title: Three-dimensional engineered bone from bone marrow stromal cells and their autogenous extracellular matrix.
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 +/- 0.5 MPa at 7 days post-3D construct formation and 29 +/- 9 MPa 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.
authors.affiliation: Department of Materials Science and Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Fatima N
authors.initials: FN
authors.lastname: Syed-Picard
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Larkin
authors.forename: Charles M
authors.initials: CM
authors.lastname: Shaw
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Arruda