A digital micro-mirror device-based system for the microfabrication of complex, spatially patterned tissue engineering scaffolds.

Our ability to create precise, pre-designed, spatially patterned biochemical and physical microenvironments inside polymer scaffolds could provide a powerful tool in studying progenitor cell behavior and differentiation under biomimetic, three-dimensional (3D) culture conditions. We have developed a simple and fast, layer-by-layer microstereolithography system consisting of an ultra-violet light source, a digital micro-mirror masking device, and a conventional computer projector, that allows fabrication of complex internal features along with precise spatial distribution of biological factors inside a single scaffold. Photo-crosslinkable poly(ethylene glycol) diacrylates were used as the scaffold material, and murine bone marrow-derived cells were successfully encapsulated or seeded on fibronectin-functionalized scaffolds. Fluorescently-labeled polystyrene microparticles were used to show the capability of this system to create scaffolds with complex internal architectures and spatial patterns. We demonstrate that precisely controlled pore size and shapes can be easily fabricated using a simple, computer-aided process. Our results further indicate that multi-layered scaffolds with spatially distributed factors in the same layer or across different layers can be efficiently manufactured using this technique. These microfabricated scaffolds are conducive for osteogenic differentiation of marrow-derived stem cells, as indicated by efficient matrix mineralization.

[1]  New microstereolithography (Super-IH process) to create 3D freely movable micromechanism without sacrificial layer technique , 1998, MHA'98. Proceedings of the 1998 International Symposium on Micromechatronics and Human Science. - Creation of New Industry - (Cat. No.98TH8388).

[2]  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.

[3]  Linda G Griffith,et al.  Emerging Design Principles in Biomaterials and Scaffolds for Tissue Engineering , 2002, Annals of the New York Academy of Sciences.

[4]  S. Bryant,et al.  Hydrogel properties influence ECM production by chondrocytes photoencapsulated in poly(ethylene glycol) hydrogels. , 2002, Journal of biomedical materials research.

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

[6]  A I Caplan,et al.  In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells. , 1998, Experimental cell research.

[7]  A. Metters,et al.  Fundamental studies of biodegradable hydrogels as cartilage replacement materials. , 1999, Biomedical sciences instrumentation.

[8]  Cheng Sun,et al.  Micro-stereolithography of polymeric and ceramic microstructures , 1999 .

[9]  Krishnendu Roy,et al.  Laser-layered microfabrication of spatially patterned functionalized tissue-engineering scaffolds. , 2005, Journal of biomedical materials research. Part B, Applied biomaterials.

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

[11]  Christian Vogt,et al.  Rapid prototyping of small size objects , 2000 .

[12]  Nicholas X. Fang,et al.  Projection micro-stereolithography using digital micro-mirror dynamic mask , 2005 .

[13]  K. Marra,et al.  Composition options for tissue-engineered bone. , 2002, Tissue engineering.

[14]  Alyssa Panitch,et al.  Biologically engineered protein-graft-poly(ethylene glycol) hydrogels: a cell adhesive and plasmin-degradable biosynthetic material for tissue repair. , 2002, Biomacromolecules.

[15]  Hubert Lorenz,et al.  3D microfabrication by combining microstereolithography and thick resist UV lithography , 1999 .

[16]  Jennifer H. Elisseeff,et al.  Engineering Structurally Organized Cartilage and Bone Tissues , 2004, Annals of Biomedical Engineering.

[17]  Masayuki Yamato,et al.  Cell micropatterning using photopolymerization with a liquid crystal device commercial projector. , 2004, Biomaterials.

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

[19]  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.

[20]  Lindolfo da Silva Meirelles,et al.  Murine marrow‐derived mesenchymal stem cell: isolation, in vitro expansion, and characterization , 2003, British journal of haematology.

[21]  E. Sachlos,et al.  Making tissue engineering scaffolds work. Review: the application of solid freeform fabrication technology to the production of tissue engineering scaffolds. , 2003, European cells & materials.

[22]  Christopher G Williams,et al.  In vitro chondrogenesis of bone marrow-derived mesenchymal stem cells in a photopolymerizing hydrogel. , 2003, Tissue engineering.

[23]  S. Kasturi,et al.  Covalent conjugation of polyethyleneimine on biodegradable microparticles for delivery of plasmid DNA vaccines. , 2005, Biomaterials.

[24]  Kristi S Anseth,et al.  Controlled release from crosslinked degradable networks. , 2002, Critical reviews in therapeutic drug carrier systems.