Gene Therapy for Bone Engineering

Abstract

Bone has an intrinsic healing capacity that may be exceeded when the fracture gap is too big or unstable. In that moment, osteogenic measures need to be taken by physicians. It is important to combine cells, scaffolds and growth factors, and the correct mechanical conditions. Growth factors are clinically administered as recombinant proteins. They are, however, expensive and needed in high supraphysiological doses. Moreover, their half-life is short when administered to the fracture. Therefore, gene therapy may be an alternative. Cells can constantly produce the protein of interest in the correct folding, with the physiological glycosylation and in the needed amounts. Genes can be delivered in vivo or ex vivo by viral or non-viral methods. Adenovirus is mostly used. For the non-viral methods, hydrogels and recently sonoporation seem to be promising means. This review will give an overview of recent advancements in gene therapy approaches for bone regeneration strategies.

Adenovirus-mediated bone morphogenetic protein-2 promotes osteogenic differentiation in human mesenchymal stem cells in vitro

“…Of note, gene therapy provides a possibility for intra-cellular production of proteins, thus facilitating therapeutic pathways to occur (32). Following treatment with Ad-BMP-2, hMSCs not only adopted osteoblastic features regarding their shape and growth patterns, but also had an increased expression of ALP.…”

Preclinical testing of drug delivery systems to bone

“…However, it would go beyond the scope of this review to deal with that issue here. Moreover, a co-worker and I have recently extensively reviewed gene therapy approaches for bone regeneration [69].…”

Recent advances in gene‐enhanced bone tissue engineering

“…Therefore, gene transfer strategies have been developed offering a sophisticated way of growth factor delivery. Gene therapy enables small amounts of effector molecules to be administered in a sustained, precise fashion, reducing the risk of unwanted side effects . The regeneration of bone appears to be an ideal application of gene therapy approaches because existing gene transfer vectors provide a transient expression of transgenes over several weeks and many genes with powerful regenerative potential have been identified.…”