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Morphogen Gradient Patterns within Three-Dimensional Matrices to Direct Stem Cell Responses

Charu Vepari, Chemical and Biological Engineering, Tufts University, 4 Colby St, Medford, MA 02155, Gordana Vunjak-Novakovic, Biomedical Engineering, Columbia University, New York, NY, and David Kaplan, Biomedical Engineering, Tufts University, 4 Colby St, Medford, MA 02155.

Development of bone occurs within compartmentalized segments containing gradients of BMP-2. BMP-2 concentration gradients act as chemo tactic factors resulting in the recruitment of stem cells which aid bone tissue regeneration. Stable BMP-2 gradient patterns within a three-dimensional biomaterial are important for studying stem cell migration and differentiation in vitro. Recombinant BMP-2 was immobilized in a gradient fashion within porous silk fibroin scaffolds to study the migration of undifferentiated bone marrow derived human mesenchymal stem cells (MSCs). Different gradient profiles were prepared experimentally and compared with a theoretical model. Scaffolds with immobilized BMP-2 gradients were seeded with MSCs and cultured in osteogenic media for 5 weeks resulting in a controlled spatial gradient deposition of calcium mineral by differentiated cells along the length of the immobilized gradient of the scaffold. Immobilized BMP-2 silk fibroin scaffolds were also implanted within intramuscular flaps of rats to study the response of cells in vivo. The advantage of the current technique of developing gradients is that it is flexible for in vivo systems, thus reducing the transitional issues created by evaluations between in vitro and in vivo models.