Fabrication of combinatorial polymer scaffold libraries.

We have designed a novel combinatorial research platform to help accelerate tissue engineering research. Combinatorial methods combine many samples into a single specimen to enable accelerated experimentation and discovery. The platform for fabricating combinatorial polymer scaffold libraries can be used to rapidly identify scaffold formulations that maximize tissue formation. Many approaches for screening cell-biomaterial interactions utilize a two-dimensional format such as a film or surface to present test substrates to cells. However, cells in vivo exist in a three-dimensional milieu of extracellular matrix and cells in vitro behave more naturally when cultured in a three-dimensional environment than when cultured on a two-dimensional surface. Thus, we have designed a method for fabricating combinatorial biomaterial libraries where the materials are presented to cells in the form of three-dimensional, porous, salt-leached, polymer scaffolds. Many scaffold variations and compositions can be screened in a single experiment so that optimal scaffold formulations for tissue formation can be rapidly identified. In summary, we have developed a platform technology for fabricating combinatorial polymer scaffold libraries that can be used to screen cell response to materials in a three-dimensional, scaffold format.

[1]  S. Bhatia,et al.  An extracellular matrix microarray for probing cellular differentiation , 2005, Nature Methods.

[2]  Newell R Washburn,et al.  Combinatorial screening of cell proliferation on poly(L-lactic acid)/poly(D,L-lactic acid) blends. , 2005, Biomaterials.

[3]  R G Smith,et al.  Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. , 1998, Science.

[4]  Bin Li,et al.  A technique for preparing protein gradients on polymeric surfaces: effects on PC12 pheochromocytoma cells. , 2005, Biomaterials.

[5]  A. Abbott Cell culture: Biology's new dimension , 2003, Nature.

[6]  E. D. Rekow,et al.  Performance of degradable composite bone repair products made via three-dimensional fabrication techniques. , 2003, Journal of biomedical materials research. Part A.

[7]  R. Nerem,et al.  Altered response of vascular smooth muscle cells to exogenous biochemical stimulation in two- and three-dimensional culture. , 2003, Experimental cell research.

[8]  Ali Khademhosseini,et al.  Fabrication of gradient hydrogels using a microfluidics/photopolymerization process. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[9]  Kenneth M. Yamada,et al.  Taking Cell-Matrix Adhesions to the Third Dimension , 2001, Science.

[10]  M. Disney,et al.  The use of carbohydrate microarrays to study carbohydrate-cell interactions and to detect pathogens. , 2004, Chemistry & biology.

[11]  Robert Langer,et al.  Biomaterial microarrays: rapid, microscale screening of polymer-cell interaction. , 2005, Biomaterials.

[12]  Ying Mei,et al.  Tuning cell adhesion on gradient poly(2-hydroxyethyl methacrylate)-grafted surfaces. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[13]  Matthias Epple,et al.  Hierarchically structured polyglycolide - a biomaterial mimicking natural bone , 1998 .

[14]  Y. Amagai,et al.  In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria , 1983, The Journal of cell biology.

[15]  M. Shoichet,et al.  Immobilized concentration gradients of neurotrophic factors guide neurite outgrowth of primary neurons in macroporous scaffolds. , 2006, Tissue engineering.

[16]  John K. Tomfohr,et al.  Measurement of cell migration on surface-bound fibronectin gradients. , 2004, Langmuir : the ACS journal of surfaces and colloids.

[17]  H. C. van der Mei,et al.  Adhesion and spreading of human skin fibroblasts on physicochemically characterized gradient surfaces. , 1995, Journal of biomedical materials research.

[18]  R. Pfister,et al.  A visual assay for quantitating neutrophil chemotaxis in a collagen gel matrix. A novel chemotactic chamber. , 1991, Journal of immunological methods.

[19]  K. Shakesheff,et al.  Using a Core–Sheath Distribution of Surface Chemistry through 3D Tissue Engineering Scaffolds to Control Cell Ingress , 2006 .

[20]  Alamgir Karim,et al.  Combinatorial characterization of cell interactions with polymer surfaces. , 2003, Journal of biomedical materials research. Part A.

[21]  D. Mooney,et al.  Engineered bone development from a pre-osteoblast cell line on three-dimensional scaffolds. , 2000, Tissue engineering.

[22]  Daniel G. Anderson,et al.  Nanoliter-scale synthesis of arrayed biomaterials and application to human embryonic stem cells , 2004, Nature Biotechnology.

[23]  X. Cao,et al.  Defining the concentration gradient of nerve growth factor for guided neurite outgrowth , 2001, Neuroscience.

[24]  Carl G Simon,et al.  Preliminary report on the biocompatibility of a moldable, resorbable, composite bone graft consisting of calcium phosphate cement and poly(lactide‐co‐glycolide) microspheres , 2002, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[25]  R T Tranquillo,et al.  A fibrin or collagen gel assay for tissue cell chemotaxis: assessment of fibroblast chemotaxis to GRGDSP. , 1999, Experimental cell research.

[26]  Michael J Lysaght,et al.  Tissue engineering: the end of the beginning. , 2004, Tissue engineering.

[27]  R. Tompkins,et al.  Hepatocyte function and extracellular matrix geometry: long‐term culture in a sandwich configuration , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  Roy M. Smeal,et al.  Comparison of human fibroblast ECM-related gene expression on elastic three-dimensional substrates relative to two-dimensional films of the same material. , 2003, Biomaterials.

[29]  Paul C. Letourneau Chemotactic response of nerve fiber elongation to nerve growth factor. , 1978, Developmental biology.

[30]  Newell R Washburn,et al.  Combinatorial screen of the effect of surface energy on fibronectin-mediated osteoblast adhesion, spreading and proliferation. , 2006, Biomaterials.

[31]  Alessandro Sannino,et al.  Fabricating tubular scaffolds with a radial pore size gradient by a spinning technique. , 2006, Biomaterials.

[32]  J M Bidlack,et al.  An all D-amino acid opioid peptide with central analgesic activity from a combinatorial library. , 1994, Science.

[33]  Newell R Washburn,et al.  High-throughput investigation of osteoblast response to polymer crystallinity: influence of nanometer-scale roughness on proliferation. , 2004, Biomaterials.

[34]  Richard A Gemeinhart,et al.  Cellular alignment by grafted adhesion peptide surface density gradients. , 2004, Journal of biomedical materials research. Part A.

[35]  S Brocchini,et al.  Structure-property correlations in a combinatorial library of degradable biomaterials. , 1998, Journal of biomedical materials research.

[36]  P. Benya,et al.  Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels , 1982, Cell.

[37]  Deborah E Leckband,et al.  Regiospecific control of protein expression in cells cultured on two-component counter gradients of extracellular matrix proteins. , 2005, Langmuir : the ACS journal of surfaces and colloids.

[38]  A Tampieri,et al.  Porosity-graded hydroxyapatite ceramics to replace natural bone. , 2001, Biomaterials.

[39]  R. Tranquillo,et al.  Cytokine-stimulated chemotaxis of human neutrophils in a 3-D conjoined fibrin gel assay. , 1995, Journal of immunological methods.

[40]  M. Ishiyama,et al.  A New Sulfonated Tetrazolium Salt That Produces a Highly Water-Soluble Formazan Dye , 1993 .

[41]  X. Cao,et al.  Investigating the synergistic effect of combined neurotrophic factor concentration gradients to guide axonal growth , 2003, Neuroscience.

[42]  M J Lysaght,et al.  An economic survey of the emerging tissue engineering industry. , 1998, Tissue engineering.

[43]  M J Bissell,et al.  Lumen formation by epithelial cell lines in response to collagen overlay: a morphogenetic model in culture. , 1982, Proceedings of the National Academy of Sciences of the United States of America.