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Three-Dimensional Engineered Bone from Bone Marrow Stromal Cells and Their Autogenous Extracellular Matrix
Syed-Picard, Fatima N.; Larkin, Lisa M.; Shaw, Charles M.; Arruda, Ellen M.
Syed-Picard, Fatima N.; Larkin, Lisa M.; Shaw, Charles M.; Arruda, Ellen M.
2009
Citation:Syed-Picard, Fatima N.; Larkin, Lisa M.; Shaw, Charles M.; Arruda, Ellen M. (2008/08/31). "Three-Dimensional Engineered Bone from Bone Marrow Stromal Cells and Their Autogenous Extracellular Matrix." Tissue Engineering Part A, 15(1): 187-195 <http://hdl.handle.net/2027.42/78137>
Abstract: Most bone tissue engineering research uses porous three-dimensional (3D) scaffolds for cell seeding. In this work, scaffold-less 3D bone-like tissues were engineered from rat bone marrow stromal cells (BMSCs) and their autogenous extracellular matrix (ECM). The BMSCs were cultured on a 2D substrate in medium that induced osteogenic differentiation. After reaching confluence and producing a sufficient amount of their own ECM, the cells contracted their tissue monolayer around two constraint points, forming scaffold-less cylindrical engineered bone-like constructs (EBCs). The EBCs exhibited alizarin red staining for mineralization and alkaline phosphatase activity and contained type I collagen. The EBCs developed a periosteum characterized by fibroblasts and unmineralized collagen on the periphery of the construct. Tensile tests revealed that the EBCs in culture had a tangent modulus of 7.5+/-0.5MPa at 7 days post-3D construct formation and 29+/-9MPa at 6 weeks after construct formation. Implantation of the EBCs into rats 7 days after construct formation resulted in further bone development and vascularization. Tissue explants collected at 4 weeks contained all three cell types found in native bone: osteoblasts, osteocytes, and osteoclasts. The resulting engineered tissues are the first 3D bone tissues developed without the use of exogenous scaffolding.