{"title":"Oxytocin-loaded hydrogel promotes cartilage regeneration and regulates microenvironment.","authors":"Tianming Wang, Xiao Zhao, Jiayi Li, Chongchong Yin, Bo Jiang, Jiaming Xie, Binghao Wang, Yufeng Wang, Zhicheng Cao, Qingqiang Yao, Shengnai Zheng, Jisheng Sui, Kun Zhu","doi":"10.1088/1758-5090/adc158","DOIUrl":"10.1088/1758-5090/adc158","url":null,"abstract":"<p><p>Osteoarthritis is a common orthopedic condition, and traditional treatment methods often fail to regenerate cartilage effectively. Oxytocin (OXT) is a neuropeptide that plays a crucial role in the skeletal system. Hyaluronic acid (HAMA) hydrogel has emerged as a key carrier for cartilage repair due to its excellent biocompatibility and biodegradability. Combining OXT with HAMA hydrogel and implanting it at the site of cartilage defects can effectively promote cartilage regeneration. Cartilage damage often results in an altered microenvironment, characterized by macrophage polarization and high levels of reactive oxygen species (ROS). Oxidative stress can stimulate macrophages to produce more pro-inflammatory factors. OXT can inhibit the secretion of pro-inflammatory cytokines such as TNF-<i>α</i>, IL-6, and IL-1<i>β</i>by interacting with the STAT3/NF-<i>κ</i>B signaling pathway, as well as the PI3K/Akt and mitogen-activated protein kinase pathways, thereby inducing the polarization of macrophages from the M1 phenotype to the M2 phenotype and alleviating the inflammatory response. OXT can also enhance the expression of NRF and HO-1, which helps eliminate ROS and suppress the expression of pro-inflammatory factors. Regulating the microenvironment of cartilage damage is beneficial for cartilage protection and repair. OXT activates the CFOS/AP-1 and STAT1/JAK2 pathways, which together act on MMP2 and MMP9 to alleviate cartilage degeneration. The STAT1/JAK2 pathway can further increase the expression of Col2, thereby protecting chondrocytes. Additionally, OXT can directly boost the protein levels of SOX9 and COMP, promoting chondrocyte proliferation and cartilage protection, ultimately achieving the therapeutic goal for arthritis. This study explores the potential of HAMA hydrogel as a delivery system for OXT and analyzes their impact on cartilage regeneration and anti-inflammatory properties. This research provides a novel strategy for the treatment of cartilage injuries.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143647221","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":"Biomedical implication of microfluidics in disease diagnosis and therapeutics: from fabrication to prognosis.","authors":"Shivani Yadav, Manish Dwivedi, Sukriti Singh, Pooja Jangir","doi":"10.1088/1758-5090/adc0c2","DOIUrl":"10.1088/1758-5090/adc0c2","url":null,"abstract":"<p><p>Microfluidics has given us an approach to regulate the fluids' behaviour and influence at the microscale level, including the microchannels as an integral element. Microchannels encompass the high surface area-to-volume ratio, causing the rapid diffusion and mixing of substances within the tiny canals and facilitating predictable and stable fluid dynamics. This precise regulatory mechanism of fluid behaviour by microchannels is significant for several biological and chemical processes. In the present scenario, microfluidics plays a significant role in pharmaceutical industries for efficient drug synthesis, DNA analysis, protein crystallization and cell culture. They have also been exploited in fabricating site-directed drug delivery systems such as microchannels. This review has illustrated the different strategies for fabricating microfluidic devices (e.g. microchannels) and their potential implications in biomedical sciences. It also includes a discussion about the challenges associated with standardisation, cost-effective production, biocompatibility and safety concerning microchannel fabrication and its biological application, as well as possible approaches to overcome these issues. These microfluidic devices have the potential for diagnosis, drug delivery, disease monitoring and other applications in human health and diseases and require more attention from researchers to fabricate them precisely and efficiently.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630106","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}
BiofabricationPub Date : 2025-03-20DOI: 10.1088/1758-5090/adbcdd
Hongyu Zhao, Xiao Niu, Shitong Wei, Wei Lin, Hao Luo, Bin Zou, Qinghua Chen, Hongyu Xing, Qingguo Lai
{"title":"Graphene oxide and<i>in-situ</i>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":"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<i>in-situ</i>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<i>in-situ</i>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<i>in-situ</i>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<i>in-situ</i>carbon and GO synergistically promoted more effective bone mineralization, demonstrating enhanced osteoinductivity<i>in vitro.</i>In a rodent model, the bioceramic scaffolds also exhibited improved osteogenesis in critical bone defects. Therefore,<i>in-situ</i>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":"2025-03-20","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}
BiofabricationPub Date : 2025-03-20DOI: 10.1088/1758-5090/adb7c1
Ke Wang, Yushen Wang, Junlei Han, Zhixiang Liang, Wenhong Zhang, Xinyu Li, Jun Chen, Li Wang
{"title":"Biofabrication and simulation techniques for gut-on-a-chip.","authors":"Ke Wang, Yushen Wang, Junlei Han, Zhixiang Liang, Wenhong Zhang, Xinyu Li, Jun Chen, Li Wang","doi":"10.1088/1758-5090/adb7c1","DOIUrl":"10.1088/1758-5090/adb7c1","url":null,"abstract":"<p><p>Biomimetic gut models show promise for enhancing our understanding of intestinal disorder pathogenesis and accelerating therapeutic strategy development. Current<i>in vitro</i>models predominantly comprise traditional static cell culture and animal models. Static cell culture lacks the precise control of the complex microenvironment governing human intestinal function. Animal models provide greater microenvironment complexity but fail to accurately replicate human physiological conditions due to interspecies differences. As the available models do not accurately reflect the microphysiological environment and functions of the human intestine, their applications are limited. An optimal approach to intestinal modeling is yet to be developed, but the field will probably benefit from advances in biofabrication techniques. This review highlights biofabrication strategies for constructing biomimetic intestinal models and research approaches for simulating key intestinal physiological features. We also discuss potential biomedical applications of these models and provide an outlook on multi-scale intestinal modeling.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448016","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}
BiofabricationPub Date : 2025-03-18DOI: 10.1088/1758-5090/adbcdc
Malin Becker, Francisca Gomes, Isa Porsul, Jeroen Leijten
{"title":"ATPS-enabled single-step printing of chemically and mechanically on-demand tunable perfusable channels in ejectable constructs.","authors":"Malin Becker, Francisca Gomes, Isa Porsul, Jeroen Leijten","doi":"10.1088/1758-5090/adbcdc","DOIUrl":"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. To showcase 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":"2025-03-18","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}
BiofabricationPub Date : 2025-03-13DOI: 10.1088/1758-5090/adb999
Gaddam Kiranmai, Shibu Chameettachal, Yeleswarapu Sriya, Sarah Duin, Anja Lode, Michael Gelinsky, Ashwini Rahul Akkineni, Falguni Pati
{"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}
BiofabricationPub Date : 2025-03-13DOI: 10.1088/1758-5090/adbc22
Ceren Babayigit, Jorge Alfonso Tavares-Negrete, Rahim Esfandyarpour, Ozdal Boyraz
{"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<sup>-2</sup>) 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}
BiofabricationPub Date : 2025-03-13DOI: 10.1088/1758-5090/adb891
Alessandro Margarita, Simone Giovanni Gugliandolo, Silvia Santoni, Davide Moscatelli, Bianca Maria Colosimo
{"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}
BiofabricationPub Date : 2025-03-13DOI: 10.1088/1758-5090/adbd79
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
{"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}