPCs and atorvastatin‐loaded poly(lactic‐co‐glycolic) acid microspheres. The therapeutic efficacy of cell/drug‐laden BBVs is evaluated in an ischemia model at nude mouse hind limb, which exhibits enhanced survival and differentiation of EPCs, increased rate of neovascularization, and remarkable salvage of ischemic limbs. These outcomes suggest that the 3D‐printed ECM‐mediated cell/drug implantation can be a new therapeutic approach for the treatment of various ischemic diseases.
The extracellular matrix of vascular tissue is formulated as a bioink to engineer a bioinspired blood vessel using the 3D coaxial cell printing technique. Carrying progenitor cells and proangiogenic drugs, the transplanted construct exhibits remarkable therapeutic efficacy for ischemic diseases.
The fabrication of a highly controlled gold (Au) nanohole (NH) array via tip-based lithography is improved by incorporating a sacrificial layer-a tip-crash buffer layer. This inclusion mitigates ...scratches during the nano-indentation process by employing a 300 nm thick poly(methyl methacrylate) layer as a sacrificial layer on top of the Au film. Such a precaution ensures minimal scratches on the Au film, facilitating the creation of sub-50 nm Au NHs with a 15 nm gap between the Au NHs. The precision of this method exceeds that of fabricating Au NHs without a sacrificial layer. Demonstrating its versatility, this Au NH array is utilized in two distinct applications: as a dry etching mask to form a molybdenum disulfide hole array and as a catalyst in metal-assisted chemical etching, resulting in conical-shaped silicon nanostructures. Additionally, a significant electric field is generated when Au nanoparticles (NPs) are placed within the Au NHs. This effect arises from coupling electromagnetic waves, concentrated by the Au NHs and amplified by the Au NPs. A notable result of this configuration is the enhancement factor of surface-enhanced Raman scattering, which is an order of magnitude greater than that observed with just Au NHs and Au NPs alone.
Artificial intelligence (AI) will likely affect various fields of medicine. This article aims to explain the fundamental principles of clinical validation, device approval, and insurance coverage ...decisions of AI algorithms for medical diagnosis and prediction. Discrimination accuracy of AI algorithms is often evaluated with the Dice similarity coefficient, sensitivity, specificity, and traditional or free-response receiver operating characteristic curves. Calibration accuracy should also be assessed, especially for algorithms that provide probabilities to users. As current AI algorithms have limited generalizability to real-world practice, clinical validation of AI should put it to proper external testing and assisting roles. External testing could adopt diagnostic case-control or diagnostic cohort designs. A diagnostic case-control study evaluates the technical validity/accuracy of AI while the latter tests the clinical validity/accuracy of AI in samples representing target patients in real-world clinical scenarios. Ultimate clinical validation of AI requires evaluations of its impact on patient outcomes, referred to as clinical utility, and for which randomized clinical trials are ideal. Device approval of AI is typically granted with proof of technical validity/accuracy and thus does not intend to directly indicate if AI is beneficial for patient care or if it improves patient outcomes. Neither can it categorically address the issue of limited generalizability of AI. After achieving device approval, it is up to medical professionals to determine if the approved AI algorithms are beneficial for real-world patient care. Insurance coverage decisions generally require a demonstration of clinical utility that the use of AI has improved patient outcomes.
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Engineered heart tissue (EHT) has ample potential as a model for in vitro tissue modeling or tissue regeneration. Using 3D cell printing technology, various hydrogels have been ...utilized as bioinks to fabricate EHT to date. However, its efficacy has remained limited due to poor functional properties of the cultured cardiomyocytes stemming from a lack of proper microenvironmental cues. Specifically, the surrounding matrix plays a key role in modulating cardiomyocyte differentiation and maturation. Recently, the use of heart tissue-derived extracellular matrix (hdECM) bioink has come to be seen as one of the most promising candidates due to its functional and structural similarities to native tissue. Here, we demonstrated a correlation between the synthesis of cardiomyocyte-specific proteins and the surrounding microenvironment irrespective of the similar material chemistry. Primary cardiomyocytes isolated from neonatal rats were encapsulated in different composition and concentration of bioinks (hdECM and collagen). The bioinks were sequentially printed using an extrusion-based 3D bioprinter and cultured either statically or dynamically. Qualitative and quantitative evaluation revealed enhanced maturation of cardiomyocytes in hdECM, unlike the collagen group under similar culture conditions. Specifically, 3D-printed EHT using a low concentration of hdECM promoted early differentiation of cardiomyocytes. Hence, the present study provides experimental insights regarding the establishment of a 3D-printed cardiac tissue model, highlighting that the matrix and the culture microenvironment can be decisive factors for cell-material interactions that affect cardiomyocyte maturation.
The regulation of signal transduction and responses to extracellular matrices (ECMs) is of particular relevance in tissue maturation. In particular, there is a clear need to understand the structural and phenotypical modulation in cardiomyocytes with respect to the surrounding microenvironment. Exploration of the key regulators, such as the compositional and the biophysical properties of bioinks associated directly with cell-cell and cell-matrix interactions would assist with the fabrication of cardiac tissue constructs with enhanced functionality. Hence, we documented the synergistic effects of surrounding matrices and culture conditions on the maturation of cardiomyocytes. Additionally, we highlighted the potential of using 3D bioprinting techniques to fabricate uniformly aligned cardiac constructs for mid- to high-throughput drug testing platforms that have great reproducibility and versatility.
Volumetric muscle loss (VML) is an irrecoverable injury associated with muscle loss greater than 20%. Although hydrogel-based 3D engineered muscles and the decellularized extracellular matrix (dECM) ...have been considered for VML treatment, they have shown limited efficacy. We established a novel VML treatment with dECM bioink using 3D cell printing technology. Volumetric muscle constructs composed of cell-laden dECM bioinks were generated with a granule-based printing reservoir. The 3D cell printed muscle constructs exhibited high cell viability without generating hypoxia and enhanced de novo muscle formation in a VML rat model. To improve functional recovery, prevascularized muscle constructs that mimic the hierarchical architecture of vascularized muscles were fabricated through coaxial nozzle printing with muscle and vascular dECM bioinks. Spatially printing tissue-specific dECM bioinks offers organized microenvironmental cues for the differentiation of each cell and improves vascularization, innervation, and functional recovery. Our present results suggest that a 3D cell printing and tissue-derived bioink-based approach could effectively generate biomimetic engineered muscles to improve the treatment of VML injuries.
Methods for the mass fabrication of 3D silicon (Si) microstructures with a 100 nm resolution are developed using scanning probe lithography (SPL) combined with metal‐assisted chemical etching (MACE). ...Protruding Si structures, including Si nanowires of over 10 µm in length and atypical shaped Si nano‐ and micropillars, are obtained via the MACE of a patterned gold film (negative tone) on Si substrates by dip‐pen nanolithography (DPN) with polymer or by nanoshaving alkanethiol self‐assembled monolayers (SAMs). Furthermore, recessed Si structures with arbitrary patterning and channels less than 160 nm wide and hundreds of nanometers in depth are obtained via the MACE of a patterned gold film (positive tone) on Si substrates by alkanethiol DPN. As an example of applications using protruded Si structures, nanoimprinting in an area of up to a centimeter is demonstrated through 1D and 2D SPL combined with MACE. Similarly, submicrometer polydimethylsiloxane (PDMS) stamps are employed over millimeter‐scale areas for applications using recessed Si structures. In particular, the mass production of arbitrarily shaped Si microparticles at submicrometer resolution is developed using silicon‐on‐insulator substrates, as demonstrated using optical microresonators, surface‐enhanced Raman scattering templates, and smart microparticles for fluorescence signal coding.
Mass fabrication of 3D silicon nano‐/microstructures and atypical shaped silicon microparticles is developed through scanning probe lithography in conjunction with metal‐assisted chemical etching. Fabricated structures are successfully utilized as nanoimprinting stamps, polydimethylsiloxane templates, optical resonators, surface‐enhanced Raman scattering templates, and fluorescence signal‐coded smart particles.
Purpose
To determine the intra- and extralesional factors that predict sclerotic degeneration of hepatic hemangiomas in the cirrhotic liver on long-term follow-up computed tomography (CT) ...examinations.
Materials and methods
Fifty-seven hepatic hemangiomas (> 5 mm in diameter) in 41 cirrhotic patients, recruited over a 5-year period (January 2005–December 2009), were subjected to CT to determine which factors predict sclerotic contraction or degeneration in hemangiomas. Prior and follow-up CT examinations (from 2000 to 2018) were included to observe time-related changes. The patients’ gender, age, cause of cirrhosis, progression of background liver cirrhosis, lesion size/location/contrast enhancement pattern, and serum aspartate transaminase to platelet ratio index were correlated with sclerotic changes of each lesion.
Results
According to the dynamic CT features, 36 of 57 (63%) hemangiomas were determined to have sclerotic changes during the follow-up period (1.1–14.4 years, median: 7.8 years), including 28 lesions (49%) reduced by ≥ 20% in diameter. In univariate analysis, age (
p
= 0.047) and morphological progression of background cirrhosis (
p
= 0.013) were significantly related to sclerotic change of hemangiomas. In the logistic regression analysis, only morphological progression of background liver cirrhosis independently predicted sclerotic change (odds ratio: 4.88,
p
= 0.007). With the exception of exophytic location free from size reduction (
p
= 0.023 in multivariate analysis), no other analyzed factors were significantly correlated with sclerotic changes.
Conclusion
Overall, sclerotic changes of hepatic cavernous hemangioma followed the morphological progression of background liver cirrhosis, while exophytic lesions tended to be free of size reduction.
Tip‐Based LithographyIn article number 2309484, Jae‐Won Jang and co‐workers report the tip‐based lithography with a sacrificial layer. The sacrificial layer minimizes the scratching of the gold film ...by nano‐indentation during tip‐based lithography, which enables the fabrication of sub‐50 nm‐sized gold nanoholes. A single 20 nm diameter gold particle was trapped in a 35 nm diameter gold nanohole via wettability‐controlled self‐assembly. This structure causes strong electromagnetic wave enhancement and can be utilized in surface‐enhanced Raman scattering.
With the prevalence of degenerative diseases due to the increase in the aging population, we have encountered many spine-related disorders. Since the spine is a crucial part of the body, fast and ...accurate diagnosis is critically important. Generally, clinicians use X-ray images to diagnose the spine, but X-ray images are commonly occluded by the shadows of some bones, making it hard to identify the whole spine. Therefore, recently, various deep-learning-based spinal X-ray image analysis approaches have been proposed to help diagnose the spine. However, these approaches did not consider the characteristics of frequent occlusion in the X-ray image and the properties of the vertebra shape. Therefore, based on the X-ray image properties and vertebra shape, we present a novel landmark detection network specialized in lumbar X-ray images. The proposed network consists of two stages: The first step detects the centers of the lumbar vertebrae and the upper end plate of the first sacral vertebra (S1), and the second step detects the four corner points of each lumbar vertebra and two corner points of S1 from the image obtained in the first step. We used random spine cutout augmentation in the first step to robustify the network against the commonly obscured X-ray images. Furthermore, in the second step, we used CoordConv to make the network recognize the location distribution of landmarks and part affinity fields to understand the morphological features of the vertebrae, resulting in more accurate landmark detection. The proposed network was evaluated using 304 X-ray images, and it achieved 98.02% accuracy in center detection and 8.34% relative distance error in corner detection. This indicates that our network can detect spinal landmarks reliably enough to support radiologists in analyzing the lumbar X-ray images.
For decades, co-relating different data domains to attain the maximum potential of machines has driven research, especially in neural networks. Similarly, text and visual data (images and videos) are ...two distinct data domains with extensive research in the past. Recently, using natural language to process 2D or 3D images and videos with the immense power of neural nets has witnessed a promising future. Despite the diverse range of remarkable work in this field, notably in the past few years, rapid improvements have also solved future challenges for researchers. Moreover, the connection between these two domains is mainly subjected to GAN, thus limiting the horizons of this field. This review analyzes Text-to-Image (T2I) synthesis as a broader picture, Text-guided Visual-output (T2Vo), with the primary goal being to highlight the gaps by proposing a more comprehensive taxonomy. We broadly categorize text-guided visual output into three main divisions and meaningful subdivisions by critically examining an extensive body of literature from top-tier computer vision venues and closely related fields, such as machine learning and human–computer interaction, aiming at state-of-the-art models with a comparative analysis. This study successively follows previous surveys on T2I, adding value by analogously evaluating the diverse range of existing methods, including different generative models, several types of visual output, critical examination of various approaches, and highlighting the shortcomings, suggesting the future direction of research.
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