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Fully bioresorbable vascular scaffolds (BVSs) aim to overcome the limitations of metallic drug-eluting stents (DESs). However, polymer-based BVSs, such as Abbott's Absorb, the only US FDA-approved BVS, have had limited use due to increased strut thickness (157 µm for Absorb), exacerbated tissue inflammation, and increased risk of major cardiac events leading to inferior clinical performance when compared to metallic DESs. Herein we report the development of a drug-eluting BVS (DE-BVS) through the innovative use of a photopolymerizable, citrate-based biomaterial and a high-precision additive manufacturing process. BVS with a clinically relevant strut thickness of 62 µm can be produced in a high-throughput manner, i.e. one BVS per minute, and controlled release of the anti-restenosis drug everolimus can be achieved by engineering the structure of polymer coatings to fabricate drug-eluting BVS. We achieved the successful deployment of BVSs and DE-BVSs in swine coronary arteries using a custom-built balloon catheter and BVS delivery system and confirmed BVS safety and efficacy regarding maintenance of vessel patency for 28 days, observing an inflammation profile for BVS and DE-BVS that was comparable to the commercial XIENCE™ DES (Abbott Vascular).

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This decade has witnessed the tremendous progress in miniaturizing optical imaging systems. Despite the advancements in 3D printing optical lenses at increasingly smaller dimensions, challenges remain in precisely manufacturing the dimensionally compatible optomechanical components and assembling them into a functional imaging system. To tackle this issue, the use of 3D printing to enable digitalized optomechanical component manufacturing, part-count-reduction design, and the inclusion of passive alignment features is reported here, all for the ease of system assembly. The key optomechanical components of a penny-sized accommodating optical microscope are 3D printed in 50 min at a significantly reduced unit cost near $4. By actuating a built-in voice-coil motor, its accommodating capability is validated to focus on specimens located at different distances, and a focus-stacking function is further utilized to greatly extend depth of field. The microscope can be readily customized and rapidly manufactured to respond to task-specific needs in form factor and optical characteristics.

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3D-printed hydrogel scaffolds functionalized with conductive polymers have demonstrated significant potential in regenerative applications for their structural tunability, physiochemical compatibility, and electroactivity. Controllably generating conductive hydrogels with fine features, however, has proven challenging. Here, micro-continuous liquid interface production (µCLIP) method is utilized to 3D print poly(2-hydroxyethyl methacrylate) (pHEMA) hydrogels. With a unique in-situ polymerization approach, a sulfonated monomer is first incorporated into the hydrogel matrix and subsequently polymerized into a conjugated polyelectrolyte, poly(4-(2,3-dihydro-thieno[3,4-b][1,4]dioxin-2-ylmethoxy)-butane-1 sulfonic acid sodium salt (PEDOT-S). Rod structures are fabricated at different crosslinking levels to investigate PEDOT-S incorporation and its effect on bulk hydrogel electronic and mechanical properties. After demonstrating that PEDOT-S does not significantly compromise the structures of the bulk material, pHEMA scaffolds are fabricated via µCLIP with features smaller than 100 µm. Scaffold characterization confirms PEDOT-S incorporation bolstered conductivity while lowering overall modulus. Finally, C2C12 myoblasts are seeded on PEDOT-pHEMA structures to verify cytocompatibility and the potential of this material in future regenerative applications. PEDOT-pHEMA scaffolds promote increased cell viability relative to their non-conductive counterparts and differentially influence cell organization. Taken together, this study presents a promising new approach for fabricating complex conductive hydrogel structures for regenerative applications.

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3D printing, formally known as additive manufacturing, creates complex geometries via layer-by-layer addition of materials. While 3D printing has been historically perceived as the static addition of build layers, 3D printing is now considered as a dynamic assembly process. In this context, here a new 3D printing process is reported that executes full degree-of-freedom (DOF) transformation (translating, rotating, and scaling) of each individual building layer while utilizing continuous fabrication techniques. Transforming individual building layers within the sequential layered manufacturing process enables dynamic transformation of the 3D printed parts on-the-fly, eliminating the time-consuming redesign steps. Preserving the locality of the transformation to each layer further enables the discrete conformal transformation, allowing objects such as vascular scaffolds to be optimally fabricated to properly fit within specific patient anatomy obtained from the magnetic resonance imaging (MRI) measurements. Finally, exploiting the freedom to control the orientation of each individual building layer, multimaterials, multiaxis 3D printing capability are further established for integrating functional modules made of dissimilar materials in 3D printed devices. This final capability is demonstrated through 3D printing a soft pneumatic gripper via heterogenous integration of rigid base and soft actuating limbs.

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Continuous liquid interface production (CLIP) utilizes projection ultraviolet (UV) light and oxygen inhibition to transform the sequential layered three-dimensional (3D) manufacturing into a continuous fabrication flow with tremendous improved fabrication speed and structure integrity. Incorporating ceramic particles to the photo-curable polymers allows for additive manufacturing of ceramic parts featuring sophisticated geometries, mitigating the difficulties associated with traditional manufacturing processes. The presence of ceramic particles within the ink, however, strongly scatters the incident UV light. In the high-resolution CLIP (microCLIP) process, the scattering effect can significantly alter the process characteristics, resulting in broadening of lateral feature dimensions alongside curing depth reduction. Varying exposure conditions to accommodate scattering additionally affects the oxygen deadzone thickness (DZ), which is dependent on power of incident light. This introduces a systematic defocusing error for large deadzone thickness to further complicate process control, such as the unwanted narrowing of part features. In this work, we developed a systematic framework for process optimization by balancing those effects via experimental characterization. We showed that the reported method can provide a set of optimal process parameters (UV power and stage speed) for high-resolution 3D fabrication in accommodating the distinct characteristics of given photo-curable ceramic ink. The method to optimize process parameter was validated experimentally via fabricating a gradient index Luneburg lens comprising densely packed woodpile building-blocks with a strut width of 100 µm and a layer thickness of 60 µm using microCLIP at dimensionally accurate exposure conditions.

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Advancements in three-dimensional (3D) printing technology have the potential to transform the manufacture of customized optical elements, which today relies heavily on time-consuming and costly polishing and grinding processes. However the inherent speed-accuracy trade-off seriously constrains the practical applications of 3D-printing technology in the optical realm. In addressing this issue, here, a new method featuring a significantly faster fabrication speed, at 24.54 mm3 h-1 , without compromising the fabrication accuracy required to 3D-print customized optical components is reported. A high-speed 3D-printing process with subvoxel-scale precision (sub 5 µm) and deep subwavelength (sub 7 nm) surface roughness by employing the projection micro-stereolithography process and the synergistic effects from grayscale photopolymerization and the meniscus equilibrium post-curing methods is demonstrated. Fabricating a customized aspheric lens 5 mm in height and 3 mm in diameter is accomplished in four hours. The 3D-printed singlet aspheric lens demonstrates a maximal imaging resolution of 373.2 lp mm-1 with low field distortion less than 0.13% across a 2 mm field of view. This lens is attached onto a cell phone camera and the colorful fine details of a sunset moth's wing and the spot on a weevil's elytra are captured. This work demonstrates the potential of this method to rapidly prototype optical components or systems based on 3D printing.

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OBJECTIVE: Coreference resolution of concepts, although a very active area in the natural language processing community, has not yet been widely applied to clinical documents. Accordingly, the 2011 i2b2 competition focusing on this area is a timely and useful challenge. The objective of this research was to collate coreferent chains of concepts from a corpus of clinical documents. These concepts are in the categories of person, problems, treatments, and tests. DESIGN: A machine learning approach based on graphical models was employed to cluster coreferent concepts. Features selected were divided into domain independent and domain specific sets. Training was done with the i2b2 provided training set of 489 documents with 6949 chains. Testing was done on 322 documents. RESULTS: The learning engine, using the un-weighted average of three different measurement schemes, resulted in an F measure of 0.8423 where no domain specific features were included and 0.8483 where the feature set included both domain independent and domain specific features. CONCLUSION: Our machine learning approach is a promising solution for recognizing coreferent concepts, which in turn is useful for practical applications such as the assembly of problem and medication lists from clinical documents.

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OBJECTIVE The authors developed a natural language processing (NLP) framework that could be used to extract clinical findings and diagnoses from dictated physician documentation. DESIGN De-identified documentation was made available by i2b2 Bio-informatics research group as a part of their NLP challenge focusing on obesity and its co-morbidities. The authors describe their approach, which used a combination of concept detection, context validation, and the application of a variety of rules to conclude patient diagnoses. RESULTS The framework was successful at correctly identifying diagnoses as judged by NLP challenge organizers when compared with a gold standard of physician annotations. The authors overall kappa values for agreement with the gold standard were 0.92 for explicit textual results and 0.91 for intuited results. The NLP framework compared favorably with those of the other entrants, placing third in textual results and fourth in intuited results in the i2b2 competition. CONCLUSIONS The framework and approach used to detect clinical conditions was reasonably successful at extracting 16 diagnoses related to obesity. The system and methodology merits further development, targeting clinically useful applications.

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