Mechanical and biological augmentation of allograft and synthetic graft in impaction bone grafting

Aims:<br/><br/>This thesis has three main aims:<br/><br/>• To investigate the potential role of human bone marrow stromal cells<br/>(HBMSC) in Impaction Bone Grafting (IBG).<br/><br/>• To investigate the potential role of a synthetic graft, Poly (DL-lactic acid),<br/>(PDLLA) as a tissue engineering scaffold and a graft extender in IBG.<br/><br/>• To investigate methods to improve graft compaction and reduce fracture risk<br/>in IBG.<br/><br/>Methods:<br/><br/>Part I: The biocompatibility and mechanical properties of HBMSC seeded onto<br/>allograft or PDLLA were compared to allograft or PDLLA alone in vitro.<br/><br/>Part II: Evidence of biocompatibility, neovascularisation and new bone formation in<br/>impacted allograft and PDLLA scaffolds seeded with HBMSC, in vivo was assessed<br/>and compared to allograft and PDLLA alone.<br/><br/>Part III: The laboratory work was translated into the clinical setting with implantation<br/>of impacted allograft seeded with HBMSC for the treatment of bone defects in two<br/>case studies.<br/><br/>Part IV: The role of vibration in IBG technique to reduce fracture risk and improve<br/>graft compaction and prosthetic stability was assessed in an in vitro femoral IBG<br/>model.<br/><br/>Results:<br/><br/>Part I: HBMSC seeded onto morsellised allograft or PDLLA, and cultured under<br/>osteogenic conditions in vitro were able to withstand the forces equivalent to a<br/>standard femoral impaction and were able to differentiate and proliferate along the<br/>osteogenic lineage. The living composite formed provided a biomechanical<br/>advantage, with increased interparticulate cohesion and shear strength when compared<br/>to allograft alone.<br/><br/>Part II: HBMSC seeded onto morsellised allograft or PDLLA, impacted and implanted<br/>subcutaneously in nude mice demonstrated cell viability and histological evidence of<br/>new bone formation and neovascularisation after 28 days.<br/><br/>Part III: In two case studies impacted allograft augmented with marrow-derived<br/>autogenous cells was used to treat bone voids in the proximal femur. Both patients<br/>made an uncomplicated clinical recovery. Imaging confirmed filling of the defects<br/>with very encouraging initial graft incorporation. Histochemical staining of graft<br/>samples demonstrated that a live composite graft with osteogenic activity had been<br/>introduced into the defects. Alkaline phosphatase and immunohistochemical staining<br/>techniques confirmed the bone phenotype of the autotransplanted cells.<br/><br/>Part IV: Vibration assisted compaction of morsellised allograft reduced the peak<br/>loads and hoop strains transmitted to the femoral cortex during graft compaction,<br/>improved graft compaction in the proximal and middle femoral regions, which in turn<br/>conferred improved mechanical stability of the prosthesis under cyclical loading,<br/>demonstrated by a reduction in stem subsidence.<br/><br/>Conclusions:<br/><br/>• HBMSC when combined with either allograft or synthetic graft (PDLLA) can<br/>survive the forces of a standard IBG and under osteogenic conditions, differentiate<br/>and proliferate along the osteogenic lineage. HBMSC and allograft / PDLLA<br/>composites confer an additional biomechanical advantage over allograft / PDLLA<br/>alone.<br/><br/>• Increased new bone formation and neovascularisation has been demonstrated in<br/>vivo in allograft and PDLLA / HBMSC composites compared to allograft or PDLLA<br/>alone.<br/><br/>• Tissue engineering principles combining morsellised allograft and HBMSC<br/>composites have been utilised to fill bony voids in two clinical cases, with good<br/>clinical outcome.<br/><br/>• By reducing peak loads, hoop strains and femoral fracture risk, and improving<br/>graft compaction and prosthetic stability the use of vibration and a perforated tamp<br/>is a potential new safer more flexible IBG technique.<br/><br/>• Utilising tissue engineering techniques and improved graft impaction methods<br/>provides avenues to augment the biological and mechanical properties of<br/>morsellised allograft, and potentially increase the longevity of revision hip<br/>arthroplasty performed using the IBG technique.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of Southampton

Year dc:date.issued

2008

Author dc:creator

• Bolland, Benjamin J.R.F.

Advisors dc:contributor.advisor

• Oreffo, R.
• Dunlop, D.