A North-South collaboration is looking for new ways to grow living bone on shaped scaffolds as an alternative to bone grafts, writes Kirstin Goldring
Tissue researchers in a North-South collaboration are developing new ways of growing living bone on shaped scaffolds as a way to provide replacements for damaged or lost bones.
This interdisciplinary project is an important collaboration in regenerative medicine between Belfast and Dublin, says head of the tissue engineering research team at Queen's University Belfast, Dr Glenn Dickson. "Our objective is that ideally the [ bone] product would be one of the first clinically functional, bio-compatible, mechanically competent, bone-promoting graft substitutes."
Only blood transfusions are ahead of bone grafts on the list of transplanted material. "Every year up to four million bone-replacement procedures are performed worldwide, which require the use of a bone graft or bone graft substitute," says Dickson.
Currently, "autografts", using bones from the patient's own body, or "allografts", using bone from a donor, are used to help repair damaged bones. However, tissue engineering techniques are now being used to produce bone graft substitutes, which would reduce the need for grafted bone material.
Bones consist of living cells that are supported on a mineralised matrix. The matrix is produced by one of the cells in bone, the osteoblast. This matrix consists of two main components - an inorganic part and an organic part.
The inorganic component, in the form hydroxyapatite (HA), consists of calcium and phosphate crystals. The organic component is mainly collagen, in the form of fibrils, which create a scaffold containing other molecules such as growth factors.
The bone matrix is hard, unlike the matrix of any other cell. For a suitable graft, the two components of the matrix need to be right.
Dr Fergal O'Brien has been working on collagen scaffolds for many years. "We needed to combine the soft material, or collagen scaffolds that we have expertise in, with something harder, so that it can be transplanted into patients," explains O'Brien, who is head of the tissue engineering research group at the Royal College of Surgeons in Ireland.
They started using a commercially available medical grade form of HA, currently used in hip implants. "The problem with it was that the ceramic particles [ HA] are large and not broken down well in the body, so they are not resorbed," says O'Brien. It is important to have a smaller molecule that would be resorbed by the body, as the substance is only in the body temporarily to support new bone growth.
O'Brien discussed this with Dickson at a conference. Dickson explained he was making "nano HA", a much smaller version of the molecule, and so began their collaboration.
PhD student Grainne Cunniffe is based in Belfast with Dickson. Her aim is to produce HA of the appropriate size and in a form that will mix well with the collagen scaffolds.
In Dublin, PhD student Amir Al-Munajjed is using a freeze-drying technique under various conditions to produce scaffolds with different properties. The conditions alter the size of the ice crystals formed by the collagen when it is cooled and hence the pore size of the scaffold.
"Depending on the conditions you get different sized ice crystals; bigger crystals mean bigger pores. It depends on the cells to be grown on it as to what is the best," explains O'Brien.
The two parts are put together to find the strongest and most biologically active scaffolds. Many tests are carried out on the resulting products. Mechanical properties, for example porosity and permeability, are examined.
There are various potential applications for the bone scaffolds being produced, Dickson says. "For bone trauma, for example tumours of face and skull, when the diseased tissue is excised, this material could be used to replace the bone. It would also be of use in fractures."
This collaboration is funded under the Research Frontiers Programme at Science Foundation Ireland.
Kirstin Goldring is based at Imperial College London and is on placement at The Irish Times as a British Association for the Advancement of Science Media Fellow