Fluid and cell behaviors along a 3D printed alginate/gelatin/fibrin channel

Three‐dimensional (3D) cell manipulation is available with the integration of microfluidic technology and rapid prototyping techniques. High‐Fidelity (Hi‐Fi) constructs hold enormous therapeutic potential for organ manufacturing and regenerative medicine. In the present paper we introduced a quasi‐three‐dimensional (Q3D) model with parallel biocompatible alginate/gelatin/fibrin hurdles. The behaviors of fluids and cells along the microfluidic channels with various widths were studied. Cells inside the newly designed microfluidic channels attached and grew well. Morphological changes of adipose‐derived stem cells (ADSCs) in both two‐dimensional (2D) and 3D milieu were found on the printed constructs. Endothelialization occurred with the co‐cultures of ADSCs and hepatocytes. This study provides insights into the interactions among fluids, cells and biomaterials, the behaviors of fluids and cells along the microfluidic channels, and the applications of Q3D techniques. Biotechnol. Bioeng. 2015;112: 1683–1695. © 2015 Wiley Periodicals, Inc.

[1]  D. Figeys,et al.  Lab-on-a-chip: a revolution in biological and medical sciences , 2000, Analytical chemistry.

[2]  Xinru Zhao,et al.  Preparation of an adipose-derived stem cell/fibrin–poly(d,l-lactic-co-glycolic acid) construct based on a rapid prototyping technique , 2013 .

[3]  Takanori Takebe,et al.  Vascularized and functional human liver from an iPSC-derived organ bud transplant , 2013, Nature.

[4]  G. Lin,et al.  Defining adipose tissue-derived stem cells in tissue and in culture. , 2010, Histology and histopathology.

[5]  Yongdoo Park,et al.  Synthesis of cell-laden alginate hollow fibers using microfluidic chips and microvascularized tissue-engineering applications. , 2009, Small.

[6]  A. Wagers,et al.  The stem cell niche in regenerative medicine. , 2012, Cell stem cell.

[7]  Yongnian Yan,et al.  Direct Fabrication of a Hybrid Cell/Hydrogel Construct by a Double-nozzle Assembling Technology: , 2009 .

[8]  Kristi S. Anseth,et al.  Mechanical memory and dosing influence stem cell fate , 2014, Nature materials.

[9]  Yongnian Yan,et al.  Gelatin-Based Hydrogels for Controlled Cell Assembly , 2010 .

[10]  D. Ingber,et al.  Microfluidic organs-on-chips , 2014, Nature Biotechnology.

[11]  George E. Davis,et al.  Endothelial tubes assemble from intracellular vacuoles in vivo , 2006, Nature.

[12]  Philip J. Kitson,et al.  Configurable 3D-Printed millifluidic and microfluidic 'lab on a chip' reactionware devices. , 2012, Lab on a chip.

[13]  Xiaohong Wang,et al.  Intelligent freeform manufacturing of complex organs. , 2012, Artificial organs.

[14]  Wei Xu,et al.  Rapid prototyping of a double-layer polyurethane-collagen conduit for peripheral nerve regeneration. , 2009, Tissue engineering. Part C, Methods.

[15]  Xiaohong Wang,et al.  Incorporation of DMSO and dextran-40 into a gelatin/alginate hydrogel for controlled assembled cell cryopreservation. , 2010, Cryobiology.

[16]  Nitzan Resnick,et al.  Fluid shear stress and the vascular endothelium: for better and for worse. , 2003, Progress in biophysics and molecular biology.

[17]  Verena Charwat,et al.  Lab-on-a-chip technologies for stem cell analysis. , 2014, Trends in biotechnology.

[18]  A few good tricks , 2004, Nature materials.

[19]  Wei Xu,et al.  A Polyurethane-Gelatin Hybrid Construct for Manufacturing Implantable Bioartificial Livers , 2008 .

[20]  L. Ricci-Vitiani,et al.  Tumour vascularization via endothelial differentiation of glioblastoma stem-like cells , 2011, Nature.

[21]  Yongnian Yan,et al.  An cell-assembly derived physiological 3D model of the metabolic syndrome, based on adipose-derived stromal cells and a gelatin/alginate/fibrinogen matrix. , 2010, Biomaterials.

[22]  K. Anseth,et al.  Fibroblast growth factor represses Smad-mediated myofibroblast activation in aortic valvular interstitial cells , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[23]  Kimiko Yamamoto,et al.  Proliferation, differentiation, and tube formation by endothelial progenitor cells in response to shear stress. , 2003, Journal of applied physiology.

[24]  K. Anseth,et al.  Hydrogel Cell Cultures , 2007, Science.

[25]  Wei Xu,et al.  Rapid Prototyping of Polyurethane for the Creation of Vascular Systems , 2008 .

[26]  Yongnian Yan,et al.  Direct Construction of a Three-dimensional Structure with Cells and Hydrogel , 2005 .

[27]  Gi Seok Jeong,et al.  Microfluidic assay of endothelial cell migration in 3D interpenetrating polymer semi-network HA-Collagen hydrogel , 2011, Biomedical microdevices.

[28]  Saeid Nahavandi,et al.  Dielectrophoretic platforms for bio-microfluidic systems. , 2011, Biosensors & bioelectronics.

[29]  Jason P. Gleghorn,et al.  Microfluidic scaffolds for tissue engineering. , 2007, Nature materials.

[30]  Amber N. Stratman,et al.  Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation. , 2009, Blood.

[31]  Brendon M. Baker,et al.  Rapid casting of patterned vascular networks for perfusable engineered three-dimensional tissues , 2012 .

[32]  Kai He,et al.  Optimizing the fabrication processes for manufacturing a hybrid hierarchical polyurethane–cell/hydrogel construct , 2013 .

[33]  Ali Khademhosseini,et al.  A controlled-release strategy for the generation of cross-linked hydrogel microstructures. , 2006, Journal of the American Chemical Society.

[34]  D. Mooney,et al.  Polymeric system for dual growth factor delivery , 2001, Nature Biotechnology.

[35]  G. Davis,et al.  This Review Is Part of a Thematic Series on Vascular Cell Diversity, Which Includes the following Articles: Heart Valve Development: Endothelial Cell Signaling and Differentiation Molecular Determinants of Vascular Smooth Muscle Cell Diversity Endothelial/pericyte Interactions Endothelial Extracellu , 2022 .

[36]  Govind V Kaigala,et al.  Rapid prototyping of microfluidic devices with a wax printer. , 2007, Lab on a chip.

[37]  B. Derby.  Inkjet Printing of Functional and Structural Materials: Fluid Property Requirements, Feature Stability, and Resolution , 2010 .

[38]  Steve Edmondson,et al.  Design and additive manufacture for flow chemistry. , 2013, Lab on a chip.

[39]  Todd C McDevitt,et al.  Stem cell microencapsulation for phenotypic control, bioprocessing, and transplantation , 2013, Biotechnology and bioengineering.

[40]  R. Busse,et al.  Preadipocytes in the human subcutaneous adipose tissue display distinct features from the adult mesenchymal and hematopoietic stem cells , 2005, Journal of cellular physiology.

[41]  Esther Novosel,et al.  Vascularization is the key challenge in tissue engineering. , 2011, Advanced drug delivery reviews.

[42]  B. Lévy,et al.  Plasticity of Human Adipose Lineage Cells Toward Endothelial Cells: Physiological and Therapeutic Perspectives , 2004, Circulation.

[43]  C. Hughes.  Endothelial–stromal interactions in angiogenesis , 2008, Current opinion in hematology.

[44]  Yoon-Kyoung Cho,et al.  Three dimensional multicellular co-cultures and anti-cancer drug assays in rapid prototyped multilevel microfluidic devices , 2013, Biomedical microdevices.

[45]  F. Lin,et al.  Fabrication of viable tissue-engineered constructs with 3D cell-assembly technique. , 2005, Biomaterials.

[46]  G. Mestres,et al.  New Processing Approaches in Calcium Phosphate Cements and Their Applications in Regenerative Medicine , 2011 .

[47]  E. Jaffe.  Endothelial cells and the biology of factor VIII. , 1977, The New England journal of medicine.

[48]  Brian Derby,et al.  Printing and Prototyping of Tissues and Scaffolds , 2012, Science.

[49]  Kristi S Anseth,et al.  Cell–cell communication mimicry with poly(ethylene glycol) hydrogels for enhancing β-cell function , 2011, Proceedings of the National Academy of Sciences.

[50]  Xiaohong Wang,et al.  Rapid prototyping as a tool for manufacturing bioartificial livers. , 2007, Trends in biotechnology.

[51]  H. Craighead,et al.  Fabrication of an artificial 3-dimensional vascular network using sacrificial sugar structures , 2009 .

[52]  Yooli K. Light,et al.  Microfluidic fluorescence in situ hybridization and flow cytometry (μFlowFISH). , 2011, Lab on a chip.

[53]  Yongnian Yan,et al.  Rapid Prototyping Three-Dimensional Cell/Gelatin/Fibrinogen Constructs for Medical Regeneration , 2007 .

[54]  Bo Lu,et al.  3D microfilter device for viable circulating tumor cell (CTC) enrichment from blood , 2011, Biomedical microdevices.

[55]  Cheng-Hsien Liu,et al.  Controlled release of growth factors for regenerative medicine. , 2015, Current pharmaceutical design.

[56]  Jiayin Wang,et al.  Vascularization and adipogenesis of a spindle hierarchical adipose-derived stem cell/collagen/ alginate-PLGA construct for breast manufacturing , 2015 .

[57]  J. Merchuk,et al.  Hepatocyte behavior within three-dimensional porous alginate scaffolds. , 2000, Biotechnology and bioengineering.

[58]  Joshua M. Pearce,et al.  Building Research Equipment with Free, Open-Source Hardware , 2012, Science.

[59]  Kristi S Anseth,et al.  Synthesis of photodegradable hydrogels as dynamically tunable cell culture platforms , 2010, Nature Protocols.

[60]  J. Mao,et al.  Stem cell‐based composite tissue constructs for regenerative medicine , 2005, Biotechnology and bioengineering.

[61]  Hai-bin Wang,et al.  Transplantation of Co-Microencapsulated Hepatocytes and HUVECs for Treatment of Fulminant Hepatic Failure , 2012, The International journal of artificial organs.

[62]  Jean-Louis Viovy,et al.  A review of microfabrication and hydrogel engineering for micro-organs on chips. , 2014, Biomaterials.

[63]  W. Risau,et al.  Mechanisms of angiogenesis , 1997, Nature.

[64]  Xiaohong Wang,et al.  Overview on "Chinese-Finnish workshop on biomanufacturing and evaluation techniques". , 2011, Artificial organs.

[65]  Mark W. Tibbitt,et al.  Dynamic Microenvironments: The Fourth Dimension , 2012, Science Translational Medicine.

[66]  Santosh Devasia,et al.  Bio-mimetic silicone cilia for microfluidic manipulation. , 2009, Lab on a chip.

[67]  Kai He,et al.  Rapid prototyping of tubular polyurethane and cell/hydrogel constructs: , 2011 .

[68]  Kristi S. Anseth,et al.  3D Polymeric Microfluidic Device Fabrication via Contact Liquid Photolithographic Polymerization (CLiPP) , 2006 .

[69]  Tiago G Fernandes,et al.  Three‐dimensional cell culture microarray for high‐throughput studies of stem cell fate , 2010, Biotechnology and bioengineering.

[70]  Paul C H Li,et al.  Microfluidic DNA microarray analysis: a review. , 2011, Analytica chimica acta.

[71]  Stephen F Badylak,et al.  RETRACTED: Engineered whole organs and complex tissues , 2012, The Lancet.

[72]  Kaija-Stiina Paloheimo,et al.  The Integrations of Biomaterials and Rapid Prototyping Techniques for Intelligent Manufacturing of Complex Organs , 2013 .

[73]  M. Hedrick,et al.  Plasticity of human adipose stem cells toward endothelial cells and cardiomyocytes , 2006, Nature Clinical Practice Cardiovascular Medicine.

[74]  G. Whitesides,et al.  Rapid Prototyping of Microfluidic Systems in Poly(dimethylsiloxane). , 1998, Analytical chemistry.

[75]  D. Klenerman,et al.  Single-Molecule Measurements of Transient Biomolecular Complexes through Microfluidic Dilution , 2013, Analytical chemistry.

[76]  D. Ingber,et al.  From 3D cell culture to organs-on-chips. , 2011, Trends in cell biology.

[77]  J. Gimble,et al.  Adipose-derived stem cells for regenerative medicine. , 2007, Circulation research.

[78]  J. Hunt.  Regenerative medicine: Materials in a cellular world. , 2008, Nature Materials.

[79]  Gabriel Villar,et al.  A Tissue-Like Printed Material , 2013, Science.

[80]  Yongnian Yan,et al.  In Vitro Angiogenesis of 3D Tissue Engineered Adipose Tissue , 2009 .

[81]  F. Lin,et al.  Generation of three-dimensional hepatocyte/gelatin structures with rapid prototyping system. , 2006, Tissue engineering.

[82]  E. Kapetanovic,et al.  Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells. , 2014, Acta biomaterialia.

[83]  Xiaohong Wang,et al.  Application of 3D biomimetic models in drug delivery and regenerative medicine. , 2015, Current pharmaceutical design.

[84]  M. Sehested,et al.  Factor VIII related antigen as an endothelial cell marker in benign and malignant diseases , 2004, Virchows Archiv A.

[85]  Ali Khademhosseini,et al.  Microfluidic techniques for development of 3D vascularized tissue. , 2014, Biomaterials.

[86]  Xiaohong Wang,et al.  Overview on Biocompatibilities of Implantable Biomaterials , 2013 .

[87]  Kristi S. Anseth,et al.  Photodegradable, Photoadaptable Hydrogels via Radical-Mediated Disulfide Fragmentation Reaction , 2011, Macromolecules.

[88]  G. Mestres,et al.  New processing approaches in calcium phosphate cements and their applications in regenerative medicine. , 2010, Acta biomaterialia.

[89]  S. Quake,et al.  Microfluidic Large-Scale Integration , 2002, Science.

[90]  P. Bártolo,et al.  Additive manufacturing of tissues and organs , 2012 .

[91]  R. Jain,et al.  Vascular normalizing doses of antiangiogenic treatment reprogram the immunosuppressive tumor microenvironment and enhance immunotherapy , 2012, Proceedings of the National Academy of Sciences.

[92]  Noriaki Tanaka,et al.  Differentiation of mouse embryonic stem cells to hepatocyte-like cells by co-culture with human liver nonparenchymal cell lines , 2007, Nature Protocols.

[93]  Yuanwen Huang,et al.  Rapid prototyping of a hybrid hierarchical polyurethane-cell/hydrogel construct for regenerative medicine. , 2013, Materials science & engineering. C, Materials for biological applications.

[94]  Xiaohong Wang,et al.  Recent trends and challenges in complex organ manufacturing. , 2010, Tissue engineering. Part B, Reviews.

[95]  P. Kohl,et al.  Fabrication of microchannels using polycarbonates as sacrificial materials , 2001 .

[96]  Mark W. Tibbitt,et al.  Hydrogels as extracellular matrix mimics for 3D cell culture. , 2009, Biotechnology and bioengineering.

[97]  Hyoungshin Park,et al.  3D Structural Patterns in Scalable, Elastomeric Scaffolds Guide Engineered Tissue Architecture , 2013, Advanced materials.

[98]  Jonathan V Sweedler,et al.  Design and fabrication of a multilayered polymer microfluidic chip with nanofluidic interconnects via adhesive contact printing. , 2006, Lab on a chip.

[99]  Xinru Zhao,et al.  In vitro vascularization of a combined system based on a 3D printing technique , 2016, Journal of tissue engineering and regenerative medicine.

[100]  Kristi S Anseth,et al.  Controlling network structure in degradable thiol-acrylate biomaterials to tune mass loss behavior. , 2006, Biomacromolecules.

[101]  Yongnian Yan,et al.  Gradient Hydrogel Construct Based on an Improved Cell Assembling System , 2009 .

[102]  Yongnian Van,et al.  Controlled Adipose-derived Stromal Cells Differentiation into Adipose and Endothelial Cells in a 3D Structure Established by Cell-assembly Technique , 2009 .