Abstract
The demographic challenges of an advancing aged population emphasise the need for innovative approaches to tissue reconstruction to augment and repair tissue lost as a consequence of trauma or degeneration. Currently, the demand for bone graft outstrips supply, a key issue in the field of revision hip surgery where impaction bone grafting of the femur and acetabulum has impressive results in the short and medium term but often requires up to 6 donated femoral heads. Spine and selected tumour and trauma cases are also eminently suitable for this mode of bone stock replacement. In the current study, we examined the histological and biochemical findings of two parallel in-vitro and in-vivo studies using human mesenchymal stem cells on synthetic scaffolds for possible bone augmentation. The first study confirmed that culture expanded bone marrow cells from 3 patients (mean age 76 +/−4) could be successfully seeded onto washed morsellised allograft. The seeded graft was then exposed to a force equivalent to a standard femoral impaction (impulse=474 J/m2) and cultured for 4 weeks in osteogenic media. Examination of cell viability using cell tracker green and ethidium homodimer-1 and confocal microscopy confirmed extensive cell proliferation and viability following impaction and culture. Alcian blue/ Sirius red confirmed matrix production, alkaline phosphatase immunocytochemistry production of enzyme activity and Goldners trichrome enhanced osteoid formation. The second study compared 3 scaffolds; bone allograft, a ß – Tricalcium Phosphate (ß-TCP) graft substitute and a 50:50 mixture of allograft and ß-TCP. The scaffolds were seeded with either immunoselected STRO-1+ human mesenchymal stem cells or unselected marrow cells. The scaffolds were similarly exposed to impaction forces and cultured for 4 weeks in vitro or in vivo, implanted subcutaneously in MF1nu/nu mice. Both studies demonstrated cellular viability, activity and osteogenesis as assessed using confocal microscopy, Goldners trichrome and alcian blue/Sirius cytochemistry. The demonstration of enhanced osteoid formation as a consequence of stem cell proliferation after impaction grafting augers well for the success of autologous stem cell implantation on impacted graft substitute with or without the addition of morsellised allograft. The implications therein for clinical use in the future await clinical trials.
Correspondence should be addressed to Mr Carlos Wigderowitz, Honorary Secretary BORS, University Dept of Orthopaedic & Trauma Surgery, Ninewells Hospital & Medical School, Dundee DD1 9SY.
One or more of the authors has received something of value from a commercial or other party related directly or indirectly to the subject of the presentation
