Associations Between Multiple Dimensions of Sleep and Mood During Early Adolescence: A Longitudinal Daily Diary Study.

Prior research has observed reciprocal associations between sleep and mood. However, these findings are primarily based on the examination of one or two aspects of sleep behaviors (e.g., duration, quality), neglecting how multiple dimensions of sleep (particularly indicators pertinent to adolescence, e.g., sleep variability) are linked to adolescent mood both daily and longitudinally. Drawing on a multidimensional framework for sleep, this study addressed the knowledge gap by examining the directionality of and differential effects for associations between multiple dimensions of sleep and mood during early adolescence. Participants were 273 Chinese early adolescents (34.39% girls; Mage = 11.57, SD = 1.31), who filled out a pre-survey on demographics (T1) and 7-day diaries on sleep (i.e., duration, quality, disturbance, and latency) and mood (i.e., positive and negative mood). Adolescents completed another wave of diary reports 1 year later (T2). Findings revealed both bidirectional and unidirectional, within-person effects depending on specific sleep parameters, suggesting differential associations between multiple dimensions of sleep and mood. Specifically, on days when adolescents had longer sleep latency and greater disturbance than usual, they reported higher negative mood the next day, whereas higher negative mood was linked to poorer sleep quality the next day. The longitudinal investigation found that greater variability in sleep quality at T1 was associated with higher negative mood at T2. These findings underscore the importance of understanding the complex interplay between sleep and mood by examining the directionality of and differential effects for the daily and longer-term associations between multiple dimensions of sleep and mood among early adolescents.

BZW1 is a prognostic and immunological biomarker in pancreatic adenocarcinoma.

Pancreatic adenocarcinoma is the most common malignant tumor of the digestive system and is called the "king of cancer" because it has been labeled with high malignancy, rapid progression, poor survival, and poor prognosis. Previously, it was reported that the basic leucine zipper and W2 domains 1 (BZW1) is involved in the progression of many tumors. However, its research in digestive system tumors such as pancreatic cancer is rarely studied. To explore potential biomarkers related to survival and prognosis of pancreatic cancer and provide a new targeted therapy for it. We first analyzed the mRNA and protein expression of BZW1 in pancreatic cancer. We then explored the correlation of BZW1 with survival prognosis and immune infiltration in pancreatic cancer patients. Finally, we explored BZW1-related gene enrichment analysis, including protein-protein interaction networks, gene ontology functional enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The mRNA and protein expression of the BZW1 gene in pancreatic cancer tissues were higher than those in adjacent normal tissues, and pancreatic cancer patients with high BZW1 expression had a poor prognosis. In addition, the expression of BZW1 was positively or negatively correlated with different immune cells of pancreatic cancer, such as CD4 + T lymphocytes, CD8 + T lymphocytes, B cells, macrophages, neutrophils, etc. Correlation enrichment analysis showed that we obtained 50 available experimentally determined BZW1-binding proteins and 100 targeted genes related to BZW1, and the intersection genes were eukaryotic translation termination factor 1 and Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3. Moreover, there was a positive correlation between BZW1 and eukaryotic translation termination factor 1 and Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 genes in pancreatic cancer. Gene ontology enrichment analysis showed BZW1 was mainly related to biological processes such as "mRNA processing," "RNA splicing," "regulation of translational initiation," and "activation of innate immune response." The results of Kyoto Encyclopedia of Genes and Genomes pathway analysis further indicated that BZW1 may be involved in pancreatic carcinogenesis through the "spliceosome" and "ribosome." The BZW1 gene may be a potential immunotherapy target and a promising prognostic marker for pancreatic cancer.

Microgels for bioprinting: recent advancements and challenges.

Microgels have become a popular and powerful structural unit in the bioprinting field due to their advanced properties, ranging from the tiny size and well-connected hydrogel (nutrient) network to special rheological properties. Different microgels can be fabricated by a variety of fabrication methods including bulk crushing, auxiliary dripping, multiphase emulsion, and lithography technology. Traditionally, microgels can encapsulate specific cells and are used for in vitro disease models and in vivo organ regeneration. Furthermore, microgels can serve as a drug carrier to realize controlled release of drug molecules. Apart from being used as an independent application unit, recently, these microgels are widely applied as a specific bioink component in 3D bioprinting for in situ tissue repair or building special 3D structures. In this review, we introduce different methods used to generate microgels and the microgel-based bioink for bioprinting. Besides, the further tendency of microgel development in future is introduced and predicted to provide guidance for related researchers in exploring more effective ways to fabricate microgels and more potential bioprinting application cases as multifunctional bioink components.

Ethnic/Racial Identity, Adolescent Sleep, and Somatic Health: Discrimination and Stress Responses as Mediating Mechanisms.

PURPOSE: This study sought to examine whether the daily associations between ethnic/racial discrimination and stress responses served as mediators linking ethnic/racial identity (ERI), adolescent sleep health, and somatic symptoms. METHODS: Data were drawn from 279 adolescents of color (69% female; 24% African Americans; 31% Asian Americans; 41% Latinx; and 4% unknown ethnicity/race; Mage = 14.31 years, SD = 0.65). Adolescents first completed an online survey about ERI exploration and commitment; and then 14-day diaries on ethnic/racial discrimination and stress responses (i.e., rumination and problem-solving coping), and finally, a post-diary survey about sleep and somatic health over the past two weeks. This study adopts slope-as-mediator mediation modeling, a novel approach highlighting the role of daily-level experiences in developmental processes by examining the day-to-day association between two variables as an explanatory mechanism. RESULTS: The daily associations between ethnic/racial discrimination and two stress responses significantly mediated the link between ERI exploration and adolescents' subsequent sleep and somatic health. For ERI commitment, only the mediating pathway of the association between ethnic/racial discrimination and problem-solving coping was significant. DISCUSSION: Daily responses to ethnic/racial discrimination, both adaptively and maladaptively, could in part explain the association between ERI exploration and adolescent health. Active participation in cultural activities may increase adaptive responses to ethnic/racial discrimination; meanwhile, uncertainty about ERI may lead to maladaptive reactions such as rumination. For ERI commitment, only problem-solving coping with ethnic/racial discrimination mediated the links to health outcomes, an observation possibly explained by the benefits of holding a strong sense of commitment to ERI.

Varying mechanical forces drive sensory epithelium formation.

The mechanical cues of the external microenvironment have been recognized as essential clues driving cell behavior. Although intracellular signals modulating cell fate during sensory epithelium development is well understood, the driving force of sensory epithelium formation remains elusive. Here, we manufactured a hybrid hydrogel with tunable mechanical properties for the cochlear organoids culture and revealed that the extracellular matrix (ECM) drives sensory epithelium formation through shifting stiffness in a stage-dependent pattern. As the driving force, moderate ECM stiffness activated the expansion of cochlear progenitor cell (CPC)-derived epithelial organoids by modulating the integrin α3 (ITGA3)/F-actin cytoskeleton/YAP signaling. Higher stiffness induced the transition of CPCs into sensory hair cells (HCs) through increasing the intracellular Ca2+ signaling mediated by PIEZO2 and then activating KLF2 to accomplish the cell specification . Our results identify the molecular mechanism of sensory epithelium formation guided by ECM mechanical force and contribute to developing therapeutic approaches for HC regeneration.

Is it a vicious circle and for whom? The reciprocal association between rumination and somatic symptoms and moderation by stress: A daily diary study among Chinese college students.

College students who experienced somatic symptoms during the COVID-19 pandemic may engage in rumination, but their bidirectional nature remains underexplored. Symptom perception theory suggests a reciprocal relationship between rumination and somatic symptoms, and the multiple-stressor perspective and the perseverative cognition hypothesis assume that the reciprocal association might be exacerbated by high stress. In this study, we examined temporal associations between rumination and somatic symptoms and variations by patterns of stress related to COVID-19 and daily hassles. A total of 582 Chinese college students provided daily reports on rumination, somatic symptoms, COVID-related stress, and daily hassles for seven consecutive days in November 2020. A cross-lagged panel model showed a positive reciprocal association between rumination and somatic symptoms. Greater rumination predicted more next-day somatic symptoms, and more somatic symptoms increased next-day rumination. Dual trajectory analysis identified four stress patterns of COVID-related stress and daily hassles (i.e. low-low, low-high, high-low, and high-high), and multi-group analysis found the reciprocal association only presented in the high-high group. Our findings indicate a vicious circle between rumination and somatic symptoms that is dependent on heterogeneous stress patterns. Attention should be paid to the high-risk group with both high levels of COVID-related stress and daily hassles.

HDAC11 is related to breast cancer prognosis and inhibits invasion and proliferation of breast cancer cells.

OBJECTIVE: Histone deacetylases (HDACs) not only regulate histone acetylation but also participate in many pathophysiologic processes, especially the development of cancer, including breast cancer. However, whether Histone deacetylase 11 can influence breast cancer is still unknown. This study investigated the relationship between HDAC11 expression in breast cancers and clinicopathologic parameters, and used small interference RNA (siRNA) to determine the biological behavioural changes after knockdown of HDAC11. METHODS: Immunohistochemical (IHC) staining was employed to detect the expression of HDAC11 in a tissue microarray (TMA) of 145 patients with invasive ductal breast carcinoma. Transwell and wound healing assays were employed to analyze cell invasion and migration. The proliferation ability of cells was determined by Cell Counting Kit (CCK8). RESULTS: The results show that the expression of HDAC11 was positively correlated with the overall survival (OS) of breast cancer patients. Specific HDAC11 knockdown enhanced MDA-MB-231 cell proliferation, migration, and invasion. CONCLUSION: In conclusion, this study found that HDAC11 expression is positively correlated with the overall survival rate of patients. HDAC11 can inhibit the invasion and proliferation of breast cancer cells to a certain extent and can be used as a good prognosis marker.

Parent-Child Separation and Diurnal Cortisol Rhythms Among Left-Behind Adolescents: The Moderating Role of Sex.

Prior research examining parent-child separation and the hypothalamic-pituitary-adrenal (HPA) axis functioning has primarily focused on separation due to parental divorce or loss or forced migration. Less clear is the impact of parental economic migration on adolescents' HPA axis functioning. The present study fills this gap by examining diurnal cortisol patterns among left-behind adolescents who experienced separation from their migrant parents. Participants were 293 Chinese adolescents (33.4% girls, 66.21% left-behind adolescents; Mage = 10.80 years old, SD = 0.82 years). Two-level multilevel modeling was conducted to examine the associations between parent-child separation experiences and diurnal cortisol patterns. Although no significant differences were found between left-behind adolescents and their non-left-behind peers, results revealed that left-behind adolescents who experienced parent-child separation at earlier ages had more blunted diurnal cortisol slopes (usually signaling poorer mental and physical health), compared to their counterparts who experienced separation at older ages. Left-behind adolescent girls who had more adverse separation experiences exhibited smaller waking cortisol and blunted diurnal slopes; these findings were not observed among left-behind adolescent boys. Observing the association between timing of parent-child separation and adolescents' diurnal cortisol and the moderating effects of child sex, this study contributes uniquely to the developmental science of left-behind adolescents' physiological health.

3D-printed tortuous vessels with Photodissociable and morphology-controllable ink.

Acute ischemic stroke (AIS) is a high mortality cerebrovascular disease associated with vessel curvature. However, the relevant mechanism remains unclear due to a lack of appropriate tortuous vascular models to investigate and validate. This study explores the combination of projection-based 3D bioprinting (PBP) with photo-stimulus-responsive techniques to fabricate a sodium alginate (SA)/acrylamide (AAM) hydrogel vascular scaffold capable of bending deformation. The coordination of Fe3+ ions with carboxylate groups in the alginate chains of the vascular scaffold acts as a molecular switch, which can be dissociated through photoreduction to enable the deformation response. Fourier Transform Infrared (FTIR) and X-ray Photoelectron Spectroscopy (XPS) results verified the deformation principle. By subjecting the scaffold to UV light exposure, Fe3+ is reduced to Fe2+ in spatially selected regions, resulting in the release of strain and subsequent deformation. Furthermore, it also controlled the degree and direction of curvature of the vessels. The cell seeding experiment verified that the vascular scaffold showed excellent biocompatibility. Overall, our approach could be used to generate an in vitro model of curved vascular pathology to investigate the pathogenesis and provide new directions for the diagnosis and treatment of vascular diseases in the future.

Trajectories of Perceived Stress among Students in Transition to College: Mindset Antecedents and Adjustment Outcomes.

There is growing evidence of a clear association between students' perceived stress and their adjustment to life at college. However, the predictors and implications of distinct changing patterns of perceived stress during the transition to college life are less clear. To address these research gaps, the current study aims to identify distinct patterns of perceived stress trajectories among 582 Chinese first-year college students (Mage = 18.11, SDage = 0.65; 69.40% female) across the first 6 months upon enrollment. Three distinct profiles of perceived stress trajectories, i.e., low-stable (15.63%), middle-decreasing (69.07%), and high-decreasing (15.29%), were identified. Moreover, individuals who followed the low-stable trajectory showed better distal outcomes (specifically, higher levels of well-being and academic adjustment) 8 months after enrollment than those who followed the other two trajectories. Furthermore, two types of positive mindset (a growth mindset of intelligence and a stress-is-enhancing mindset) contributed to differences in perceived stress trajectory, either independently or jointly. These findings highlight the significance of identifying different patterns of perceived stress among students during the transition to college, as well as the protective roles of both a stress mindset and a mindset of intelligence.

Effect of C content on the microstructures and mechanical properties of laser additive manufactured Ni-base superalloys.

In this study, we fabricated a Ni-base superalloy with three different carbon contents using laser metal deposition (LMD) and systematically investigated its microstructure and mechanical properties. The characterization results showed that carbides precipitated along the grain boundaries in the additive manufactured alloys, the amount increased with the carbon content, and the residual stress reduced with the carbon content. In addition, carbide precipitation was mainly MC (M is mainly Ti, Ta). These samples exhibited excellent mechanical properties compared to the cast samples. Rupture tests conducted at 760 °C/780 MPa indicated that the high carbon content in the additively manufactured alloy affected the rupture life, with the medium-carbon additive manufactured alloy exhibiting better mechanical properties than the other carbon content.

3D Prestress Bioprinting of Directed Tissues.

Many mammalian tissues adopt a specific cellular arrangement under stress stimulus that enables their unique function. However, conventional 3D encapsulation often fails to recapitulate the complexities of these arrangements, thus motivating the need for advanced cellular arrangement approaches. Here, an original 3D prestress bioprinting approach of directed tissues under the synergistic effect of static sustained tensile stress and molecular chain orientation, with an aid of slow crosslinking in bioink, is developed. The semi-crosslinking state of the designed bioink exhibits excellent elasticity for applying stress on the cells during the sewing-like process. After bioprinting, the bioink gradually forms complete crosslinking and keeps the applied stress force to induce cell-orientated growth. More importantly, multiple cell types can be arranged directionally by this approach, while the internal stress of the hydrogel filament is also adjustable. In addition, compared with conventional bioprinted skin, the 3D prestress bioprinted skin results in a better wound healing effect due to promoting the angiogenesis of granulation tissue. This study provides a prospective strategy to engineer skeletal muscles, as well as tendons, ligaments, vascular networks, or combinations thereof in the future.

Gelatin Methacryloyl Hydrogel, from Standardization, Performance, to Biomedical Application.

Gelatin methacryloyl (GelMA), a photocurable hydrogel, is widely used in 3D culture, particularly in 3D bioprinting, due to its high biocompatibility, tunable physicochemical properties, and excellent formability. However, as the properties and performances of GelMA vary under different synthetic conditions, there is a lack of standardization, leading to conflicting results. In this study, a uniform standard is established to understand and enhance GelMA applications. First, the basic concept of GelMA and the density of the molecular network (DMN) are defined. Second, two properties, degrees of substitution and ratio of solid content, as the main measurable parameters determining the DMN are used. Third, the mechanisms and relationships between DMN and its performance in various applications in terms of porosity, viscosity, formability, mechanical strength, swelling, biodegradation, and cytocompatibility are theoretically explained. The main questions that are answered: what does performance mean, why is it important, how to optimize the basic parameters to improve the performance, and how to characterize it reasonably and accurately? Finally, it is hoped that this knowledge will eliminate the need for researchers to conduct tedious and repetitive pre-experiments, enable easy communication for achievements between groups under the same standard, and fully explore the potential of the GelMA hydrogel.

Daucosterol combined with umbilical cord mesenchymal stem cell-derived exosomes can alleviate liver damage in liver failure mice by regulating the IL-6/STAT3 signaling pathway.

Daucosterol is a phytosterol glycoside with hepatoprotective properties. The objective of the present study was to confirm the role of daucosterol in liver failure. Exosomes were isolated from primary mouse umbilical cord mesenchymal stem cells (UCMSCs). A liver failure mouse model was generated by injecting lipopolysaccharide/D-galactosamine. Mice were treated with exosomes alone or in combination with daucosterol (5, 10, or 20 mg/kg). Liver tissue damage was examined by hematoxylin-eosin, Masson's trichrome, and TUNEL staining. The levels of genes, proteins, and inflammatory factors were determined using real-time qPCR, western blotting, and enzyme-linked immunosorbent assay, respectively. Compared with normal mice, we noted severe damage, fibrosis, and apoptosis in the liver tissues of liver failure-induced mice. UCMSC-derived exosomes effectively alleviated hepatic damage in the mouse model. Compared with exosome treatment alone, exosomes combined with daucosterol significantly and dose-dependently reduced pathological changes in model mice. Exosome treatment alone or combined with daucosterol also markedly decreased the liver index and reduced levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 in model mice. Exosome treatment alone or combined with daucosterol suppressed mRNA expression levels of IL-6 and signal transducer and activator of transcription (STAT3) and STAT3 protein expression in model mice. Our findings revealed that treatment with daucosterol combined with UCMSC-derived exosomes was superior to exosomes alone for alleviating hepatic damage in mice with liver failure by regulating the IL-6/STAT3 signaling pathway. Accordingly, daucosterol combined with UCMSC-derived exosomes may be a prospective treatment strategy for liver failure.

Precise Printing of Microfiber Scaffold with Gelatin Methacryloyl (GelMA)/Polyethylene Oxide (PEO) Bioink.

Gelatin methacryloyl scaffolds with microscale fiber structures own great significance because they can effectively mimic the extracellular matrix environment. Compared with extruding bioprinting, electrospinning technology is more suitable for establishing accurate hydrogel microfibers. However, electrospinning accurate gelatin methacryloyl microfiber remains a big challenge restricted by its bad spinnability. In this paper, polyethylene oxide, which owns promising spinnability, is added into gelatin methacryloyl hydrogel precursor to improve the spinnability of gelatin methacryloyl bioink. A three-dimensional motion platform for electrospinning is designed and built and the spinning process of microfibers under far-electric-field and near-electric-field conditions is systematically studied, respectively. As a result, scaffolds consisted of unordered and ordered microfibers are successfully fabricated under far-electric-field and near-electric field, respectively. In vitro culture experiments of human umbilical vein endothelial cells are carried out using the prepared gelatin methacryloyl microfiber scaffolds. The results show that the cells can easily attach to the microfibers and grow well. Moreover, the gelatin methacryloyl/ polyethylene oxide microfiber scaffold was directly spun on the polycaprolactone mesh scaffold printed by fused modeling printing method. The results showed that the macroscopic ordered and microscopic disordered microfiber scaffold could be successfully established, which could lead to directed cell growth. We believe that this method can effectively solve the problem of hydrogel spinnability and be a powerful tool for various biomedical engineering methods in the future.

Exposure-lag response of fine particulate matter on intrauterine fetal death: an analysis using a distributed lag non-linear model in Linxia Hui Autonomous Prefecture, China.

The results of studies on intrauterine fetal death (IUFD) caused by exposure to fine particulate matter (PM2.5) during pregnancy are inconsistent. Further exploration of the dose-response relationship and exposure window is required. We aimed to provide a reference for policy formulation by estimating the exposure-lag relationship of PM2.5 on IUFD and looking for sensitive exposure windows. IUFD data was obtained from China Children Under 5 Death Surveillance Network in Linxia Hui Autonomous Prefecture from 2016 to 2020. Air pollution data and temperature data were obtained from ambient air monitoring stations and China Meteorological Data Network, respectively. The moving average is used to describe the trend and seasonality of PM2.5 exposure; the distributed lag non-linear model (DLNM) is used to estimate the exposure-lag effect; the sandwich estimators are used to correct the variance-covariance matrix; and the model selected by Akaike's Information Criterion (AIC) finally adjusts gender, temperature, and district. About 180,622 infants were enrolled in the study, including 952 IUFDs (5.27‰). The median of PM2.5 exposure is 34.08 µg/m3. There is an exposure-lag effect of PM2.5 on IUFD approximate to a wavy shape; the concentration with effect is 40-90 µg/m3; and the sensitive lag time is 1, 2, 3, 8, 9, and 10 months. The maximum RR value of the exposure-lag effect of PM2.5 on IUFD is 1.61 [95% CI 1.19, 2.19], in which the concentration of PM2.5 is 62 µg/m3, and the lag month is 9 months. In the case of less than 6 months lag, the maximum RR value of the exposure-lag effect of PM2.5 on IUFD is 1.43 [95% CI 1.24, 1.67], in which the concentration of PM2.5 is 73 µg/m3, and the lag month is 3 months. Exposure to PM2.5 concentrations above 40 µg/m3 may increase the risk of IUFD, especially in the first and third trimesters.

Psychological and Physical Abuse and Cortisol Response to Stress: The Moderating Role of Psychosocial Resources.

Child abuse is associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis functioning. However, the unique effects of psychological and physical abuse and protective factors against these effects remain largely unknown. To close these gaps, the present study examined the unique effects of psychological and physical abuse on cortisol stress response and explored the moderating role of psychosocial resources in these associations among a sample of Chinese preadolescent children (N = 150; aged 9-13 years; Mage = 10.69 years; 51% boys). The results showed that both psychological and physical abuse were associated with blunted cortisol reactivity slopes. Psychological abuse, but not physical abuse, was associated with lower peak cortisol values and flatter cortisol recovery slopes. Further, psychosocial resources moderated the association between abuse and hyporesponsiveness of the HPA axis. The association between psychological abuse and lower peak cortisol values and the association between physical abuse and steeper cortisol recovery slopes (faster cortisol recovery following the stressor) were observed only among children with low levels of psychosocial resources. These findings indicate the differential effects of psychological and physical abuse on various phases of cortisol stress response, and the protective role of psychosocial resources. This study also has practical implications, given that preadolescence serves as a critical period for maximizing benefit of interventions of adversity.

Associations between trait and state perceived stress and daily moods: COVID-19 stressful experiences as a moderator.

Drastically disrupting daily routines, the global pandemic of COVID-19 has posed critical mental health threats to adolescents and young adults worldwide. Many of the extant empirical findings, however, have focused on individuals' psychological adjustment during the initial phase of the pandemic. It is less clear how COVID-19 stressful experiences impact young people's daily lives in the post-pandemic "new normal." Drawing on 7-day diary reports, the present study fills this gap by examining: (1) how daily perceived stress impacted daily emotional adjustment; and (2) the moderating effects of COVID-19 stressful experiences on these associations among 582 Chinese young adults (M age = 18.12, SD = .65; 69% females). Results indicated that higher levels of both trait (i.e., average levels) and state (i.e., daily fluctuations) perceived stress were associated with greater negative and anxious moods, and that prior pandemic-related experiences exacerbated the adverse impact of both trait and state perceived stress on daily moods. Specifically, young adults reporting greater COVID-19 stressful experiences demonstrated poorer emotional adjustment (i.e., lower levels of positive mood and higher levels of negative mood) on days when they had more fluctuations in perceived stress; the aggravating impact was stronger when the average levels of perceived stress were higher. By illuminating the moderating effects of COVID-19 stressful experiences, this study contributes to the limited, but burgeoning, research examining the prolonged impact of the COVID-19 health crisis on daily emotional adjustment in post-pandemic life.

Perfusable Vessel-on-a-Chip for Antiangiogenic Drug Screening with Coaxial Bioprinting.

Vessel-on-a-chips, which can be used to study microscale fluid dynamics, tissue-level biological molecules delivery and intercellular communication under favorable three-dimensional (3D) extracellular matrix microenvironment, are increasingly gaining traction. However, not many of them can allow for long-term perfusion and easy observation of angiogenesis process. Since angiogenesis is necessary for the expansion of tumor, antiangiogenic drugs play a significant role in cancer treatment. In this study, we established an innovative and reliable antiangiogenic drug screening chip that was highly modularly integrated for long-term perfusion (up to 10 days depending on the hydrogel formula) and real-time monitoring. To maintain an unobstructed flow of cell-laden tubes for subsequent perfusion culture on the premise of excellent bioactivities, a polycaprolactone stent inspired by coronary artery stents was introduced to hold up the tubular lumen from the inside, while the perfusion chip was also elaborately designed to allow for convenient observation. After 3 days of perfusion screening, distinct differences in human umbilical vein endothelial cell sprouting were observed for a gradient of concentrations of bevacizumab, which pointed to the effectiveness and reliability of the drug screening perfusion system. Overall, a perfusion system for antiangiogenic drug screening was developed, which can not only conduct drug evaluation, but also be potentially useful in other vessel-mimicking scenarios in the area of tissue engineering, drug screening, pharmacokinetics, and regenerative medicine.

Thermo-sensitive Sacrificial Microsphere-based Bioink for Centimeter-scale Tissue with Angiogenesis.

Centimeter-scale tissue with angiogenesis has become more and more significant in organ regeneration and drug screening. However, traditional bioink has obvious limitations such as balance of nutrient supporting, printability, and vascularization. Here, with "secondary bioprinting" of printed microspheres, an innovative bioink system was proposed, in which the thermo-crosslinked sacrificial gelatin microspheres encapsulating human umbilical vein endothelial cells (HUVECs) printed by electrospraying serve as auxiliary component while gelatin methacryloyl precursor solution mixed with subject cells serve as subject component. Benefiting from the reversible thermo-crosslinking feature, gelatin microspheres would experience solid-liquid conversion during 37°C culturing and form controllable porous nutrient network for promoting the nutrient/oxygen delivery in large-scale tissue and accelerate the functionalization of the encapsulated cells. Meanwhile, the encapsulated HUVECs would be released and attach to the pore boundary, which would further form three-dimensional vessel network inside the tissue with suitable inducing conditions. As an example, vascularized breast tumor tissue over 1 cm was successfully built and the HUVECs showed obvious sprout inside, which indicate the great potential of this bioink system in various biomedical applications.