Biofabrication最新文献

{"title":"Intervertebral disc spheroids as an<i>in vitro</i>multicellular platform for recapitulating the microenvironment of intervertebral disc degeneration.","authors":"Tae-Won Kim, An-Gi Kim, Min-Ho Hwang, Hyuk Choi","doi":"10.1088/1758-5090/ade56c","DOIUrl":"10.1088/1758-5090/ade56c","url":null,"abstract":"<p><p>Intervertebral disc (IVD) degeneration (IVDD) is a major contributor to chronic low back pain, representing a substantial burden on the spinal healthcare system and serving as a leading cause of long-term disability worldwide. Biomimetic<i>in vitro</i>models that accurately replicate histological characteristics, three-dimensional structures, and multicellular interactions are lacking. Consequently, monocultures of cell lines and two-dimensional culture models are still used to study the pathomechanisms of IVDD. We established functional multicellular IVD spheroid cultures using primary human annulus fibrosus and nucleus pulposus cells. The spheroids maintained the IVD-specific phenotype, including hypoxic conditions and lamellar structures. Additionally, the spheroid markedly increased the expression level of inflammatory mediators and chemokines in the presence of the pro-inflammatory cytokine IL-1<i>β</i>, a master regulator of IVDD. Furthermore, we implemented our microfluidic chemotaxis platform to investigate microglial neuroinflammation in response to our reconstituted IVD spheroid models. Transcriptome sequencing revealed that microglia stimulated by potential contributing factors derived from IVDD spheroids exhibited a significant upregulation of the expression levels of chemotactic factors and cytokines including CCL-2, -3, -4, -5, IL-8 and IL-6 (<i>p</i>< 0.05). Moreover, we observed considerable activation and infiltration of microglia induced by soluble factors derived from IVDD spheroids, which are expected to occur during IVDD. The chemotactic effects on microglia were reduced upon the neutralization of CCL-2 or IL-8 or inhibition of NF-<i>κ</i>B signaling. These robust<i>in vitro</i>IVD spheroids can be used to model IVDD and provide a valuable platform for the assessment and development of IVDD therapeutics.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315859","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":"Non-destructive luminescence and PET imaging to monitor tissue microenvironment in microphysiological systems during brain metastasis using dissociated cerebral organoids.","authors":"Catherine Reed-McBain, Rithvik V Turaga, Seth R T Zima, Janmesh Patel, Anderson Weber Faletti Cunha, Jason Mixdorf, Lauren E Wehner, Jonathan W Engle, Reinier Hernandez, Stevens K Rehen, Helena L Borges, Jose M Ayuso","doi":"10.1088/1758-5090/ade1fb","DOIUrl":"10.1088/1758-5090/ade1fb","url":null,"abstract":"<p><p>During brain metastasis, tumor cells interact with the surrounding stroma, including neurons and astrocytes, to create a tumor-promoting microenvironment. However, the molecular and cellular factors driving tumor-neural stroma interactions remain unclear. Here, we developed a co-culture model of metastatic melanoma by combining metastatic melanoma cells with dissociated human iPSC-derived cerebral organoids, consisting of neurons and astrocytes, in a microfluidic device. We cultured these astrocytes and neurons in a 3D hydrogel that contained a domain with metastatic melanoma cells. This approach generated a spatially organized co-culture system with no physical boundary between the tumor and stromal compartments. Then, we leveraged several imaging modalities to study tumor-stroma interactions and changes in the microenvironment. Using non-destructive, luminescence-based methods, we spatially resolved changes in cell viability, metabolite concentration, and other biochemical parameters. We also used luminescence to analyze the effect of radionuclides on tumor cell viability and used PET imaging to monitor their diffusion across the system.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246252","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":"Microgels: from synthesis to tissue regeneration applications.","authors":"Sung Yun Hann, Yunsung Kang, Haitao Cui, Lijie Grace Zhang","doi":"10.1088/1758-5090/addde9","DOIUrl":"10.1088/1758-5090/addde9","url":null,"abstract":"<p><p>Microgels have emerged as a versatile platform in tissue engineering and regenerative medicine, offering unique physicochemical properties, modularity, and the ability to mimic native extracellular matrix microenvironments. Derived from natural or synthetic hydrogels, microgels exhibit biocompatibility, controllability, and injectability, which make them suitable for diverse tissue engineering applications. This review systematically explores the fabrication methods of microgels and highlights their role in cell encapsulation, therapeutic delivery, and structural tissue development. Advanced strategies in microgel manufacturing, such as injectable hydrogels, assembled microgel platforms, and in-gel assemblies, have enabled the creation of highly customizable and functional tissue constructs. Additionally, three-dimensional bioprinting of microgels provides a high-throughput strategy to generate patient-specific scaffolds with precise spatial organization and enhanced cellular viability. It is expected that more efficient and cost-effective strategies for mass production and customization of microgel systems to specific cell types or patient needs are essential for future studies. The innovations, including stimuli-responsive and four-dimensional microgels, will expand their potential by enabling dynamic<i>in situ</i>tunable microenvironments. These advancements will enable optimal design, scalability, and integration into therapeutic applications, thereby accelerating the clinical translation of microgel-based therapies and driving the development of multifunctional tissue products.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172459","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":"Formation of functionally robust human neocartilage from multiple donors using highly expanded costochondral cells.","authors":"Takumi Takahashi, Wendy E Brown, Cecilia T Trinh, Jerry C Hu, Kyriacos A Athanasiou","doi":"10.1088/1758-5090/ade18c","DOIUrl":"10.1088/1758-5090/ade18c","url":null,"abstract":"<p><p>Successful translation of allogeneic tissue-engineered neocartilage requires abundant functional cells. Human costal cartilage is a promising cell source, yet the effects of donor variability and extensive passaging remain unexplored. Therefore, this study investigated the functional (i.e. morphological, histological, mechanical, and biochemical) properties of hyaline-like neocartilage generated from high-passage human costochondral cells. A cell banking system was applied to seven donors to create master cell banks and subsequently working cell banks to fabricate P5 and P9 constructs using the processes of conservative chondrogenic passaging, aggregate rejuvenation, and self-assembly. Cell morphology or gene expression levels of these cells were correlated with mechanical and biochemical properties to identify predictive markers of neocartilage functional properties. Cells from younger donors (⩽3 months) expanded 8.7-fold more than cells from older donors (9-14 years). Cumulative expansion factors from P0 reached 3124-17397 at P5 and 1.4-36.2 million at P9. Aggregate rejuvenation was as effective at P9 as at P5 in restoring a hyaline cartilage-like phenotype, evidenced by increased cell circularity, upregulation of chondrogenic genes (e.g. >310-fold for<i>ACAN</i>; >200 000-fold for<i>COL2A1</i>; >2500-fold for<i>Chm-1</i>), and robust neocartilage functional properties. At P5, one young donor exhibited the highest functional properties (e.g. aggregate modulus = 310 kPa, Young's modulus = 2.9 MPa, GAG/ww = 9.5%, COL/ww = 3.1%). At P9, a different young donor had the highest functional properties (e.g. aggregate modulus = 220 kPa, Young's modulus = 2.3 MPa, GAG/ww = 8.6%, COL/ww = 3.4%). Gene expression levels after aggregate rejuvenation were identified to be predictive of neocartilage functional properties. For example,<i>ACAN, Chm-1</i>, and<i>MIA</i>positively correlated with Young's modulus, ultimate tensile strength (UTS), and GAG/dw, with<i>Chm-1</i>also correlating with shear modulus.<i>SOX9</i>correlated with Young's modulus and GAG/dw, while<i>MMP13</i>inversely correlated with UTS and GAG/dw. These findings support the translational potential of extensively passaged human costochondral cells, the need for donor screening, and the utility of gene expression markers to predict neocartilage functional properties.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233074","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":"3D bioprinting in tissue engineering: current state-of-the-art and challenges towards system standardization and clinical translation.","authors":"Tarun Agarwal, Valentina Onesto, Dishary Banerjee, Shengbo Guo, Alessandro Polini, Caleb D Vogt, Abhishek Viswanath, Timothy Esworthy, Haitao Cui, Aaron O'Donnell, Kiran Yellappa Vajanthri, Lorenzo Moroni, Ibrahim T Ozbolat, Angela Panoskaltsis-Mortari, Lijie Grace Zhang, Marco Costantini, Tapas Kumar Maiti","doi":"10.1088/1758-5090/ade47a","DOIUrl":"https://doi.org/10.1088/1758-5090/ade47a","url":null,"abstract":"<p><p>Over the past decade, 3D bioprinting has made significant progress, transforming into a key innovation in tissue engineering. Despite the early strides, critical challenges remain in 3D bioprinting that must be addressed to accelerate clinical translation. In particular, there is still a long way to go before functionally-mature, clinically-relevant tissue equivalents are developed. Current limitations range from the sub-optimal bioink properties and degree of biomimicry of bioprintable architectures, to the lack of stem/progenitor cells for massive cell expansion, and fundamental knowledge regarding in vitro culturing conditions. In addition to these problems, the absence of guidelines and well-regulated international standards is creating uncertainty among the biofabrication community stakeholders regarding the reliable and scalable production processes.&#xD;This review aims at exploring the latest developments in 3D bioprinting approaches, including various additive manufacturing techniques and their applications. A through discussion of common bioprinting techniques and recent progresses are compiled along with notable recent studies. Later we discuss the current challenges in clinical application of 3D bioprinting and the major bottlenecks in the commercialization of 3D bioprinted tissue equivalents, including the longevity of bioprinted organs, meeting biomechanical requirements, and the often underrated ethical and legal aspects. Amidst the progress of regulatory efforts for regenerative medicine, we also present an overview of the current regulatory concerns which should be taken into account to translate bioprinted tissues into clinical practice. At last, this review emphasizes future directions in 3D bioprinting that includes the transformative ideas like bioprinting in microgravity and the integration of artificial intelligence. The study concludes with the discussions on the need for collaborative efforts in resolving the technical and regulatory constraints to improve the quality, reliability, and reproducibility of bioprinted tissue equivalents to ultimately accomplish their successful clinical implementation.&#xD.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293274","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 hepatic zonation chip with an oxygen concentration gradient embracing the spatial distribution of metabolic function.","authors":"Min Kyeong Kim, Kyurim Paek, Kyungwon Park, Sungho Tak, Kyuhwan Na, Jung Hoon Choi, Sang-Mi Woo, HanByeol Kim, Yeo Min Yoon, Seok Chung, Jeong Ah Kim","doi":"10.1088/1758-5090/adde86","DOIUrl":"10.1088/1758-5090/adde86","url":null,"abstract":"<p><p>The development of hepatic<i>in vitro</i>models that replicate the physiological characteristics of liver tissue is critical for the accurate translation of drug test results. Current models often fail to mimic the spatial zonation by an oxygen concentration gradient in the hepatic acinus, limiting their ability to predict drug-induced hepatotoxicity. This study aimed to develop a hepatic zonation chip (H-chip) that replicates the oxygen gradient of the hepatic acinus, enhancing physiological relevance for drug testing applications. The H-chip was fabricated with a circular microfabricated chip chamber covered by oxygen-impermeable glass substrates, generating a radial oxygen concentration gradient through oxygen consumption by hepatic cells. This gradient mimics the portal-to-central oxygen distribution observed<i>in vivo</i>, enabling zone-specific hepatic functionality. We showed that the H-chip successfully reproduced the oxygen gradients found in the<i>in vivo</i>hepatic acinus along with corresponding cell cytocompatibility of hepatic cells. Notably, pericentral-specific hepatic functionality increased in the H-chip and decreased in the normoxia chip (N-chip). Spatial transcriptomic analysis revealed heterogeneous gene expression patterns aligned with local metabolic functions in each zone across the H-chip. Furthermore, toxicity evaluation of acetaminophen, a representative drug known for its spatial hepatotoxicity, revealed increased zonation-specific sensitivity in the H-chip, linked to elevated cytochrome P450 gene expression and toxic metabolite formation. These findings highlight the ability of the H-chip to replicate hepatic zonal characteristics, thus providing a robust platform for evaluating hepatotoxicity in drug testing. This platform promises to advance safer and more effective drug development by enabling more physiologically relevant assessments.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144180597","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":"Progress in the application of organoids for exploring the relationship between macrophages and various lung diseases.","authors":"Jiawang Wu, Ting Liu, Xinting Zhang, Chongchang Qu, Juan Wu, Shuanglan Xu, Jiao Yang, Xiqian Xing","doi":"10.1088/1758-5090/adde15","DOIUrl":"10.1088/1758-5090/adde15","url":null,"abstract":"<p><p>Organoids cultured<i>ex vivo</i>mimic<i>in vivo</i>tissue and organ characteristics. They have become a focus in research for their potential in modeling macrophage function in respiratory diseases, offering insights into disease mechanisms and therapeutic strategies. A number of studies have confirmed organoids' utility in dissecting microbial interactions, disease modeling, genetic manipulation, and high-throughput drug screening for efficacy and safety. This review summarizes the research progress on organoids in exploring macrophage involvement in pulmonary diseases.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172463","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":"Bioengineering fascicle-like skeletal muscle bioactuators via pluronic-assisted co-axial 3D bioprinting (PACA-3D).","authors":"Judith Fuentes, Rafael Mestre, Maria Guix, David Esporrín-Ubieto, Ibtissam Ghailan Tribak, Noelia Ruiz-González, Tania Patiño, Samuel Sánchez","doi":"10.1088/1758-5090/addc9b","DOIUrl":"10.1088/1758-5090/addc9b","url":null,"abstract":"<p><p>Advances in 3D bioprinting have opened new possibilities for developing bioengineered muscle models that can mimic the architecture and function of native tissues. However, current bioengineering approaches do not fully recreate the complex fascicle-like hierarchical organization of the skeletal muscle tissue, impacting on the muscle maturation due to the lack of oxygen and nutrient supply in the scaffold inner regions. A key challenge is the production of precise and width-controlled independent filaments that do not fuse during the printing process when subsequently extruded, ensuring the formation of fascicle-like structures. This study addresses the limitation of filament fusion by utilizing a pluronic-assisted co-axial 3D bioprinting system (PACA-3D) creates a physical confinement of the bioink during the extrusion process, effectively obtaining thin and independent printed filaments with controlled shapes. The use of PACA-3D enabled the fabrication of skeletal muscle-based bioactuators with improved cell differentiation and significantly increased force output, obtaining 3 times stronger bioengineered muscle when compared to bioactuators fabricated using conventional 3D extrusion bioprinting techniques, where a single syringe containing the bioink is used. The versatility of our technology has been demonstrated using different biomaterials, demonstrating its potential to develop more complex biohybrid tissue-based architectures with improved functionality, as well as aiming for better scalability and printing flexibility.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131868","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":"Corrigendum: Dual-core coaxial bioprinting of double-channel constructs with a potential for perfusion and interaction of cells (2022<i>Biofabrication</i>14 035012).","authors":"Yanrong Yu, Renjian Xie, Yueteng He, Furong Zhao, Quan Zhang, Wei Wang, Yong Zhang, Jiawei Hu, Dan Luo, Weijie Peng","doi":"10.1088/1758-5090/addd4b","DOIUrl":"https://doi.org/10.1088/1758-5090/addd4b","url":null,"abstract":"","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233075","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":"3D printed bioactive coated scaffolds boost osteogenesis and angiogenesis via the regulation of scaffold microstructure.","authors":"Yulin Jiang, Chen Zhou, Xi Yang, Dongxu Ke","doi":"10.1088/1758-5090/addc9c","DOIUrl":"10.1088/1758-5090/addc9c","url":null,"abstract":"<p><p>Microstructure plays a crucial role in bone regeneration, conventional bone tissue engineering scaffold fabrication techniques often lack the precision required to control microstructural features that can optimize bone healing. 3D printing, as a powerful tool for biofabrication, allows for the design and optimization of scaffold microstructures to enhance bone healing. In this study, bioactive coated scaffolds composed of polycaprolactone and tricalcium phosphate were fabricated using a micro-extrusion 3D printer with varying compositions and microstructures, resulting in different physical and mechanical properties. Among these properties, porosity and permeability played a vital role in osteogenic and angiogenic differentiation.<i>In vitro</i>studies revealed that the permeability effect was dominant in osteogenic differentiation, while the porosity effect mainly induced the angiogenic differentiation, with potential mechanisms involving crosstalk between Wnt and PI3K signaling pathways. Moreover, significantly improved osteogenesis and angiogenesis were observed in U600 scaffolds compared to sham and U300 scaffolds, supporting the<i>in vitro</i>findings. This study provides valuable insights for the microstructure optimization of 3D printed tissue engineering scaffolds, which could facilitate the translation of 3D printing technology from the benchside to clinical applications.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144131865","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}