Control of gene expression via small interfering RNA has enormous potential for the treatment of a variety of diseases, including cancer and Huntington's disease. However, before any therapies can be developed, effective techniques for controlled delivery of these molecules must be devised. In this proof-of-concept study, small interfering RNA was complexed with a polymer and loaded into a biomaterial scaffold. The scaffold was introduced primarily to control the release of the complexes, and the polymer was introduced to improve the transfection efficiency. An optimal dose and complexation ratio were selected, at which more than 50% down-regulation of the target gene Snail1 was observed in two-dimensional culture. Delayed release of the complexes was observed, and significant sustained down-regulation of Snail1 was seen in a three-dimensional scaffold system after 7 days. Thus, the use of the scaffold altered the transfection profile significantly, demonstrating the feasibility of a collagen scaffold as a controlled release system for delivery of small interfering RNA-dendrimer complexes.