Bones are constantly exposed to mechanical forces from both muscles and Earth's gravity to maintain bone homeostasis by stimulating bone formation. Mechanotransduction transforms external mechanical signals such as force, fluid flow shear, and gravity into intracellular responses to achieve force adaptation. However, the underlying molecular mechanisms on the conversion from mechanical signals into bone formation has not been completely defined yet. In the present review, we provide a comprehensive and systematic description of the mechanotransduction signaling pathways induced by mechanical stimuli during osteogenesis and address the different layers of interconnections between different signaling pathways. Further exploration of mechanotransduction would benefit patients with osteoporosis, including the aging population and postmenopausal women.

In recent decades, cementless implants have been widely used in clinical practice to replace missing organs, to replace damaged or missing bone tissue or to restore joint functionality. However, there remain risks of failure which may have dramatic consequences. The success of an implant depends on its stability, which is determined by the biomechanical properties of the bone-implant interface (BII). The aim of this review article is to provide more insight on the current state of the art concerning the evolution of the biomechanical properties of the BII as a function of the implant's environment. The main characteristics of the BII and the determinants of implant stability are first introduced. Then, the different mechanical methods that have been employed to derive the macroscopic properties of the BII will be described. The experimental multi-modality approaches used to determine the microscopic biomechanical properties of periprosthetic newly formed bone tissue are also reviewed. Eventually, the influence of the implant's properties, in terms of both surface properties and biomaterials, is investigated. A better understanding of the phenomena occurring at the BII will lead to (i) medical devices that help surgeons to determine an implant's stability and (ii) an improvement in the quality of implants.

To investigate the effect of low-intensity pulsed ultrasound (US) on periimplant bone healing and osseointegration under osteoporotic conditions.

Seventy-two 12-week-old female Sprague Dawley rats received bilateral ovariectomies. Twelve weeks later, titanium implants were bilaterally placed in the proximal tibial metaphysis. The right tibia was exposed to low-intensity pulsed US (40 mW/cm2, spatial and temporal average) for 20 min/d starting the 2nd day after implantation, and the left tibia served as a control without stimulation. The rats were randomly assigned to 6 groups of 12 each according to the US duration (group 1: weeks 0–2, 280 minutes; group 2: weeks 0–4, 560 minutes; group 3: weeks 0–6, 840 minutes; group 4: weeks 0–8, 1120 minutes; group 5: weeks 0–10, 1400 minutes; group 6: weeks 0–12, 1680 minutes). At the end of the 2nd, 4th, 6th, 8th, 10th, and 12th weeks, the rats were euthanized, and bilateral tibias were harvested. Peri-implant bone volume and bone-implant contact were assessed by micro–computed tomography; the implantbone interface was assessed histologically; and implant fixation strength was determined by a removal torque test.

Low-intensity pulsed US increased bone-implant contact at the 4th, 6th, 8th, 10th, and 12th weeks (P = .019, .017, <.001, <.001, and <.001, respectively) and periimplant bone volume at all times (P = <.001, .002, .012, .007, .005, and .010). Removal torque on the US side was improved at the 6th, 8th, 10th, and 12th weeks (P= .012, <.001, .006, and .009). Ultrasound evoked a favorable bone response in the histologic study.

Low-intensity pulsed US might enhance new bone formation, especially at an early stage, and improve osseointegration in osteoporotic bone as an auxiliary method. However, further studies are needed to elucidate the mechanisms underlying its action.

Ultrasound stimulation produces significant multifunctional effects that are directly relevant to alveolar bone formation, which is necessary for periodontal healing and regeneration. We focused to find out effects of specific duty cycles and the percentage of time that ultrasound is being generated over one on/off pulse period, under ultrasound stimulation. Low-intensity pulsed ultrasound ((LIPUS) 1 MHz) with duty cycles of 20% and 50% was used in this study, and human alveolar bone-derived mesenchymal stem cells (hABMSCs) were treated with an intensity of 50 mW/cm(2) and exposure time of 10 min/day. hABMSCs exposed at duty cycles of 20% and 50% had similar cell viability (O.D.), which was higher (*P < 0.05) than that of control cells. The alkaline phosphatase (ALP) was significantly enhanced at 1 week with LIPUS treatment in osteogenic cultures as compared to control. Gene expressions showed significantly higher expression levels of CD29, CD44, COL1, and OCN in the hABMSCs under LIPUS treatment when compared to control after two weeks of treatment. The effects were partially controlled by LIPUS treatment, indicating that modulation of osteogenesis in hABMSCs was related to the specific stimulation. Furthermore, mineralized nodule formation was markedly increased after LIPUS treatment than that seen in untreated cells. Through simple staining methods such as Alizarin red and von Kossa staining, calcium deposits generated their highest levels at about 3 weeks. These results suggest that LIPUS could enhance the cell viability and osteogenic differentiation of hABMSCs, and could be part of effective treatment methods for clinical applications.

Although doctors try their best to protect transplants during surgery, there remain great challenges for the higher survival rate and less rejection of transplants after organ transplantation. Growing evidence indicates that the stem cells could function after injury rather than aging, implying that suitable injury may activate the stem cells of damaged organs. Furthermore, it has been revealed that stem cells can be used to induce tolerance in transplantation and the ultrasound has great biological effects on organs. Basing on these facts, we hypothesize that the stem cells within the transplants can be activated by ultrasound with high-frequency and medium-intensity. Therefore, the stem-cell-activated organs (SCAO) can be derived, and the SCAO will be better transplant option for organ transplantation. We postulate the ultrasound can change the molecular activity and/or quantity of the stem cells, the membrane permeability, the cell-cell junctions, and their surrounding microenvironments. As a result, the stem cells are activated, and the SCAO will acquire more regenerative capacity and less rejection. In the paper, we also discuss the process, methods and models for verifying the theory, and the consequences. We believe the theory may provide a practical method for the clinical application of the ultrasound and stem cells in organ transplantation.

Osteoblasts are key components of the bone multicellular unit and have a seminal role in bone remodeling, which is an essential function for the maintenance of the structural integrity and metabolic capacity of the skeleton. The coordinated function of skeletal cells is regulated by several hormones, growth factors and mechanical cues that act via interconnected signaling networks, resulting in the activation of specific transcription factors and, in turn, their target genes. Bone cells are responsive to mechanical stimuli and this is of pivotal importance in developing biomechanical strategies for the treatment of osteodegenerative diseases. Here, we review the molecular pathways and players activated by mechanical stimulation during osteoblastic growth, differentiation and activity in health, and consider the role of mechanostimulatory approaches in treating various bone pathophysiologies.