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

Abstract

Aims:

This thesis has three main aims:

• To investigate the potential role of human bone marrow stromal cells
(HBMSC) in Impaction Bone Grafting (IBG).

• To investigate the potential role of a synthetic graft, Poly (DL-lactic acid),
(PDLLA) as a tissue engineering scaffold and a graft extender in IBG.

• To investigate methods to improve graft compaction and reduce fracture risk
in IBG.

Methods:

Part I: The biocompatibility and mechanical properties of HBMSC seeded onto
allograft or PDLLA were compared to allograft or PDLLA alone in vitro.

Part II: Evidence of biocompatibility, neovascularisation and new bone formation in
impacted allograft and PDLLA scaffolds seeded with HBMSC, in vivo was assessed
and compared to allograft and PDLLA alone.

Part III: The laboratory work was translated into the clinical setting with implantation
of impacted allograft seeded with HBMSC for the treatment of bone defects in two
case studies.

Part IV: The role of vibration in IBG technique to reduce fracture risk and improve
graft compaction and prosthetic stability was assessed in an in vitro femoral IBG
model.

Results:

Part I: HBMSC seeded onto morsellised allograft or PDLLA, and cultured under
osteogenic conditions in vitro were able to withstand the forces equivalent to a
standard femoral impaction and were able to differentiate and proliferate along the
osteogenic lineage. The living composite formed provided a biomechanical
advantage, with increased interparticulate cohesion and shear strength when compared
to allograft alone.

Part II: HBMSC seeded onto morsellised allograft or PDLLA, impacted and implanted
subcutaneously in nude mice demonstrated cell viability and histological evidence of
new bone formation and neovascularisation after 28 days.

Part III: In two case studies impacted allograft augmented with marrow-derived
autogenous cells was used to treat bone voids in the proximal femur. Both patients
made an uncomplicated clinical recovery. Imaging confirmed filling of the defects
with very encouraging initial graft incorporation. Histochemical staining of graft
samples demonstrated that a live composite graft with osteogenic activity had been
introduced into the defects. Alkaline phosphatase and immunohistochemical staining
techniques confirmed the bone phenotype of the autotransplanted cells.

Part IV: Vibration assisted compaction of morsellised allograft reduced the peak
loads and hoop strains transmitted to the femoral cortex during graft compaction,
improved graft compaction in the proximal and middle femoral regions, which in turn
conferred improved mechanical stability of the prosthesis under cyclical loading,
demonstrated by a reduction in stem subsidence.

Conclusions:

• HBMSC when combined with either allograft or synthetic graft (PDLLA) can
survive the forces of a standard IBG and under osteogenic conditions, differentiate
and proliferate along the osteogenic lineage. HBMSC and allograft / PDLLA
composites confer an additional biomechanical advantage over allograft / PDLLA
alone.

• Increased new bone formation and neovascularisation has been demonstrated in
vivo in allograft and PDLLA / HBMSC composites compared to allograft or PDLLA
alone.

• Tissue engineering principles combining morsellised allograft and HBMSC
composites have been utilised to fill bony voids in two clinical cases, with good
clinical outcome.

• By reducing peak loads, hoop strains and femoral fracture risk, and improving
graft compaction and prosthetic stability the use of vibration and a perforated tamp
is a potential new safer more flexible IBG technique.

• Utilising tissue engineering techniques and improved graft impaction methods
provides avenues to augment the biological and mechanical properties of
morsellised allograft, and potentially increase the longevity of revision hip
arthroplasty performed using the IBG technique.

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Identifiers

ORCID for R. Oreffo: orcid.org/0000-0001-5995-6726

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