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P1 TRANSLATION FROM LABORATORY TO THEATRE: AUGMENTATION OF IMPACTED ALLOGRAFT WITH HUMAN BONE MARROW STROMAL CELLS



Abstract

Introduction: Bone is unique with a vast potential for regeneration from cells with stem cell characteristics. With an increasing aging population, clinical imperatives to augment and facilitate tissue repair have highlighted the therapeutic potential of harnessing mes-enchymal populations from bone. We describe laboratory and clinical findings from two clinical cases, where different proximal femoral conditions (AVN, bone cyst) were treated with impacted allograft augmented with marrow-derived allogeneic progenitor cells.

Methods: Marrow was aspirated from the posterior superior iliac crest and seeded onto prepared washed morsellised allograft. The seeded graft was left for 40 minutes to allow adherence of the marrow-derived osteoprogenitor cells prior to impaction into the defect. Samples of the impacted graft were taken for in-vitro analysis of cell viability, histology and biochemical analysis of cell number and osteogenic enzyme activity. The total force imparted during impaction was calculated using a load cell, with three independent surgeons performing a laboratory simulation of the impaction technique.

Results: Both patients made a rapid clinical recovery after an overnight stay. Imaging confirmed filling of the defects with increased density on plain radiographs suggesting good impaction of the graft composite. Immu-nohistochemical staining of graft samples demonstrated that a living composite graft with osteogenic activity had been introduced into the defects as evidenced by cell tracker green viability and alkaline phosphatase (osteogenic marker) expression and specific activity. The average peak forces during impaction were 0.7kN corresponding to average peak stresses within the graft of 8.3MPa. Similar forces were seen between operators.

Discussion: Replacement of bone loss remains a major challenge in orthopaedic practice. Although allograft remains the gold standard where large volumes preclude autograft, allograft has little osteoinductive potential. We demonstrate that marrow-derived cells can adhere to highly washed morsellised allograft, survive the impaction process, and are of the osteoblastic phenotype creating a living composite. Thus we conclude, impacted allograft seeded with autologous marrow cells allows the delivery of a biologically active scaffold for the treatment of bone deficiency. In addition this is a novel straightforward technique, surgeon independent and with applications in a number of orthopaedic scenarios.

Correspondence should be addressed to Mr Carlos Wigderowitz, Senior Lecturer, University Department of Orthopaedic and Trauma Surgery, Ninewells Hospital and Medical School, Dundee DD1 9SY.