Biomaterial Scaffolds for Controlled, Localized Gene Delivery of Regenerative Factors.

SIGNIFICANCE: Biomaterials play central roles in tissue regeneration by maintaining a space for tissue growth and facilitating its integration with the host. The regenerative capacity of materials can be enhanced through delivery of factors that promote tissue formation. Gene delivery is a versatile strategy to obtain sustained production of tissue inductive factors. Biomaterial scaffolds capable of gene delivery have been shown to induce transgene expression and tissue growth. CRITICAL ISSUES: The widespread application of biomaterial scaffold systems requires identifying the design principles for the material and vectors that modulate transgene expression temporally and spatially. These technologies and others will ultimately enable spatial and temporal control over expression to recreate the cellular organization and gene expression required for formation of complex tissues. RECENT ADVANCES: The design parameters for the biomaterials and vectors that modulate the extent and duration of transgene expression and the distribution of transgene-expressing cells within and around the injury are emerging. The cellular interactions with the biomaterial, such as adhesion or migration rate, can influence expression. Furthermore, modulating the interaction between the vector and biomaterial can control vector release while minimizing the exposure to harsh processing conditions. FUTURE DIRECTIONS: Biomaterial scaffolds that deliver genes encoding for regenerative factors may provide a platform for regenerating complex tissues such as skin, blood vessels, and nerves. Biomaterials capable of localized gene delivery can synergistically target multiple cell processes and will have application to the regeneration of many tissues, with great promise for clinical therapies.