Nucleic acids and analogs for bone regeneration

Abstract

With the incidence of different bone diseases increasing, effective therapies are needed that coordinate a combination of various technologies and biological materials. Bone tissue engineering has also been considered as a promising strategy to repair various bone defects. Therefore, different biological materials that can promote stem cell proliferation, migration, and osteoblastic differentiation to accelerate bone tissue regeneration and repair have also become the focus of research in multiple fields. Stem cell therapy, biomaterial scaffolds, and biological growth factors have shown potential for bone tissue engineering; however, off-target effects and cytotoxicity have limited their clinical use. The application of nucleic acids (deoxyribonucleic acid or ribonucleic acid) and nucleic acid analogs (peptide nucleic acids or locked nucleic acids), which are designed based on foreign genes or with special structures, can be taken up by target cells to exert different effects such as modulating protein expression, replacing a missing gene, or targeting specific gens or proteins. Due to some drawbacks, nucleic acids and nucleic acid analogs are combined with various delivery systems to exert enhanced effects, but current studies of these molecules have not yet satisfied clinical requirements. In-depth studies of nucleic acid or nucleic acid analog delivery systems have been performed, with a particular focus on bone tissue regeneration and repair. In this review, we mainly introduce delivery systems for nucleic acids and nucleic acid analogs and their applications in bone repair and regeneration. At the same time, the application of conventional scaffold materials for the delivery of nucleic acids and nucleic acid analogs is also discussed.

Fig. 1

Main methods and essentials procedures that compose new bone tissue engineering and the major bone injury sites in body where strategies using 3D scaffolds. a Scaffolds combined with functional nucleic acid sequences. b MSCs culture and 3D culture with scaffolds and functional nucleic acid sequences. c Nucleic acids as bridge to connect factors to scaffolds. d MSCs culture and 3D culture with scaffolds and functional nucleic acid sequences which combined with factors

Fig. 2

Traditional scaffolds for delivery of nucleic acids

Fig. 3

Target of nucleic acid following delivery to cells. pDNA, small-interfering RNA (siRNA) and microRNA(miRNA), TDNs, etc. can be delivered into cells by no-viral vector systems

Fig. 4

Different applications of functional nucleic acids in bone tissue engineering to promote the differentiation of MSCs