title: Synchrotron X-ray phase nano-tomography-based analysis of the lacunar-canalicular network morphology and its relation to the strains experienced by osteocytes in situ as predicted by case-specific finite element analysis.
abstract: Osteocytes are hypothesized to regulate bone remodeling guided by both biological and mechanical stimuli. Morphology of the lacunar-canalicular network of osteocytes has been hypothesized to be strongly related to the level of mechanical loading and to various bone diseases. Finite element modeling could help to better understand the mechanosensation process by predicting the physiological strain environment. The aims of this study were to (i) quantify the lacunar-canalicular morphology in the cortex of the human femur; (ii) predict the in situ local deformations around and in osteocytes by means of case-specific finite element models; and (iii) investigate the potential relationship between morphology and deformations. Human femoral cortical bone samples were imaged using synchrotron X-ray phase nano-tomography with 50 nm voxel size. Rectangular volumes of interest were selected to contain single osteocyte lacunae and the surrounding matrix. Lacunar-canalicular morphology was quantified and the cell geometry was artificially reconstructed based on a priori assumptions. Finite element models of the volumes of interest were generated, containing the extracellular matrix, osteocyte and peri-cellular matrix, and subjected to uniaxial compression. The morphological analysis revealed that canalicular number was dictated by lacunar size, that the spacing of canaliculi fell within a narrow range, suggesting that these pores are well distributed throughout the bone matrix and indicated the trend that lacunae at the outer osteon boundary were less elongated than others. No apparent relationship was found between the morphological parameters and the predicted strains. The globally applied strain was amplified locally by factors up to 10 and up to 70 in the extracellular matrix and the in cells, respectively. Cell deformations were localized mainly at the body-dendrite junctions, with magnitudes reaching the in vitro stimulatory threshold reported for osteocytes.
authors.affiliation: Julius Wolff Institute, Berlin-Brandenburg School for Regenerative Therapies, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 , Berlin, Germany, peter.varga@charite.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Varga
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hesse
authors.forename: Max
authors.initials: M
authors.lastname: Langer
authors.forename: Susanne
authors.initials: S
authors.lastname: Schrof
authors.forename: Nils
authors.initials: N
authors.lastname: Männicke
authors.forename: Heikki
authors.initials: H
authors.lastname: Suhonen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Pacureanu
authors.forename: Dieter
authors.initials: D
authors.lastname: Pahr
authors.forename: Françoise
authors.initials: F
authors.lastname: Peyrin
authors.forename: Kay
authors.initials: K
authors.lastname: Raum
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D020342:Finite Element Analysis; D006801:Humans; D021621:Imaging, Three-Dimensional; D008297:Male; D008954:Models, Biological; D036103:Nanotechnology / Q000379:methods*; D010011:Osteocytes / Q000502:physiology*; D013314:Stress, Mechanical; D017356:Synchrotrons; D014054:Tomography / Q000379:methods*; D014965:X-Rays