Abstract
Background
Skeletal stem cells can be combined with human allograft, and impacted to produce a mechanically stable living bone composite. This strategy has been used for the treatment of femoral head avascular necrosis, and has been translated to four patients, of which three remain asymptomatic at up to three year follow-up. In one patient collapse occurred in both hips due to widely distributed and advanced AVN disease, necessitating bilateral hip arthroplasty. However this has provided the opportunity to retrieve the femoral heads and analyse human tissue engineered bone.
Aims
Analysis of retrieved human tissue-engineered bone in conjunction with clinical follow-up of this translational case series.
Methods
A parallel in vitro culture of the implanted cell-graft constructs was set up at the time of surgery, with serial cell viability stains performed up to six weeks. Patient follow-up was by serial clinical and radiological examination. Tissue engineered bone from the two retrieved femoral heads was analysed histologically by Alcian blue & Sirius red stain and bi-refringence, by micro computed tomography (microCT) for both bone density and morphology, and by compression testing for mechanical strength. Normal trabecular and cortical bone from the femoral heads was used as controls.
Results
Parallel in vitro analysis demonstrated sustained cell growth and viability on the allograft. Histologically, the retrieved tissue engineered specimens demonstrated a mature trabecular micro-architecture and organization identical to normal trabecular bone. MicroCT revealed trabecular morphology within the tissue-engineered bone, with bone density of 1400 Grey scale units (compared to 1200 for natural trabecular bone and 1800 for cortical bone). Axial compression testing showed no difference in strength between engineered and trabecular bone.
Conclusions
Widespread residual necrosis in the femoral heads of one patient resulted in collapse requiring hip arthroplasty, but analysis of the tissue engineered bone sections has demonstrated the translational potential of a living bone composite to restore both the biological and mechanical characteristics of bone defects. Clinical follow-up shows this to be an effective new treatment for focal early stage avascular necrosis of the femoral head, and this unique retrieval analysis data confirms the potential of cell-based strategies for clinical treatment of bone defects.
