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":"Biofabrication of an in situ hypoxia-delivery scaffold for cartilage regeneration.","authors":"Roberto Di Gesù, Antonio Palumbo Piccionello, Giampiero Vitale, Silvestre Buscemi, Silvia Panzavolta, Maria Francesca Di Filippo, Angelo Leonarda, Monica Cuccia, Alessia Di Prima, Riccardo Gottardi","doi":"10.1088/1758-5090/adbd79","DOIUrl":"https://doi.org/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 - MACI) has been developed to overcome the total joint replacement (TJR) 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.&#xD;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":"2025-03-06","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":"Graphene oxide and in-situ carbon reinforced hydroxyapatite scaffolds via ultraviolet-curing 3D printing technology with high osteoinductivity for bone regeneration.","authors":"Hongyu Zhao, Xiao Niu, Shitong Wei, Wei Lin, Hao Luo, Bin Zou, Qinghua Chen, Hongyu Xing, Qingguo Lai","doi":"10.1088/1758-5090/adbcdd","DOIUrl":"https://doi.org/10.1088/1758-5090/adbcdd","url":null,"abstract":"<p><p>Ultraviolet photopolymerization additive manufacturing has been used to fabricate calcium phosphate (Ca-P) ceramic scaffolds for repairing bone defects, but it is still a challenge for 3D printed Ca-P scaffolds to simultaneously enhance the mechanical strength and osteoinductivity. Here, we successfully developed a high-performance hydroxyapatite (HA) scaffold containing in-situ carbon and graphene oxide (GO) by precisely regulating the degreasing and sintering atmosphere. The results indicated that the mechanical properties of HA scaffolds could be significantly improved by regulating the amount of in-situ carbon. The HA scaffold containing 0.27 wt% carbon achieved the maximum compressive strength of 12.5 MPa with a porosity of approximately 70%. The RNA transcriptome sequencing analysis revealed that in-situ carbon could promote osteogenic differentiation by improving oxygen transport and promoting the expression of multiple angiogenic factors. More importantly, in the absence of osteoinductive agents, the in-situ carbon and GO synergistically promoted more effective bone mineralization, demonstrating enhanced osteoinductivity in vitro. In a rodent model, the bioceramic scaffolds also exhibited improved osteogenesis in critical bone defects. Therefore, in-situ carbon and GO could simultaneously enhance the mechanical strength and osteoinductivity of HA scaffolds, effectively achieving substantial endogenous bone regeneration. This strategy will provide a simple and energy-efficient approach for engineering osteoinductive ceramic scaffolds for repairing bone defects.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566011","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":"ATPS-enabled single-step printing of chemically and mechanically on-demand tunable perfusable channels in ejectable constructs.","authors":"Malin Becker, Francisca Luísa Fernandes Gomes, Isa Robin Porsul, Jeroen Leijten","doi":"10.1088/1758-5090/adbcdc","DOIUrl":"https://doi.org/10.1088/1758-5090/adbcdc","url":null,"abstract":"<p><p>3D bioprinting approaches offer highly versatile solutions to replicate living tissue and organ structures. While current bioprinting approaches can generate desired shapes and spatially determined patterns, the material selection for embedded bioprinting has remained limited, as it has relied on the use of viscous, shear-thinning, or liquid-like solid materials to create shape controlled constructs, which could then be modified downstream via multi-step processes. We here explore aqueous two-phase system stabilized 3D bioprinting of low viscous materials in combination with supramolecular complexation to fabricate intricate, perfusable engineered constructs that are both mechanically and chemically tunable in a single-step manner. To this end, we introduce Dex-TAB as a highly versatile backbone, that allows for mechanical and chemical tuning during as well as after printing. Showcasing the printability as well as spatial chemical modification and mechanical tunability of this material, ejectability, and local/gradual or bulk functionalized interconnected tube shaped constructs were generated. Subsequently, we demonstrated that these functionalized channels could be printed directly into a syringe containing crosslinkable polymer solution, which upon ejection forms pre-patterned perfusable constructs. In short, we report that ATPS enabled low viscous 3D bioprinting can produce highly functional and even potentially minimally invasive injectable yet functionalized and perfusable constructs, which offers opportunities to advance various biofabrication applications.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566009","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":"https://doi.org/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/mm2) on the viability and morphology of 3T3 fibroblasts in GelMA and GelMA-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 days 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":"2025-03-03","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":"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":"Enhanced gelatin methacryloyl nanohydroxyapatite hydrogel for high-fidelity 3D printing of bone tissue engineering scaffolds.","authors":"Toufik Naolou, Nadine Schadzek, Iliyana Pepelanova, Miriam Frommer, Jan Mathis Hornbostel, Franziska Lötz, Leopold Sauheitl, Stefan Dultz, Vincent J M N L Felde, Ola Myklebost, Cornelia Lee-Thedieck","doi":"10.1088/1758-5090/adbb90","DOIUrl":"https://doi.org/10.1088/1758-5090/adbb90","url":null,"abstract":"<p><p>Patients suffering from large bone defects are in urgent need of suitable bone replacements. Besides biocompatibility, such replacements need to mimic the 3D architecture of bone and match chemical, mechanical and biological properties, ideally promoting ossification. As natural bone mainly contains collagen type I and carbonate hydroxyapatite, a 3D-printable biomaterial consisting of methacrylated gelatin (GelMA) and nanohydroxyapatite (nHAp) would be beneficial to mimic the composition and shape of natural bone. So far, such nanocomposite hydrogels (NCH) suffered from unsatisfactory rheological properties making them unsuitable for extrusion-based 3D printing with high structural fidelity. In this study, we introduce a novel GelMA/nHAp NCH composition, incorporating the rheological modifier carbomer to improve rheological properties and addressing the challenge of calcium cations released from nHAp that hinder GelMA gelation. Leveraging its shear-thinning and self-healing properties, the NCH ink retains its shape and forms cohesive structures after deposition, which can be permanently stabilized by subsequent UV crosslinking. Consequently, the NCH enables the printing of 3D structures with high shape fidelity in all dimensions, including the z-direction, allowing the fabrication of highly macroporous constructs. Both the uncured and the UV crosslinked NCH behave like a viscoelastic solid, with G´>G´´ at deformations up to 100-200 %. After UV crosslinking, the NCH can, depending on the GelMA concentration, reach storage moduli of approximately 10 to over 100 kPa and a mean Young's Modulus of about 70 kPa. The printed scaffolds permit not only cell survival but also osteogenic differentiation, highlighting their potential for bone tissue engineering.</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":"143527860","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}

{"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}