[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382727-105":59,"doc-detail-382727-en":129},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":122,"head_meta":124,"extra_data":126,"updated_unix":128},105,"en","controlled-tumor-heterogeneity-in-a-co-culture-system-by-3d-bio-printed-tumor-on-chip-model","Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model","","Cancer treatment resistance is influenced by tumor heterogeneity and complex interactions between tumor cells and the surrounding microenvironment. The study develops 3D bioprinted in vitro breast cancer tumor microenvironment models using co-cultured cells in a hydrogel matrix with controlled architecture. A microfluidic chip generates chemical gradients to test how breast cancer cell migration responds to defined microenvironments. The system enables precise spatial arrangement, including random mixing or sequential layers, and evaluates migration patterns with epithelial growth factor gradients.",{"@graph":69,"@context":121},[70,84,104],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/controlled-tumor-heterogeneity-in-a-co-culture-system-by-3d-bio-printed-tumor-on-chip-model/382727/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/controlled-tumor-heterogeneity-in-a-co-culture-system-by-3d-bio-printed-tumor-on-chip-model/382727.png","ImageObject",300,407,{"name":92,"@type":93},"นรินทร์","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24",true,{"@type":101,"interactionType":102,"userInteractionCount":8},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"How does the 3D bioprinted co-culture model represent breast tumor heterogeneity?","Question",{"text":111,"@type":112},"It embeds different breast cell types in alginate-gelatine hydrogels with controlled spatial arrangements, creating either random mixing or sequential layered architectures to model heterogeneity.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"What role does the microfluidic system play in the experiments?",{"text":116,"@type":112},"The microfluidic chip produces a chemical gradient in a chamber, enabling study of cell migration patterns toward chemoattractant gradients.",{"name":118,"@type":109,"acceptedAnswer":119},"Which cell types and gradients are used to demonstrate the approach?",{"text":120,"@type":112},"MDA-MB-231 cells are tested for migration toward an epithelial growth factor (EGF) gradient in the presence of MCF10A cells at different ratios.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},382727,1790273076,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":8,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},2336475104957,"https://ap-avatar.wpscdn.com/avatar/22000c4c6bd8a5076e1?x-image-process=image/resize,m_fixed,w_180,h_180&k=1787554080175789136","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nControlled tumor heterogeneity in a co‑culture system by 3D bio‑printed tumor‑on‑chip model  \nNafiseh Moghimi1,2*, Seied Ali Hosseini3, Altay Burak Dalan1,4, Dorsa Mohammadrezaei1, Aaron Goldman2,5 & Mohammad Kohandel1  \nCancer treatment resistance is a caused by presence of various types of cells and heterogeneity within the tumor. Tumor cell–cell and cell‑microenvironment interactions play a significant role in the tumor progression and invasion, which have important implications for diagnosis, and resistance to chemotherapy. In this study, we develop 3D bioprinted in vitro models of the breast cancer tumor microenvironment made of co‑cultured cells distributed in a hydrogel matrix with controlled architecture to model tumor heterogeneity. We hypothesize that the tumor could be represented by a cancer cell‑laden co‑culture hydrogel construct, whereas its microenvironment can be modeled in a microfluidic chip capable of producing a chemical gradient. Breast cancer cells (MCF7 and MDA‑MB‑231) and non‑tumorigenic mammary epithelial cells (MCF10A) were embedded in the alginate‑gelatine hydrogels and printed using a multi‑cartridge extrusion bioprinter. Our approach allows for precise control over position and arrangements of cells in a co‑culture system, enabling the design of various tumor architectures. We created samples with two different types of cells at specific initial locations, where the density of each cell type was carefully controlled. The cells were either randomly mixed or positioned in sequential layers to create cellular heterogeneity. To study cell migration toward chemoattractant, we developed a chemical microenvironment in a chamber with a gradual chemical gradient. As a proof of concept, we studied different migration patterns of MDA‑MB‑231 cells toward the epithelial growth factor gradient in presence of MCF10A cells in different ratios using this device. Our approach involves the integration of 3D bioprinting and microfluidic devices to create diverse tumor architectures that are representative of those found in various patients. This provides an excellent tool for studying the behavior of cancer cells with high spatial and temporal resolution.  \nAbbreviations  \nTME Tumor microenvironment  \n2D Two-dimensional  \n3D Three-dimensional  \nECM Extracellular matrix  \nEGF Epithelial growth factor DMSO Dimethyl sulfoxide  \nDMEM Dulbecco’s modified Eagle’s medium  \nMTT 3-(4,5-Dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide FBS Fetal bovine serum  \nBreast cancer is the most common cancer in women and the second most common cancer overall1. There were over two million new cases in 2018, and more than 30% of those women died1. The aggressiveness of breast cancer maybe due to the known heterogeneity of breast tumors2. Tumor heterogeneity has been observed among patients (inter-tumor heterogeneity) and in each individual tumor (intratumor heterogeneity), which leads to breast cancer aggressiveness and challenges in treatment3. Since tumor may consist of phenotypically different cancer cell populations with different properties, tumor specimen obtained by biopsy does not represent the exact  \n1Department of Applied Mathematics, University of Waterloo, Waterloo, Canada. 2Department of Medicine, Harvard Medical School, Boston, MA, USA. 3Electrical Engineering Department, University of Waterloo, Waterloo, Canada. 4Department of Medical Genetics, School of Medicine, Yeditepe University, Istanbul, Turkey. 5Division of Engineering in Medicine, Brigham and Women’s Hospital, Boston, MA, USA.* email: [nmoghimi@uwaterloo.ca](nmoghimi@uwaterloo.ca)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \ntumor composition. In the case of intratumor heterogeneity, the tumor consists of different phenotypical cell populations, which can be identified by different cell phenotypes, cell density, or their localization in the tumor4","cbCaiosR2KIBxpiM","https://ap.wps.com/l/cbCaiosR2KIBxpiM","pdf",4732694,14,"English","# Abstract\n## Tumor heterogeneity background and rationale\n## 3D bioprinted co-culture hydrogel model design\n## Microfluidic chemical gradient migration experiments\n## Limitations of conventional models and relevance of tumor-on-chip","[{\"question\":\"How does the 3D bioprinted co-culture model represent breast tumor heterogeneity?\",\"answer\":\"It embeds different breast cell types in alginate-gelatine hydrogels with controlled spatial arrangements, creating either random mixing or sequential layered architectures to model heterogeneity.\"},{\"question\":\"What role does the microfluidic system play in the experiments?\",\"answer\":\"The microfluidic chip produces a chemical gradient in a chamber, enabling study of cell migration patterns toward chemoattractant gradients.\"},{\"question\":\"Which cell types and gradients are used to demonstrate the approach?\",\"answer\":\"MDA-MB-231 cells are tested for migration toward an epithelial growth factor (EGF) gradient in the presence of MCF10A cells at different ratios.\"}]","Controlled tumor heterogeneity in a co-culture system by 3D bio-printed tumor-on-chip model | PDF",1790252108,35]