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Bone tissue engineering (BTE) enforces the concerted participation and combination of different biomaterials, cells, and bioactive molecules to make biosynthetic grafts for bone regeneration. Electrospinning has been used to fabricate fibrous scaffolds, which provide nanoscale architecture comprising interconnecting pores, resembling the natural hierarchy of tissues, and enabling the formation of artificial functional tissues. Electrospun fibers for BTE applications have been mostly made from polymers (chitosan, alginate, polycaprolactone, polylactic acid) and bioceramics (hydroxyapatite). Stem cells are among the most prolific members employed in regenerative medicine due to their self-renewal and differentiation capacity. Most importantly, the bioactive molecules such as synthetic drugs, growth factors, phytocompounds consistently regulate cell behavior inducing differentiation towards osteoblast lineage. A growing literature now evidenced these electrospun fibers loaded with bioactive molecules supporting the differentiation of stem cells towards osteoblasts. Thus, this review briefly describes the current development of polymers and bioceramics-based electrospun fibers and the influence of bioactive molecules in these electrospun fibers for bone tissue regeneration.

The dynamic biology of bone involving an enormous magnitude of cellular interactions and signaling transduction provides ample biomolecular targets, which can be enhanced or repressed to mediate a rapid regeneration of the impaired bone tissue. The delivery of nucleic acids such as DNA and RNA can enhance the expression of osteogenic proteins. Members of the RNA interference pathway such as miRNA and siRNA can repress negative osteoblast differentiation regulators. Advances in nanomaterials have provided researchers with a plethora of delivery modules that can ensure proper transfection. Combining the nucleic acid carrying vectors with bone scaffolds has met with tremendous success in accomplishing bone formation. Recent years have witnessed the advent of CRISPR and DNA nanostructures in regenerative medicine. This review focuses on the delivery of nucleic acids and touches upon the prospect of CRISPR and DNA nanostructures for bone tissue engineering, emphasizing their potential in treating bone defects.