Journal of Tissue Engineering最新文献

{"title":"Development of a reliable method for human triple-negative breast cancer organotypic culture: Improving imaging and genomic studies in 3D cultures.","authors":"Mercedes Olvera-Valencia, Verónica Garcia-Castillo, Rosalío Ramos-Payan, Maribel Aguilar-Medina, Samuel Trujano-Camacho, Alejandro López-Saavedra, Laurence A Marchat, Cesar López-Camarillo, Ronen Sumagin, Eloy Pérez-Yepez, Carlos Pérez-Plasencia","doi":"10.1177/20417314251326668","DOIUrl":"https://doi.org/10.1177/20417314251326668","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is highly aggressive and lacks targeted therapies, posing a major challenge in oncology. Traditional two-dimensional (2D) cell cultures fail to capture the tumor microenvironment's complexity, whereas three-dimensional (3D) cultures provide a more accurate model of tumor biology. We developed an advanced 3D culture system for TNBC cell lines BT-20 and MDA-MB-231, enhancing the hanging-drop method with Matrigel to restore essential extracellular matrix interactions. Confocal imaging showed MDA-MB-231 cells forming clusters typical of aggressive carcinoma, while BT-20 cells organized into duct-like structures. Molecular analysis of PI3K and β-catenin target genes revealed distinct expression patterns, with PI3K overexpressed and β-catenin downregulated in 3D cultures. Moreover, β-catenin distribution in the 3D cell culture closely resembles its pattern in tissue. These findings underscore the value of 3D models in understanding TNBC progression and in supporting the exploration of novel therapeutic strategies.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251326668"},"PeriodicalIF":6.7,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of an iPSC-derived immunocompetent skin model for identification of skin sensitizing substances.","authors":"Marla Dubau, Tarada Tripetchr, Lava Mahmoud, Fabian Schumacher, Burkhard Kleuser","doi":"10.1177/20417314251336296","DOIUrl":"https://doi.org/10.1177/20417314251336296","url":null,"abstract":"<p><p>The development of immunocompetent skin models marks a significant advancement in in vitro methods for detecting skin sensitizers while adhering to the 3R principles, which aim to reduce, refine, and replace animal testing. This study introduces for the first time an advanced immunocompetent skin model constructed entirely from induced pluripotent stem cell (iPSC)-derived cell types, including fibroblasts (iPSC-FB), keratinocytes (iPSC-KC), and fully integrated dendritic cells (iPSC-DC). To evaluate the skin model's capacity, the model was treated topically with a range of well-characterized skin sensitizers varying in potency. The results indicate that the iPSC-derived immunocompetent skin model successfully replicates the physiological responses of human skin, offering a robust and reliable alternative to animal models for skin sensitization testing, allowing detection of extreme and even weak sensitizers. By addressing critical aspects of immune activation and cytokine signaling, this model provides an ethical, comprehensive tool for regulatory toxicology and dermatological research.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251336296"},"PeriodicalIF":6.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring osseointegration and degradation of Mg-alloy implants through plasma biomarkers of inflammation and bone regeneration.","authors":"Eduarda Mota-Silva, Diana C Martinez, Giuseppina Basta, Serena Babboni, Serena Del Turco, Davide Fragnito, Stefano Salvadori, Claudia Kusmic, Leon Riehakainen, Daniele Panetta, Beatrice Campanella, Massimo Onor, Tomasz Plocinski, Wojciech Swieszkowski, Luca Menichetti","doi":"10.1177/20417314241290595","DOIUrl":"https://doi.org/10.1177/20417314241290595","url":null,"abstract":"<p><p>Magnesium-degradable implants have excellent mechanical and osteogenic properties for temporary orthopedic use but are underutilized due to insufficient methods to monitor implant osseointegration and tissue healing. This study evaluated the use of circulatory biomarkers to monitor the bilateral implantation of a Mg-alloy in rats' femurs. A total of 16 biomarkers were measured from plasma samples collected at multiple timepoints up to 90 days post-implantation. Mg-alloy, Ti-alloy, and Sham (noncritical bone defect) groups were followed with computed tomography, histological, and SEM-EDX analysis. The Sham group showed higher DKK1, OPG, VEGF, and KIM-1 levels than implanted groups. The Mg-alloy group had delayed bone regeneration due to gas release but demonstrated active regeneration up to 180 days and superior osseointegration. Elevated IL-10 and reduced FGF23 at day 28 correlated with accelerated implant degradation. These results underline the complex interactions between biomaterials and biological systems in orthopedic applications and show the value of circulating markers to follow-up implantation.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314241290595"},"PeriodicalIF":6.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12056334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of human salivary gland cell lines for modeling radiation-induced damage in three-dimensional spheroid cultures.","authors":"Sangeeth Pillai, Jose G Munguia-Lopez, Younan Liu, Jordan Gigliotti, Anthony Zeitouni, Joseph M Kinsella, Simon D Tran","doi":"10.1177/20417314251326667","DOIUrl":"https://doi.org/10.1177/20417314251326667","url":null,"abstract":"<p><p>No permanent cure exists for salivary gland (SG) damage and consequent xerostomia (dry mouth) in patients undergoing radiotherapy for head and neck cancers. The lack of commercially available healthy human SG-derived cell lines has hindered in vitro studies of radiation-induced glandular injury. In this study, we successfully immortalized and characterized two novel human major SG-derived cell lines. Leveraging these cell lines and hyaluronic-acid hydrogels, we bioengineered distinct multicellular SG spheroids and microtissues expressing key acinar, ductal, myoepithelial, and mesenchymal cell markers in long-term cultures. Further, using this platform, we developed a proof-of-concept radiation injury model, demonstrating spheroid disruption characterized by actin depolymerization, DNA damage, apoptosis, and loss of SG-specific markers following radiation exposure. Notably, these detrimental effects were partially mitigated with a radioprotective agent. Our findings demonstrate that the bioengineered SG spheroids provide a scalable and versatile platform with significant potential for disease modeling and drug testing, thereby accelerating the development of targeted therapies for radiation-induced xerostomia.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251326667"},"PeriodicalIF":6.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles: From large-scale production and engineering to clinical applications.","authors":"Yuxuan Wang, Jiali Xiong, Kun Ouyang, Mingwang Ling, Junyi Luo, Jiajie Sun, Qianyun Xi, Ting Chen, Yongliang Zhang","doi":"10.1177/20417314251319474","DOIUrl":"https://doi.org/10.1177/20417314251319474","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) have emerged as a promising strategy for treating a wide spectrum of pathologies, as they can deliver their cargo to recipient cells and regulate the signaling pathway of these cells to modulate their fate. Despite the great potential of EVs in clinical applications, their low yield and the challenges of cargo loading remain significant obstacles, hindering their transition from experimental research to clinical practice. Therefore, promoting EV release and enhancing EV cargo-loading are promising fields with substantial research potential and broad application prospects. In this review, we summarize the clinical applications of EVs, the methods and technologies for their large-scale production, engineering, and modification, as well as the challenges that must be addressed during their development. We also discuss the future perspectives of this exciting field of research to facilitate its transformation from bench to clinical reality.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251319474"},"PeriodicalIF":6.7,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering growth factor gradients to drive spatiotemporal tissue patterning in organ-on-a-chip systems.","authors":"Timothy Hopkins, Swati Midha, Simon Grossemy, Hazel R C Screen, Angus K T Wann, Martin M Knight","doi":"10.1177/20417314251326256","DOIUrl":"https://doi.org/10.1177/20417314251326256","url":null,"abstract":"<p><p>Spatial heterogeneity plays a key role in the development and function of human tissues and therefore needs to be incorporated within in vitro models to maximise physiological relevance and predictive power. Here, we developed and optimised methods to generate spatial heterogeneity of hydrogel-embedded bioactive signalling molecules within organ-on-a-chip (OOAC) systems, to drive spatiotemporal tissue patterning through controlled stem cell differentiation. As an exemplar application, we spatially patterned bone morphogenetic protein-2 (BMP-2) in both closed-channel and open-chamber OOAC formats. The resulting BMP-2 gradient in 3D heparin methacryloyl/gelatin methacryloyl, successfully drove spatially divergent differentiation of human bone marrow-derived stem cells into bone-like and cartilage-like regions, mimicking the process of endochondral ossification in the growth plate. The application of hydrogel-embedded morphogens to drive spatial tissue patterning within OOAC systems represents a significant technological advancement and has broad-ranging applicability for a diverse range of tissues and organs, and a wide variety of OOAC platforms.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251326256"},"PeriodicalIF":6.7,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies to overcome the limitations of current organoid technology - engineered organoids.","authors":"Xulong Fan, Kun Hou, Gaojian Liu, Ruolin Shi, Wenjie Wang, Gaofeng Liang","doi":"10.1177/20417314251319475","DOIUrl":"https://doi.org/10.1177/20417314251319475","url":null,"abstract":"<p><p>Organoids, as 3D in vitro models derived from stem cells, have unparalleled advantages over traditional cell and animal models for studying organogenesis, disease mechanisms, drug screening, and personalized diagnosis and treatment. Despite the tremendous progress made in organoid technology, the translational application of organoids still presents enormous challenges due to the complex structure and function of human organs. In this review, the limitations of the translational application of traditional organoid technologies are first described. Next, we explore ways to address many of the limitations of traditional organoid cultures by engineering various dimensions of organoid systems. Finally, we discuss future directions in the field, including potential roles in drug screening, simulated microphysiology system and personalized diagnosis and treatment. We hope that this review inspires future research into organoids and microphysiology system.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251319475"},"PeriodicalIF":6.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of artificial lung tissue structure with 3D-inkjet bioprinting core for pulmonary disease evaluation.","authors":"Weimin Wan, Xi Wang, Rongtao Zhang, Yixuan Li, Haonan Wu, Yiman Liu, Fan Zhang, Jia Liu, Guiquan Liu, Lin Zhou, Zhenhua Wu, Hongju Mao, Jian Yang","doi":"10.1177/20417314251328128","DOIUrl":"10.1177/20417314251328128","url":null,"abstract":"<p><p>By integrating 3D-inkjet bioprinting technology, differentiated human cells can be assembled into artificial lung tissue structure to achieve a rapid, efficient, and reproducible disease model construction process. Here, we developed a novel 3D-inkjet bioprinting-based method to construct artificial lung tissue structure (ALTs) for acute lung injury (ALI) disease modeling, research and application. It can also be used to study the role of relevant cells in the disease by adjusting the cell type and adapted to study the bio-functions of immune cells during the cell-cell interactions. Firstly, a series of process optimizations were done to mass-produce the alginate hydrogel microspheres (Alg) with a particle size of 262.63 ± 5 μm using a 3D bioprinter, then the type I collagen and polydopamine were deposited in turns to construct a cell adhesion layer on the surfaces of Alg (P-Alg) and the particle size was increased to 328.41 ± 3.81 μm. This platform exhibites good stability, timescale-dependent behavior, and long-term cell adhesion. Subsequently, several human cells including endothelial, epithelial, fibroblast, and even immune cells such as macrophages were adhered to P-Alg through rotational culture, leading to cell contractions and aggregation, subsequently formed ALTs or ALTs with macrophages (ALTs@M) with human alveolar-like structure. Finally, we successfully constructed an ALI model with lung barrier damage on ALTs using lipopolysaccharide stimulation in vitro, and comparison of secreted inflammatory factors between ALTs and ALTs@M. Results demonstrated that ALTs@M was more effective than ALTs in stimulating the inflammatory microenvironment of the lungs, providing a novel in vitro model for cellular interactions and human macrophage research. Altogether, this artificial lung tissue structure construction strategy using 3D-inkjet bioprinting technology allowed the flexible development of artificial lung tissue structures as potential disease models for preclinical studies.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251328128"},"PeriodicalIF":6.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143764291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gum-on-a-Chip Exploring Host-Microbe Interactions: Periodontal Disease Modeling and Drug Discovery.","authors":"Qin Hu, Aneesha Acharya, Ho Cheung Shum, Wai Keung Leung, George Pelekos","doi":"10.1177/20417314251314356","DOIUrl":"10.1177/20417314251314356","url":null,"abstract":"<p><p>Periodontal disease is a pervasive and serious health issue, affecting millions globally and leading to severe oral and systemic health complications. This underscores the urgent need to thoroughly understand the complex host-microbe interactions involved. Developing models that allow crosstalk among various bacteria, periodontal component cells, and circulating immune cells is crucial for investigating periodontal disease and discovering new treatments. This study aimed to develop a biomimetic gum tissue model. Within four days, a bio-fabricated tissue with well-established barrier and immune functions was created. In this model, the key periodontal pathogen, <i>Porphyromonas gingivalis</i>, was observed to suppress the recruitment and migration of immune cells and dysregulate CD14 expression in THP-1 cells, leading to significant inflammation and tissue damage. Conversely, the probiotic <i>Akkermansia muciniphila</i> enhanced the host's defensive immune response, highlighting its potential as a therapeutic agent in periodontal disease.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251314356"},"PeriodicalIF":6.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioactivated scaffolds promote angiogenesis and lymphangiogenesis for dermal regeneration in vivo.","authors":"Benedikt Fuchs, Sinan Mert, Daniel Hofmann, Constanze Kuhlmann, Alexandra Birt, Paul Severin Wiggenhauser, Riccardo E Giunta, Myra N Chavez, Jörg Nickelsen, Thilo Ludwig Schenck, Nicholas Moellhoff","doi":"10.1177/20417314251317542","DOIUrl":"10.1177/20417314251317542","url":null,"abstract":"<p><p>Chronic wounds represent an unresolved medical challenge with significant impact for patients' quality of life and global healthcare. Diverse in origin, ischemic-hypoxic and inflammatory conditions play central roles as pathological features that impede proper tissue regeneration. In this study, we propose an innovative approach to address this challenge. Our novel strategy utilizes photosynthetic biomaterials to restore the wound healing process firstly by promoting a normoxic, regeneration-supporting environment and secondly by mitigating inflammation through restoring lymphatic fluid transport and improving blood perfusion. We designed bioartificial scaffolds with photosynthetic cyanobacteria (Syn<i>echococcus sp. PCC</i> 7002) and assessed their functional integration in a bilateral full-thickness skin defect on the backs of mice over a period of 7 days. Illuminated photosynthetic cyanobacteria facilitated local tissue oxygenation independent of blood perfusion. Additionally, genetic modification enabled the secretion of lymphangiogenic hyaluronic acid (HA) into the wound area. After 7 days, the scaffolds were explanted and histologically examined, assessing cell migration (HE staining) and protein expression (CD31, LYVE-1, VEGFR3, Ly6G, and F4/80). Results demonstrated successful colonization of bioartificial scaffolds with cyanobacteria. Following implantation into bilateral full-thickness skin defects, we observed an adherent vascularized basal layer beneath the bioactivated scaffolds after 7 days. Substantial increases in cell migration within bacteria-loaden scaffolds were noted, accompanied by a heightened expression of lymphatic (LYVE-1 and VEGFR3) and endothelial cell markers (CD31). Simultaneously, an augmented expression of acute (Ly6G) and late (F4/80) inflammatory proteins was observed. In summary, we developed a viable photosynthetic scaffold by integrating cyanobacteria into dermal regeneration materials (DRM), promoting the expression of lymphatic, endothelial, and inflammatory proteins under hypoxic conditions. The findings from this study represent a significant advancement in establishing autotrophic tissue engineering approaches, advocating for the use of photosynthetic cells in treating a broad spectrum of hypoxic conditions.</p>","PeriodicalId":17384,"journal":{"name":"Journal of Tissue Engineering","volume":"16 ","pages":"20417314251317542"},"PeriodicalIF":6.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143615728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}