The Long-Term Residual Effects of Low-Magnitude Mechanical Stimulation on Murine Femoral Mechanics.

As an alternative to drug treatments, low-magnitude mechanical stimulation (LMMS) may improve skeletal health without potential side effects from drugs. LMMS has been shown to increase bone health short term in both animal and clinical studies. Long-term changes to the mechanical properties of bone from LMMS are currently unknown, so the objective of this research was to establish the methodology and preliminary results for investigating the long-term effects of whole body vibration therapy on the elastic and viscoelastic properties of bone. In this study, 10-week-old female BALB/cByJ mice were given LMMS (15 min/day, 5 days/week, 0.3 g, 90 Hz) for 8 weeks; SHAM did not receive LMMS. Two sets of groups remained on study for an additional 8 or 16 weeks post-LMMS (N = 17). Micro-CT and fluorochrome histomorphology of these femurs were studied and results were published by Bodnyk et al. (2020, "The Long-Term Residual Effects of Low-Magnitude Mechanical Stimulation Therapy on Skeletal Health," J. Biol. Eng., 14, Article No. 9.). Femoral quasi-static bending stiffness trended 4.2% increase in stiffness after 8 weeks of LMMS and 1.3% increase 8 weeks post-LMMS compared to SHAM. Damping, tan delta, and loss stiffness significantly increased by 17.6%, 16.3%, and 16.6%, respectively, at 8 weeks LMMS compared to SHAM. Finite element models of applied LMMS signal showed decreased stress in the mid-diaphyseal region at both 8-week LMMS and 8-week post-LMMS compared to SHAM. Residual mechanical changes in bone during and post-LMMS indicate that LMMS could be used to increase long-term mechanical integrity of bone.

The long-term residual effects of low-magnitude mechanical stimulation therapy on skeletal health.

BACKGROUND: Low-magnitude mechanical stimulation (LMMS) may improve skeletal health. The objective of this research was to investigate the long-term residual effects of LMMS on bone health. 10-week old female mice were given LMMS for 8 weeks; SHAM did not receive LMMS. Some groups remained on study for an additional 8 or 16 weeks post treatment (N = 17). RESULTS: Epiphyseal trabecular mineralizing surface to bone surface ratio (MS/BS) and bone formation rate (BFR/BS) were significantly greater in the LMMS group compared to the SHAM group at 8 weeks by 92 and 128% respectively. Mineral apposition rate (MAR) was significantly greater in the LMMS group 16 weeks post treatment by 14%.Metaphyseal trabecular bone mineral density (BMD) increased by 18%, bone volume tissue volume ratio (BV/TV) increased by 37%, and trabecular thickness (Tb.Th.) increased by 10% with LMMS at 8 weeks post treatment. Significant effects 16 weeks post treatment were maintained for BV/TV and Tb.Th. The middle-cortical region bone volume (BV) increased by 4% and cortical thickness increased by 3% with 8-week LMMS. CONCLUSIONS: LMMS improves bone morphological parameters immediately after and in some cases long-term post LMMS. Results from this work will be helpful in developing treatment strategies to increase bone health in younger individuals.

Relationships of bone characteristics in MYO9B deficient femurs.

The objective of this study was to examine relationships among a variety of bone characteristics, including volumetric, mineral density, geometric, dynamic mechanical analysis, and static fracture mechanical properties. As MYO9B is an unconventional myosin in bone cells responsible for normal skeletal growth, bone characteristics of wild-type (WT), heterozygous (HET), and MYO9B knockout (KO) mice groups were compared as an animal model to express different bone quantity and quality. Forty-five sex-matched 12-week-old mice were used in this study. After euthanization, femurs were isolated and scanned using microcomputed tomography (micro-CT) to assess bone volumetric, tissue mineral density (TMD), and geometric parameters. Then, a non-destructive dynamic mechanical analysis (DMA) was performed by applying oscillatory bending displacement on the femur. Finally, the same femur was subject to static fracture testing. KO group had significantly lower length, bone mineral density (BMD), bone mass and volume, dynamic and static stiffness, and strength than WT and HET groups (p < 0.019). On the other hand, TMD parameters of KO group were comparable with those of WT group. HET group showed volumetric, geometric, and mechanical properties similar to WT group, but had lower TMD (p < 0.014). Non-destructive micro-CT and DMA parameters had significant positive correlations with strength (p < 0.015) without combined effect of groups and sex on the correlations (p > 0.077). This comprehensive characterization provides a better understanding of interactive behavior between the tissue- and organ-level of the same femur. The current findings elucidate that MYO9B is responsible for controlling bone volume to determine the growth rate and fracture risk of bone.

Designing a tissue-engineered tracheal scaffold for preclinical evaluation.

OBJECTIVE: Recent efforts to tissue engineer long-segment tracheal grafts have been complicated by stenosis and malacia. It has been proposed that both the mechanical characteristics and cell seeding capacity of TETG scaffolds are integral to graft performance. Our aim was to design a tracheal construct that approximates the biomechanical properties of native sheep trachea and optimizes seeding with bone marrow derived mononuclear cells prior to preclinical evaluation in an ovine model. METHODS: A solution of 8% polyethylene terephthalate (PET) and 3% polyurethane (PU) was prepared at a ratio of either 8:2 or 2:8 and electrospun onto a custom stainless steel mandrel designed to match the dimensional measurements of the juvenile sheep trachea. 3D-printed porous or solid polycarbonate C-shaped rings were embedded within the scaffolds during electrospinning. The scaffolds underwent compression testing in the anterior-posterior and lateral-medial axes and the biomechanical profiles compared to that of a juvenile ovine trachea. The most biomimetic constructs then underwent vacuum seeding with ovine bone marrow derived mononuclear cells. Fluorometric DNA assay was used to quantify scaffold seeding. RESULTS: Both porous and solid rings approximated the biomechanics of the native ovine trachea, but the porous rings were most biomimetic. The load-displacement curve of scaffolds fabricated from a ratio of 2:8 PET:PU most closely mimicked that of native trachea in the anterior-posterior and medial-lateral axes. Solid C-ringed scaffolds had a greater cell seeding efficiency when compared to porous ringed scaffolds (Solid: 19 × 104 vs. Porous: 9.6 × 104 cells/mm3, p = 0.0098). CONCLUSION: A long segment tracheal graft composed of 2:8 PET:PU with solid C-rings approximates the biomechanics of the native ovine trachea and demonstrates superior cell seeding capacity of the two prototypes tested. Further preclinical studies using this graft design in vivo would inform the rational design of an optimal TETG scaffold.

Regional variation of bone tissue properties at the human mandibular condyle.

The temporomandibular joint (TMJ) bears different types of static and dynamic loading during occlusion and mastication. As such, characteristics of mandibular condylar bone tissue play an important role in determining the mechanical stability of the TMJ under the macro-level loading. Thus, the objective of this study was to examine regional variation of the elastic, plastic, and viscoelastic mechanical properties of human mandibular condylar bone tissue using nanoindentation. Cortical and trabecular bone were dissected from mandibular condyles of human cadavers (9 males, 54-96 years). These specimens were scanned using microcomputed tomography to obtain bone tissue mineral distribution. Then, nanoindentation was conducted on the surface of the same specimens in hydration. Plastic hardness (H) at a peak load, viscoelastic creep (Creep/Pmax), viscosity (η), and tangent delta (tan δ) during a 30 second hold period, and elastic modulus (E) during unloading were obtained by a cycle of indentation at the same site of bone tissue. The tissue mineral and nanoindentation parameters were analyzed for the periosteal and endosteal cortex, and trabecular bone regions of the mandibular condyle. The more mineralized periosteal cortex had higher mean values of elastic modulus, plastic hardness, and viscosity but lower viscoelastic creep and tan δ than the less mineralized trabecular bone of the mandibular condyle. These characteristics of bone tissue suggest that the periosteal cortex tissue may have more effective properties to resist elastic, plastic, and viscoelastic deformation under static loading, and the trabecular bone tissue to absorb and dissipate time-dependent viscoelastic loading energy at the TMJ during static occlusion and dynamic mastication.