Stop-flow lithography to generate cell-laden microgel particles.

Encapsulating cells within hydrogels is important for generating three-dimensional (3D) tissue constructs for drug delivery and tissue engineering. This paper describes, for the first time, the fabrication of large numbers of cell-laden microgel particles using a continuous microfluidic process called stop-flow lithography (SFL). Prepolymer solution containing cells was flowed through a microfluidic device and arrays of individual particles were repeatedly defined using pulses of UV light through a transparency mask. Unlike photolithography, SFL can be used to synthesize microgel particles continuously while maintaining control over particle size, shape and anisotropy. Therefore, SFL may become a useful tool for generating cell-laden microgels for various biomedical applications.

[1]  J. Crocker,et al.  Reversible self-assembly and directed assembly of DNA-linked micrometer-sized colloids. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[2]  George M. Whitesides,et al.  Three-dimensional self-assembly of millimetre-scale components , 1997, Nature.

[3]  D. Szarowski,et al.  Biological functionalization and surface micropatterning of polyacrylamide hydrogels. , 2006, Biomaterials.

[4]  S. Bhatia,et al.  Assessment of hepatocellular function within PEG hydrogels. , 2007, Biomaterials.

[5]  F. Hendrikse,et al.  New biodegradable networks of poly(N-vinylpyrrolidinone) designed for controlled nonburst degradation in the vitreous body. , 1999, Journal of biomedical materials research.

[6]  R. Misra,et al.  Biomaterials , 2008 .

[7]  William B. Liechty,et al.  The influence of N-vinyl pyrrolidone on polymerization kinetics and thermo-mechanical properties of crosslinked acrylate polymers , 2007 .

[8]  S. Cohen,et al.  Ethanol Production by Saccharomyces cerevisiae Immobilized in Hollow-Fiber Membrane Bioreactors , 1983, Applied and environmental microbiology.

[9]  Kristi S. Anseth,et al.  New Directions in Photopolymerizable Biomaterials , 2002 .

[10]  Ali Khademhosseini,et al.  Micromolding of shape-controlled, harvestable cell-laden hydrogels. , 2006, Biomaterials.

[11]  Ali Khademhosseini,et al.  Microengineered hydrogels for tissue engineering. , 2007, Biomaterials.

[12]  S J Bryant,et al.  Cytocompatibility of UV and visible light photoinitiating systems on cultured NIH/3T3 fibroblasts in vitro , 2000, Journal of biomaterials science. Polymer edition.

[13]  J. A. Hubbell,et al.  Comparison of covalently and physically cross-linked polyethylene glycol-based hydrogels for the prevention of postoperative adhesions in a rat model. , 1995, Biomaterials.

[14]  Ali Khademhosseini,et al.  Interplay of biomaterials and micro-scale technologies for advancing biomedical applications , 2006, Journal of biomaterials science. Polymer edition.

[15]  A. Khademhosseini,et al.  Hydrogels in Biology and Medicine: From Molecular Principles to Bionanotechnology , 2006 .

[16]  J. Vacanti,et al.  Tissue engineering : Frontiers in biotechnology , 1993 .

[17]  Nalinkanth G. Veerabadran,et al.  Nanoencapsulation of stem cells within polyelectrolyte multilayer shells. , 2007, Macromolecular bioscience.

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

[19]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]/Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[20]  Vinothan N Manoharan,et al.  Dense Packing and Symmetry in Small Clusters of Microspheres , 2003, Science.

[21]  S. Bhatia,et al.  Three-Dimensional Photopatterning of Hydrogels Containing Living Cells , 2002 .

[22]  Robert L Sah,et al.  Probing the role of multicellular organization in three-dimensional microenvironments , 2006, Nature Methods.

[23]  A Ratcliffe,et al.  Formulation of PEG-based hydrogels affects tissue-engineered cartilage construct characteristics , 2001, Journal of materials science. Materials in medicine.

[24]  M. C. Rowland,et al.  Photolithographic patterning of polyethylene glycol hydrogels. , 2006, Biomaterials.

[25]  Paul N Manson,et al.  Variable cytocompatibility of six cell lines with photoinitiators used for polymerizing hydrogels and cell encapsulation. , 2005, Biomaterials.

[26]  J L West,et al.  Smooth muscle cell growth in photopolymerized hydrogels with cell adhesive and proteolytically degradable domains: synthetic ECM analogs for tissue engineering. , 2001, Biomaterials.

[27]  Michael V. Pishko,et al.  Biomems Materials and Fabrication Technology: Control of Mammalian Cell and Bacteria Adhesion on Substrates Micropatterned with Poly(ethylene Glycol) Hydrogels , 2022 .

[28]  C. Heinzen,et al.  Characterization of an encapsulation device for the production of monodisperse alginate beads for cell immobilization. , 2000, Biotechnology and bioengineering.

[29]  Amritha Srinivasan,et al.  Controlled assembly of mesoscale structures using DNA as molecular bridges. , 2002, Journal of the American Chemical Society.

[30]  Daniel A. Hammer,et al.  DNA-driven assembly of bidisperse, micron-sized colloids , 2003 .

[31]  Jason A Burdick,et al.  Photoencapsulation of osteoblasts in injectable RGD-modified PEG hydrogels for bone tissue engineering. , 2002, Biomaterials.

[32]  S. Bhatia,et al.  Fabrication of 3D hepatic tissues by additive photopatterning of cellular hydrogels , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  G. Whitesides,et al.  Self-Assembly of Mesoscale Objects into Ordered Two-Dimensional Arrays , 1997, Science.

[34]  A. Ahluwalia,et al.  Fabrication of PLGA scaffolds using soft lithography and microsyringe deposition. , 2003, Biomaterials.

[35]  Dhananjay Dendukuri,et al.  Continuous-flow lithography for high-throughput microparticle synthesis , 2006, Nature materials.

[36]  Kristi S Anseth,et al.  In vitro osteogenic differentiation of human mesenchymal stem cells photoencapsulated in PEG hydrogels. , 2004, Journal of biomedical materials research. Part A.

[37]  Samuel K Sia,et al.  Direct patterning of composite biocompatible microstructures using microfluidics. , 2007, Lab on a chip.

[38]  Mehmet Toner,et al.  Multifunctional Encoded Particles for High-Throughput Biomolecule Analysis , 2007, Science.

[39]  H. Chang,et al.  MICROENCAPSULATION OF YEAST CELLS IN THE CALCIUM ALGINATE MEMBRANE , 1993 .

[40]  R. Lanza,et al.  Encapsulated cell technology , 1996, Nature Biotechnology.

[41]  Dhananjay Dendukuri,et al.  Stop-flow lithography in a microfluidic device. , 2007, Lab on a chip.

[42]  G. Orive,et al.  Cell microencapsulation technology for biomedical purposes: novel insights and challenges. , 2003, Trends in pharmacological sciences.

[43]  Alison P McGuigan,et al.  Vascularized Organoid Engineered by Modular Assembly Enables Blood Perfusion , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[44]  A. Khademhosseini,et al.  Microscale technologies for tissue engineering and biology. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Robert Langer,et al.  Controlled degradation and mechanical behavior of photopolymerized hyaluronic acid networks. , 2005, Biomacromolecules.

[46]  V. Yadavalli,et al.  Fabrication of poly(ethylene glycol) hydrogel microstructures using photolithography. , 2001, Langmuir : the ACS journal of surfaces and colloids.

[47]  M. Grinstaff,et al.  Photocrosslinkable polysaccharides for in situ hydrogel formation. , 2001, Journal of biomedical materials research.

[48]  Dhananjay Dendukuri,et al.  Synthesis and self-assembly of amphiphilic polymeric microparticles. , 2007, Langmuir : the ACS journal of surfaces and colloids.