The Components of Bone and What They Can Teach Us about Regeneration

Abstract

The problem of bone regeneration has engaged both physicians and scientists since the beginning of medicine. Not only can bone heal itself following most injuries, but when it does, the regenerated tissue is often indistinguishable from healthy bone. Problems arise, however, when bone does not heal properly, or when new tissue is needed, such as when two vertebrae are required to fuse to stabilize adjacent spine segments. Despite centuries of research, such procedures still require improved therapeutic methods to be devised. Autologous bone harvesting and grafting is currently still the accepted benchmark, despite drawbacks for clinicians and patients that include limited amounts, donor site morbidity, and variable quality. The necessity for an alternative to this "gold standard" has given rise to a bone-graft and substitute industry, with its central conundrum: what is the best way to regenerate bone? In this review, we dissect bone anatomy to summarize our current understanding of its constituents. We then look at how various components have been employed to improve bone regeneration. Evolving strategies for bone regeneration are then considered.

Keywords: bone anatomy; bone healing; bone tissue engineering; fracture healing.

Figure 1

Bone anatomy. Modified and combined from Wikimedia Commons by OpenStar College CC BY 3.0 license [11].

Figure 2

Schematic representation of a basic multicellular unit and the associated bone remodelling process. Permission obtained from ASBMB. © Liza J. R. and Nicola C.P. J. Biol. Chem. 285: 25103 (2010) [38].

Figure 3

Organization of collagen and hydroxyapatite (HAP) in bone. (a) Hierarchical structure of bone ranging from the macroscale skeleton to nanoscale collagen (green) and HAP (red). (b) Collagen microfibril model with 0% mineralization (inset shows the collagen triple-helix structure), 20% mineral content (inset shows a HAP unit cell) and 40% mineral content. The HAP crystals are arranged such that the c axis of crystal aligns with the fibril axis. Ca atoms plotted in green, OH groups plotted in red and white, and the tetrahedron structure visualizes the PO4 group. Permission obtained from Springer Nature. © Nair, A.K. et al., Nat Commun. 4: p. 1724. (2013) [100].