3D-Printed Flexible Microfluidic Health Monitor for In Situ Sweat Analysis and Biomarker Detection.

Wearable sweat biosensors have shown great progress in noninvasive, in situ, and continuous health monitoring to demonstrate individuals' physiological states. Advances in novel nanomaterials and fabrication methods promise to usher in a new era of wearable biosensors. Here, we introduce a three-dimensional (3D)-printed flexible wearable health monitor fabricated through a unique one-step continuous manufacturing process with self-supporting microfluidic channels and novel single-atom catalyst-based bioassays for measuring the sweat rate and concentration of three biomarkers. Direct ink writing is adapted to print the microfluidic device with self-supporting structures to harvest human sweat, which eliminates the need for removing sacrificial supporting materials and addresses the contamination and sweat evaporation issues associated with traditional sampling methods. Additionally, the pick-and-place strategy is employed during the printing process to accurately integrate the bioassays, improving manufacturing efficiency. A single-atom catalyst is developed and utilized in colorimetric bioassays to improve sensitivity and accuracy. A feasibility study on human skin successfully demonstrates the functionality and reliability of our health monitor, generating reliable and quantitative in situ results of sweat rate, glucose, lactate, and uric acid concentrations during physical exercise.

Recent advances in biomedical applications of 2D nanomaterials with peroxidase-like properties.

Significant progress has been made in developing two-dimensional (2D) nanomaterials owing to their ultra-thin structure, high specific surface area, and many other advantages. Recently, 2D nanomaterials with enzyme-like properties, especially peroxidase (POD)-like activity, are highly desirable for many biomedical applications. In this review, we first classify the types of 2D POD-like nanomaterials and then summarize various strategies for endowing 2D nanomaterials with POD-like properties. Representative examples of biomedical applications are reviewed, emphasizing in antibacterial, biosensing, and cancer therapy. Last, the future challenges and prospects of 2D POD-like nanomaterials are discussed. This review is expected to provide an in-depth understanding of 2D POD-like materials for biomedical applications.

Excellent Specific Mechanical and Electrical Properties of Anisotropic Freeze-Cast Native and Carbonized Bacterial Cellulose-Alginate Foams.

Native and carbonized freeze-cast bacterial cellulose-alginate (BC-ALG) foams possess an ice-templated honeycomb-like architecture with remarkable properties. Their unique pore morphology consists of two levels of porosity: 20-50 µm diameter pores between, and 0.01-10 µm diameter pores within the cell-walls. The mechanical properties of the BC-ALG foams, a Young's modulus of up to 646.2 ± 90.4 kPa and a compressive yield strength of up to 37.1 ± 7.9 kPa, are high for their density and scale as predicted by the Gibson-Ashby model for cellular materials. Carbonizing the BC-ALG foams in an inert atmosphere at 1000-1200 °C in a second processing step, both pore morphology and mechanical properties of the BC-ALG remain well preserved with specific mechanical properties that are higher than those reported in the literature for similar foams. Also the electrical conductivity of the BC-ALG foams is high at 1.68 ± 0.04 S cm-1 at a density of only 0.055 g cm-3, and is found to increase with density as predicted, and as a function of the degree of carbonization determined by both carbonization temperature and atmosphere. The property profile makes freeze-cast BC-ALG foams and their carbonized foams attractive for energy applications and as a sorbent.

Long Non-Coding RNA (lncRNA) RAMS11 Promotes Metastatis and Cell Growth of Prostate Cancer by CBX4 Complex Binding to Top2α.

INTRODUCTION: Studies have confirmed that parts of the non-coding genes in the human genome play an important role in the pathogenesis and metastasis of prostate cancer. Among them, long non-coding RNAs (lncRNAs) are vitally involved in the biological regulation of prostate cancer. In addition, lncRNAs are closely associated with the recurrence, metastasis and prognosis of prostate cancer. However, the molecular pathogenesis of lncRNAs in regulating cell growth and metastasis of prostate cancer remains unclear. Therefore, this study was designed to explore the function and mechanism of lncRNA RAMS11 in cell growth and metastasis of prostate cancer. METHODS: Prostate cancer and para-carcinoma tissue samples were obtained from 42 patients who were diagnosed from March 2013 to September 2014 at Quanzhou First Hospital Affiliated to Fujian Medical University. Microarray experiments and real-time polymerase chain reaction (PCR) measured the expression of lncRNA. RWPE-2, LNCap, PC3 and DU145 cells were used for an in vitro model. RESULTS: The expression of lncRNA RAMS11 was up-regulated in prostate cancer tissue samples. LncRNA RAMS11 promoted cell growth and metastasis of prostate cancer cells. Down-regulation of lncRNA RAMS11 attenuated cell growth and metastasis of prostate cancer cells. We also demonstrated that lncRNA RAMS11 bound to CBX4 to activate expression of Top2α. LncRNA RAMS11 promoted tumor growth of prostate cancer in the mouse model. The inhibition of CBX4 attenuated the pro-cancer effects of lncRNA AMS11 in prostate cancer cells, while the activation of Top2α attenuated the anti-cancer effects of si-lncRNA RAMS11 in prostate cancer cells. DISCUSSION: Our results indicated that lncRNA RAMS11 promoted cell growth and metastasis of prostate cancer by CBX4 complex via binding to Top2α, and might be developed for the treatment of prostate cancer.

3D printed patient-specific aortic root models with internal sensors for minimally invasive applications.

Minimally invasive surgeries have numerous advantages, yet complications may arise from limited knowledge about the anatomical site targeted for the delivery of therapy. Transcatheter aortic valve replacement (TAVR) is a minimally invasive procedure for treating aortic stenosis. Here, we demonstrate multimaterial three-dimensional printing of patient-specific soft aortic root models with internally integrated electronic sensor arrays that can augment testing for TAVR preprocedural planning. We evaluated the efficacies of the models by comparing their geometric fidelities with postoperative data from patients, as well as their in vitro hemodynamic performances in cases with and without leaflet calcifications. Furthermore, we demonstrated that internal sensor arrays can facilitate the optimization of bioprosthetic valve selections and in vitro placements via mapping of the pressures applied on the critical regions of the aortic anatomies. These models may pave exciting avenues for mitigating the risks of postoperative complications and facilitating the development of next-generation medical devices.

In Situ Expansion, Differentiation, and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid.

RATIONALE: One goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be achieved using 3-dimensional bioprinting. Yet, inclusion of contiguous, living muscle to support pump function has not been achieved. This is largely due to the challenge of attaining high densities of cardiomyocytes-a notoriously nonproliferative cell type. An alternative strategy is to print with human induced pluripotent stem cells, which can proliferate to high densities and fill tissue spaces, and subsequently differentiate them into cardiomyocytes in situ. OBJECTIVE: To develop a bioink capable of promoting human induced pluripotent stem cell proliferation and cardiomyocyte differentiation to 3-dimensionally print electromechanically functional, chambered organoids composed of contiguous cardiac muscle. METHODS AND RESULTS: We optimized a photo-crosslinkable formulation of native ECM (extracellular matrix) proteins and used this bioink to 3-dimensionally print human induced pluripotent stem cell-laden structures with 2 chambers and a vessel inlet and outlet. After human induced pluripotent stem cells proliferated to a sufficient density, we differentiated the cells within the structure and demonstrated function of the resultant human chambered muscle pump. Human chambered muscle pumps demonstrated macroscale beating and continuous action potential propagation with responsiveness to drugs and pacing. The connected chambers allowed for perfusion and enabled replication of pressure/volume relationships fundamental to the study of heart function and remodeling with health and disease. CONCLUSIONS: This advance represents a critical step toward generating macroscale tissues, akin to aggregate-based organoids, but with the critical advantage of harboring geometric structures essential to the pump function of cardiac muscle. Looking forward, human chambered organoids of this type might also serve as a test bed for cardiac medical devices and eventually lead to therapeutic tissue grafting.

Long intergenic noncoding RNA 00844 promotes apoptosis and represses proliferation of prostate cancer cells through upregulating GSTP1 by recruiting EBF1.

Accumulating evidence have suggested the function of long noncoding RNAs as crucial players in the pathogenesis of prostate cancer (PC), a urologic tumor in male with poor prognosis. This study was designed to explore the functions of long intergenic noncoding RNA 00844 (LINC00844) in PC progression. The expression of LINC00844 and glutathione S-transferase P1-1 (GSTP1) was detected by reverse transcription quantitative polymerase chain reaction, followed by the identification of the relationship among LINC00844, GSTP1, and early B cell factor 1 (EBF1) by dual luciferase reporter gene assay, RNA immunoprecipitation assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay. Using loss- and gain-of-function assays, the effects of LINC00844, GSTP1, and EBF1 on the biological characteristics of PC cells were assessed by cell counting kit-8 assay, 5-ethynyl-2'-deoxyuridine assay, and flow cytometry. Lastly, the results from in vitro experiments were verified in vivo by establishing a xenograft tumor model in nude mice. LINC00844 and GSTP1 both displayed low expression in PC tissues and cells. LINC00844 positively regulated the expression of GSTP1 via recruiting EBF1. Overexpression of LINC00844 reduced proliferation and elevated apoptosis of PC cells through recruiting EBF1, which subsequently upregulated GSTP1. In vivo experiments confirmed that LINC00844 or GSTP1 upregulation attenuated tumor growth. LINC00844 elevated GSTP1 expression by recruiting EBF1 to the promoter region of GSTP1, thereby suppressing PC progression. Hence, LINC00844 is a novel therapeutic target for the development of new treatment protocols for PC.

3D Printed Polymer Photodetectors.

Extrusion-based 3D printing, an emerging technology, has been previously used in the comprehensive fabrication of light-emitting diodes using various functional inks, without cleanrooms or conventional microfabrication techniques. Here, polymer-based photodetectors exhibiting high performance are fully 3D printed and thoroughly characterized. A semiconducting polymer ink is printed and optimized for the active layer of the photodetector, achieving an external quantum efficiency of 25.3%, which is comparable to that of microfabricated counterparts and yet created solely via a one-pot custom built 3D-printing tool housed under ambient conditions. The devices are integrated into image sensing arrays with high sensitivity and wide field of view, by 3D printing interconnected photodetectors directly on flexible substrates and hemispherical surfaces. This approach is further extended to create integrated multifunctional devices consisting of optically coupled photodetectors and light-emitting diodes, demonstrating for the first time the multifunctional integration of multiple semiconducting device types which are fully 3D printed on a single platform. The 3D-printed optoelectronic devices are made without conventional microfabrication facilities, allowing for flexibility in the design and manufacturing of next-generation wearable and 3D-structured optoelectronics, and validating the potential of 3D printing to achieve high-performance integrated active electronic materials and devices.

3D Printed Organ Models with Physical Properties of Tissue and Integrated Sensors.

The design and development of novel methodologies and customized materials to fabricate patient-specific 3D printed organ models with integrated sensing capabilities could yield advances in smart surgical aids for preoperative planning and rehearsal. Here, we demonstrate 3D printed prostate models with physical properties of tissue and integrated soft electronic sensors using custom-formulated polymeric inks. The models show high quantitative fidelity in static and dynamic mechanical properties, optical characteristics, and anatomical geometries to patient tissues and organs. The models offer tissue-mimicking tactile sensation and behavior and thus can be used for the prediction of organ physical behavior under deformation. The prediction results show good agreement with values obtained from simulations. The models also allow the application of surgical and diagnostic tools to their surface and inner channels. Finally, via the conformal integration of 3D printed soft electronic sensors, pressure applied to the models with surgical tools can be quantitatively measured.

3D Printed Organ Models for Surgical Applications.

Medical errors are a major concern in clinical practice, suggesting the need for advanced surgical aids for preoperative planning and rehearsal. Conventionally, CT and MRI scans, as well as 3D visualization techniques, have been utilized as the primary tools for surgical planning. While effective, it would be useful if additional aids could be developed and utilized in particularly complex procedures involving unusual anatomical abnormalities that could benefit from tangible objects providing spatial sense, anatomical accuracy, and tactile feedback. Recent advancements in 3D printing technologies have facilitated the creation of patient-specific organ models with the purpose of providing an effective solution for preoperative planning, rehearsal, and spatiotemporal mapping. Here, we review the state-of-the-art in 3D printed, patient-specific organ models with an emphasis on 3D printing material systems, integrated functionalities, and their corresponding surgical applications and implications. Prior limitations, current progress, and future perspectives in this important area are also broadly discussed.

3D Printed Stretchable Tactile Sensors.

The development of methods for the 3D printing of multifunctional devices could impact areas ranging from wearable electronics and energy harvesting devices to smart prosthetics and human-machine interfaces. Recently, the development of stretchable electronic devices has accelerated, concomitant with advances in functional materials and fabrication processes. In particular, novel strategies have been developed to enable the intimate biointegration of wearable electronic devices with human skin in ways that bypass the mechanical and thermal restrictions of traditional microfabrication technologies. Here, a multimaterial, multiscale, and multifunctional 3D printing approach is employed to fabricate 3D tactile sensors under ambient conditions conformally onto freeform surfaces. The customized sensor is demonstrated with the capabilities of detecting and differentiating human movements, including pulse monitoring and finger motions. The custom 3D printing of functional materials and devices opens new routes for the biointegration of various sensors in wearable electronics systems, and toward advanced bionic skin applications.

Reversal of Early Diabetic Nephropathy by Islet Transplantation under the Kidney Capsule in a Rat Model.

Objective. Diabetic nephropathy (DN) is a common microvascular complication of diabetes mellitus, and insulin therapy has many side effects in the treatment of DN. Islet transplantation has emerged as a promising therapy for diabetic patients. This study was established to investigate its advantageous effects in a rat model of early DN. Methods. Streptozotocin was administered to the rats to induce diabetes. Twelve weeks later, the diabetic rats were divided into 3 groups: the islet-transplanted group (IT group), the insulin-treated group (IN group), and the untreated group (DN group). Renal injury and kidney structure were assessed by urinalysis and transmission electron microscopy (TEM) detection. Immunohistochemical staining and western blotting were performed to assess renal fibrosis levels. Results. The early DN features were reversed and the glomerular filtration barrier and basement membrane structures were improved at 4 weeks after islet transplantation. The urine microalbumin-to-creatinine ratio (ACR), protein-to-creatinine ratio, and mean thickness of the glomerular basement membrane (GBM) were significantly decreased in the IT group. The expression of renal fibrotic factors was also significantly decreased. Conclusions. These data suggest that early DN can be reversed after islet transplantation, and they may facilitate the development of a clinical therapeutic strategy for human diabetes mellitus.

Using PG-Liposome-Based System to Enhance Puerarin Liver-Targeted Therapy for Alcohol-Induced Liver Disease.

A critical issue for alcohol-induced liver disease (ALD) therapeutics is the lack of a highly efficient delivery system. In this study, a Puerarin-propylene glycol-liposome system was prepared for the purpose of targeting puerarin, an isoflavon, to the liver. Transmission electron microscope (TEM) results showed the liposomes to be spherical in shape with an average diameter of 182 nm with a polydispersity index of 0.239. The zeta potential of the particles was about -30 mV. The entrapment efficiency of puerarin was above 90%. MTT-based assay in HpeG2 cells showed no significant cytotoxicity in the presence of up to 25% concentration of the system containing 3% puerarin. In vivo performance of this system was studied in mice. Pharmacokinetics and distribution of puerarin-PG-liposome system was studied relative to puerarin solution at the same dose levels. The results show that puerarin-PG-liposome prolonged drug retention time and decreased elimination of puerarin in mice (AUC of liposome system and solution was 9.5 and 4.0 mg h L-1, respectively). Furthermore, propylene glycol (PG)-liposome system enhanced puerarin distribution into liver and spleen, while decreasing puerarin distribution in other tissues. Overall, the puerarin-PG-liposome system showed enhanced therapeutic effect in mice with ALD.