Adult stem cell biology and musculoskeletal tissue engineering: research projects

Regenerative Medicine - Adult stem cell biology and musculoskeletal tissue engineering - Current

Production of a safer, osteogenic, tissue engineered bone allograft

Duration of the project

October 2011 - September 2014

Funding body

British Orthopaedic Association

Members of the project

Professor Judith HoylandSupervisor
Dr Stephen RichardsonSupervisor
Mr Christopher SmithPhD student

Bone grafts are crucial in the treatment of damaged bone lost through disease injury or surgery. Grafts are either biological, autograft (from the host themselves) or allograft (from a donor), or synthetic. Whilst autografts are considered the most appropriate and deemed the gold standard, they are limited to the host, often detrimental to the health and wellbeing of the patient and indeed can complicate their recovery.  Interestingly, the development of increasingly sophisticated allografts sees them becoming more common; utilising the biological structural capabilities of the donor bone, they appear to be the most effective alternative. The allografts, however, impose problems too:  the need for tissue typing to reduce the risk of an immune response and the possibility of disease transfer hinders their use, and requires processing techniques to remove potentially damaging material.

The processing of the allografts is aimed to remove all trace of cells, DNA, viral, bacterial load and prions and many processing techniques are available for the sterilisation of bone including gamma irradiation, detergents and oxidizing agents. The processing of the allograft is a main step but importantly should not alter the biological and mechanical properties of the graft thus causing a diminished osteoconductive, inductive and osteogenic response from the host.   Thus such parameters must be tested before use.

Significantly, tissue engineering has the potential to revitalise these diminished characteristics. This process involves utilising the qualities of the biological matrix with the addition of stem cells or progeniotor cells and growth factors, creating a viable alternative to the use of autografts. A pseudo-autograft therefore would allow for the large production of osteogenic grafts, which mimic or improve upon normal bone healing.

Recently, the group    have developed a method (including a combination of warm water washes, chemical washes and centrifugation, together with a sterilisation step)   to clean whole femoral heads which has been successful in removing in excess of 99% of haemoglobin, soluble protein and DNA.    However for this to be of use clinically, comprehensive biomechanical and biological data is required.   The overall aims of this project are to assess the biomechanical and biological properties of this new washed bone and to assess its potential for clinical application as a tissue engineered allograft, through integration of mesenchymal stem cells.   The main objectives of this project are three-fold:

  • to investigate the biological properties (e.g. biocompatibility) of the washed bone;
  • to investigate the biomechanical properties (e.g. parameters of Young’s modulus, yield stress and yield strain) of the washed bone;
  • to determine the potential of the washed bone to allow fresh bone marrow and culture expanded mesenchymal cell adhesion and differentiation into bone