RNA-based scaffolds for bone regeneration: application and mechanisms of mRNA, miRNA and siRNA

Globally, more than 1.5 million patients undergo bone graft surgeries annually, and the development of biomaterial scaffolds that mimic natural bone for bone grafting remains a tremendous challenge. In recent decades, due to the improved understanding of the mechanisms of bone remodeling and the rapid development of gene therapy, RNA (including messenger RNA (mRNA), microRNA (miRNA), and short interfering RNA (siRNA)) has attracted increased attention as a new tool for bone tissue engineering due to its unique nature and great potential to cure bone defects. Different types of RNA play roles via a variety of mechanisms in bone-related cells in vivo as well as after synthesis in vitro. In addition, RNAs are delivered to injured sites by loading into scaffolds or systemic administration after combination with vectors for bone tissue engineering. However, the challenge of effectively and stably delivering RNA into local tissue remains to be solved. This review describes the mechanisms of the three types of RNAs and the application of the relevant types of RNA delivery vectors and scaffolds in bone regeneration. The improvements in their development are also discussed.