Abstract
INTRODUCTION
Autologous bone grafts are considered gold standard in the repair of bone defects. However they are limited in supply and are associated with donor site morbidity. This has led to the development of synthetic bone graft substitute (BGS) materials, many of which have been reported as being osteoinductive. The structure of the BGS is important and bone formation has been observed in scaffolds with a macroporous morphology. Smaller pores termed ‘strut porosity’ may also be important for osteoinduction. The aim of this study was to compare the osteoinductive ability of one silicate-substituted calcium phosphate (SiCaP) with differing strut porosities in an ectopic ovine model. Our hypothesis was that SiCaP with greater strut porosity would be more osteoinductive.
METHODS
The osteoinduction of SiCaP BGS with two different strut porosities (AF and AF++) was investigated. The materials had an identical chemical composition and morphological structure but differing strut porosity (AF=22.5%, AF++=47%). Implants were inserted into the paraspinal muscles in skeletally mature sheep. Procedures were carried out in compliance with UK Home Office regulations. There were 12 implants in each group. Implants remained in vivo for 8 and 12 weeks and on retrieval were prepared for undecalcified histology. Sections were stained and examined using light microscopy. A line intersection method was used to quantify bone, implant and implant surface/bone contact within seven random regions of interest along each implant. A Mann-Whitney U test was used for statistical analysis where p values < 0.05 were considered significant.
RESULTS
Bone formation was observed to be greater in the AF++ group at 8 (AF=0.2%+/−0.15; AF++=0.44%+/−0.12) and significantly higher at 12 weeks (AF=1.33% +/−0.84; AF++=6.17%+/−1.51) (p=0.04). Significantly higher implant surface/bone contact was observed in the AF++ group at 8 (AF=0.67%+/−0.52; AF++=3.30%+/−1.17) (p=0.04) and 12 weeks (AF=3.06%+/−1.89; AF++=21.82%+/−5.59) (p=0.01). The % implant measured was less in the AF++ group at 8 (AF=39.06%+/−1.26; AF++=33.09%+/−2.14) and 12 weeks (AF=36.05% +/−3.55; AF++=30.60%+/−2.29) but this was not significant. Histology revealed bone formation within BGS strut pores measuring < 50um. Endochondral and intramembranous ossification were also observed in both groups.
DISCUSSION
The results indicate that higher strut porosity promotes greater osteoinduction in SiCaP materials. This could be attributed to the micropores providing a greater surface area for the action of growth factors and osteoblasts leading to the formation of bone at an earlier time point. Endochondral ossification was an unusual finding as this is usually associated with bone formation secondary to Bone Morphogenetic proteins (BMPs). This suggests that the osteoinductive mechanisms by SiCaP may involve cytokines such as BMPs.
