Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion.

Cite this article: Bone Joint Res 2019;9(1):1–14.

Despite total knee arthroplasty demonstrating high levels of success, 20% of patients report dissatisfaction with their result. Wellness Stasis Socks are embedded with a proprietary pattern of neuro-receptor activation points that have been proven to activate a precise neuro-response, as according to the pattern theory of haptic perception, which stimulates improvements in pain and function. Technologies that manipulate this sensory environment, such as textured insoles, have proven to be effective in improving gait patterns in patients with knee osteoarthritis. In regard to patients undergoing TKA using this new technology may prove beneficial as an adjunct to recovery as many patients suffer from further deficits to their proprioceptive system caused by ligamentous damage and alterations to mechanoreceptors during procedure. We hypothesized that the Wellness Stasis Socks are a safe, cost-effective and easily scalable strategy to support TKA patients through their recovery. Double-blinded, placebo-controlled randomized trial. Randomization using a computer-generated program . All study coordinators, healthcare personel and patients were blinded to patient groups. All surgical procedures were conducted by the same technique and orthopaedic surgeon. Intervention group: Wellness Stasis socks containing receptor point-activation technology. Control group: indentical appearing Wellness Stasis socks without receptor point-activation technology. Sock use during the waking hours . All additional post-operative protocols remained consistent between groups including same facility physiotherapy . Additional modalities (ice machines, soft-tissue massages, acupuncture) were prohibited. WOMAC questionnaire completed at baseline, 2 weeks, and 6 weeks to assess pain, stiffness and physical function. G. *. Power software to determine minimum sample of 50 in each group. No patients were lost to follow up and all followed study protocol. Data analysis using SPSS software. P-values, effect sizes, and confidence intervals are reported to assess clinical relevance of the finding. Physical status classifications were compared using t-test. Within-subject and between-subject differences in the mean WOMAC were analyzed by ANOVA. Cramer's V statistical analysis noted that other variables of Sex, BMI, ASA classification and Age were not statistically different between the control and intervention groups. No statistical difference between groups in Preop Womac scores. The data showed a consistent improvement in Womac scores for pain and stiffness at 2 weeks post op in the interventional group over the control group. The womac scores assessing physical function showed a consistent improvement at both 2 and 6 weeks post op in the intervention group compared to the control group. There were no complications in either group associated the sock use. The intervention proved to be a low cost and safe additional intervention post operatively from TKA to help patients improve with regard to pain, stiffness and physical function. This study suggests this modality can be added to the list of other commonly used post op interventions such as cryocuffs, physiotherapy, and relaxation techniques as safe post op interventions to help patients improve post op TKA and can act as an adjunct in providing non narcotic pain control

We aimed to determine if there are mechanoreceptors in hip joint capsule and ligamentum capitis femoris of the patients with developmental dysplasia of the hip. We took capsule and ligamentum capitis femoris biopsies from 20 hips of 20 patients who were operated because of developmental dysplasia of the hip. Meanage was 10.2 months (ranges 6-20 months) on the time of surgery. There were 12 girls and 8 boys. Teratologic and secondary hip dislocations were not included in this study. 0.5x 0.5 cm full thickness anterior capsule and liga-mentum capitis femoris portions were taken for biopsy specimen. Specimens were stained with hemotoxylin eosin and examined immunohistochemically using poly-clonal antibodyagainst S-100 Protein. In both analysis no mechanoreceptors was found in any samples of capsule and ligamentum capitis femoris. Conclusion: We think that there is a possibility that developmental dysplasia of the hip can be caused from a defect in formation of mechanoreceptors on localized capsule and ligamentum capitis femoris and we emphasize the need for further studies on the subject

The October 2012 Knee Roundup. 360. looks at: autologous chondrocytes and chondromalacia patellae; drilling the femoral tunnel at ACL reconstruction; whether we repair the radially torn lateral meniscus; factors associated with patellofemoral pain; mechanoreceptors and the allografted ACL; whether high tibial osteotomy can delay the need for knee replacement; return to sport after ACL reconstruction; tissue-engineered cartilage; and the benefits of yoga

Ligament fibroblasts must be mechanosensitive and possess sufficient adaptability to a novel mechanomilieu ensuring the permanent load capacity of the tissue. Once mechanoreceptors are activated, the fibroblasts react with a specific signal transmission (mechanotransduction), which ultimately leads to an adaption of their cytoskeletal organization and protein synthesis. However, the cellular response of anterior cruciate ligament (ACL) fibroblasts to cyclic mechanical stretching is still unclear. Hence, this study should allow a deeper understanding of the reaction profile of mechanically stretched ACL cells in two- (2D) and three-dimensional (3D) biomaterial-free and biomaterial cultures with respect to cell survival, size, orientation, migration and distribution. For the 2D approach consisting of monolayers with 6000 lapine (L) ACL cells per cm2 and for the 3D cultures using preformed LACL cell spheroids (2.5–4/cm2) with 25.000 cells per spheroid, silicone chambers were coated with geltrex and statically colonized with the LACL cells for 24 h before cyclically stretched for 48 h (14 percent uniaxial stretch). A second approach using 3D scaffold cultures was performed which were seeded dynamically for 24 h with LACL cells before cyclically stretched in a novel custom-made mechanostimulator. The scaffolds [polylactic acid (PLA) and polycaprolactone (PCL)] were functionalized with 10 percent gas fluorination and a collagen foam. Scaffolds (120 mm2) were precolonized dynamically with an LACL cell suspension (1 mio cells/mL) for 24 h before stretched for 72 h (4 percent uniaxial stretch). Cell vitality and numbers were monitored. The cytoskeleton orientation was shown by cytochemistry (F-actin) and evaluated (ImageJ). Cell proliferation, based on the DNA content was measured. Cell viability in stretched samples (2D, 3D and scaffold) remained above 90 percent. Stretching on the silicone chambers led to increased cell counts, length and significantly higher colonized areas than in unstretched controls. Higher numbers of LACL cells migrated out of the 3D spheroids under stretching conditions. In response to intermittent stretching, cells oriented in a 70 degrees' angle against the stretch direction in silicone chambers, whereas cell arrangement was more compact on the threads of the scaffolds than in unstretched cultures. In summary, stretching induced a rapid (48 h) cell and cytoskeletal alignment in 2D as well as in 3D cultures. The natural ACL is characterized by a strongly uniaxial cell and extracellular matrix organization which might be achieved in tissue engineered constructs by a suitable cyclic stretching protocol in future

Introduction. Preservation of the anterior cruciate ligament (ACL), along with the posterior cruciate ligament, is believed to improve functional outcomes in total knee replacement (TKR). The purpose of this study was to examine gait differences and muscle activation levels between ACL sacrificing (ACL-S) and bicruciate retaining (BCR) TKR subjects during level walking, downhill walking, and stair climbing. Methods. Ten ACL-S (Vanguard CR) (69±8 yrs, 28.7±4.7 kg/m2) and eleven BCR (Vanguard XP, Zimmer-Biomet) (63±11 yrs, 31.0±7.6 kg/m2) subjects participated in this IRB approved study. Except for the condition of the ACL, both TKR designs were similar. Subjects were tested 8–14 months post-op in a motion analysis lab using a point cluster marker set and surface electrodes applied to the Vastus Medialis Oblique (VMO), Rectus Femoris (RF), Biceps Femoris (BF) and Semitendinosus (ST). 3D motion and force data and electromyography (EMG) data were collected simultaneously. Subjects were instructed to walk at a comfortable walking speed across a walkway, down a 12.5% downhill slope, and up a staircase. Five trials per activity were collected. Knee kinematics and kinetics were analyzed using BioMove (Stanford, Stanford, CA). The EMG dataset underwent full-wave rectification and was smoothed using a 300ms RMS window. Gait cycle was time normalized to 100%; relative voluntary contraction (RVC) was calculated by dividing the average activation during downhill walking by the maximum EMG value during level walking and multiplying by 100%. Results. There were no significant kinematic or kinetic differences between implant groups for level walking (p≥0.19). Both groups walked at 1.1 m/s on average during level and approximately 0.1 m/s slower during downhill walking, with no differences in speed (p= 0.91 and 0.77, respectively). For both ACL-S and BCR groups, gait changes from level to downhill walking were similar. For downhill walking, ACL-S subjects were significantly more variable (p<0.001) over the gait cycle for all measured kinematics and kinetics. During both downhill walking and stair climbing, the ACL-S group showed an external peak abduction moment (Fig. 1) significantly greater than that of the BCR group (p=0.05, 0.01). Also during stair climbing, ACL-S subjects showed trending higher peak knee adduction moments (p=0.14) and a more pronounced internal/external rotation pattern (Fig. 2) than BCR subjects. Since no peak kinematic/kinetic differences between groups during level walking exist, the mean maximum muscle activation from level walking was used for RVC normalization for other activities. On average, BCR subjects had lower maximum RVCs during downhill walking than the ACL-S subjects. Effect sizes were large for RF (d=0.94), ST (d=0.88), and VMO (d=1.21), the latter being borderline significant (p=0.05). Discussion. Previous studies on the natural knee have established that the ACL contains mechanoreceptors that improve stability of the knee joint. In this study, BCR subjects show less variable gait measures than subjects with traditional posterior cruciate retaining (ACL-S) TKR, possibly indicating more controlled contact kinematics. In addition, EMG results suggest lower muscle co-contraction during downhill walking, also implying greater knee stability in the BCR group. These results are preliminary and more subjects are needed for definite conclusions

Despite several anatomical and neurophysiological studies have demonstrated the sensory role of anterior cruciate ligament (ACL), it is still unclear how significant the absence of the ACL will affect knee proprioception. Also because some mechanoreceptors has been discovered in the injured bundle commonly resected during ACL reconstruction. In fact recently it has been observed that subjects with long standing ACL deficiency have not a knee joint pro-prioceptive deficit as measured by threshold of passive movement detenction and the ability to reproduce flex-ion angles, commonly accepted methods. The aim of this study was to investigate the possibility to recognize a sensorial and behavior impairment in ACL deficient knee. Through a computerized device the kinaesthetic data were collected from 120 sportsmen between 20–49 years (mean 32,4) affected by unilateral isolated ACL injury diagnosed with MRI and verified arthroscopically. The protocol consisted in four exercises, two bipodal on static and dynamic stance and two monopodal on healthy and injured lower limb. The balance index was divided in four areas on two dimensional plane for a qualitative assessment. The mathematical and statistical elaboration revealed on bipodal static test a significant and costant displacement on the left side indipendently by the injured side and age. The kinaesthetic awarness was confirmed also by a significant increase of balance index in all exercises. Further studies are necessary to a better knowledge as a possible new tool. In conclusion, this is the first report of a typical sensorial and behavior impairment in ACL deficient knee with intriguing clinical significance

Purpose of Study: The neck is the most mobile region of the spine, so neck muscles must provide stability, and control spinal movements. This action requires effective sensory and motor control mechanisms which, if impaired, may increase the risk of injury and pain. The aim of this study was to investigate sensorimotor function of neck muscles in healthy volunteers in order to provide normative data for comparative studies on neck pain patients. Methods: Thirty-one healthy volunteers participated. Position sense was evaluated using an electromagnetic tracking device (3-Space FASTRAK) to assess errors in repositioning the head in upright and flexed postures. Movement sense was assessed as time to detect head motion at 1°s-1 and 10°s-1, using a KinCom dynamometer. Latency of reflex muscle activation following rapid perturbation of the head was assessed bilaterally in trapezius and sternocleidomastoid muscles using surface electromyography. Results: Mean repositioning errors were 2.20±1.46° and 2.54±1.69° for upright and flexed postures respectively. Time to detect head motion was greater at 1°s-1 (739±349ms and 556±213ms, in extension and flexion respectively) compared to 10°s-1 (375±89ms and 377±66ms). Mean reflex latencies were shorter for trapezius (left: 77.9±43.4ms, right: 72.3±35.1ms) than for sternocledomastoid (left: 106.1±29.2ms, right: 102.7±35.9ms). Conclusion: Position sense in the cervical spine is superior to that reported in thoracolumbar regions, especially in flexed postures. Detection of head movement is velocity-dependent suggesting input occurs from both phasic and tonic mechanoreceptors. Reflex latencies were shorter for trapezius than for sternocledomastoid suggesting that stretch reflexes in trapezius play a predominant role in preventing excessive flexion of the cervical spine

The management of symptomatic single bundle Anterior Cruciate Ligament (ACL) ruptures is still a surgical dilemma. Preservation of the intact fibres of the ACL bundle is considered to be a possible source of reinnervation of the ACL autograft which reflects on better proprioceptive knee control after major ligament reconstruction. Results of a prospective study of 67 patients who had a double stranded but single bundle Anterior Cruciate Ligament (ACL) reconstruction for partial ACL ruptures are presented. There were 43 males and 24 females in this study with a mean age at the time of injury of twenty-five years (14 – 40). Eight played sport professionally and thirty-four played at a competitive level. A valgus twisting force was the most common mechanism of injury. Mean injury to operation time was 7.5 weeks (2–12). All procedures were done arthroscopically without using tourniquet, but using an arthroscopy pump and irrigation fluid containing adrenaline. The semitendinosis hamstring graft was used in all reconstructions. The mean follow-up period was 3.3 years (2–5.4). There was one major complication, who developed a reflex sympathetic dystrophy following a saphenous nerve neuroma. The Quality of Life (QOL) score was assessed using the Mohtadi index. The mean pre-operative QOL score of 30 (13–50) was improved to 93 (70–100) post-operatively. Fifty patients were able to return to their previous sporting level at a mean duration of 9 months (6–12). Preservation of mechanoreceptors by performing a double stranded, single bundle ACL reconstruction in partial ACL ruptures in high demand patients yields good results and enables early return to high demand sports

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.

Osteoarthritis (OA) is a highly prevalent degenerative joint disorder characterized by joint pain and physical disability. Aberrant subchondral bone induces pathological changes and is a major source of pain in OA. In the subchondral bone, which is highly innervated, nerves have dual roles in pain sensation and bone homeostasis regulation. The interaction between peripheral nerves and target cells in the subchondral bone, and the interplay between the sensory and sympathetic nervous systems, allow peripheral nerves to regulate subchondral bone homeostasis. Alterations in peripheral innervation and local transmitters are closely related to changes in nociception and subchondral bone homeostasis, and affect the progression of OA. Recent literature has substantially expanded our understanding of the physiological and pathological distribution and function of specific subtypes of neurones in bone. This review summarizes the types and distribution of nerves detected in the tibial subchondral bone, their cellular and molecular interactions with bone cells that regulate subchondral bone homeostasis, and their role in OA pain. A comprehensive understanding and further investigation of the functions of peripheral innervation in the subchondral bone will help to develop novel therapeutic approaches to effectively prevent OA, and alleviate OA pain.

Cite this article: Bone Joint Res 2022;11(7):439–452.

Introduction: Experimental pinealectomy in chickens shortly after hatch produces scoliosis with morphological characteristics similar to that of human idiopathic scoliosis (Coillard et al., 1996). The objective of this study was to develop a finite element model (FEM) incorporating vertebral growth to analyse how bone growth modulation by mechanical loading affects development of scoliosis in chicken. Materials and Methods: We have adapted the experimental set-up of Bagnall et al. (1999) to study spine growth of pinealectomised chickens. Three groups were followed for a period of six weeks:. wild-type (controls) (n=25);. shams (surgical controls) (n=20);. pinealectomised (n=76). The experimental data was used to adapt a FEM previously developed to simulate the scoliosis deformation process in human (Villemure et al. 2002). The FEM consists of 7 thoracic vertebrae and the first lumbar, the intervertebral discs and the zygapophyseal joints. The geometry was measured on specimens using a calliper. The material properties of human spines were used as initial approximation. The growth process included a baseline growth (0.130 mm/day) and a growth modulation behaviour proportional to the stress and to a sensitivity factor. It was implemented through an iterative process (from the 14th to the 28th day). Asymmetric loads (2–14 Nmm) were applied to represent different paravertebral muscle abnormalities influenced by the induced melatonin defect. Results: Within the pinealectomised group, 55% of the animals (n = 42) developed a scoliosis. In the FEM model, by varying the value of the applied moment, different scoliosis configurations were simulated. The resulting Cobb angle varied between 6° and 37°, while the maximal vertebral wedging appeared at T4 or T5 (range between 5° to 28°). A descriptive comparison of the simulation results with the experimental deformation patterns (n = 41; mean Cobb angle: 26°) was made as a preliminary validation. In 2 typical cases, the scoliotic shapes were quite similar to that seen in the scoliotic chickens. Discussion and Conclusion: The basic mechanisms by which the metabolism of the growing spine is affected by mechanical factors remain not well known, and especially the role of tissue remodelling and growth adaptation in scoliosis. The agreement between the experimental study and preliminary simulation results shows the feasibility of the model to simulate the scoliotic deformation process in pinealectomised chickens. When completely developed and validated this modelling approach could help investigating the pathomechanisms involved in the scoliotic deformation process. Especially, computer simulations could be used to complement bio-molecular and mechanobiological studies concerning the neuroendocrinal hypothesis implicating melatonin signalling dysfunction, which could trigger a complex cascade of molecules and mechanoreceptors leading to an accumulation of specific factors in specialised tissues (Moreau et al. 2004), directly or indirectly implicated in proprioception, and which can be implicated in the pathomechanisms of scoliotic deformities

Introduction: Insufficiency of poroelastic bone bending as the sole mechanism driving bone interstitial fluid flow (BIFF) to account for the shear stress required to activate mechanoreceptors on osteocytes and osteoblasts, has stimulated a search for alternative or complementary mechanisms in the quest for a comprehensive bone remodeling model. Some investigators, noting that a substantial amount of interstitial fluid is exchanged with blood and lymphatic capillaries, have suggested that this exchange may play a substantial role in both microtransport through the collagen matrix and lacunar-canalicular transport. In order to accept the vascular system as a significant source of transport driving BIFF, it must first be demonstrated that capillary filtration, the proc ess by which fluid is transported from blood vasculature, is sufficiently convective to drive interstitial percolation. We have proposed that while, as shown by Otter et al., resting transmural vascular pressures are sufficient to generate streaming potentials across cortical bone, it is likely that these forces must be complemented by muscle pump contractions during exercise to generate convective percolation flows which will develop the required mechanotransducer shear stress activation threshold. To determine a minimal baseline for a muscle pump driven BIFF (MPD-BIFF) model, we have investigated the role of repetitive skeletal muscle contractions, uncoupled from gravitational loading, on blood flow and capillary filtration in cortical bone of the rabbit tibia. We tested the hypothesis that these effects increased when the muscle pump was activated. Materials & Methods: The experimental model combined non-invasive, low magnitude transcutaneous neuromuscular stimulation (TENS), with real-time measurements from intravital microscopy (IVM) of optical bone chamber implants. Sling suspension of rabbits was utilized to eliminate gravitational reaction forces throughout TENS and data collection. TENS-induced muscle contraction forces were measured in situ, resultant bone strains were calculated, and systemic circulatory parameters were monitored, in order to eliminate these factors as contributors to blood flow changes. Blood flow rates and capillary filtration were measured by video-image analysis of 1 μm fluorescent microspheres and dextran-conjugated fluorescein isothiocyanate (FITC) and rhodamine (ITC) injected intravascularly during IVM. Bone formation, angiogenesis, and mineral apposition rates (tetracycline labelling) were analyzed from weekly microscopy pictures. Changes in bone mineral content and density were determined with CT scans obtained at implantation and termination. Results: Mechanical loading and baseline systemic circulation did not significantly contribute to the findings. Rhythmic muscle contractions were shown to increase cortical blood flow, rate of capillary filtration, rate of bone apposition, and angiogenesis. Discussion: The hypothesis was supported by the data. However, since no measurements were made on single capillaries, we could not confirm previous reports by this laboratory of convective extravasation

Objectives

Many in vitro studies have investigated the mechanism by which mechanical signals are transduced into biological signals that regulate bone homeostasis via periodontal ligament fibroblasts during orthodontic treatment, but the results have not been systematically reviewed. This review aims to do this, considering the parameters of various in vitro mechanical loading approaches and their effects on osteogenic and osteoclastogenic properties of periodontal ligament fibroblasts.

Objectives

The exact aetiology and pathogenesis of microdamage-induced long bone fractures remain unknown. These fractures are likely to be the result of inadequate bone remodelling in response to damage. This study aims to identify an association of osteocyte apoptosis, the presence of osteocytic osteolysis, and any alterations in sclerostin expression with a fracture of the third metacarpal (Mc-III) bone of Thoroughbred racehorses.

Introduction

The pathogenesis of rotator cuff disease (RCD) is complex and not fully understood. This systematic review set out to summarise the histological and molecular changes that occur throughout the spectrum of RCD.