A truly remarkable paper in the journal Advanced Healthcare Materials by Fergal J. O’Brien and his co-workers from the Tissue Engineering Research Group at the Royal College of Surgeons in Dublin, Ireland has examined a unique way to greatly speed up bone regeneration.
Mesenchymal stem cells from bone marrow (other locations as well) can differentiate into bone-making cells (osteoblasts) that will make architecturally normal bone under particular conditions. The use of mesenchymal stem cells and a variety of manufactured biomaterial matrices and administered growth factors enhance bone formation by mesenchymal stem cells (M. Noelle Knight and Kurt D. Hankenson, Adv Wound Care 2013; 2(6): 306–316; also see Marx RE, Harrell DB. Int J Oral Maxillofac Implants 2014 29(2)e201-9; and Kaigler D, et al., Cell Transplant 2013;22(5):767-77).
Protein growth factors tend to have rather short half-lives when applied to growth scaffolds. A better way to apply growth factors is to use the genes for these growth factors and apply them to “gene activated scaffolds.” Gene-activated scaffolds consist of biomaterial scaffolds modified to act as depots for gene delivery while simultaneously offering structural support and a matrix for new tissue deposition. A gene-activated scaffold can therefore induce the body’s own cells to steadily produce specific proteins providing a much more efficient alternative.
In this paper by O’Brien and his groups, the genes for two growth factors, VEGF and BMP2, were applied to a gene-activated scaffold that consisted of collagen-nanohydroxyapatite. VEGF drives the formation of new blood vessels, and this fresh vascularization, coupled with increase bone deposition, which is induced by BMP2, accelerated bone repair.
Mind you, the assays in the paper were conducted in cell culture systems. However, O’Brien and his colleagues implanted these gene-activated scaffolds with their mesenchymal stem cells into rats that had large gaps in their skulls. In this animal model system for bone repair, stem cell-mediated bone production, in addition to increased blood vessel formation accelerated bone repair in these animals. Tissue examinations of the newly-formed bone showed that bone made from gene-activated scaffolds with mesenchymal stem cells embedded in them made thicker, more vascularized bone than the other types of strategies.
This is not a clinical trial, but this preclinical trial shows that vascularization and bone repair by host cells is enhanced by the use of nanohydroxyapatite vectors to deliver a combination of genes, thus markedly enhancing bone healing.