(155a) Delivery of DNA, Proteins, and Cells with Injectable Hydrogels

Although the presence of a scaffolding material is necessary for the repair of many tissue defects, numerous studies have demonstrated that scaffolds alone often fail to provide a sufficient template to guide tissue regeneration. Consequently, our laboratory has developed a class of fumarate-based polymers for the controlled delivery of cells and bioactive agents to improve tissue repair. We have employed this technology to fabricate synthetic hydrogel scaffolds from a hydrophilic fumarate-based polymer, oligo(poly(ethylene glycol) fumarate). Such scaffolds have been explored as injectable carriers for marrow stromal progenitor cells and have been shown to promote cellular differentiation and calcified matrix production in vitro. For the repair of cartilage tissue, gelatin microparticles have been loaded with growth factors and embedded within the hydrogel network. Similarly for bone regeneration, cationized gelatin microparticles have been loaded with plasmid DNA encoding an osteogenic growth factor and embedded within the hydrogel network. In both cases, as the microparticles undergo enzymatic degradation, the growth factors or plasmid DNA are released to the surrounding tissue, and newly created pores allow for cell infiltration. As these examples demonstrate, fumarate-based materials can be easily tailored for specific applications and hold great promise as injectable carriers for delivery of cells and bioactive factors to a variety of complex defect sites.