Microfluidic Spinning of Cell‐Responsive Grooved Microfibers

Engineering living tissues that simulate their natural counterparts is a dynamic area of research. Among the various models of biological tissues being developed, fiber‐shaped cellular architectures, which can be used as artificial blood vessels or muscle fibers, have drawn particular attention. However, the fabrication of continuous microfiber substrates for culturing cells is still limited to a restricted number of polymers (e.g., alginate) having easy processability but poor cell–material interaction properties. Moreover, the typical smooth surface of a synthetic fiber does not replicate the micro‐ and nanofeatures observed in vivo, which guide and regulate cell behavior. In this study, a method to fabricate photocrosslinkable cell‐responsive methacrylamide‐modified gelatin (GelMA) fibers with exquisite microstructured surfaces by using a microfluidic device is developed. These hydrogel fibers with microgrooved surfaces efficiently promote cell encapsulation and adhesion. GelMA fibers significantly promote the viability of cells encapsulated in/or grown on the fibers compared with similar grooved alginate fibers used as controls. Importantly, the grooves engraved on the GelMA fibers induce cell alignment. Furthermore, the GelMA fibers exhibit excellent processability and could be wound into various shapes. These microstructured GelMA fibers have great potential as templates for the creation of fiber‐shaped tissues or tissue microstructures.

[1]  Ali Khademhosseini,et al.  Skeletal muscle tissue engineering: methods to form skeletal myotubes and their applications. , 2014, Tissue engineering. Part B, Reviews.

[2]  Ali Khademhosseini,et al.  Myotube formation on gelatin nanofibers - multi-walled carbon nanotubes hybrid scaffolds. , 2014, Biomaterials.

[3]  A. Khademhosseini,et al.  Composite Living Fibers for Creating Tissue Constructs Using Textile Techniques , 2014, Advanced functional materials.

[4]  Sang-Hoon Lee,et al.  Microfluidic spinning of micro- and nano-scale fibers for tissue engineering. , 2014, Lab on a chip.

[5]  K. Venkatakrishnan,et al.  Nanostructured hybrid of immiscible gold and silicon and its effect on proliferation and adhesion of fibroblasts and osteoblasts. , 2014, Journal of Biomedical Nanotechnology.

[6]  Dietmar W Hutmacher,et al.  Gelatine methacrylamide-based hydrogels: an alternative three-dimensional cancer cell culture system. , 2014, Acta biomaterialia.

[7]  Ali Khademhosseini,et al.  Periosteum‐Mimetic Structures Made from Freestanding Microgrooved Nanosheets , 2014, Advanced materials.

[8]  Hui Wen,et al.  Flexible Fabrication of Biomimetic Bamboo‐Like Hybrid Microfibers , 2014, Advanced materials.

[9]  S. Gerecht,et al.  Creating polymer hydrogel microfibres with internal alignment via electrical and mechanical stretching. , 2014, Biomaterials.

[10]  R. Reis,et al.  Nanostructured Hollow Tubes Based on Chitosan and Alginate Multilayers , 2014, Advanced healthcare materials.

[11]  Vahid Hosseini,et al.  Skeletal Muscle Tissue Engineering: Methods to Form Skeletal Myotubes and Their Applications , 2014 .

[12]  Chaenyung Cha,et al.  25th Anniversary Article: Rational Design and Applications of Hydrogels in Regenerative Medicine , 2014, Advanced materials.

[13]  Ali Khademhosseini,et al.  Microfluidics-Assisted Fabrication of Gelatin-Silica Core–Shell Microgels for Injectable Tissue Constructs , 2013, Biomacromolecules.

[14]  Ali Khademhosseini,et al.  Electrospun scaffolds for tissue engineering of vascular grafts. , 2014, Acta biomaterialia.

[15]  A. Khademhosseini,et al.  Cell‐laden Microengineered and Mechanically Tunable Hybrid Hydrogels of Gelatin and Graphene Oxide , 2013, Advanced materials.

[16]  R. Hopkins,et al.  Wet spun microfibers: potential in the design of controlled-release scaffolds? , 2013, Therapeutic delivery.

[17]  Ali Khademhosseini,et al.  Fiber-based tissue engineering: Progress, challenges, and opportunities. , 2013, Biotechnology advances.

[18]  Tze Chiun Lim,et al.  Patterned prevascularised tissue constructs by assembly of polyelectrolyte hydrogel fibres , 2013, Nature Communications.

[19]  Ali Khademhosseini,et al.  Micro/Nanometer‐Scale Fiber with Highly Ordered Structures by Mimicking the Spinning Process of Silkworm , 2013, Advanced materials.

[20]  Hongkai Wu,et al.  Gradient‐Regulated Hydrogel for Interface Tissue Engineering: Steering Simultaneous Osteo/Chondrogenesis of Stem Cells on a Chip , 2013, Advanced healthcare materials.

[21]  Shoji Takeuchi,et al.  Metre-long cell-laden microfibres exhibit tissue morphologies and functions. , 2013, Nature materials.

[22]  Ashok Kumar,et al.  Signaling Mechanisms in Mammalian Myoblast Fusion , 2013, Science Signaling.

[23]  Rangam Rajkhowa,et al.  Silk fibroin biomaterials for tissue regenerations. , 2013, Advanced drug delivery reviews.

[24]  W. Tsai,et al.  Modulation of cell attachment and collagen production of anterior cruciate ligament cells via submicron grooves/ridges structures with different cell affinity , 2013, Biotechnology and bioengineering.

[25]  Ali Khademhosseini,et al.  Directed endothelial cell morphogenesis in micropatterned gelatin methacrylate hydrogels. , 2012, Biomaterials.

[26]  Hongkai Wu,et al.  Directing Osteogenesis of Stem Cells with Drug‐Laden, Polymer‐Microsphere‐Based Micropatterns Generated by Teflon Microfluidic Chips , 2012 .

[27]  Jin-Hee Moon,et al.  Microfluidic Spinning of Flat Alginate Fibers with Grooves for Cell‐Aligning Scaffolds , 2012, Advanced materials.

[28]  Ali Khademhosseini,et al.  Functional Human Vascular Network Generated in Photocrosslinkable Gelatin Methacrylate Hydrogels , 2012, Advanced functional materials.

[29]  H. Fan,et al.  Bottom-up approach to build osteon-like structure by cell-laden photocrosslinkable hydrogel. , 2012, Chemical communications.

[30]  A. Khademhosseini,et al.  Carbon nanotube reinforced hybrid microgels as scaffold materials for cell encapsulation. , 2012, ACS nano.

[31]  Younan Xia,et al.  Electrospun Nanofibers for Regenerative Medicine , 2012, Advanced healthcare materials.

[32]  A. Wan,et al.  Multicomponent Fibers by Multi‐interfacial Polyelectrolyte Complexation , 2012, Advanced healthcare materials.

[33]  Ali Khademhosseini,et al.  Controlled release of drugs from gradient hydrogels for high-throughput analysis of cell-drug interactions. , 2012, Analytical chemistry.

[34]  Nenad Bursac,et al.  Local tissue geometry determines contractile force generation of engineered muscle networks. , 2012, Tissue engineering. Part A.

[35]  Ali Khademhosseini,et al.  Digitally tunable physicochemical coding of material composition and topography in continuous microfibres. , 2011, Nature materials.

[36]  Teruo Fujii,et al.  Integration of a pump and an electrical sensor into a membrane-based PDMS microbioreactor for cell culture and drug testing , 2011, Biomedical microdevices.

[37]  Ali Khademhosseini,et al.  Directed 3D cell alignment and elongation in microengineered hydrogels. , 2010, Biomaterials.

[38]  A. Khademhosseini,et al.  Cell-laden microengineered gelatin methacrylate hydrogels. , 2010, Biomaterials.

[39]  E. J. Chung,et al.  Advances and Applications of Biodegradable Elastomers in Regenerative Medicine , 2010 .

[40]  U. Müller,et al.  Talin 1 and 2 are required for myoblast fusion, sarcomere assembly and the maintenance of myotendinous junctions , 2009, Development.

[41]  Michael Balter,et al.  Archaeology. Clothes make the (hu) man. , 2009, Science.

[42]  Hongkai Wu,et al.  Generation of alginate microfibers with a roller-assisted microfluidic system. , 2009, Lab on a chip.

[43]  Dong-An Wang,et al.  The control of anchorage-dependent cell behavior within a hydrogel/microcarrier system in an osteogenic model. , 2009, Biomaterials.

[44]  Shuichi Takayama,et al.  Microfeature guided skeletal muscle tissue engineering for highly organized 3-dimensional free-standing constructs. , 2009, Biomaterials.

[45]  P. Schaaf,et al.  Re‐endothelialization of Human Umbilical Arteries Treated with Polyelectrolyte Multilayers: A Tool for Damaged Vessel Replacement , 2007 .

[46]  Seeram Ramakrishna,et al.  Design strategies of tissue engineering scaffolds with controlled fiber orientation. , 2007, Tissue engineering.

[47]  Shyni Varghese,et al.  Multifunctional chondroitin sulphate for cartilage tissue-biomaterial integration. , 2007, Nature materials.

[48]  Thomas A Rando,et al.  Focal adhesion kinase is essential for costamerogenesis in cultured skeletal muscle cells. , 2006, Developmental biology.

[49]  Joseph W Freeman,et al.  Fiber-based tissue-engineered scaffold for ligament replacement: design considerations and in vitro evaluation. , 2005, Biomaterials.

[50]  J. Hubbell,et al.  Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering , 2005, Nature Biotechnology.

[51]  Smadar Cohen,et al.  Ultrastructural and functional investigations of adult hepatocyte spheroids during in vitro cultivation. , 2004, Tissue engineering.

[52]  S. Ostrovidov,et al.  Membrane-Based PDMS Microbioreactor for Perfused 3D Primary Rat Hepatocyte Cultures , 2004, Biomedical microdevices.

[53]  Jennifer H Elisseeff,et al.  Synthesis and characterization of a novel degradable phosphate-containing hydrogel. , 2003, Biomaterials.

[54]  M. Wiberg,et al.  Addition of fibronectin to alginate matrix improves peripheral nerve regeneration in tissue-engineered conduits. , 2003, Tissue engineering.

[55]  Jennifer L. West,et al.  Tethered-TGF-β increases extracellular matrix production of vascular smooth muscle cells , 2001 .

[56]  D. Hutmacher,et al.  Scaffolds in tissue engineering bone and cartilage. , 2000, Biomaterials.

[57]  N. Peppas,et al.  Hydrogels in Pharmaceutical Formulations , 1999 .

[58]  R. Hynes Cell adhesion: old and new questions. , 1999, Trends in cell biology.

[59]  J. West,et al.  Modification of surfaces with cell adhesion peptides alters extracellular matrix deposition. , 1999, Biomaterials.

[60]  N A Peppas,et al.  Highly crosslinked, PEG-containing copolymers for sustained solute delivery. , 1999, Biomaterials.

[61]  B. Gumbiner,et al.  Cell Adhesion: The Molecular Basis of Tissue Architecture and Morphogenesis , 1996, Cell.

[62]  C. Mackay,et al.  Cell adhesion in the immune system. , 1993, Immunology today.