Trends in three malnutrition factors in the global burden of disease: iodine deficiency, vitamin A deficiency, and protein-energy malnutrition (1990-2019).

Background: Vitamin A deficiency, iodine deficiency, and protein-energy malnutrition are prevalent malnutrition issues that disproportionately affect low-income countries and pose significant risks to the health and development of children and adolescents. This study offers a detailed examination of these deficiencies' prevalence trends and gender and regional variations using Global Burden of Disease Study data from 1990 to 2019. It also assesses the specific impact on various age groups, providing essential insights for targeted health interventions and policy-making. Methods: Data spanning from 1990 to 2019 on Vitamin A deficiency, iodine deficiency, and protein-energy malnutrition were extracted from the 2019 Global Burden of Disease Study. Age-Standardized Incidence Rates (ASR) were computed by gender, region, and etiology, utilizing the estimated annual percentage change (EAPC) to assess temporal trends. Results: In 2019, Central Sub-Saharan Africa had the highest prevalence of Vitamin A deficiency, particularly among males, and iodine deficiency peaked in the same region for both genders. South Asia had the highest incidence of protein-energy malnutrition for both genders. Regions with a low Socio-Demographic Index (SDI) showed lower ASR for these deficiencies. Notably, Cameroon, Equatorial Guinea, and Maldives recorded the highest ASR for vitamin A deficiency, iodine deficiency, and protein-energy malnutrition, respectively. The declining ASR trend for vitamin A deficiency, especially among males, suggests effective interventions. East Asia saw a significant increase in iodine deficiency ASR from 1990 to 2019, particularly among women, requiring targeted interventions. The rising ASR of protein-energy malnutrition in several regions, especially among men, raises concerns. Vitamin A deficiency primarily affected children and adolescents, iodine deficiency predominantly impacted adolescents and young adults, and protein-energy malnutrition was chiefly observed among children under 5 years old. These findings underscore the necessity for tailored interventions considering age-specific nutritional needs and challenges.

Investigation of Axial Tensile Fracture Performance of Recycled Brick Coarse Aggregate Concrete Using a Cohesion Model.

Currently, microscopic research on the tensile fracture properties of recycled brick coarse aggregate concrete has mainly adopted microscopy techniques, which can clearly observe the actual damage situations of each phase material but are unable to individually analyze the effect of a specific material factor on the tensile properties of recycled concrete. This brings much uncertainty to the practical application of recycled concrete. Therefore, this study proposes a cohesive zone model (CZM) for simulating the tensile fracture of recycled brick coarse aggregate (RBCA) concrete. To this end, the study explores the effects of various critical factors on the fracture mode and bearing capacity of recycled brick aggregate concrete, including the replacement rate of recycled brick coarse aggregate, pore structure, interfacial transition zone (ITZ) strength, mortar strength, and volume fraction of brick aggregate. The results indicate that, when the minor to major axis ratio of elliptical pores is 0.5 ≤ K < 1, the following order of influence can be observed: random convex polygonal pores, circular pores, and elliptical pores. Moreover, excessively strengthening the ITZ and mortar does not significantly enhance the tensile performance of RBCA concrete. The distribution location of aggregate has a significant impact on the crack shape of recycled concrete, as does the pore structure, due to their randomness. Therefore, this article also discusses these. These findings contribute to a comprehensive understanding of the tensile properties of recycled brick coarse aggregate and provide insights into optimizing its behavior.

Take-out food enhances the risk of MPs ingestion and obesity, altering the gut microbiome in young adults.

Young people are consuming large amounts of microplastics (MPs) due to the booming development of the take-out industry. To investigate the association between MPs exposure and obesity, 121 volunteers were divided into high MPs exposure (HME) and low MPs exposure (LME) according to the frequency of take-out food consumption. Fecal samples were collected for MPs detection using Raman spectra analysis, and identification of the gut microbiota was based on 16 S rDNA/ITS, while metabolite analysis was performed by LC-MS/MS. High levels of MPs and body mass index (BMI) were observed in the HME group (P < 0.05). Both the multiple linear regression (MLR) model and the binary logistic regression (BLR) (OR: 1.264, 95 % CI: 1.108-1.441, P < 0.001) analysis showed a positive correlation between MPs content and BMI. Microbial community analysis revealed that Veillonella, Alistipes and Dothideomycotes (pathogenic fungi) increased in HME participants, whereas Faecalibacterium and Coprococcus decreased. Meanwhile, analysis of stool metabolites showed that vancomycin resistance, selenocompound metabolism and drug metabolism pathways were enhanced in HME participants. These findings indicate that frequent consumption of take-out food may elevate the intake of microplastics, consequently modifying the gut microbiota and metabolites of young adults, and could represent a potential risk factor for obesity.

Soft Millirobot Capable of Switching Motion Modes on the Fly for Targeted Drug Delivery in the Oviduct.

Small-scale magnetic robots with fixed magnetizations have limited locomotion modes, restricting their applications in complex environments in vivo. Here we present a morphology-reconfigurable millirobot that can switch the locomotion modes locally by reprogramming its magnetizations during navigation, in response to distinct magnetic field patterns. By continuously switching its locomotion modes between the high-velocity rigid motion and high-adaptability soft actuation, the millirobot efficiently navigates in small lumens with intricate internal structures and complex surface topographies. As demonstrations, the millirobot performs multimodal locomotion including woodlouse-like rolling and flipping, sperm-like rotating, and snake-like gliding to negotiate different terrains, including the unrestricted channel and high platform, narrow channel, and solid-liquid interface, respectively. Finally, we demonstrate the drug delivery capability of the millirobot through the oviduct-mimicking phantom and ex vivo oviduct. The magnetization reprogramming strategy during navigation represents a promising approach for developing self-adaptive robots for performing complex tasks in vivo.

Robust explanation supervision for false positive reduction in pulmonary nodule detection.

BACKGROUND: Lung cancer is the deadliest and second most common cancer in the United States due to the lack of symptoms for early diagnosis. Pulmonary nodules are small abnormal regions that can be potentially correlated to the occurrence of lung cancer. Early detection of these nodules is critical because it can significantly improve the patient's survival rates. Thoracic thin-sliced computed tomography (CT) scanning has emerged as a widely used method for diagnosing and prognosis lung abnormalities. PURPOSE: The standard clinical workflow of detecting pulmonary nodules relies on radiologists to analyze CT images to assess the risk factors of cancerous nodules. However, this approach can be error-prone due to the various nodule formation causes, such as pollutants and infections. Deep learning (DL) algorithms have recently demonstrated remarkable success in medical image classification and segmentation. As an ever more important assistant to radiologists in nodule detection, it is imperative ensure the DL algorithm and radiologist to better understand the decisions from each other. This study aims to develop a framework integrating explainable AI methods to achieve accurate pulmonary nodule detection. METHODS: A robust and explainable detection (RXD) framework is proposed, focusing on reducing false positives in pulmonary nodule detection. Its implementation is based on an explanation supervision method, which uses nodule contours of radiologists as supervision signals to force the model to learn nodule morphologies, enabling improved learning ability on small dataset, and enable small dataset learning ability. In addition, two imputation methods are applied to the nodule region annotations to reduce the noise within human annotations and allow the model to have robust attributions that meet human expectations. The 480, 265, and 265 CT image sets from the public Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) dataset are used for training, validation, and testing. RESULTS: Using only 10, 30, 50, and 100 training samples sequentially, our method constantly improves the classification performance and explanation quality of baseline in terms of Area Under the Curve (AUC) and Intersection over Union (IoU). In particular, our framework with a learnable imputation kernel improves IoU from baseline by 24.0% to 80.0%. A pre-defined Gaussian imputation kernel achieves an even greater improvement, from 38.4% to 118.8% from baseline. Compared to the baseline trained on 100 samples, our method shows less drop in AUC when trained on fewer samples. A comprehensive comparison of interpretability shows that our method aligns better with expert opinions. CONCLUSIONS: A pulmonary nodule detection framework was demonstrated using public thoracic CT image datasets. The framework integrates the robust explanation supervision (RES) technique to ensure the performance of nodule classification and morphology. The method can reduce the workload of radiologists and enable them to focus on the diagnosis and prognosis of the potential cancerous pulmonary nodules at the early stage to improve the outcomes for lung cancer patients.

Multifunctional Nanofibrous Scaffolds Capable of Localized Delivery of Theranostic Nanoparticles for Postoperative Cancer Management.

Postoperative recovery of cancer patients can be affected by complications, such as tissue dysfunction or disability caused by tissue resection, and also cancer recurrence resulting from residual cancer cells. Despite impressive progress made for tissue engineering scaffolds that assist tissue regeneration for postoperative cancer patients, the majority of existing tissue engineering scaffolds still lack functions for monitoring and killing residual cancer cells, if there are any, upon their detection. In this study, multifunctional scaffolds that comprise biodegradable nanofibers and core-shell structured microspheres encapsulated with theranostic nanoparticles (NPs) are developed. The multifunctional scaffolds possess an extracellular matrix-like nanofibrous architecture and soft tissue-like mechanical properties, making them excellent tissue engineering patch candidates for assisting in the repair and regeneration of tissues at the cancerous sites after surgery. Furthermore, they are capable of localized delivery of theranostic NPs upon quick degradation of core-shell structured microspheres that contain theranostic NPs. Leveraging on folic acid-mediated ligand-receptor binding, surface-enhanced Raman scattering activity, and near-infrared-responsive photothermal effect of the theranostic gold NPs (AuNPs) delivered locally, the multifunctional scaffolds display excellent active targeting, diagnosis, and photothermal therapy functions for cancer cells, showing great promise for adaptive postoperative cancer management.

The benefits of edible mushroom polysaccharides for health and their influence on gut microbiota: a review.

The gut microbiome is a complex biological community that deeply affects various aspects of human health, including dietary intake, disease progression, drug metabolism, and immune system regulation. Edible mushroom polysaccharides (EMPs) are bioactive fibers derived from mushrooms that possess a range of beneficial properties, including anti-tumor, antioxidant, antiviral, hypoglycemic, and immunomodulatory effects. Studies have demonstrated that EMPs are resistant to human digestive enzymes and serve as a crucial source of energy for the gut microbiome, promoting the growth of beneficial bacteria. EMPs also positively impact human health by modulating the composition of the gut microbiome. This review discusses the extraction and purification processes of EMPs, their potential to improve health conditions by regulating the composition of the gut microbiome, and their application prospects. Furthermore, this paper provides valuable guidance and recommendations for future studies on EMPs consumption in disease management.

The Nutrients and Volatile Compounds in Stropharia rugoso-annulata by Three Drying Treatments.

This study aimed to examine the differences in the nutrients and volatile compounds of Stropharia rugoso-annulata after undergoing three different drying treatments. The fresh mushrooms were dried using hot air drying (HAD), vacuum freeze drying (VFD), and natural air drying (NAD), respectively. After that, the nutrients, volatile components, and sensory evaluation of the treated mushrooms were comparably analyzed. Nutrients analysis included proximate compositions, free amino acids, fatty acids, mineral elements, bioactive compositions, and antioxidant activity. Volatile components were identified by headspace-solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS) and analyzed with principal component analysis (PCA). Finally, sensory evaluation was conducted by ten volunteers for five sensory properties. The results showed that the HAD group had the highest vitamin D2 content (4.00 µg/g) and antioxidant activity. Compared with other treatments, the VFD group had higher overall nutrient contents, as well as being more preferred by consumers. Additionally, there were 79 volatile compounds identified by HS-SPME-GC-MS, while the NAD group showed the highest contents of volatile compounds (1931.75 µg/g) and volatile flavor compounds (1307.21 µg/g). PCA analysis suggested the volatile flavor compositions were different among the three groups. In summary, it is recommended that one uses VFD for obtaining higher overall nutritional values, while NAD treatment increased the production of volatile flavor components of the mushroom.

Electrospinning and Cell Fibers in Biomedical Applications.

Human body tissues such as muscle, blood vessels, tendon/ligaments, and nerves have fiber-like fascicle morphologies, where ordered organization of cells and extracellular matrix (ECM) within the bundles in specific 3D manners orchestrates cells and ECM to provide tissue functions. Through engineering cell fibers (which are fibers containing living cells) as living building blocks with the help of emerging "bottom-up" biomanufacturing technologies, it is now possible to reconstitute/recreate the fiber-like fascicle morphologies and their spatiotemporally specific cell-cell/cell-ECM interactions in vitro, thereby enabling the modeling, therapy, or repair of these fibrous tissues. In this article, a concise review is provided of the "bottom-up" biomanufacturing technologies and materials usable for fabricating cell fibers, with an emphasis on electrospinning that can effectively and efficiently produce thin cell fibers and with properly designed processes, 3D cell-laden structures that mimic those of native fibrous tissues. The importance and applications of cell fibers as models, therapeutic platforms, or analogs/replacements for tissues for areas such as drug testing, cell therapy, and tissue engineering are highlighted. Challenges, in terms of biomimicry of high-order hierarchical structures and complex dynamic cellular microenvironments of native tissues, as well as opportunities for cell fibers in a myriad of biomedical applications, are discussed.

The Relationship between the Dietary Inflammatory Index (DII) and Metabolic Syndrome (MetS) in Middle-Aged and Elderly Individuals in the United States.

(1) Background: With the aging demographic shift in society, there is a growing number of middle-aged and elderly individuals affected by metabolic syndrome (MetS), a risk factor contributing to all causes of mortality. Inflammation plays a crucial role in the development of MetS. This study aims to examine the correlation between MetS and pro-inflammatory diets in middle-aged and elderly individuals, utilizing the Dietary Inflammation Index (DII) as a measure. (2) Methods: Data were extracted from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) database for individuals who were 45 years of age or older. The DII was determined for each participant through 24-h dietary recall interviews. The relationship between DII and MetS was assessed using binary logistic regression analysis, and the association between DII and MetS-related indicators was further explored through generalized linear model (GLM) and quantile regression analysis. (3) Results: A total of 3843 middle-aged and elderly individuals were included in the study. After controlling for confounding factors, the highest quartile of DII was associated with a higher risk of MetS (ORQ4:Q1 = 1.339; 95% CI: 1.013, 1.769; p for trend = 0.018). The top DII quartile also increased the risk of reduced HDL-C (ORQ4:Q1 = 1.499; 95% CI: 1.005, 2.234; p for trend = 0.048) and raised FG (ORQ4:Q1 = 1.432; 95% CI: 1.095, 1.873; p for trend = 0.010) compared to the lowest DII quartile. The levels of DII were found to be positively correlated with BMI (ß = 0.258, p = 0.001), FPG (ß = 0.019, p = 0.049), TG (ß = 2.043, p = 0.013), waistline (ß = 0.580, p = 0.002), and negatively correlated with HDL-C (ß = -0.672, p = 0.003). (4) Conclusions: In middle-aged and elderly individuals in the United States, a high DII score has been linked to the presence of MetS, low HDL-C, and hyperglycemia. Therefore, dietary recommendations for the middle-aged and elderly should focus on reducing the DII by choosing foods rich in antioxidants, dietary fiber, and unsaturated fatty acids.

Reconfigurable scaffolds for adaptive tissue regeneration.

Tissue engineering and regenerative medicine have offered promising alternatives for clinical treatment of body tissue traumas, losses, dysfunctions, or diseases, where scaffold-based strategies are particularly popular and effective. Over the decades, scaffolds for tissue regeneration have been remarkably evolving. Nevertheless, conventional scaffolds still confront grand challenges in bio-adaptions in terms of both tissue-scaffold and cell-scaffold interplays, for example complying with complicated three-dimensional (3D) shapes of biological tissues and recapitulating the ordered cell regulation effects of native cell microenvironments. Benefiting from the recent advances in "intelligent" biomaterials, reconfigurable scaffolds have been emerging, demonstrating great promise in addressing the bio-adaption challenges through altering their macro-shapes and/or micro-structures. This mini-review article presents a brief overview of the cutting-edge research on reconfigurable scaffolds, summarizing the materials for forming reconfigurable scaffolds and highlighting their applications for adaptive tissue regeneration. Finally, the challenges and prospects of reconfigurable scaffolds are also discussed, shedding light on the bright future of next-generation reconfigurable scaffolds with upgrading adaptability.

Biomanufacturing of biomimetic three-dimensional nanofibrous multicellular constructs for tissue regeneration.

Biomanufacturing of functional tissue analogues is of great importance in regenerative medicine. However, this is still highly challenging due to extreme difficulties in recreating/recapitulating complicated anatomies of body tissues that have both well-defined three-dimensional (3D) multicellular organizations and bioactive nanofibrous extracellular matrix (ECM). In the current investigation, a biomanufacturing approach via concurrent emulsion electrospinning and coaxial cell electrospraying was developed, which could fabricate 3D nanofibrous multicellular constructs that resemble both the multicellular organizations and bioactive nanofibrous microenvironments of body tissues. In the proof-of-concept study, endothelial cells (ECs) and smooth muscle cells (SMCs) were placed in respective layers of multilayer-structured constructs. The two different construct layers consisted of nanofibers providing different topographies (randomly oriented nanofibers or aligned nanofibers) and contained different growth factors (vascular endothelial growth factor or platelet-derived growth factor). The ECs and SMCs in the different construct layers showed high cell densities (> 4 ×105 cells/cm2 after 4-day incubation) and high cell viabilities (> 95%). Owing to the contact guidance/stimulation by different fibrous topographies and sequential release of different growth factors, ECs and SMCs exhibited distinct morphologies (uniformly stretched plaque-shaped or directionally elongated) and displayed enhanced proliferative activities. Our biomanufacturing approach is shown to be effective and efficient in reconstituting/replicating cell-ECM organizations as well as their interactions similar to those in body tissues such as blood vessels, indicating the great promise to produce a range of tissue analogues with biomimetic structures and functions for modeling or regenerating body tissues.

Synthesis and investigation of phosphorus-free ionic liquids as multifunctional lubricating additives.

Ionic liquids (ILs) have been extensively studied as lubricants or lubricant additives for two decades by virtue of their unique physical and chemical properties. Here, two phosphorus-free multifunctional protic ILs were synthesized by reacting oleic acid and a dimer acid with an alkyl aromatic amine. Both were completely miscible in various base fluids like mineral oil, polyether, synthetic ester, and polyalpha olefin. Furthermore, no corrosion towards copper strips was found for these additives due to the absence of phosphorus, halogen, and sulfur in their molecular structures. Tribological tests found that they could significantly improve the tribological performance of base oil in a wide range of test conditions. Additionally, due to the presence of an alkyl diphenylamine group, they could considerably enhance the oxidative stability of the base oil. Overall, the facile preparation approach, good solubility, low corrosion, and excellent tribological behavior and antioxidation property make them suitable as multifunctional additives in various lubricants.

Morphing-to-Adhesion Polysaccharide Hydrogel for Adaptive Biointerfaces.

Reliable functions of medical implants highly depend on biocompatible, conformal, and stable biointerfaces for seamless biointegration with biological tissues. Though flexible biointerfaces based on synthetic hydrogels have shown promise in optimizing implant biointegration via surgical suturing, physical attachment, or manual preshaping, they still suffer from poor adaptability, such as tissue damage by surgical suturing, low bioactivity, and difficulties in conformal contact and stable fixation, especially for specific tissues of large surface curvatures. Here, we report a bilayer hydrogel-based adaptive biointerface (HAB) made of two polysaccharide derivates, N-hydroxysuccinimide (NHS) ester-activated alginate and chitosan, harnessing dual advantages of their different swelling and active groups. Leveraging on the differential swelling between the two hydrogel layers and covalent linkages with active groups at hydrogel interfaces, HABs can be programmed into sealed tubes with tunable diameters via water-induced compliable shape morphing and instant interfacial adhesion. We further demonstrate that the polysaccharide-based morphing-to-adhesion HAB possesses outstanding bioactivity in directing cellular focal adhesion and intercellular junction, versatile geometrical adaptability to diverse tubular tissues with a wide range of surface curvatures (2.8 × 102-1.3 × 103 m-1), and excellent mechanical stability in high load-/shear-bearing physiological environments (blood flow volume: 85 mm·s-1). HABs overcome the limitations of existing biointerfaces in terms of poor bioactivity and difficult biointegration with biological tissues of large surface curvatures, holding promise to open new avenues for adaptive biointerfaces and reliable medical implants.

Light-induced charged slippery surfaces.

Slippery lubricant-infused porous (SLIPS) and superhydrophobic surfaces have emerged as promising interfacial materials for various applications such as self-cleaning, anti-icing, and antifouling. Paradoxically, the coverage/screening of lubricant layer on underlying rough matrix endows functionalities impossible on superhydrophobic surfaces; however, the inherent flexibility in programming droplet manipulation through tailoring structure or surface charge gradient in underlying matrix is compromised. Here, we develop a class of slippery material that harnesses the dual advantages of both solid and lubricant. This is achieved by rationally constructing a photothermal-responsive composite matrix with real-time light-induced surface charge regeneration capability, enabling photocontrol of droplets in various working scenarios. We demonstrate that this light-induced charged slippery surface (LICS) exerts photocontrol of droplets with fast speed, long distance, antigravity motion, and directionally collective motion. We further extend the LICS to biomedical domains, ranging from specific morphological hydrogel bead formation in an open environment to biological diagnosis and analysis in closed-channel microfluidics.

Corrigendum to A stage-specific cell-manipulation platform for inducing endothelialization on demand.

[This corrects the article DOI: 10.1093/nsr/nwz188.].

Circular RNA circ_0020123 Promotes Non-Small Cell Lung Cancer Progression Through miR-384/TRIM44 Axis.

BACKGROUND: It was reported that circular RNAs (circRNAs) and microRNAs (miRNAs) were related to non-small cell lung cancer (NSCLC) development. However, the detailed mechanisms of circ_0020123 and miR-384 in NSCLC are elusive. METHODS: QRT-PCR and Western blot assay were performed to detect the transcription and protein levels of genes, respectively. Then, the functional experiments, including MTT assay, flow cytometry, and transwell assay, were employed. Besides, the interaction between miR-384 and circ_0020123 or tripartite motif­containing protein 44 (TRIM44) was predicted by starbase or targetscan, and then verified by the dual-luciferase reporter, RNA pull-down assays and RNA immunoprecipitation assay (RIP). Mouse xenograft assay was performed to evaluate the effect of circ_0020123 on tumor growth in vivo. RESULTS: Levels of circ_0020123 and TRIM44 were enhanced, and the miR-384 level was attenuated in NSCLC tissues and cells. Circ_0020123 depletion attenuated the abilities of NSCLC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT), and induced apoptosis. Besides, circ_0020123 interacted with miR-384, and miR-384 targeted TRIM44. Circ_0020123 regulated cell progression by regulating miR-384 and subsequently mediated TRIM44 expression. Besides, circ_0020123 depletion repressed tumor growth in vivo. CONCLUSION: We demonstrated that circ_0020123 knockdown suppressed NSCLC cell progression by regulating the miR-384/TRIM44 axis, providing the theoretical basis for the therapy of NSCLC.

Nanofibrous bicomponent scaffolds for the dual delivery of NGF and GDNF: controlled release of growth factors and their biological effects.

Electrospun fibrous scaffolds capable of providing dual growth factor delivery in a controlled manner have distinctive advantages for tissue engineering. In this study, we have investigated the formation, structure, and characteristics/properties of fibrous bicomponent scaffolds for the dual delivery of glial cell line-derived neurotrophic factor (GDNF) and nerve growth factor (NGF) for peripheral nerve tissue regeneration. GDNF and NGF were incorporated into core-shell structured poly(lactic-co-glycolic acid) (PLGA) and poly (D,L-lactic acid) (PDLLA) nanofibers, respectively, through emulsion electrospinning. Using dual-source dual-power electrospinning, bicomponent scaffolds composed of GDNF/PLGA fibers and NGF/PDLLA fibers with different fiber component ratios were produced. The structure, properties, and in vitro release behavior of mono- and bicomponent scaffolds were systematically investigated. Concurrent and sustained release of GDNF and NGF from bicomponent scaffolds was achieved and their release profiles could be tuned. In vitro biological investigations were conducted. Rat pheochromocytoma cells were found to attach, spread, and proliferate on all scaffolds. The release of growth factors from scaffolds could induce much improved neurite outgrowth and neural differentiation. GDNF and NGF released from GDNF/PLGA scaffolds and NGF/PDLLA scaffolds, respectively, could induce dose-dependent neural differentiation separately. GDNF and NGF released from bicomponent scaffolds exerted a synergistic effect on promoting neural differentiation.

Three-dimensional endothelial cell incorporation within bioactive nanofibrous scaffolds through concurrent emulsion electrospinning and coaxial cell electrospraying.

Nanofibrous scaffolds hold great promise in tissue engineering owing to their extracellular matrix (ECM)-mimicking architectures. Electrospinning, with its ease for producing nanofibrous scaffolds, has therefore been widely employed for various tissue engineering applications. However, electrospun nanofibrous scaffolds have faced the inherent challenge of three-dimensional (3D) cell distribution due to the small sizes of interconnected pores in these scaffolds when conventional approach of scaffold fabrication with subsequent cell seeding is adopted, which severely limits their applications in repairing/regenerating human body tissues with thick and vascularized structures. In this study, we demonstrate a method to directly place living endothelial cells within bioactive nanofibrous scaffolds in 3D through concurrent emulsion electrospinning and coaxial cell electrospraying. Using this concurrent manufacturing method, endothelial cells are encapsulated in hydrogel microspheres and deposited along with vascular endothelial growth factor (VEGF)-containing nanofibers in the scaffold fabrication process, resulting in nanofibrous scaffolds with 3D embedded cell-encapsulated microspheres. After selective disruption of the hydrogel microspheres, the encapsulated endothelial cells are released, yielding bioactive nanofibrous scaffolds with tissue-like 3D cell-incorporated nanofibrous structures. It is shown that cell viability is well preserved (>98%) during the concurrent manufacturing process and that a deep cell distribution (~100 µm) through the scaffold thickness has been achieved. With combined structural and biochemical cues via the 3D cell-incorporated architectures, endothelial cells can freely stretch, display enhanced intercellular connections, and maintain the phenotype in the bioactive nanofibrous scaffolds. Our investigations offer a promising platform technology for creating bioactive nanofibrous scaffolds with 3D cell incorporation and for overcoming inherent problems of electrospun nanofibrous scaffolds, which should open new avenues for biomanufacturing tissue-mimicking constructs with vascularized structures and complex anatomy. STATEMENT OF SIGNIFICANCE: Electrospun nanofibrous scaffolds face challenges in three-dimensional (3D) cell incorporation and vascularization. Enhancing cell penetration via enlarged interconnected pores is a common strategy to address that. However, there are conflicts between cell penetration and structural integrity for scaffolds formed using such strategy, as deep cell penetration, if possible, can only achieve in highly loose architectures. In this investigation, we demonstrate a concurrent emulsion electrospinning and coaxial cell electrospraying technique, realizing 3D endothelial cell incorporation in electrospun nanofibrous scaffolds independent of cell penetration. Our technology appropriately addresses the conflict between deep 3D cell incorporation and structural integrity. In the scaffolds, the 3D incorporated endothelial cells show well-preserved viability, phenotype and functions, implying improved vascularization potential.

Shape-adaptable biodevices for wearable and implantable applications.

Emerging wearable and implantable biodevices have been significantly revolutionizing the diagnosis and treatment of disease. However, the geometrical mismatch between tissues and biodevices remains a great challenge for achieving optimal performances and functionalities for biodevices. Shape-adaptable biodevices enabling active compliance with human body tissues offer promising opportunities for addressing the challenge through programming their geometries on demand. This article reviews the design principles and control strategies for shape-adaptable biodevices with programmable shapes and actively compliant capabilities, which have offered innovative diagnostic/therapeutic tools and facilitated a variety of wearable and implantable applications. The state-of-the-art progress in applications of shape-adaptable biodevices in the fields of smart textiles, wound care, healthcare monitoring, drug and cell delivery, tissue repair and regeneration, nerve stimulation and recording, and biopsy and surgery, is highlighted. Despite the remarkable advances already made, shape-adaptable biodevices still confront many challenges on the road toward the clinic, such as enhanced intelligence for actively sensing and operating in response to physiological environments. Next-generation paradigms will shed light on future directions for extending the breadth and performance of shape-adaptable biodevices for wearable and implantable applications.