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2016 ; 5
(4
): 106-15
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Osteogenic, stem cell and molecular characterisation of the human induced
membrane from extremity bone defects
#MMPMID27056768
Gruber HE
; Ode G
; Hoelscher G
; Ingram J
; Bethea S
; Bosse MJ
Bone Joint Res
2016[Apr]; 5
(4
): 106-15
PMID27056768
show ga
OBJECTIVES: The biomembrane (induced membrane) formed around
polymethylmethacrylate (PMMA) spacers has value in clinical applications for bone
defect reconstruction. Few studies have evaluated its cellular, molecular or stem
cell features. Our objective was to characterise induced membrane morphology,
molecular features and osteogenic stem cell characteristics. METHODS: Following
Institutional Review Board approval, biomembrane specimens were obtained from 12
patient surgeries for management of segmental bony defects (mean patient age 40.7
years, standard deviation 14.4). Biomembranes from nine tibias and three femurs
were processed for morphologic, molecular or stem cell analyses. Gene expression
was determined using the Affymetrix GeneChip Operating Software (GCOS). Molecular
analyses compared biomembrane gene expression patterns with a mineralising
osteoblast culture, and gene expression in specimens with longer spacer duration
(> 12 weeks) with specimens with shorter durations. Statistical analyses used the
unpaired student t-test (two tailed; p < 0.05 was considered significant).
RESULTS: Average PMMA spacer in vivo time was 11.9 weeks (six to 18). Trabecular
bone was present in 33.3% of the biomembrane specimens; bone presence did not
correlate with spacer duration. Biomembrane morphology showed high vascularity
and collagen content and positive staining for the key bone forming regulators,
bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2
(RUNX2). Positive differentiation of cultured biomembrane cells for osteogenesis
was found in cells from patients with PMMA present for six to 17 weeks. Stem cell
differentiation showed greater variability in pluripotency for osteogenic
potential (70.0%) compared with chondrogenic or adipogenic potentials (100% and
90.0%, respectively). Significant upregulation of BMP2 and 6, numerous collagens,
and bone gla protein was present in biomembrane compared with the cultured cell
line. Biomembranes with longer resident PMMA spacer duration (vs those with
shorter residence) showed significant upregulation of bone-related, stem cell,
and vascular-related genes. CONCLUSION: The biomembrane technique is gaining
favour in the management of complicated bone defects. Novel data on biological
mechanisms provide improved understanding of the biomembrane's osteogenic
potential and molecular properties.Cite this article: Dr H. E. Gruber.
Osteogenic, stem cell and molecular characterisation of the human induced
membrane from extremity bone defects. Bone Joint Res 2016;5:106-115. DOI:
10.1302/2046-3758.54.2000483.