Gene- and RNAi-activated scaffolds for bone tissue engineering: Current progress and future directions.

Large bone defects are usually managed by replacing lost bone with non-biological prostheses or with bone grafts that come from the patient or a donor. Bone tissue engineering, as a field, offers the potential to regenerate bone within these large defects without the need for grafts or prosthetics. Such therapies could provide improved long- and short-term outcomes in patients with critical-sized bone defects. Bone tissue engineering has long relied on the administration of growth factors in protein form to stimulate bone regeneration, though clinical applications have shown that using such proteins as therapeutics can lead to concerning off-target effects due to the large amounts required for prolonged therapeutic action. Gene-based therapies offer an alternative to protein-based therapeutics where the genetic material encoding the desired protein is used and thus loading large doses of protein into the scaffolds is avoided. Gene- and RNAi-activated scaffolds are tissue engineering devices loaded with nucleic acids aimed at promoting local tissue repair. A variety of different approaches to formulating gene- and RNAi-activated scaffolds for bone tissue engineering have been explored, and include the activation of scaffolds with plasmid DNA, viruses, RNA transcripts, or interfering RNAs. This review will discuss recent progress in the field of bone tissue engineering, with specific focus on the different approaches employed by researchers to implement gene-activated scaffolds as a means of facilitating bone tissue repair.