Bone Tissue Engineering with Multiple-Factor Delivery Platform

Tissue development and regeneration is regulated by an interplay among various tissue inductive growth factors, formation of an appropriate vascular bed to support the metabolic needs of the forming tissue mass, and a cell population capable of responding to the chemical cues and creating the new tissue. There has been considerable interest in understanding this signaling interplay in bone, due to its limited ability to heal upon serious fracture or trauma and the limitations in common treatments for bone morbidity or replacement. Bone morphogenetic proteins (BMPs) are responsible for initiating cartilage and bone progenitor cell differentiation [1], and sequencing new bone formation via endochondral ossification [2]. Vascular endothelial growth factor (VEGF), a potent angiogenic molecule, appears to be particularly important in bone formation [3, 4]. Ultimately, these factors must act on a population of cells capable of responding to local factors and forming bone tissue. Multipotent stem cells originating from the bone marrow stroma, or bone marrow stromal cells (BMSCs), are a particularly attractive source for osteogenic precursors for bone tissue engineering [5] as they can be easily harvested and expanded in vitro, and induced to differentiate into bone forming cells. We report a material system that allows combined delivery of inductive molecules and cells without the need for viral vector-mediated ex vivo or in vivo genetic engineering. This scaffold delivery system is capable of combined delivery of condensed plasmid DNA encoding for BMP-4, VEGF, and human bone marrow stromal cells from biodegradable polymer to promote bone formation.