Biofabrication最新文献

{"title":"Simulating big mechanically-active culture systems (BigMACS) using paired biomechanics-histology FEA modelling to derive mechanobiology design relationships.","authors":"Sabrina Schoenborn, Mingyang Yuan, Cody A Fell, Chuanhai Liu, David F Fletcher, Selene Priola, Hon Fai Chan, Mia Woodruff, Zhiyong Li, Yi-Chin Toh, Mark C Allenby","doi":"10.1088/1758-5090/adcd9f","DOIUrl":"https://doi.org/10.1088/1758-5090/adcd9f","url":null,"abstract":"<p><p>Big mechanically-active culture systems (BigMACS) are promising to stimulate, control, and pattern cell and tissue behaviours with less soluble factor requirements. However, it remains challenging to predict if and how distributed mechanical forces impact single-cell behaviours to pattern tissue. In this study, we introduce a tissue-scale finite element analysis framework able to correlate sub-cellular quantitative histology with centimetre-scale biomechanics. Our framework is relevant to diverse BigMACS, including media perfusion, tensile-stress, magnetic, and pneumatic tissue culture platforms. We apply our framework to understand how the design and operation of a multi-axial soft robotic bioreactor can spatially control mesenchymal stem cell (MSC) proliferation, orientation, differentiation to smooth muscle, and extracellular vascular matrix deposition. We find MSC proliferation and matrix deposition to positively correlate with mechanical stimulation but cannot be locally patterned by soft robot mechanical stimulation within a centimetre scale tissue. In contrast, local stress distribution was able to locally pattern MSC orientation and differentiation to smooth muscle phenotypes, where MSCs aligned perpendicular to principal stress direction and expressed increased α-SMA with increasing 3D Von Mises Stresses from 0 to 15 kPa. Altogether, our new biomechanical-histological simulation framework is a promising technique to derive the future mechanical design equations to control cell behaviours and engineer patterned tissue.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960869","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":"Filamented light (FLight) biofabrication of mini-tendon models show tunable matrix confinement and nuclear morphology.","authors":"Hao Liu, Lynn Scherpe, Linnea B Hummer, Jess Gerrit Snedeker, Marcy Zenobi-Wong","doi":"10.1088/1758-5090/adce35","DOIUrl":"https://doi.org/10.1088/1758-5090/adce35","url":null,"abstract":"<p><p>One hallmark of healthy tendon tissue is the high confinement of tenocytes between tightly packed, highly aligned collagen fibers. During tendinopathy, this organization becomes dysregulated, leading to cells with round-shaped morphology and collagen fibers which exhibit crimping and misalignment. The elongated nuclei in healthy tendons are linked to matrix homeostasis through distinct mechanotransduction pathways, and it is believed that the loss of nuclear confinement could upregulate genes associated with abnormal matrix remodeling. Replicating the cell and nuclear morphology of healthy and diseased states of tendon, however, remains a significant challenge for engineered<i>in vitro</i>tendon models. Here we report on a high throughput biofabrication of mini-tendons that mimick the tendon core compartment based on the filamented light (FLight) approach. Each mini-tendon, with a length of 4 mm, was composed of parallel hydrogel microfilaments (2-5<i>µ</i>m diameter) and microchannels (2-10<i>µ</i>m diameter) that confined the cells. We generated four distinct matrices with varying stiffness (7-40 kPa) and microchannel dimensions. After 14 d of culture, 29% of tenocytes in the softest matrix with the largest microchannel diameter were aligned, exhibiting an average nuclear aspect ratio (nAR) of 2.1. In contrast, 84% of tenocytes in the stiffest matrix with the smallest microchannel diameter were highly aligned, with a mean nAR of 3.4. When tenocytes were cultured<i>on</i>the FLight hydrogels (2D) as opposed to within the hydrogels three-dimensional (3D), the mean nAR was less than 1.9, indicating that nuclear morphology is significantly more confined in 3D environments. By tuning the stiffness and microarchitecture of the FLight matrix, we demonstrated that mechanical confinement can be modulated to exert control over the extent of nuclear confinement. This high-throughput, tunable platform offers a promising approach for studying the mechanobiology of healthy and diseased tendons and for eventual testing of drug compounds against tendinopathy.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974166","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":"Cardiomyocyte sheet stacking using fibrin enables high-speed construction of three-dimensional myocardial tissue and high transplantation efficiency.","authors":"Katsuhisa Sakaguchi, Kazuki Nakazono, Kodai Tahara, Yuto Hinata, Yusuke Tobe, Jun Homma, Hidekazu Sekine, Katsuhisa Matsuura, Kiyotaka Iwasaki, Satoshi Tsuneda, Tatsuya Shimizu","doi":"10.1088/1758-5090/adcb6e","DOIUrl":"https://doi.org/10.1088/1758-5090/adcb6e","url":null,"abstract":"<p><p>Despite the development of three-dimensional (3D) tissues that promises remarkable advances in myocardial therapies and pharmaceutical research, vascularization is required for the repair of damaged hearts using cardiac tissue engineering. In this study, we developed a method for rapid generation of a 3D cardiac tissue, with extremely high engraftment efficiency, by stacking cardiomyocyte sheets using fibrin as an adhesive. Cell sheets were created by peeling off confluent cultured cells from a culture dish grafted with a polymer that induced surface hydrophilicity in response to low temperatures. The high engraftment rate was attributed to the retention of the adhesive protein. The multistacked vascularized cell sheets prepared using fibrin, when transplanted into the subcutaneous tissue and at myocardial infarction site in rats, yielded a transplanted 3D myocardial tissue. Furthermore, multilayered cardiomyocyte sheets were transplanted twice at 1 week intervals to create a 3D myocardial tissue. Our data suggest that fibrin-based rapidly layered cell sheets can advance tissue-engineered transplantation therapy and should aid the development of next-generation tissue-engineered products in the fields of regenerative medicine and drug screening.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975926","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":"Review of 3D-printed bioceramic/biopolymer composites for bone regeneration: fabrication methods, technologies and functionalized applications.","authors":"Yumeng Tang, Yi Zhang, Li Zou, Chengli Sun, Weizhe Tang, Youce Zou, Aiwu Zhou, Weili Fu, Fuyou Wang, Kang Li, Qiang Zhang, Xiaosheng Zhang","doi":"10.1088/1758-5090/adcbd7","DOIUrl":"https://doi.org/10.1088/1758-5090/adcbd7","url":null,"abstract":"<p><p>Biomaterials for orthopedic applications must have biocompatibility, bioactivity, and optimal mechanical performance. A suitable biomaterial formulation is critical for creating desired devices. Bioceramics with biopolymer composites and biomimetics with components similar to that of bone tissue, have been recognized as an area of research for orthopedic applications. The combination of bioceramics with biopolymers has the advantage of satisfying the need for robust mechanical support and extracellular matrices at the same time. Three-dimensional (3D) printing is a powerful method for restoring large bone defects and skeletal abnormalities owing to the favorable merits of preparing large, porous, patient-specific, and other intricate architectures. Bioceramic/biopolymer composites produced using 3D printing technology have several advantages, including desirable optimal architecture, enhanced tissue mimicry, and improved biological and physical properties. This review describes various 3D printing bioceramic/biopolymer composites for orthopedic applications. We hope that these technologies will inspire the future design and fabrication of 3D printing bioceramic/biopolymer composites for clinical and commercial applications.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972715","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 small-diameter vascular graft with acellular human amniotic membrane: a proof-of-concept study in pig.","authors":"O Aung, Peter J Rossi, Yingnan Zhai, Kenneth P Allen, Mitchell R Dyer, Jackie Chang, Xiaolong Wang, Chase Caswell, Austin Stellpflug, Yiliang Chen, Brandon J Tefft, Linxia Gu, Rongxue Wu, Bo Wang","doi":"10.1088/1758-5090/adcb6d","DOIUrl":"https://doi.org/10.1088/1758-5090/adcb6d","url":null,"abstract":"<p><p>Expanded polytetrafluoroethylene (ePTFE) grafts are Food and Drug Administration approved and effective for large vessel surgeries but face challenges in smaller vessels (Inner Diameter, ID ⩽ 6 mm) due to reduced blood flow and higher risks of thrombosis, stenosis, and infection. This study developed a vascular graft with an ID of 6 mm from decellularized human amniotic membrane (DAM graft) and compared its performance to ePTFE grafts in a porcine carotid artery model for one month. DAM grafts retained key extracellular matrix structures and mechanical properties post-decellularization, with customizable layers and stiffness to meet specific clinical needs. DAM grafts demonstrated successful carotid artery replacement, showing good surgical feasibility, patency, and post-operative recovery in all animals. In contrast to ePTFE grafts, which exhibited significant neointimal hyperplasia (NIH), poor endothelialization, and inflammation, DAM grafts displayed organized endothelial coverage, smooth muscle alignment, and reduced inflammation, minimizing NIH, thrombosis, and graft failure. These findings position DAM grafts as a promising alternative to synthetic grafts, especially for small-diameter applications. Future research should focus on improving endothelialization, exploring molecular mechanisms, and assessing long-term outcomes to further optimize DAM grafts for clinical use.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960745","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":"Injectable microgel and micro-granular hydrogels for bone tissue engineering.","authors":"Melika Mansouri Moghaddam, Elaheh Jooybar, Rana Imani","doi":"10.1088/1758-5090/adcc58","DOIUrl":"https://doi.org/10.1088/1758-5090/adcc58","url":null,"abstract":"<p><p>Injectable microgels, made from both natural and synthetic materials, are promising platforms for the encapsulation of cells or bioactive agents, such as drugs and growth factors, for delivery to injury sites. They can also serve as effective micro-scaffolds in bone tissue engineering (BTE), offering a supportive environment for cell proliferation or differentiation into osteoblasts. Microgels can be injected in the injury sites individually or in the form of aggregated/jammed ones named micro-granular hydrogels. This review focuses on common materials and fabrication techniques for preparing injectable microgels, as well as their characteristics and applications in BTE. These applications include their use as cell carriers, delivery systems for bioactive molecules, micro-granular hydrogels, bio-inks for bioprinting, three-dimensional microarrays, and the formation of microtissues. Furthermore, we discuss the current and potential future applications of microgels in bone tissue regeneration.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":"17 3","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967602","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":"Combinatorial strategy for engineering cartilage and bone microtissues using microfluidic cell-laden microgels.","authors":"Suntae Kim, Siyuan Li, Seung Yeop Baek, Chaenyung Cha, Sang Jin Lee","doi":"10.1088/1758-5090/adc840","DOIUrl":"10.1088/1758-5090/adc840","url":null,"abstract":"<p><p>Osteochondral defects (OCD) refer to localized injuries affecting both the avascular cartilage and subchondral bone. Current treatments, such as transplantation or microfracture surgery, are hindered by limitations like donor availability and the formation of small, rigid fibrocartilage. Tissue engineering presents a promising alternative, yet challenges arise from limited oxygen and nutrient supply when fabricating human-scale tissue constructs. To address this, we propose assembling engineered micro-scale tissue constructs as building blocks for human-scale constructs. In this study, we aimed to develop bone and cartilage microtissues as building blocks for osteochondral tissue engineering. We fabricated placental stem cell (PSC)-laden microgels, inducing differentiation into osteogenic and chondrogenic microtissues. Utilizing a microfluidics chip platform, these microgels comprised a cell-laden core containing bone-specific and cartilage-specific growth factor-mimetic peptides, respectively, along with an acellular hydrogel shell. Additionally, we investigated the effect of culture conditions on microtissue formation, testing dynamic and static conditions. Results revealed over 85% cell viability within the microgels over 7 d of continuous growth. Under static conditions, approximately 60% of cells migrated from the core to the periphery, while dynamic conditions exhibited evenly distributed cells. Within 4 weeks of differentiation, growth factor-mimetic peptides accelerated PSC differentiation into bone and cartilage microtissues. These findings suggest the potential clinical applicability of our approach in treating OCD.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of highly vascularized hepatic spheroids of primary hepatocytes via pro-angiogenic strategy<i>in vitro</i>.","authors":"Yen-Hsiang Huang, Masafumi Watanabe, Tadahiro Yamashita, Ryo Sudo","doi":"10.1088/1758-5090/adc8d4","DOIUrl":"10.1088/1758-5090/adc8d4","url":null,"abstract":"<p><p>Primary hepatocytes are widely recognized for their ability to accurately represent the<i>in vivo</i>hepatocyte phenotype. However, traditional avascular primary hepatocyte culture models are limited by inadequate mass transfer, which leads to a rapid decline in hepatocyte function and survival. To address these challenges, vascularization of hepatic spheroids is crucial for enhancing oxygen and nutrient supply, thereby enabling the construction of larger and more complex hepatic tissues<i>in vitro</i>. In this study, we achieved vascularization of hepatic spheroids containing freshly isolated primary hepatocytes by incorporating fibroblasts as a source of paracrine factors to induce angiogenesis. Multicellular spheroids composed of primary hepatocytes and fibroblasts were formed in non-adhesive concave wells, and one of the spheroids was subsequently embedded in a fibrin-collagen hydrogel within a microfluidic device. Endothelial cells were then seeded onto adjacent microfluidic channels. They formed microvascular networks that extended toward and penetrated the hepatic spheroid. The vascularized hepatic spheroid closely mimicked hepatic sinusoids, with hepatocytes in close contact with microvessels. Moreover, the vascularized spheroid exhibited significantly enhanced hepatic function, specifically albumin secretion and urea synthesis. Our findings provide insights into the establishment of highly vascularized hepatic spheroids<i>in vitro</i>, which is crucial for constructing scalable hepatic tissues in the context of biofabrication.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778901","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":"Advancements in selective laser melting (SLM) of titanium alloy scaffolds for bone tissue engineering.","authors":"Kelun Yan, Nor Hasrul Akhmal Ngadiman, Muhammad Zameri Mat Saman, Nur Syahirah Mustafa","doi":"10.1088/1758-5090/adc6c0","DOIUrl":"10.1088/1758-5090/adc6c0","url":null,"abstract":"<p><p>Selective Laser Melting (SLM) has emerged as a transformative technology in bone tissue engineering, particularly for fabricating porous scaffolds from titanium alloys. These scaffolds offer a promising solution for treating critical-sized bone defects, providing mechanical support while promoting bone regeneration. A comprehensive review on recent advancements of SLM is provided by presenting a detailed analysis of cutting-edge research in the application of SLM for titanium alloy scaffold production. Key areas explored include structural designs like Triply Periodic Minimal Surfaces, material and process parameters optimization to enhance scaffold properties such as porosity, mechanical strength, and biocompatibility. Furthermore, the review emphasizes recent innovations in surface modification techniques which improve bioactivity and osseointegration to enable scaffolds to mimic the host tissues. In addition, this review provides essential insights in related to the potential of SLM to be adopted in producing personalized and high-performance medical implants. By synthesizing the latest trends and identifying key areas for future research, this paper aims to serve as a vital resource for the advancement and usage of SLM-fabricated scaffolds in clinical applications. The findings underscore the importance of continued innovation in this field, which has the potential to significantly improve patient outcomes in orthopaedics and beyond.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741812","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":"Fabrication of multilayer heterogeneous cell assembly for pathophysiologically relevant 3D<i>in-vitro</i>IBD disease model for high throughput drug screening.","authors":"Mamta Kumari, Kamare Alam, Santanu Kaity, Sunil Kumar Sah, Velayutham Ravichandiran, Subhadeep Roy","doi":"10.1088/1758-5090/adc50e","DOIUrl":"10.1088/1758-5090/adc50e","url":null,"abstract":"<p><p>Regarding the approval of novel pharmaceuticals, the most common reason for failure is inadequate oral drug bioavailability. Owing to the complex physiological milieu of the human intestine, which is characterized by its varied composition, various functions, and one-of-a-kind dynamic conditions, it is difficult to reproduce the organ<i>in vitro</i>. Traditional monolayers in two dimensions, sophisticated three-dimensional systems, and developing fluid-dynamic platforms are examples of<i>in-vitro</i>intestinal models. Caco-2 cells have been the gold standard for studying drug permeability for over two decades, particularly for BCS Class II/III/IV drugs. Other intestinal<i>in vitro</i>models exist; however, pharmaceutical corporations and regulatory authorities use the Caco-2 cell line to predict human intestinal permeability. To predict oral drug absorption and study normal intestinal epithelial physiology, it is necessary to have advanced technologies capable of creating human intestinal epithelial cells (hIECs) with cellular variety and functions. There is a strong link between the permeability data obtained<i>in vitro</i>and the fractions absorbed by humans in complex multicellular models. However, although microphysiological systems accurately replicate physiological cues of the digestive tract, they still require standardization. We critically reviewed a step towards tissue-created 3D intestinal organoids and 3D heterocellular multicompartmental models without compromising cellular variety and function. To bridge the gap between 2D and 3D intestinal culture models, a physiologically appropriate hIEC model provides a novel platform for patient-specific testing and translational applications. A comprehensive understanding of numerous 3D<i>in-vitro</i>models of inflammatory bowel disease has been discussed. Additionally, this review will provide insights into the benefits and limitations of these models and their relevance in understanding intestinal physiology and accelerating drug discovery through high-throughput screening.</p>","PeriodicalId":8964,"journal":{"name":"Biofabrication","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708319","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}