Bone repair in the twenty–first century: biology, chemistry or engineering?

Abstract

Increases in reconstructive orthopaedic surgery, such as total hip replacement and spinal fusion, resulting from advances in surgical practice and the ageing population, have lead to a demand for bone graft that far exceeds supply. Consequently, a number of synthetic bone-graft substitutes (BGSs) have been developed with mixed success and surgical acceptance. Skeletal tissue regeneration requires the interaction of three basic elements: cells, growth factors (GFs) and a permissive scaffold. This can be achieved by pre-loading a synthetic scaffold with GFs or pre-expanded cells; however, a 'simpler' approach is to design intrinsic 'osteoinductivity' into your BGS, i.e. the capability to recruit and stimulate the patient's own GFs and stem cells. Through investigation of the mechanisms controlling bone repair in BGSs, linking interactions between the local chemical and physical environment, scientists are currently developing osteoinductive materials that can stimulate bone regeneration through control of the scaffold chemistry and structure. Moreover, this body of research is providing the foundations for future generations of BGSs and bone-repair therapies and may ultimately contribute towards improving the quality of life through maintenance of the skeleton and reversal of disease states, as opposed to the mending of broken bones that we currently practice. Will we be able to grow our own bones in a bioreactor for use as autologous graft materials in the future? Could surgery be limited to accidental trauma cases, with greater restoration of function through biochemical or gene therapies? The technology and research probes necessary to this task are currently being developed with the advent of nanotechnology, genomics and proteomics: are we about to embark on a chemical revolution in medicine? This paper aims to discuss some of the current thinking on the mechanisms behind bioactivity and biocompatibility in bone and how a fuller understanding of the interactions between cells and the materials used today could bring about completely new approaches for the treatment of bone fracture and disease tomorrow.

Method Development of Efficient Protein Extraction in Bone Tissue for Proteome Analysis

“…33 Moreover, BMPs possessed the greatest in vivo bone stimulatory capacity and were recognized as the only growth factors to simulate mesenchymal stem cells to differentiate along osteoblastic and chondrogenic lineages, 34 which promoted the formation of bone and the skeleton and mended broken bones. 35,36 Other noncollagenous glycoproteins in bone matrix, such as osteonectin, fibronectin, osteopontin, and bone sialoprotein (BSP), which comprised 15% of the total noncollagens proteins in bone, 30 were also identified, which were produced at different stages of osteoblast maturation. Those identified proteins exhibited a broad spectrum of func- tions including the control of cell proliferation, cell-matrix interactions, and mediation of hydroxyapatite deposition.…”

“…Osteocalcin was one of the most abundant noncollagens proteis in bone, comprising up to 20% of the total noncollagen proteins in bone. 30 It was produced by mature osteoblasts and primarily deposited in the ECM of skeletal tissue, and its levels reflected the rate of bone formation 31 and might be a potential diagnostic marker for bone diseases such as oteoporosis. 32 Matrix Gla-protein (MGP), γ-carboxyglutamic acid (GLA)-rich, vitamin K-dependent, and apatite-binding protein were the regulator of bone and cartilage mineralization during development.…”

The effect of an alginate carrier on bone formation in a hydroxyapatite scaffold

“…Bone formation begins with the formation of an apatite layer which enhances protein adsorption resulting in the differentiation of osteoprogenitor cells into osteoblasts leading to the deposition of bone (25). In order for the apatite layer to form, the bone graft material must first come into contact with blood, which facilitates the dissolution of the graft and its re-precipitation onto the surface (14,24,25). In addition, blood is an abundant source of proteins, which would further enhance this process.…”

“…Allografts and xenografts which are only osteoconductive, can overcome these limitations, but the risk of immune reactions and in some countries, limited availability of tissue banks, patient compliance and regulatory restrictions are at present, significant problems (12,13). Synthetic bone graft substitutes based on calcium phosphate materials are valid alternatives to tissue transplants and have been utilised clinically for over three decades, with varying efficacy and success (14). A limitation with current CaP bone substitute materials is that they often exist in a dry granular form, limiting handling ability during surgery (3).…”

Correlating cell morphology and osteoid mineralization relative to strain profile for bone tissue engineering applications

“…The main routes to producing tissue-engineered bone incorporate three basic elements, namely cells, growth factors and three-dimensional polymeric scaffolds ( Hing 2004). Cell-seeded constructs are generally cultured in bioreactors, for example spinner flasks and rotating wall vessel reactors, to increase diffusion throughout the system and in an attempt to mimic the dynamics of in vivo conditions, where mechanical stimulation, in the form of hydrostatic pressure and shear stress, is experienced by cells and tissues (Salgado et al 2004).…”