The U-CUP perfusion bioreactor is a user-friendly tool to establish and control your 3D cell and tissue cultures.


U-CUP has been specifically designed to be used by any scientist or lab technician working in the life science related field, without necessarily requiring any previous experience with the use of bioreactors.

Applications

• Organotypic models (Bone remodeling, Tumor microenvironment)
• 3D cell expansion and differentiation  
• Investigation of cell-scaffold interactions  
• Investigation of cell-extracellular matrix interactions  
• Generation of 3D cell-scaffold constructs suitable for preclinical experimentation

Apply instantly your current cell culture concepts and simply let U-CUP further extend them by performing the seamless transition to the 3D context.

Features	Advantages	Benefits
Direct perfusion	Unifrom cell seeding	Uniform tissue
	Efficient nutrition and waste removal	Viable tissue, up to several weeks of culture
	Physiological conditions (mimicking inetrstitial fluid flow and associated induced shears	Physiologically relevant tissue
Simple and smart design (patented)	Easy and ready to use	No previous experience with 3D cell cultures required
	Minimized manual operations	Highly reproducible results
	Efficient with many cell types	Versatile cell and tissue culture models
Supple scaffold adaptors	Compatible with a wide spectrum of 3D porous scaffolds of various composition, architecture and sizes
Access to cell culture medium through valves	Suitable to seed and co-culture several cell types, even at different culture time points	Possibility to investigate complex cell-cell and cell-extracellular matrix interaction
	Efficient cell retrieval from scaffolds after culture (with standard enzymatic treatment)	Easy cell analyses (cytofluorimetry, gene expression etc.)

Product Configuration

1x syringe pump		1x rack		10x U-CUP disposable bioreactor kits		1x Starter kit
	+		+		=
The driving force of the system. It generates the oscillating fluid flow of the cell/medium suspension. It cannot be purchased separately.		A rotating rack for easy and correct positioning of U-CUP disposable bioreactors. It can also be purchased separately.		The central core of the system. It is disposable and it comes with 10x adaptors to fit the specific size of your scaffolds. Scaffolds can also be purchased separately.		It provides all what you need to start your 3D cell cultures. Additional accessories (e.g. forceps, syringes) and testing units are also included.

The performance of U-CUP has been extensively validated and certified by scientific publications in peer-review journals.

If you are convinced of the benefits that a 3D culture environment can provide,the U-CUP bioreactor is the essential tool to conduct with your experiments.

For assistance and advice to set up your experiment, do not hesitate to contact CELLEC’s expert team to address your questions.

REPAIRLab, University Medical Center, Mainz, Germany

We have been using the U-CUP perfusion bioreactor for approximately 1 year. Due to excellent technical assistance, detailed protocols and a hands-on introduction at the facilities, only a short time was needed to get everything up and running in our lab.  We have carried out studies for up to 28 days with primary cells.  The system takes up little space, is easily handled and manipulated ensuring sterility and the results are highly reproducible between multiple samples. The team at CellecBiotek AG, especially Ms. Anna Gril and Dr. Adam Papadimitropoulos have provided professional guidance before and after the purchase, as well as well as excellent scientific support. It is not a matter of course that critical questions are discussed and that scientific details are openly shared – and for this we are very grateful!

Dr. Thomas Böse
REPAIRLab, University Medical Center
Johannes Gutenberg University Mainz

We work on hematopoietic niches, more precisely on the interactions between hematopoietic stem cells and their microenvironment. We had previously developed an in vitro 3D niche composed of different bone marrow stromal cells and demonstrate the functionality of our model by its capacity to maintain or promote stemness/quiescence of hematopoietic stem cells. We wanted to increment our system by adding flow to better fit with the bone marrow physiology. We have purchased the U-CUP perfusion bioreactor from CELLEC. We really see that CELLEC proposes a “ready-to-use” system. 

However, despite the very user-friendly side of the U-CUP, we faced several difficulties to have a good flow and to correctly colonize our biomaterial. We wrote to the scientific expert to have advices and each time we had a quick and powerful answer adapted to our problems. They really perfectly know their product and have a large scientific culture to bring adapted solutions.

The U-CUP from Cellec fulfilled our wishes and, even more, open to us new research fields!

Adrienne Anginot, PhD

INSERM U972 Institut André Lwoff

Université Paris XI, Hôpital Paul Brousse

Villejuif, FRANCE

Saggioro et al. 2023 A new organotypic model for aggressive childhood cancer, alveolar rhabdomyosarcoma (ARMS), has been developed. It replicates key features of invasive ARMS, showing increased cell proliferation, secretion of MMP-2, and upregulation of genes associated with tumor aggressiveness. This model holds potential for personalized chemotherapy screening using patient-derived cells. (Title: A perfusion-based three-dimensional cell culture system to model alveolar rhabdomyosarcoma pathological features, Scientific Reports)

Bhangu et al. 2022 The authors generated a microtissues by co-culturing BT474 and 3T3 cells on a collagen scaffold in U-Cup perfusion bioreactor device and studied the ability of doxorubicin nanodrug to accumulate in such a complex tumor model. (Title: Transforming the Chemical Structure and Bio-Nano Activity of Doxorubicin by Ultrasound for Selective Killing of Cancer Cells, Advanced Materials)

Huo et al. 2022 The authors describe an approach for drug testing, relying on an advanced 3D culture system combined with a rapid and highly sensitive metabolic assessment that could facilitate the development of personalized treatment strategies for neuroblastoma. (Title: Perfusion-Based Bioreactor Culture and Isothermal Microcalorimetry for Preclinical Drug Testing with the Carbonic Anhydrase Inhibitor SLC-0111 in Patient-Derived Neuroblastoma, International Journal of Molecular Sciences)

Shekarian et al. 2022 This study demonstrates that ex vivo immunotherapy of GBM explants enables an active antitumoral immune response within the tumor center in a subset of patients, and provides a framework for multidimensional personalized assessment of tumor response to immunotherapy. (Title: Immunotherapy of glioblastoma explants induces interferon-γ responses and spatial immune cell rearrangements in tumor center, but not periphery, Science Advances)

García-García and Martin. 2021 The authors propose an in vitro 3D culture system combining perfusion bioreactors, scaffolds and human primary cells to engineer fully-humanized, biomimetic and customizable bone marrow tissues. This system could serve as a model to investigate human hematopoietic stem cell niches, but also as a drug testing platform for pharmaceutical research and patient-personalized medicine. (Title: Biomimetic human bone marrow tissues: models to study hematopoiesis and platforms for drug testing, Molecular & Cellular Oncology)

García-García et al. 2021 The authors developed a unique platform to investigate human leukemogenesis and response to drugs in customized environments, mimicking defined features of native hematopoietic niches and compatible with the establishment of personalized settings. (Title: Culturing patient-derived malignant hematopoietic stem cells in engineered and fully humanized 3D niches, PNAS)

Born et al. 2021 The authors present vascularize 3D osteoblastic bone marrow niches engineered in perfusion bioreactors. This system provides a unique modular platform to explore hemato-vascular interactions in human healthy/pathological hematopoiesis (Title: Engineering of fully humanized and vascularized 3D bone marrow niches sustaining undifferentiated human cord blood hematopoietic stem and progenitor cells, Journal of Tissue Engineering)

Asnaghi et al. 2021 The authors developed a decellularization procedure of murine thymus in perfusion bioreactor that allows efficient removal of cells and nuclear matter, while preserving extracellular matrix native architecture and protein composition. The decellularized murine thymus was then used for the production of 3D porous scaffolds with preserved ECM composition. When seeded with either fetal or adult thymic epithelial cells, the scaffold could support with different efficiency the maturation of lymphoid precursors to conventional and regulatory T cells able to respond to mitogenic stimuli. (Title: Thymus Extracellular Matrix-Derived Scaffolds Support Graft-Resident Thymopoiesis and Long-Term In Vitro Culture of Adult Thymic Epithelial Cells, Advanced Functional Material)

Panseri et al. 2021 In this paper, a new concept of a structural scaffold design is presented where the physiological multi-scale architecture is fully incorporated in a single-scaffold solution. Hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP) bioceramic scaffolds with different bioinspired porosity, mimicking the spongy and cortical bone tissue, were studied. In vitro experiments, looking at the mesenchymal stem cells behaviour, were conducted in a perfusion bioreactor that mimics the physiological conditions in terms of interstitial fluid flow and associated induced shear stress. (Title: Bone-like ceramic scaffolds designed with bioinspired porosity induce a different stem cell response, Journal of Materials Science. Materials in Medicine)

Ismail and Lunger et al. 2020 Their findings indicate that human thrombin‐activated platelet‐rich plasma is a suitable substitute for FBS to generate vascularized, osteogenic grafts from SVF cells and could thus be implemented in protocols for clinical translation of this strategy towards the treatment of bone loss and avascular necrosis of bone. (Title: Platelet-rich plasma and stromal vascular fraction cells for the engineering of axially vascularized osteogenic grafts, Journal of Tissue Engineering and Regenerative Medicine)

Pigeot et al. 2020 This work demonstrates the suitability of engineered devitalized hypertrophic cartilage extracellular matrix as a bone substitute material, with a performance superior to a state-of-the-art commercial graft. Streamlined generation of the devitalized tissue transplant within a perfusion bioreactor is relevant towards standardized and automated manufacturing of a clinical product. (Title: Orthotopic Bone Formation by Streamlined Engineering and Devitalization of Human Hypertrophic Cartilage, International Journal of Molecular Sciences)

Hyung-Seop Han et al. 2020 To stimulate the circulation of blood to perfuse and facilitate transportation of oxygen and nutrients to the cells in 3D scaffolds, an advanced perfusion bioreactor system was developed to mimic the complex biological environment of bone. (Title: Biodegradable Magnesium Alloys Promote Angio‐Osteogenesis to Enhance Bone Repair, Advanced Science)

Amedeo et al. 2020 In the present report, the Authors showed that alternate perfusion promoted the rapid growth of valve cells inside the pericardial material and the activity of a proliferation-supporting pathway, likely controlled by the YAP transcription factor, a crucial component of the Hippo-dependent signaling cascade, especially between 3 and 14 days of culture. (Title: Culture Into Perfusion-Assisted Bioreactor Promotes Valve-Like Tissue Maturation of Recellularized Pericardial Membrane, Frontiers in Cardiovascular Medicine)

Harvestine et al. 2020 To determine whether osteogenic preconditioning would improve the bone-forming potential of unfractionated bone marrow aspirate (BMA), the authors perfused cells on ECM-coated scaffolds to generate naïve and preconditioned constructs. They demonstrated that bioreactor-based preconditioning augments the bone-forming potential of BMA. (Title: Osteogenic preconditioning in perfusion bioreactors improves vascularization and bone formation by human bone marrow aspirates, Science Advances)

Vukasovic and Asnaghi et al. 2019 By demonstrating the safety and efficacy of bioreactor‐generated grafts in two large animal models, this work represents a pivotal step towards implementing the bioreactor‐based manufacturing system for the production of human cartilage grafts for clinical applications. (Title: Bioreactor‐manufactured cartilage grafts repair acute and chronic osteochondral defects in large animal studies, Cell Proliferation)

Neutzner et al. 2019 To overcome the lack of suitable in vitro models that faithfully recapitulate the intricate three-dimensional architecture, complex cellular interactions, and fluid dynamics within the subarachnoid space, the Authors have developed a perfusion bioreactor-based 3D in vitro model using primary human meningothelial cells to generate meningeal tissue constructs. (Title: A perfusion bioreactor-based 3D model of the subarachnoid space based on a meningeal tissue construct, Fluids and Barriers of the CNS)

Gambari et al. 2019 The authors evaluated the use of Hydrogen sulfide-releasing silk fibroin scaffolds for bone healing and regeneration applications, using the U-CUP Perfusion Bioreactor to seed, expand and differentiate hMSCs. (Title: Hydrogen sulfide-releasing silk fibroin scaffold for bone tissue engineering, Materials Science and Engineering: C)

Parejo et al. 2019 Accurate autophagy studies are challenging given the dynamic nature of the process and the difficulty of measuring the rate of autophagosome degradation (autophagic flux). In this chapter, the Authors provide protocols for a careful assessment of the autophagic flux in all-trans retinoic acid (ATRA) treated 2D and 3D breast cancer cultures. (Title: Assessing Autophagy During Retinoid Treatment of Breast Cancer Cells, Methods in Molecular Biology)

Manfredonia and Muraro et al. 2019 The authors investigated whether a bioreactor‐based 3D culture system can preserve the main TME cellular components in primary CRC samples. (Title: Maintenance of Primary Human Colorectal Cancer Microenvironment Using a Perfusion Bioreactor‐Based 3D Culture System, Advanced Biosystems)

Panek et al. 2019 The authors studied the formation of bone tissue under perfusion flow, using DEX-loaded RADA 16-I hydrogel characterized by an efficient delivery of small molecules for sustained release applications.  (Title: Bone Tissue Engineering in a Perfusion Bioreactor Using Dexamethasone-Loaded Peptide Hydrogel, Materials)

Harvestine et al. 2019 In this study, the authors hypothesized that cell-secreted ECM could be used to sequester MSCs and accessory cells from bone marrow aspirate for bone regeneration and they used the U-CUP perfusion bioreactor system to generate 3D implantable constructs.  (Title: Cell-secreted extracellular matrix influences cellular composition sequestered from unprocessed bone marrow aspirate for osteogenic grafts, Biomaterials Science)

Mitra et al. 2019 In this study, the authors suggested a potentially new strategy for engineering osteogenic grafts with a mature ECM by modulating crosslink formation (Title: Exogenous Lysyl Oxidase-Like 2 and Perfusion Culture Induce Collagen Crosslink Formation in Osteogenic Grafts, Biotechnology Journal)

Duchi et al. 2019 In this work, the authors present a human osteochondral model that represents a valuable preclinical ex vivo tool for studying cartilage therapies, such as hydrogel-based bioscaffolds, and they envision that it will reduce the number of animals needed for in vivo testing (Title: Protocols for Culturing and Imaging a Human Ex Vivo Osteochondral Model for Cartilage Biomanufacturing Applications, Materials)

Schimke et al. 2019 In this study, the authors have explored the potential application of a poly-L-lactic acid (PLLA) and poly-ε-caprolactone (PCL) based scaffold for cell cultivation in 3D and facial reconstruction after trauma or tumor resection  (Title: Hard Tissue Augmentation of Aged Bone by Means of a Tin-Free PLLA-PCL Co-Polymer Exhibiting in vivo Anergy and Long-Term Structural Stability, Gerontology)

Mytsyk et al. 2019 In this study, the authors showed that a SVF-derived tissue patch secretome could rescue anoxia-induced nonfunctional cardiomyocytes (Title: Paracrine Potential of Adipose Stromal Vascular Fraction Cells to Recover Hypoxia-Induced Loss of Cardiomyocyte Function, Biotechnology and Bioengineering)

Foglietta et al. 2018 In this study, the authors described the preparation of keratin-based nanoparticles loaded with paclitaxel and their in vitro anticancer activity in 2D and perfusion 3D breast cancer models  (Title: Anticancer activity of paclitaxel-loaded keratin nanoparticles in two-dimensional and perfused three-dimensional breast cancer models, International Journal of Nanomedicine)

Moser et al. 2018 In this study, the authors describe the novel use of a bi-directional perfusion bioreactor to support the long term culture of human bone marrow stromal cells (BMSCs) differentiated on polylactic co-glycolic acid (PLGA) (Title: A Perfusion Culture System for Assessing Bone Marrow Stromal Cell Differentiation on PLGA Scaffolds for Bone Repair, Frontiers in Bioengineering and Biotechnology)

Burgio et al. 2018 In this study, the authors showed that dynamic cultivation of a novel porous oxygen plasma treated (OPT) HA scaffold with hBMSCs in osteogenic medium and subsequent decellularization provides a promising off-the-shelf bone tissue-engineered construct (Title: Characterization and in ovo vascularization of a 3D-printed hydroxyapatite scaffold with different extracellular matrix coatings under perfusion culture, Biology Open)

Rossi et al. 2018 The Authors engineered a tridimensional in vitro model using human progenitors differentiated into osteoblasts and osteoclasts, recapitulating physiological bone homeostasis to study the potential secondary parallel effect on bone homeostasis when targeting TREM-2, a transmembrane receptor expressed by macrophages, microglia, and osteoclasts that plays a protective role in late-onset Alzheimer Disease. (Title: An In Vitro Bone Model to Investigate the Role of Triggering Receptor Expressed on Myeloid Cells-2 in Bone Homeostasis, Tissue Engineering Part C: Methods)

Rossi et al. 2018 In this study, the authors combined the functionalities of a synthetic polymer with those of an engineered and subsequently devitalized extracellular matrix (ECM) to generate a hybrid material for adipose tissue regeneration (Title: Decoration of RGD-mimetic porous scaffolds with engineered and devitalized extracellular matrix for adipose tissue regeneration, Acta Biomaterialia)

Bourgine et al. 2018 In this study, the authors report the development of a human 3D bone marrow analogue in a perfusion-based bioreactor system, partially recapitulating structural, compositional, and organizational features of the native human osteoblastic niche environment. (Title: In vitro biomimetic engineering of a human hematopoietic niche with functional properties, PNAS)

Amedeo et al. 2018 In the present contribution, the authors optimized a decellularization procedure that is permissive for seeding and culturing valve competent cells able to colonize and reconstitute a valve-like tissue (Title: Aortic valve cell seeding into decellularized animal pericardium by perfusion-assisted bioreactor, Journal of Tissue Engineering and Regenerative Medicine)

Mitra et al. 2017 This study highlights the need for optimizing in vitro bioreactor culture duration of engineered constructs to achieve the desired level of bone formation (Title: Bioreactor culture duration of engineered constructs influences bone formation by mesenchymal stem cells, Biomaterials)

Cerino et al. 2017 Perfusion culture of SVF-cells reproducibly promoted in vitro the early formation of a capillary-like network, embedded within an ECM backbone, and the release of numerous pro-angiogenic factors. Perfusion-based engineered constructs were more rapidly vascularized and supported a superior survival of delivered cells upon in vivo ectopic implantation. (Title: Engineering of an angiogenic niche by perfusion culture of adipose-derived stromal vascular fraction cells, Scientific Reports)

Rogina et al. 2017 The authors investigated the influence of a different scaffold’s composition on the human hMSCs differentiation performed in a U-CUP bioreactor under perfusion conditioning. (Title: Human Mesenchymal Stem Cells Differentiation Regulated by Hydroxyapatite Content within Chitosan-Based Scaffolds under Perfusion Conditions, Polymers)

Jalili-Firoozinezhad et al. 2017 The aim of this study was to establish a technique based on SEM analysis of sections of paraffin-embedded tissues prepared for histological processing (Histo-SEM) for the assessment of morpho-architectural properties of native and engineered tissues (Title: Bimodal morphological analyses of native and engineered tissues, Materials Science and Engineering)

Petrenko YA et al. 2017 In this work, the Authors demonstrated that addition and removal of cryoprotective agents under perfused flow significantly increased the viability of MSC within cryopreserved 3D tissue constructs as compared to conventional diffusion-based methods. (Title: Perfusion bioreactor-based cryopreservation of 3D human mesenchymal stromal cell tissue grafts, Cryobiology)

Di Maggio and Martella et al. 2017 This study shows that ECM and regulation of α5β1-integrin signaling preserve ASC progenitor properties, including bone tissue-forming capacity, during in vitro expansion (Title: Extracellular matrix and α5β1 integrin signaling control the maintenance of bone formation capacity by human adipose-derived stromal cells, Scientific Report)

Ismail T et al. 2017 The aim of this study was to generate and test engineered, axially vascularized SVF cells-based bone substitutes in a rat model of avascular necrosis (Title: Engineered, axially-vascularized osteogenic grafts from human adipose-derived cells to treat avascular necrosis of bone in a rat model, Acta Biomaterialia)

Muraro and Muenst 2017 presents an application for ex-vivo culture of human breast cancer specimens (Title: Ex-vivo assessment of drug response on breast cancer primary tissue with preserved microenvironments, OncoImmunology)

Boccardo and Gaudiello 2016 In this paper, the perfusion-based bioreactor is used for the generation of an adipose mesenchymal stromal cells -based engineered constructs (Title: Engineered mesenchymal cell-based patches as controlled VEGF delivery systems to induce extrinsic angiogenesis, Acta Biomaterials)

Cerino 2016 presents an application for engineering an in vitro 3D multi-cellular muscle-like tissue model (Title: Three-dimensional multi-cellular muscle-like tissue engineering in perfusion-based bioreactors, Biotechnology and Bioengineering)

Hirt and Papadimitropoulos 2015 demonstrates the importance of perfusion flow in 3D cultures of tumor cells to efficiently mimic functional features observed “in vivo” and to test anticancer compounds (Title: Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed in vivo, Biomaterials)

Centola 2015 In this study, the perfusion-based bioreactor system is used to improve cartilage digestion, resulting in higher and more reproducible yield of cell populations with high proliferation and chondrogenic capacity (Title: An improved cartilage digestion method for research and clinical applications, Tissue Engineering Part C, Methods)

Bao 2015 presents a humanized in vitro model that reduces the need for experimental animal models, while recapitulating key biological events in a periodontal pocket (Title: Establishment of an oral infection model resembling the periodontal pocket in a perfusion bioreactor system, Virulence)

Papadimitropoulos 2014 presents an efficient expansion method of mesenchymal stromal cells by direct seeding and culturing fresh bone marrow preparation within the pores of 3D porous scaffold (Title: Expansion of human mesenchymal stromal cells from fresh bone marrow in a 3D scaffold-based system under direct perfusion, PLoS One)

Hirt 2014 highlights the potential of perfusion-based models to create 3D tumour microenvironment for cancer immunobiology studies and pre-clinical assessment of innovative treatments (Title: In vitro 3D models of tumor-immune system interaction, Advance Drug Delivery Review)

Papadimitropoulos 2013 presents an application/method for seeding open porous rapid prototyped polymeric scaffolds (Title: A collagen network phase improves cell seeding of open-pore structure scaffolds under perfusion, Journal of Tissue Engineering and Regenerative Medicine)

Sadr 2012 presents an application/method to generate a decellularized cell-laid extacellular matrix which enhances the biological performance of polymeric materials (Title: Enhancing the biological performance of synthetic polymeric materials by decoration with engineered, decellularized extracellular matrix, Biomaterials)

Gueven 2011 presents an application for upscaling osteogenic and vasculogenic grafts (Title: Engineering of large osteogenic grafts with rapid engraftment capacity using mesenchymal and endothelial progenitors from human adipose tissue, Biomaterials)

Papadimitropoulos 2011 presents an application for engineering an in vitro bone organ model (Title: A 3D in vitro bone organ model using human progenitor cells, European Cell & Materials)

Di Maggio 2011 a review for our approaches to engineering in 3D vitro niches (Title: Toward modeling the bone marrow niche using scaffold-based 3D culture systems, Biomaterials)

Santoro 2010 presents an application for upscaling cartilaginous grafts (Title: Bioreactor based engineering of large-scale human cartilage grafts for joint resurfacing, Biomaterials)

Scherberich 2007 presents an application for generating osteogenic and vasculogenic grafts (Title: Three-dimensional perfusion culture of human adipose tissue-derived endothelial and osteoblastic progenitors generates osteogenic constructs with intrinsic vascularization capacity, Stem Cells)

Wendt 2006 describes the system for maintaining living uniform tissues in the scaffolds (Title: Uniform tissues engineered by seeding and culturing cells in 3D scaffolds under perfusion at defined oxygen tensions, Biorheology)

Braccini 2005 presents an application for generating osteogenic grafts (Title: Three-dimensional perfusion culture of human bone marrow cells and generation of osteoinductive grafts, Stem Cells)

Wendt 2003 describes the principle of the U-CUP and its impact on cell seeding (Title: Oscillating perfusion of cell suspensions through three-dimensional scaffolds enhances cell seeding efficiency and uniformity, Biotechnology and Bioengineering)