Biofabrication最新文献

{"title":"Acetylcholine-loaded nanoparticles protect against doxorubicin-induced toxicity in<i>in vitro</i>cardiac spheroids.","authors":"Clara Liu Chung Ming, Runali Patil, Ahmed Refaat, Sean Lal, Xiaowei Wang, Carmine Gentile","doi":"10.1088/1758-5090/adb7c2","DOIUrl":"10.1088/1758-5090/adb7c2","url":null,"abstract":"<p><p>Doxorubicin (DOX) is widely used in chemotherapy, yet it significantly contributes to heart failure-associated death. Acetylcholine (ACh) is cardioprotective by enhancing heart rate variability and reducing mitochondrial dysfunction and inflammation. Nonetheless, the protective role of ACh in countering DOX-induced cardiotoxicity (DIC) remains underexplored as current approaches to increasing ACh levels are invasive and unsafe for patients. In this study, we explore the protective effects of ACh against DIC through three distinct ACh administration strategies: (i) freely-suspended 100<i>µ</i>M ACh; (ii) ACh-producing cholinergic neurons (CNs); or (iii) ACh-loaded nanoparticles (ACh-NPs). These are tested in<i>in vitro</i>cardiac spheroids (CSs), which have previously been shown to approximate the complex DIC. We assess ACh's protective effects by measuring the toxicity ratio (cell death/viability), contractile activity, gene expression changes via qPCR and nitric oxide (NO) signaling. Our findings show that ACh effectively attenuates DOX-induced cell death and contractile dysfunction. ACh also counteracts the DOX-induced downregulation of genes controlling myocardial fibrosis, endothelial and cardiomyocyte dysfunction, and autonomic dysregulation. ACh cardioprotection against DOX is dependent on NO signaling in endothelial cells but not in cardiac myocytes or fibroblasts. Altogether, this study shows for the first time that elevating ACh levels showed a promising therapeutic approach for preventing DIC.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of asymmetric microchannels in the structure and function of engineered neuronal circuits.","authors":"J C Mateus, P Melo, M Aroso, B Charlot, P Aguiar","doi":"10.1088/1758-5090/adb2e5","DOIUrl":"10.1088/1758-5090/adb2e5","url":null,"abstract":"<p><p>Understanding the intricate structure-function relationships of neuronal circuits is crucial for unraveling how the brain achieves efficient information transfer. In specific brain regions, like the hippocampus, neurons are organized in layers and form unidirectional connectivity, which is thought to help ensure controlled signal flow and information processing. In recent years, researchers have tried emulating these structural principles by providing cultured neurons with asymmetric environmental cues, namely microfluidics' microchannels, which promote directed axonal growth. Even though a few reports have claimed to achieve unidirectional connectivity of<i>in vitro</i>neuronal circuits, given the lack of functional characterization, it remains unknown if this structural connectivity correlates with functional connectivity. We have replicated and tested the performance of asymmetric microchannel designs previously reported in the literature to be successful in promoting directed axonal growth, as well as other custom variations. A new variation of 'Arrowhead', termed 'Rams', was the best-performing motif with a ∼76% probability per microchannel of allowing strictly unidirectional connections at 14 d<i>in vitro</i>. Importantly, we assessed the functional implications of these different asymmetric microchannel designs. For this purpose, we combined custom microfluidics with microelectrode array technology to record the electrophysiological activity of two segregated populations of hippocampal neurons ('Source' and 'Target'). This functional characterization revealed that up to ∼94% of the spiking activity recorded along microchannels with the 'Rams' motif propagates towards the 'Target' population. Moreover, our results indicate that these engineered circuits also tended to exhibit network-level synchronizations with defined directionality. Overall, this functional characterization of the structure-function relationships promoted by asymmetric microchannels has the potential to provide insights into how neuronal circuits use specific network architectures for effective computations. Moreover, the here-developed devices and approaches may be used in a wide range of applications, such as disease modeling or preclinical drug screening.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biotechnological advances in 3D modeling of cancer initiation. Examples from pancreatic cancer research and beyond.","authors":"C Handschin, H Shalhoub, A Mazet, C Guyon, N Dusserre, E Boutet-Robinet, H Oliveira, J Guillermet-Guibert","doi":"10.1088/1758-5090/adb51c","DOIUrl":"10.1088/1758-5090/adb51c","url":null,"abstract":"<p><p>In recent years, biofabrication technologies have garnered significant attention within the scientific community for their potential to create advanced<i>in vitro</i>cancer models. While these technologies have been predominantly applied to model advanced stages of cancer, there exists a pressing need to develop pertinent, reproducible, and sensitive 3D models that mimic cancer initiation lesions within their native tissue microenvironment. Such models hold profound relevance for comprehending the intricacies of cancer initiation, to devise novel strategies for early intervention, and/or to conduct sophisticated toxicology assessments of putative carcinogens. Here, we will explain the pivotal factors that must be faithfully recapitulated when constructing these models, with a specific focus on early pancreatic cancer lesions. By synthesizing the current state of research in this field, we will provide insights into recent advances and breakthroughs. Additionally, we will delineate the key technological and biological challenges that necessitate resolution in future endeavors, thereby paving the way for more accurate and insightful<i>in vitro</i>cancer initiation models.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 2","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating biomechanics as a key evaluation metric for organoids.","authors":"Jishizhan Chen","doi":"10.1088/1758-5090/adb802","DOIUrl":"10.1088/1758-5090/adb802","url":null,"abstract":"","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application progress of bio-manufacturing technology in kidney organoids.","authors":"Runqi Mao, Junming Zhang, Haoxiang Qin, Yuanyuan Liu, Yuxin Xing, Wen Zeng","doi":"10.1088/1758-5090/adb4a1","DOIUrl":"10.1088/1758-5090/adb4a1","url":null,"abstract":"<p><p>Kidney transplantation remains a pivotal treatment modality for kidney disease, yet its progress is significantly hindered by the scarcity of donor kidneys and ethical dilemmas surrounding their procurement. As organoid technology evolves and matures, the creation of bionic human kidney organoids offers profound potential for advancing kidney disease research, drug nephrotoxicity screening, and regenerative medicine. Nevertheless, current kidney organoid models grapple with limitations such as constrained cellular differentiation, underdeveloped functional structures, and a crucial absence of vascularization. This deficiency in vascularization, in particular, stunts organoid development, restricts their size, diminishes filtration capabilities, and may trigger immune inflammatory reactions through the resulting ischemic microenvironment. Hence, the achievement of vascularization within kidney organoids and the successful establishment of functional microvascular networks constitutes a paramount goal for their future progression. In this review, we provide an overview of recent advancements in biotechnology domains, encompassing organ-on-a-chip technology, biomimetic matrices, and bioprinting, with the aim of catalyzing technological breakthroughs that can enhance the vascularization of kidney organoids and broaden their applicability. These technologies hold the key to unlocking the full potential of kidney organoids as a transformative therapeutic option for kidney disease.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing regenerative medicine: the Aceman system's pioneering automation and machine learning in mesenchymal stem cell biofabrication.","authors":"Kai Zhu, Yi Ding, Yuqiang Chen, Kechuan Su, Jintu Zheng, Yu Zhang, Ying Hu, Jun Wei, Zenan Wang","doi":"10.1088/1758-5090/adb803","DOIUrl":"10.1088/1758-5090/adb803","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs) are pivotal in advancing regenerative medicine; however, the large-scale production of MSCs for clinical applications faces significant challenges related to efficiency, cost, and quality assurance. We introduce the Automated Cell Manufacturing System (Aceman), a revolutionary solution that leverages machine learning and robotics integration to optimize MSC production. This innovative system enhances both efficiency and quality in the field of regenerative medicine. With a modular design that adheres to good manufacturing practice standards, Aceman allows for scalable adherent cell cultures. A sophisticated machine learning algorithm has been developed to streamline cell counting and confluence assessment, while the accompanying control software features customization options, robust data management, and real-time monitoring capabilities. Comparative studies reveal that Aceman achieves superior efficiency in analytical and repeatable tasks compared to traditional manual methods. The system's continuous operation minimizes human error, offering substantial long-term benefits. Comprehensive cell biology assays, including Bulk RNA-Seq analysis and flow cytometry, support that the cells produced by Aceman function comparably to those cultivated through conventional techniques. Importantly, Aceman maintains the characteristic immunophenotype of MSCs during automated subcultures, representing a significant advancement in cell production technology. This system lays a solid foundation for future innovations in healthcare biomanufacturing, ultimately enhancing the potential of MSCs in therapeutic applications.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-time assessment of cell concentration and viability onboard a syringe using dielectric impedance spectroscopy for extrusion bioprinting.","authors":"Alicia A Matavosian, Alexandra C Griffin, Didarul B Bhuiyan, Alexander M Lyness, Vivek Bhatnagar, Lawrence J Bonassar","doi":"10.1088/1758-5090/adb4a4","DOIUrl":"10.1088/1758-5090/adb4a4","url":null,"abstract":"<p><p>Bioprinting produces personalized, cell-laden constructs for tissue regeneration through the additive layering of bio-ink, an injectable hydrogel infused with cells. Currently, bioprinted constructs are assessed for quality by measuring cellular properties post-production using destructive techniques, necessitating the creation of multiple constructs and increasing the production costs of bioprinting. To reduce this burden, cell properties in bio-ink can be monitored in real-time during printing. We incorporated dielectric impedance spectroscopy (DIS) onto a syringe for real-time measurement of primary chondrocytes suspended in phosphate buffered saline (PBS) using impedance (|<i>Z</i>|) and phase angle (<i>θ</i>) from 0.1 to 25 000 kHz. Cell concentration and viability ranged from 0.1 × 10⁶cells ml^-1to 125 × 10⁶cells ml^-1and from 0%to 94%, respectively. Samples with constant or with changing cell concentration were exposed to various flow conditions from 0.5 to 4 ml min^-1. The background PBS signal was subtracted from the sample, allowing for comparisons across devices and providing insight into the dielectric properties of the cells, and was labeled as |<i>Z_cells</i>| and<i>θ_cells</i>. |<i>Z_cells</i>| shared a linear correlation with cell concentration and viability. Flow rate had minimal effect on our results, and |<i>Z_cells</i>| responded on the order of seconds as cell concentration was altered over time. Notably, sensitivity to cell concentration and viability were dependent on frequency and were highest for |<i>Z_cells</i>| when<i>θ_cells</i>was minimized. Cell concentration and viability showed an additive effect on |<i>Z_cells</i>| that was modeled across multiple frequencies, and deconvolution of these signals could result in real-time predictions of cell properties in the future. Overall, DIS was found to be a suitable technique for real-time sensing of cell concentration and viability during bioprinting.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A cell-based drug screening assay on a centrifugal platform.","authors":"Chia-Tse Shih, Huan-Jun Guo, Chih-Hsin Shih, Yi-Chen Ethan Li","doi":"10.1088/1758-5090/adb4a2","DOIUrl":"10.1088/1758-5090/adb4a2","url":null,"abstract":"<p><p>Drug screening is an indispensable procedure in drug development and pharmaceutical research. For cell-based drug testing, cells were treated with compounds at different concentrations, and their responses were measured to assess the compounds' effects on cellular behavior. A concentration gradient test creates a growth environment with different compound concentrations for cultured cells, facilitating faster determination of the compound concentration's effect on cellular responses. However, most concentration gradient tests on cell cultures were carried out manually, which is labor-intensive and time-consuming. Microfluidic technology enables drug screening to be conducted in microstructures, which not only improves efficiency and sensitivity but also reduces reagent usage and operating time. Centrifugal microfluidics utilizes the rotation of a disk platform to perform complex fluid functions such as pumping, metering, and mixing. The complete process can be carried out with a low-cost motor without the need for an expensive pumping system. In this work, a centrifugal platform for drug screening is presented. The microfluidic platform can be divided into two parts. The inner disk features branch structures designed to establish a concentration gradient for cell growth. The outer ring contains fluidics for cell culturing, which can discharge the waste fluid when the nutrient is exhausted and replenish the new culture medium by spinning the platform. In conclusion, the proposed centrifugal platform can provide a rapid generation of the concentration gradients and automate the operation of cell culturing. It provides an efficient and low-cost platform for drug screening.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A micro-lung chip with macrophages for targeted anti-fibrotic therapy.","authors":"Jingjing Xia, Ruming Dong, Yongcong Fang, Jiabin Guo, Zhuo Xiong, Ting Zhang, Wei Sun","doi":"10.1088/1758-5090/adb338","DOIUrl":"10.1088/1758-5090/adb338","url":null,"abstract":"<p><p>Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Macrophages are implicated in the fibrotic process, but exhibit remarkable plasticity in the activated immune environment<i>in vivo</i>, presenting significant challenges as therapeutic targets. To explore the influence of macrophages on IPF and develop macrophage-targeted therapies, we engineered a micro-lung chip with a lung epithelium-interstitium tissue unit to establish a controlled immune environment containing only macrophages. We discovered that macrophages exacerbated inflammation and fibrosis by comparing microchips treated with bleomycin (BLM) in the presence and absence of macrophages. Based on the duration of BLM treatment, we established pathological models corresponding to inflammation and fibrosis stages. Transcriptome analysis revealed that activation of the PI3K-AKT signalling pathway facilitates the transition from inflammation to fibrosis. However, LY294002, a PI3K inhibitor, not only suppressed fibrosis and decreased the accumulation of M2 macrophages but also intensified the severity of inflammation. These findings suggest that macrophages play a pivotal role in the potential development at the tissue level. The micro-lung chip co-cultured with macrophages holds significant potential for exploring the pathological progression of IPF and elucidating the mechanisms of anti-fibrotic drugs.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Support-less 3D bioceramic/extracellular matrix printing in sanitizer-based hydrogel for bone tissue engineering.","authors":"Siwi Setya Utami, Naren Raja, Jueun Kim, Imam Akbar Sutejo, Honghyun Park, Aram Sung, Changwoo Gal, Hui-Suk Yun, Yeong-Jin Choi","doi":"10.1088/1758-5090/adb4a3","DOIUrl":"10.1088/1758-5090/adb4a3","url":null,"abstract":"<p><p>To meet the increasing demand for bone scaffolds, advancements in 3D printing have significantly impacted bone tissue engineering. However, the materials used must closely mimic the biological components and structural characteristics of natural bone tissue. Additionally, constructing complex, oblique structures presents considerable challenges. To address these issues, we explored 3D bioceramic printing using a sanitizer-based hydrogel. Collagen, a primary component of the bone extracellular matrix (ECM), was combined with alpha-tricalcium phosphate (<i>α</i>-TCP) to create the bioceramic ink. The sanitizer-based hydrogel was chosen as the gel bath due to its carbopol content, which provides hydrogel-like support, and ethanol, which coagulates collagen and maintains the integrity of the 3D-printed structure. The<i>α</i>-TCP/collagen bioceramic ink was printed within the sanitizer-based hydrogel, then collected, immersed in ethanol, and finally submerged in phosphate-buffer saline to initiate a self-setting reaction that converted<i>α</i>-TCP into calcium-deficient hydroxyapatite. The results demonstrated that complex ceramic/ECM structures could be successfully printed in the sanitizer bath, exhibiting excellent mechanical characteristics. Additionally, scaffolds printed in the sanitizer bath showed higher levels of cell growth and osteogenic activity compared to those produced with only<i>α</i>-TCP in an open-air environment. This bioceramic printing approach has a strong potential for constructing complex scaffolds with enhanced osteogenic potential for bone regeneration.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}