3D bioprinting strategy for engineering vascularized tissue models.

Leveraging three-dimensional (3D) bioprinting in the fields of tissue engineering and regenerative medicine has rapidly accelerated progress toward the development of living tissue constructs and biomedical devices. Ongoing vigorous research has pursued the development of 3D in vitro tissue models to replicate the key aspects of human physiology by incorporating relevant cell populations and adequate environmental cues. Given their advantages of being able to intimately mimic the heterogeneity and complexity of their native counterparts, 3D in vitro models hold promise as alternatives to conventional cell cultures or animal models for translational application to model human physiology/pathology and drug screening. Research has highlighted the importance of in vitro models, and a sophisticated biomanufacturing strategy is vitally required. In particular, vascularization is critical for the prolonged survival and functional maturation of the engineered tissues, which has remained one of the major challenges in the establishment of physiologically relevant 3D in vitro models. To this end, 3D bioprinting can efficiently generate solid and reproducible vascularized tissue models with high architectural and compositional similarity to the native tissues, leading to improve the structural maturation and tissue-specific functionality. Multiple bioprinting strategies have been developed to vascularize in vitro tissues by spatially controlled patterning of vascular precursors or generating readily perfusable vascular structures. This review presents an overview of the advanced 3D bioprinting strategies for vascularized tissue model development. We present the key elements for rebuilding functional vasculature in 3D-bioprinted tissue models and discuss the recent achievements in the engineering of 3D vascularized in vitro models using 3D bioprinting. Finally, we delineate the current challenges and future outlooks of 3D bioprinting-based vascularized tissue models.

Nanoscale Characterization of Photocurrent and Photovoltage in Polycrystalline Solar Cells.

We investigate the role of grain structures in nanoscale carrier dynamics of polycrystalline solar cells. By using Kelvin probe force microscopy (KPFM) and near-field scanning photocurrent microscopy (NSPM) techniques, we characterize nanoscopic photovoltage and photocurrent patterns of inorganic CdTe and organic-inorganic hybrid perovskite solar cells. For CdTe solar cells, we analyze the nanoscale electric power patterns that are created by correlating nanoscale photovoltage and photocurrent maps on the same location. Distinct relations between the sample preparation conditions and the nanoscale photovoltaic properties of microscopic CdTe grain structures are observed. The same techniques are applied for characterization of a perovskite solar cell. It is found that a moderate amount of PbI2 near grain boundaries leads to the enhanced photogenerated carrier collections at grain boundaries. Finally, the capabilities and the limitations of the nanoscale techniques are discussed.

Feasibility and safety of a novel 3D-printed biodegradable biliary stent in an in vivo porcine model: a preliminary study.

To assess the feasibility and safety of a novel 3D-printed biodegradable biliary stent using polycaprolactone (PCL) in an in vivo porcine model. In this animal study using domestic pigs, biodegradable radiopaque biliary stents made of polycaprolactone (PCL) and barium sulfate were produced using 3D printing and surgically inserted into the common bile duct (CBD) of pigs (stent group, n = 12). Another five pigs were allocated to the control group that only underwent resection and anastomosis of the CBD without stent insertion. To check the position and status of the stents and stent-related complications, follow-up computed tomography (CT) was performed every month. The pigs were sacrificed 1 or 3 months after surgery, and their excised CBD specimens were examined at both the macroscopic and microscopic levels. Three pigs (one in the stent group and two in the control group) died within one day after surgery and were excluded from further analysis; the remaining 11 in the stent group and 3 in the control group survived the scheduled follow-up period (1 month, 5 and 1; and 3 months, 6 and 2 in stent and control groups, respectively). In all pigs, no clinical symptoms or radiologic evidence of biliary complications was observed. In the stent group (n = 11), stent migration (n = 1 at 3 months; n = 2 at 1 month) and stent fracture (n = 3 at 2 months) were detected on CT scans. Macroscopic evaluation of the stent indicated no significant change at 1 month (n = 3) or fragmentation with discoloration at 3 months (n = 5). On microscopic examination of CBD specimens, the tissue inflammation score was significantly higher in the stent group than in the control group (mean ± standard deviation (SD), 5.63 ± 2.07 vs. 2.00 ± 1.73; P = 0.039) and thickness of fibrosis of the CBD wall was significantly higher than that of the control group (0.46 ± 0.12 mm vs. 0.21 ± 0.05 mm; P = 0.012). Despite mild bile duct inflammation and fibrosis, 3D-printed biodegradable biliary stents showed good feasibility and safety in porcine bile ducts, suggesting their potential for use in the prevention of postoperative biliary strictures.

3D Bioprinting of In Vitro Models Using Hydrogel-Based Bioinks.

Coronavirus disease 2019 (COVID-19), which has recently emerged as a global pandemic, has caused a serious economic crisis due to the social disconnection and physical distancing in human society. To rapidly respond to the emergence of new diseases, a reliable in vitro model needs to be established expeditiously for the identification of appropriate therapeutic agents. Such models can be of great help in validating the pathological behavior of pathogens and therapeutic agents. Recently, in vitro models representing human organs and tissues and biological functions have been developed based on high-precision 3D bioprinting. In this paper, we delineate an in-depth assessment of the recently developed 3D bioprinting technology and bioinks. In particular, we discuss the latest achievements and future aspects of the use of 3D bioprinting for in vitro modeling.

3D cell-printing of tendon-bone interface using tissue-derived extracellular matrix bioinks for chronic rotator cuff repair.

The tendon-bone interface (TBI) in rotator cuffs exhibits a structural and compositional gradient integrated through the fibrocartilaginous transition. Owing to restricted healing capacity, functional regeneration of the TBI is considered a great clinical challenge. Here, we establish a novel therapeutic platform based on 3D cell-printing and tissue-specific bioinks to achieve spatially-graded physiology for functional TBI regeneration. The 3D cell-printed TBI patch constructs are created via a spatial arrangement of cell-laden tendon and bone-specific bioinks in a graded manner, approximating a multi-tissue fibrocartilaginous interface. This TBI patch offers a cell favorable microenvironment, including high cell viability, proliferative capacity, and zonal-specific differentiation of encapsulated stem cells for TBI formationin vitro. Furthermore,in vivoapplication of spatially-graded TBI patches with stem cells demonstrates their regenerative potential, indicating that repair with 3D cell-printed TBI patch significantly accelerates and promotes TBI healing in a rat chronic tear model. Therefore, our findings propose a new therapeutic strategy for functional TBI regeneration using 3D cell-printing and tissue-specific decellularized extracellular matrix bioink-based approach.

Flexible Adipose-Vascular Tissue Assembly Using Combinational 3D Printing for Volume-Stable Soft Tissue Reconstruction.

A new concept, assembling cell-laden tissue modules, is for the first time proposed for soft tissue engineering. Adipose-vascular tissue modules composed of a synthetic polymer-based substructure and customized bioinks using planar 3D cell printing are engineered. Such tissue modules are systematically assembled into a synthetic polymer-based module holder fabricated with rotational 3D printing, resulting in the development of a flexible and volumetric tissue assembly. Whereas most of the previous studies about the construction of adipose tissue are limited to hypoxia, poor vascularization, rapid resorption, and mismatch in mechanical properties, it is aimed to realize the construction of nonhypoxic, flexible, and volume-stable tissue assembly in this study. The significance of engineered tissue assembly is proven through various in vitro and in vivo evaluations. In particular, stable volume and remarkable neovascularization/adipogenesis are observed in the implanted assembly over four weeks. Interestingly, the size of newly formed lipid droplets and the remodeled morphology in the assembly are comparable to those in native adipose tissue. As far as it is known, this work is a first report suggesting a cell printing-based tissue assembly for functional reconstruction of soft tissue.

Therapeutic effect of decellularized extracellular matrix-based hydrogel for radiation esophagitis by 3D printed esophageal stent.

Radiation esophagitis, the most common acute adverse effect of radiation therapy, leads to unwanted consequences including discomfort, pain, an even death. However, no direct cure exists for patients suffering from this condition, with the harmful effect of ingestion and acid reflux on the damaged esophageal mucosa remaining an unresolved problem. Through the delivery of the hydrogel with stent platform, we aimed to evaluate the regenerative capacity of a tissue-specific decellularized extracellular matrix (dECM) hydrogel on damaged tissues. For this, an esophagus-derived dECM (EdECM) was developed and shown to have superior biofunctionality and rheological properties, as well as physical stability, potentially providing a better microenvironment for tissue development. An EdECM hydrogel-loaded stent was sequentially fabricated using a rotating rod combined 3D printing system that showed structural stability and protected a loaded hydrogel during delivery. Finally, following stent implantation, the therapeutic effect of EdECM was examined in a radiation esophagitis rat model. Our findings demonstrate that EdECM hydrogel delivery via a stent platform can rapidly resolve an inflammatory response, thus promoting a pro-regenerative microenvironment. The results suggest a promising therapeutic strategy for the treatment of radiation esophagitis.

Multi-layered Free-form 3D Cell-printed Tubular Construct with Decellularized Inner and Outer Esophageal Tissue-derived Bioinks.

The incidences of various esophageal diseases (e.g., congenital esophageal stenosis, tracheoesophageal fistula, esophageal atresia, esophageal cancer) are increasing, but esophageal tissue is difficult to be recovered because of its weak regenerative capability. There are no commercialized off-the-shelf alternatives to current esophageal reconstruction and regeneration methods. Surgeons usually use ectopic conduit tissues including stomach and intestine, presumably inducing donor site morbidity and severe complications. To date, polymer-based esophageal substitutes have been studied as an alternative. However, the fabrication techniques are nearly limited to creating only cylindrical outer shapes with the help of additional apparatus (e.g., mandrels for electrospinning) and are unable to recapitulate multi-layered characteristic or complex-shaped inner architectures. 3D bioprinting is known as a suitable method to fabricate complex free-form tubular structures with desired pore characteristic. In this study, we developed a extrusion-based 3D printing technique to control the size and the shape of the pore in a single extrusion process, so that the fabricated structure has a higher flexibility than that fabricated in the conventional process. Based on this suggested technique, we developed a bioprinted 3D esophageal structure with multi-layered features and converged with biochemical microenvironmental cues of esophageal tissue by using decellularizedbioinks from mucosal and muscular layers of native esophageal tissues. The two types of esophageal tissue derived-decellularized extracellular matrix bioinks can mimic the inherent components and composition of original tissues with layer specificity. This structure can be applied to full-thickness circumferential esophageal defects and esophageal regeneration.

Visibility of Bioresorbable Vascular Scaffold in Intravascular Ultrasound Imaging.

Bioresorbable vascular scaffold (BVS) has recently been spotlighted for its unique characteristics of absorbing into blood vessels and eventually disappearing. Although intravascular ultrasound (IVUS) is the most common guiding tool for stent deployment, the echogenicity of BVS struts has changed as the center of stent lumen and scanning rotation is not concentric, which may cause a critical erroneous measurement in practice. This study investigated the physical conditions for dimming the stent brightness in IVUS images using a finite-difference method (FDM) to numerically solve acoustic wave propagation through nonhomogeneous medium. The dimmed brightness is caused by an angled rectangular cross section of a strut and its similar acoustic impedance with water. Imaging frequency is not a major cause. However, the angle between the acoustic beam and the BVS surface is the major cause of the dimmed brightness. As a solution, an approach using a frequency compounding method with signal polarity comparator was proposed to recover the reduced brightness without sacrificing spatial resolutions. Based on the simulation study, the signal level from BVS can be attenuated down by 17 dB when the angle between the acoustic beamline and the surface of BVS is more than 45°. With the proposed frequency compounding approach, the reduced signal can be recovered by 6 dB. In the experimental BVS IVUS imaging, strut brightness was reduced by 18 dB with an angled strut position and recovered by 5 dB with the proposed frequency compounding method. A pig coronary was imaged to demonstrate the performance of the proposed method.

Unveiling Defect-Mediated Charge-Carrier Recombination at the Nanometer Scale in Polycrystalline Solar Cells.

Solar cells made of polycrystalline thin-films can outperform their single-crystalline counterparts despite the presence of grain boundaries (GBs). To unveil the influence of GBs, high spatial resolution characterization techniques are needed to measure local properties in their vicinity. However, results obtained using single technique may provide limited aspects about the GB effect. Here, we employ two techniques, near-field scanning photocurrent microscopy (NSPM) and scanning transmission electron microscope based cathodoluminescence spectroscopy (STEM-CL), to characterize CdTe solar cells at the nanoscale. The signal contrast from the grain interiors (GIs) to the GBs, for high-efficiency cells where CdTe is deposited at a high substrate temperature (500 °C) and treated by CdCl2, is found reverse from one technique to another. NSPM reveals increased photocurrents at the GBs, while STEM-CL shows reduced CL intensity and energy redshifts of the spectral peak at the GBs. The results are attributed to the increased nonradiative recombination and the band bending mediated by the surface defects and the shallow-level defects at GBs, respectively. We discuss the advantages of sample geometry for room-temperature STEM-CL and present numerical simulations as well as analytical models to extract the ratio of GB recombination velocity to minority carrier diffusivity that can be used for evaluating the GB effect in other polycrystalline solar cells.

Marine-derived natural polymer-based bioprinting ink for biocompatible, durable, and controllable 3D constructs.

3D bioprinting (3DBP) is a rapid solid-form fabrication method with a high degree of automation and reproducibility for constructing structural bioscaffolds. However, the development of the 3DBP field has been slowed due to difficulty in acquiring suitable ink materials especially with natural polymers that satisfy all requirements, such as printability, mechanical integrity, and biocompatibility. In this study, a new 3DBP ink of bioengineered sea anemone-derived silk-like protein (aneroin) was used based on its durable mechanical properties and biodegradability in previous studies. The hyaluronic acid and mussel adhesive protein (MAP) were applied for improved printability and cell adhesiveness, respectively. The aneroin-based 3DBP ink (named aneroin ink) was solidified in a few second by dityrosine photo-crosslinking, and its fast reaction was suitable for noncollapsed spaces in printed 3D constructs. Actual-sized human ear, vascular graft, and rectangular multi-layered lattice were bioprinted with high controllability and durable structural integrity. Thus, the developed aneroin ink showed good printability, structural integrity, and biocompatibility for successful application to the construction of various 3D shaped bioscaffolds in tissue and biomedical engineering fields.

Development of a radiopaque, long-term drug eluting bioresorbable stent for the femoral-iliac artery.

Tubular tissues exist in various forms purported for blood supply, waste secretion, etc. to aid proper function and maintenance of the human body. Under pathological conditions, however, these tissues may undergo stenosis. A major surgical treatment for stenosis is to implant a medical device called a stent which aims to expand the narrowed tissue and maintain its patency. Most stents are currently made from metals; despite their high mechanical strength, however, interactions with the host tissue often results in restenosis and stent fracture. To solve these problems, a bioresorbable stent (BRS) is proposed as a next generation stent. In this study, a rotating rod combined 3D printing system was developed to fabricate various types of BRSs. In addition, we confirmed that a 1.5 year long-term release of paclitaxel is possible using polymeric materials. Moreover, a stent loaded with contrast powder was fabricated and was successfully viewed under fluoroscopy. The stent was then implanted in the iliac arteries of pigs and no adverse events were observed for up to 8 weeks.

Nasal Reconstruction Using a Customized Three-Dimensional-Printed Stent for Congenital Arhinia: Three-Year Follow-up.

A male Mongolian child with a complete congenital absence of both nose and nasal passage had a poor survival prognosis due to respiratory distress. To enable his survival, a new nose capable of conferring respiratory function was constructed. Following reconstructive surgery, an absence of mucoepithelium in the nasal passage can lead to rhinostenosis. To avoid this complication, a custom-made nasal silicone stent was created using three-dimensional (3D) printing technology in conjunction with the patient's computed tomography data. The stent was implanted for 2 months to maintain the shape and size of the nasal passage. At 2 months after stent implantation, the mucoepithelium tissue in the passage had successfully regenerated with no immune reaction. Three years after stent removal, respiratory function, nasal passage structure, and external nose shape were maintained without additional medical care. These results indicate the successful nasal reconstruction in an arhinia patient using a customized, 3D-printed nasal stent. Laryngoscope, 129:582-585, 2019.

Development of a functional airway-on-a-chip by 3D cell printing.

We used 3D cell printing to emulate an airway coupled with a naturally-derived blood vessel network in vitro. Decellularized extracellular matrix bioink derived from porcine tracheal mucosa (tmdECM) was used to encapsulate and print endothelial cells and fibroblasts within a designated polycarprolactone (PCL) frame. Providing a niche that emulates conditions in vivo, tmdECM gradually drives endothelial re-orientation, which leads to the formation of a lumen and blood vessel network. A fully-differentiated in vitro airway model was assembled with the printed vascular platform, and collectively reproduced a functional interface between the airway epithelium and the vascular network. The model presented respiratory symptoms including asthmatic airway inflammation and allergen-induced asthma exacerbation in physiological context. Because of the adaptable and automated nature of direct 3D cell printing, we expect that this will have relevance in vivo and high reproducibility for production of high-content platforms for preclinical trials in biomedical research.

Amnion-Analogous Medical Device for Fetal Membrane Healing: A Preclinical Long-Term Study.

Although recent invasive fetal surgeries have improved fetal outcomes, fetal membrane rupture remains a major complication, leading to premature delivery, thus undermining the complete benefits of such procedures. A biocompatible amnion-analogous medical device (AMED) consisting of polycaprolactone framework and decellularized amniotic membrane (dAM)-derived hydrogel for restoration of amniotic membrane defect is developed using 3D printing technology. Its efficacy on healing iatrogenic fetal membrane defects in vitro is evaluated, showing that the dAM gel contains migratory and proliferative properties. The fetoscope feasibility of the developed AMED is assessed using a pregnant swine model. All animals had successfully recovered from anesthesia and the fetoscopic procedure and maintained a healthy condition until the end of the pregnancy. AMED exhibits superior surgical handling characteristics and is easy to manufacture, nonimmunogenic, biocompatible, and suitable for storage and transport for off-the-shelf use; hence, it can be used in successfully sealing defect sites, thus improving the preservation of the amniotic fluid, which in turn improves fetal survival and development.

Nanoscale imaging of photocurrent enhancement by resonator array photovoltaic coatings.

Nanoscale surface patterning commonly used to increase absorption of solar cells can adversely impact the open-circuit voltage due to increased surface area and recombination. Here, we demonstrate absorptivity and photocurrent enhancement using silicon dioxide (SiO2) nanosphere arrays on a gallium arsenide (GaAs) solar cell that do not require direct surface patterning. Due to the combined effects of thin-film interference and whispering gallery-like resonances within nanosphere arrays, there is more than 20% enhancement in both absorptivity and photocurrent. To determine the effect of the resonance coupling between nanospheres, we perform a scanning photocurrent microscopy based on a near-field scanning optical microscopy measurement and find a substantial local photocurrent enhancement. The nanosphere-based antireflection coating (ARC), made by the Meyer rod rolling technique, is a scalable and a room-temperature process; and, can replace the conventional thin-film-based ARCs requiring expensive high-temperature vacuum deposition.

Indirect fabrication of versatile 3D microfluidic device by a rotating plate combined 3D printing system.

In the past decade, 3D-printing technology has been applied in the field of microfluidics to fabricate microfluidic devices for wide-ranging areas of study including chemistry, biology, medicine, and others. However, these methods face several limitations such as insufficient resolution and long fabrication time. In this study, versatile microfluidic devices with different functions were indirectly fabricated by a rapid sacrificial template printing process using a photocurable fluoropolymer with chemical durability. The Pluronic® F127 hydrogel as a sacrificial template was rapidly patterned on substrates by a non-lithographic printing process using a computer-controlled 3D-printing system. Viscous fluoropolymer was cast on the non-deformable template that was consequently removed by applying heat and negative pressure after UV curing. The chemical-resistant and transparent microchannels were oblate-hemispherical on the cross section. They were tested by performing a heterogeneous catalytic reaction as well as a photochemical reaction. The microchannels with controlled heights were devised to induce convection for functioning as a micromixer with asymmetric flows. Moreover, upon printing the Pluronic® F127 on both sides of the PFPE (perfluoropolyether-urethane dimethacrylate) membrane substrate, the 3D hybrid microfluidic device was embedded with a permeable membrane between the lower and upper channels, which is useful for gas-liquid chemical processes.

Correction: Indirect fabrication of versatile 3D microfluidic device by a rotating plate combined 3D printing system.

[This corrects the article DOI: 10.1039/C8RA08465C.].

Improving dielectric nanoresonator array coatings for solar cells.

Antireflection coatings based on dielectric nanosphere arrays are discussed in application to photovoltaic materials including silicon and gallium arsenide. We perform macro- and nanoscale characterization and finite-difference time-domain calculations demonstrating the enhanced optoelectronic properties. A significant absorptivity enhancement is achieved due to the collective resonant coupling of excited whispering gallery-like modes and thin-film interference effects. The resonant coupling is masked in macroscale measurements by the size variation of nanospheres, but it is clearly seen through imaging photocurrent at the nanoscale with near-field scanning photocurrent microscopy. The resonant coupling can be effectively tuned by the material, configuration, or size of nanospheres. Hybrid coatings combining nanospheres of different materials yield the highest efficiency gain, more than 30 %. We also evaluate an impact of manufacturing defects such as double layer formation. While the performance degrades, the antireflection coating still offers marked improvement in comparison with bare cells.

Paper in Electronic and Optoelectronic Devices.

Paper, one of the oldest materials for storage and exchange of human's information, has been reinvented as a building component of electronic and optoelectronic devices over the past decades with successful demonstration of paper-based or paper-using devices. These recent achievements can meet the demand for lightweight, cost-effective, and/or flexible electronic and optoelectronic devices with advanced functionality and reduced manufacturing costs. This article provides a review of electronic and optoelectronic devices relying on or making use of the unique properties achievable with paper-based materials. Basic scientific/technical principles, quantitative comparisons of material, electronic and/or optical properties, and benefits for each paper-based application are given. Application-specific research challenges, future design considerations, and development directions are also discussed.