Biofabrication最新文献

{"title":"Recent trends in the development of<i>in vitro</i>3D kidney models.","authors":"Gaddam Kiranmai, Shibu Chameettachal, Yeleswarapu Sriya, Sarah Duin, Anja Lode, Michael Gelinsky, Ashwini Rahul Akkineni, Falguni Pati","doi":"10.1088/1758-5090/adb999","DOIUrl":"10.1088/1758-5090/adb999","url":null,"abstract":"<p><p>The kidneys are vital for maintaining bodily homeostasis and are susceptible to various diseases that disrupt their function. Traditionally, research on kidney diseases has relied on animal models and simplistic two-dimensional cell cultures, which do not fully replicate human tissue pathology. To address this, recent advances focus on developing advanced 3D biomimetic<i>in vitro</i>models using human-derived cells. These models mimic healthy and diseased kidney tissues with specificity, replicating key elements like glomerular and tubular structures through tissue engineering. By closely mimicking human physiology, they provide a promising platform for studying renal disorders, drug-induced nephrotoxicity, and evaluating new therapies. However, the challenges include optimizing scalability, reproducibility, and long-term stability to enhance reliability in research and clinical applications. This review highlights the transformative potential of 3D biomimetic<i>in vitro</i>kidney models in advancing biomedical research and clinical applications. By focusing on human-specific cell cultures and tissue engineering techniques, these models aim to overcome the limitations of conventional animal models and simplistic 2D cell cultures. The review discusses in detail the various types of biomimetic kidney models currently under development, their specific applications, and the innovative approaches used to construct them. It also addresses the challenges and limitations associated with these models for their widespread adoption and reliability in research settings.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490148","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":"High-resolution bioprinting of complex bio-structures via engineering of the photopatterning approaches and adaptive segmentation.","authors":"Ceren Babayigit, Jorge Alfonso Tavares-Negrete, Rahim Esfandyarpour, Ozdal Boyraz","doi":"10.1088/1758-5090/adbc22","DOIUrl":"10.1088/1758-5090/adbc22","url":null,"abstract":"<p><p>Digital light processing (DLP) technology has significantly advanced various applications, including 3D bioprinting, through its precision and speed in creating detailed structures. While traditional DLP systems rely on light-emitting diodes (LEDs), their limited power spectral density, high etendue, and spectral inefficiency constrain their performance in resolution, dynamic range, printing time, and cell viability. This study proposes and evaluates a dual-laser DLP system to overcome these limitations and enhance bioprinting performance. The proposed dual-laser system resulted in a twofold increase in resolution and a twelvefold reduction in printing time compared to the LED system. The system's capability was evaluated by printing three distinct designs, achieving a maximum percentage error of 1.16% and a minimum of 0.02% in accurately reproducing complex structures. Further, the impact of exposure times (10-30 s) and light intensities (0.044-0.11 mW mm^-2) on the viability and morphology of 3T3 fibroblasts in GelMA and GelMA-poly(ethylene glycol) diacrylate (PEGDA) hydrogels is assessed. The findings reveal a clear relationship between longer exposure times and reduced cell viability. On day 7, samples exposed for extended periods exhibited the lowest metabolic activity and cell density, with differences of ∼40% between treatments. However, all samples show recovery by day 7, with GelMA samples exhibiting up to a sixfold increase in metabolic activity and GelMA-PEGDA samples showing up to a twofold increase. In contrast, light intensity variations had a lesser effect, with a maximum variation of 15% in cell viability. We introduced a segmented printing method to mitigate over-crosslinking and enhance the dynamic range, utilizing an adaptive segmentation control strategy. This method, demonstrated by printing a bronchial model with a 14.43x compression ratio, improved resolution and maintained cell viability up to 90% for GelMA and 85% for GelMA-PEGDA during 7 d of culture. The proposed dual-laser system and adaptive segmentation method were confirmed through successful prints with diverse bio-inks and complex structures, underscoring its advantages over traditional LED systems in advancing 3D bioprinting.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540054","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":"Biofabrication of an<i>in situ</i>hypoxia-delivery scaffold for cartilage regeneration.","authors":"R Di Gesù, A Palumbo Piccionello, G Vitale, S Buscemi, S Panzavolta, M F Di Filippo, A Leonarda, M Cuccia, A Di Prima, R Gottardi","doi":"10.1088/1758-5090/adbd79","DOIUrl":"10.1088/1758-5090/adbd79","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a debilitating joint condition affecting millions of people worldwide, triggering painful chondral defects (CDs) that ultimately compromise the overarching patients' quality of life. Currently, several reconstructive cartilage techniques (RCTs) (i.e.: matrix-assisted autologous chondrocytes implantation has been developed to overcome the total joint replacement limitations in the treatment of CDs. However, there is no consensus on the effectiveness of RCTs in the long term, as they do not provide adequate pro-regenerative stimuli to ensure complete CDs healing. In this study, we describe the biofabrication of an innovative scaffold capable to promote the CDs healing by delivering pro-regenerative hypoxic cues at the cellular/tissue level, to be used during RCTs. The scaffold is composed of a gelatin methacrylate (GelMA) matrix doped with hypoxic seeds of GelMA functionalized with a fluorinated oxadiazole (GelOXA), which ensures the delivery of hypoxic cues to human articular chondrocytes (hACs) embedded within the scaffold. We found that the GelMA/GelOXA scaffold preserved hACs viability, maintained their native phenotype, and significantly improved the production of type II collagen. Besides, we observed a reduction in type I and type X collagen, characteristic of unhealthy cartilage. These findings pave the way for the regeneration of healthy, hyaline-like cartilage, by delivering hypoxic cues even under normoxic conditions. Furthermore, the GelMA/GelOXA scaffold's ability to deliver healing signals directly to the injury site holds great potential for treating OA and related CDs, and has the potential to revolutionize the field of cartilage repair and regenerative medicine.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571679","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 novel solution for real-time<i>in-situ</i>cell distribution monitoring in 3D bioprinting via fluorescence imaging.","authors":"Alessandro Margarita, Simone Giovanni Gugliandolo, Silvia Santoni, Davide Moscatelli, Bianca Maria Colosimo","doi":"10.1088/1758-5090/adb891","DOIUrl":"10.1088/1758-5090/adb891","url":null,"abstract":"<p><p>3D bioprinting is rapidly evolving as a transformative technology for constructing biological tissues with precise cell and bioink placement. However, ensuring the quality and viability of bioprinted structures presents significant challenges, highlighting the need for advanced monitoring systems. Our study introduces a space-efficient, non-invasive approach for real-time,<i>in-situ</i>monitoring of cell dispersion in bioprinted constructs. Utilizing a novel<i>in-situ</i>fluorescence microscopy technique, we employ nanoparticles for cell tagging and integrate a compact digital microscope into the bioprinter for layer-by-layer imaging, significantly saving space and weight to make the solution adaptable to any commercial bioprinter. This method enhances<i>in-situ</i>analysis by combining data from the fluorescence system with conventional visible spectrum imaging. The synergy of these datasets provides a detailed method to examine cell dispersion and facilitates continuous monitoring during the bioprinting process. This allows for the immediate identification and correction of irregularities in cell deposition. Our approach aims to advance 3D bioprinting, setting new standards for the reliability and efficiency of bioprinted structures.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143466895","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":"Two-photon polymerization of miniaturized 3D scaffolds optimized for studies on glioblastoma multiforme in spaceflight-like microgravity conditions.","authors":"Giada Graziana Genchi, Claudio Conci, Özlem Şen, Alessandra Nardini, Martina Bartolucci, Attilio Marino, Rebeca Martinez Vazquez, Giulio Cerullo, Roberto Osellame, Andrea Petretto, Manuela Teresa Raimondi, Gianni Ciofani","doi":"10.1088/1758-5090/adbb21","DOIUrl":"10.1088/1758-5090/adbb21","url":null,"abstract":"<p><p>The obtainment of innovative models recalling complex tumour architectures and activities<i>in vitro</i>is a challenging drive in the understanding of pathology molecular bases, yet it is a crucial path to the identification of targets for advanced oncotherapy. Cell environment recapitulation by 3D scaffolding and gravitational unloading of cell cultures represent powerful means in tumour biomimicry processes, but their simultaneous adoption has consistently been explored only in the latest decade. Here, an unprecedented bioengineering approach capitalizing on spaceflight biology practice is proposed for modelling of glioblastoma multiforme, a highly aggressive neoplasm that affects the central nervous system and has poorly effective pharmacological and radiological countermeasures. Tumour modelling was pursued by the original implementation of two-photon polymerization in fast prototyping of 3D scaffolds on flexible substrates for U87-MG glioma cell culture, and by the exposure of cell-laden scaffolds to simulated microgravity (s-<i>μ</i>g). Realistic spaceflight conditions were applied to collect preliminary information suitable for testing of U87-MG cell-laden scaffold in low Earth orbit. Responses of glioma cells anchored to 3D scaffolds were investigated by microscopy, quantitative reverse transcription-polymerase chain reaction and proteomic analyses, revealing synergic regulatory effects of cell scaffolding and s-<i>μ</i>g on markers of tumour cell growth, metabolism and invasiveness.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522556","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 review of graded scaffolds made by additive manufacturing for tissue engineering: design, fabrication and properties.","authors":"Yue Wang, Shangsi Chen, Haowen Liang, Jiaming Bai","doi":"10.1088/1758-5090/adba8e","DOIUrl":"10.1088/1758-5090/adba8e","url":null,"abstract":"<p><p>The emergence of tissue engineering (TE) has provided new vital means for human body tissue/organ repair. TE scaffolds can provide temporary structural support for cell attachment, growth, and proliferation, until the body restores the mechanical and biological properties of the host tissues. Since native tissues are inhomogeneous and in many situations are graded structures for performing their unique functions, graded scaffolds have become increasingly attractive for regenerating particular types of tissues, which aim to offer a more accurate replication of native interactions and functions. Importantly, the advances introduced by additive manufacturing (AM) have now enabled more design freedom and are capable of tailoring both structural and compositional gradients within a single scaffold. In this context, graded TE scaffolds fabricated by AM technologies have been attracting increasing attention. In this review, we start with an introduction of common graded structures in the human body and analyse the advantages and strengths of AM-formed graded scaffolds. Various AM technologies that can be leveraged to produce graded scaffolds are then reviewed based on non-cellular 3D printing and cell-laden 3D bioprinting. The comparisons among various AM technologies for fabricating graded scaffolds are presented. Subsequently, we propose several types of gradients, structural, material, biomolecular and multi-gradients for scaffolds, and highlight the design methods, resulting mechanical properties and biological responses. Finally, current status, challenges and perspectives for AM in developing graded scaffolds are exhibited and discussed.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514719","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 extrusion-based embedded 3D bioprinting via scientific, engineering, and process innovations.","authors":"Ezgi Bakirci, Ali Asghari Adib, Syed Faaz Ashraf, Adam W Feinberg","doi":"10.1088/1758-5090/adb7c3","DOIUrl":"10.1088/1758-5090/adb7c3","url":null,"abstract":"<p><p>Extrusion-based embedded 3D bioprinting, where bioinks and biomaterials are extruded within a support bath, has greatly expanded the achievable tissue architectures and complexity of biologic constructs that can be fabricated. However, significant scientific, engineering, and process-related challenges remain to recreate the full anatomic structure and physiologic function required for many therapeutic applications. This perspective explores the future advances in extrusion-based embedded 3D bioprinting that could address these challenges, paving the way for clinical translation of bioprinted tissues.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448018","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":"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":"https://doi.org/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}