Multiscale modeling of growth plate cartilage mechanobiology.

Growth plate chondrocytes are responsible for bone growth through proliferation and differentiation. However, the way they experience physiological loads and regulate bone formation, especially during the later developmental phase in the mature growth plate, is still under active investigation. In this study, a previously developed multiscale finite element model of the growth plate is utilized to study the stress and strain distributions within the cartilage at the cellular level when rapidly compressed to 20 %. Detailed structures of the chondron are included in the model to examine the hypothesis that the same combination of mechanoregulatory signals shown to maintain cartilage or stimulate osteogenesis or fibrogenesis in the cartilage anlage or fracture callus also performs the same function at the cell level within the chondrons of growth plate cartilage. Our cell-level results are qualitatively and quantitatively in agreement with tissue-level theories when both hydrostatic cellular stress and strain are considered simultaneously in a mechanoregulatory phase diagram similar to that proposed at the tissue level by Claes and Heigele for fracture healing. Chondrocytes near the reserve/proliferative zone border are subjected to combinations of high compressive hydrostatic stresses ([Formula: see text] MPa), and cell height and width strains of [Formula: see text] to [Formula: see text] respectively, that maintain cartilage and keep chondrocytes from differentiating and provide conditions favorable for cell division, whereas chondrocytes closer to the hypertrophic/calcified zone undergo combinations of lower compressive hydrostatic stress ([Formula: see text] MPa) and cell height and width strains as low as [Formula: see text] to +4 %, respectively, that promote cell differentiation toward osteogenesis; cells near the outer periphery of the growth plate structure experience a combination of low compressive hydrostatic stress (0 to [Formula: see text] MPa) and high maximum principal strain (20-29 %) that stimulate cell differentiation toward fibrocartilage or fibrous tissue.