Advanced bone scaffold for tough cases

Bone is constantly undergoing microfracturing and repair in response to everyday loading. When bones cannot heal themselves in cases of severe injury or disease, bone grafts are usually necessary. However, they are severely limited in many ways, pointing to an urgent need for advanced tissue engineering.

Scientists have developed a novel nanoscaffold to meet this need with EU support of the project 'Development of bioactive nanocomposites for bone tissue engineering applications' (NANOFACT). The biomimetic scaffold is composed of hydroxyapatite, the main component of teeth and bones, and chitosan, a polysaccharide found in crustacean shells (exoskeletons).

Chitosan mimics the body's natural polymer collagen for improved pharmacokinetics of growth factors. Chitosan also has reported antimicrobial properties and serves as a surface for bone growth. Binding to the scaffold of osteogenic and angiogenic growth factors (bone morphogenetic protein-4 or BMP-4 and vascular endothelial growth factor-A or VEGF-A, respectively) induces bone growth and vascularisation that work together to promote bone healing.

Hydroxyapatite, chitosan and the growth factors were mixed together with an initiator and a cross-linking agent to produce a solid scaffold. The scaffold releases the growth factors progressively as the scaffold itself degrades controlled by the in vivo degradation of the chitosan.

Cytocompatibility of the scaffold was confirmed by in vitro co-culture with a bone cell line. In vivo tests of the osteogenic potential of the scaffold in a rat defect model confirmed that healing was significantly improved by the scaffold containing growth factors compared to that without.

The NANOFACT scaffold acts both as a surface for and initiator of new bone growth. It eliminates the need to culture cells harvested from patients for one to two weeks prior to re-implantation and it reduces the doses of growth factors necessary. Improvements in materials and functionality minimise the doses of expensive growth factors required and reduce the release of harmful by-products during biodegradation.

NANOFACT has reached pre-clinical demonstration of a safe and effective orthopaedic scaffold for bone healing superior to the best treatments currently available. The potential impact on patient morbidity and quality of life and on the health care system cannot be underestimated.