Search

The growing field of regenerative rehabilitation has great potential to improve clinical outcomes for individuals with disabilities. However, the science to elucidate the specific biological underpinnings of regenerative rehabilitation–based approaches is still in its infancy and critical questions regarding clinical translation and implementation still exist. In a recent roundtable discussion from International Consortium for Regenerative Rehabilitation stakeholders, key challenges to progress in the field were identified. The goal of this article is to summarize those discussions and to initiate a broader discussion among clinicians and scientists across the fields of regenerative medicine and rehabilitation science to ultimately progress regenerative rehabilitation from an emerging field to an established interdisciplinary one. Strategies and case studies from consortium institutions—including interdisciplinary research centers, formalized courses, degree programs, international symposia, and collaborative grants—are presented. We propose that these strategic directions have the potential to engage and train clinical practitioners and basic scientists, transform clinical practice, and, ultimately, optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Since 1981, we have performed school scoliosis screening (SSS) using Moiré topography in Miyazaki, Japan and attained a certain result in detecting scoliosis. However, this screening system was discontinued due to cessation of repair and production of Moiré topographic equipment. The purpose of this study was to make clear both the results and the problems of SSS by Moiré topography on the basis of our past 33 years' experiences.Methods: The subjects were 689,293 students (5th grade boys in 200,329, 5th grade girls in 191,919, 8th grade boys in 151,351, and 8th grade girls in 145,694) who were screened by Moiré topography between 1981 and 2013. The number of students received SSS, the positive rate of Moiré topography, the discovery rate of scoliosis greater than 20°, the reference rate to the second screening, and the positive predictive value of Moiré topography to detect scoliosis greater than 20° were investigated.Results: The number of students received SSS achieved a peak in 1992. The positive rate of Moiré topography and the discovery rate of scoliosis were highest in 8th grade girls. The reference rates to the second screening were 49.8% in 5th grade students and 41.4% in 8th grade students. The positive predictive values were 2.1% in 5th grade students and 7.6% in 8th grade students.Conclusion: SSS by Moiré topography seemed to be effective in detecting scoliosis although both the positive predictive value and the reference rate to the second screening were low. [ABSTRACT FROM AUTHOR]

Objective: To examine the clinical impact of coexisting lateral osteoarthritis (OA) in knees with mild medial OA.Design: In patients with Kellgren/Lawrence (K/L) grade 2 OA in the medial compartment (n = 100; age: 56-89 years; 80.0% female), anteroposterior knee radiography was used to assess the presence of lateral OA, using grading systems from the Osteoarthritis Research Society International (OARSI) atlas and the K/L classification. The Japanese Knee Osteoarthritis Measure (JKOM), knee range of motion (ROM), and performance-based functional measures (10 m walk, timed up and go and five repetition chair stand maneuvers) were evaluated. The outcomes were compared between patients with and without lateral OA using an analysis of covariance (ANCOVA) or nonparametric rank ANCOVA. Furthermore, ordinal logistic regression analysis was performed, with responses on individual JKOM pain questionnaires as the outcomes and lateral OA as the predictor.Results: Knees with coexisting lateral OA had a significantly worse score of JKOM pain question compared with those without, after adjusting for covariates. The presence of lateral OA was significantly associated with knee pain while ascending/descending stairs and standing. These results were consistent between different definitions of the K/L and OARSI grading systems. The knee ROM and performance-based functional measures were not significantly different between patients with and without lateral OA.Conclusion: Knees with concomitant lateral and mild medial OA may be more symptomatic compared to those without lateral OA. These findings might help to define a clinically distinct subgroup based on a simple radiographic finding in mild knee OA. [ABSTRACT FROM AUTHOR]

The article describes the case of two siblings with neuropathic scoliosis due to Chiari malformation type I (CMI) with syringomyelia. CMI has been regarded as a sporadic condition without a heritable etiology, however, there have been several case reports determining familial aggregation and clustering of CMI, indicating a genetic basis.

Abstract: Background: In the lumbar spinal column, an annular disruption may be sealed after annulotomy to prevent further prolapse and instability. We investigated the biomechanical effects of various material properties of an injectable sealant Methods: We used a 3-dimensional, nonlinear, osteoligamentous, experimentally validated finite-element model of the L3−L5 spine segment to study annulotomies of varying sizes and locations in the L3−L4 annulus followed by replacement with isotropic sealants (plugs) with a Young''s modulus of 0.4, 2.0, 4.0, 6.0, and 40.0MPa. Annulotomies in the region of the posterior longitudinal ligament were studied with and without the ligament in place. Intact, destabilized, and repaired models were subjected to 400N compression and 12.7Nm moment in all loading modes to compute plug forces, plug stresses, motion characteristics, and annulus bulge. Results: Changes in sealant stiffness minimally affected the overall motion characteristics of the segment. Increases in shear stress and von Mises stress were proportional to the stiffness of the sealant. The von Mises stress was inversely proportional to plug size. Removal of portions of the posterior longitudinal ligament did not significantly alter motion between spinal segments or stress in the annulus fibrosus. Removal of portions of the ligament increased the disc bulge when plugs were less stiff. Intradiscal pressure decreased when an annulotomy was created. The sealant generally restored nucleus pressure to a degree proportionate to sealant stiffness. Conclusions: Minimizing sealant stresses as well as expulsion and separation forces should lead to a minimal Young''s modulus. Sealant materials with a Young''s modulus close to 6MPa are most appropriate. The allowable variation in material properties is reduced with increased annulotomy size. Removal of posterior longitudinal ligament only allows increased sealant bulge when the sealant''s modulus of elasticity is very low. This removal does not affect spinal unit biomechanics or annulus stress in annulotomy or annulotomy with sealant repair. [Copyright &y& Elsevier]

Purpose: For successful autologous osteochondral transplantation, it is important that the cartilage in an implanted plug provide histologic replacement of damaged cartilage with cartilage that is structurally and mechanically normal. The purpose of this study was to investigate whether the press-fit technique reconstructs the normal hyaline cartilage and provides acoustic stiffness equal to that of normal intact cartilage. Methods: In 36 rabbits an osteochondral plug, 6 mm in diameter, was removed from the right patellar groove and grafted into a recipient hole, 5 mm in diameter, in the left patellar groove. Specimens at 2, 4, 8, 12, 24, and 52 weeks postoperatively were assessed by macroscopic and histologic observation and by use of an ultrasonic system. The ultrasonic acoustic stiffness, acoustic surface irregularity, and acoustic thickness of the implanted cartilage were examined and compared with normal intact cartilage. Results: The gross appearance of the implanted cartilage was glossy, maintained good surface smoothness, and survived well throughout the observation period. The cartilage recovered histologic features of hyaline cartilage. The acoustic stiffness decreased up to 12 weeks and then increased at 24 and 52 weeks after surgery. The acoustic stiffness at 8 or 12 weeks was significantly lower (acoustically softer) than that of control cartilage (P < .001). The acoustic stiffness at 52 weeks was equal to that of the control. The difference in acoustic surface irregularity was not significant. The acoustic thickness at 8 weeks was higher (acoustically thicker) than that of the control (P < .01). Conclusions: Although the reason acoustically soft cartilage in plugs becomes acoustically stiff and whether the histology of the implanted cartilage had recovered completely remain unclear, the acoustic stiffness recovered to normal control values by 52 weeks postoperatively. Clinical Relevance: Postoperative care for up to 12 weeks should be taken after autologous osteochondral transplantation. [ABSTRACT FROM AUTHOR]

Objective To examine the association between pedometer-based ambulatory physical activity (PA) and physical function in patients with knee osteoarthritis (OA). Design Cross-sectional observational study. Setting Institutional practice. Participants Participants in orthopedic clinics (N=207; age, 56–90y; 71.5% women) with diagnosed radiographic knee OA (Kellgren/Lawrence [K/L] grade ≥1). Interventions Not applicable. Main Outcome Measures Ambulatory PA was objectively measured as steps per day. Physical function was assessed using the Japanese Knee Osteoarthritis Measure (JKOM) functional subcategory, 10-m walk, Timed Up and Go (TUG), and 5-repetition chair stand (5CS) tests. Results Patients walking <2500 steps/d had a low level of physical function with a slower gait speed, longer TUG time, and worse JKOM functional score compared with those who walk 2500 to 4999, 5000 to 7499, and ≥7500 steps/d adjusted for age, sex, body mass index [BMI], and K/L grade. Ordinal logistic regression analysis revealed that steps per day (continuous) was associated with better physical function adjusted for age, sex, BMI, and K/L grade. These relationships were still robust in sensitivity analyses that included patients with K/L grades ≥2 (n=140). Conclusions Although increased ambulatory PA had a positive relationship with better physical function, walking <2500 steps/d may be a simple indicator for a decrease in physical function in patients with knee OA among standard PA categories. Our findings might be a basis for counseling patients with knee OA about their ambulatory PA and for developing better strategies for improving physical function in sedentary patients with knee OA. [ABSTRACT FROM AUTHOR]

Objective: Moderate mechanical stress generated by normal joint loading and movement is essential for the maintenance of healthy articular cartilage. However, the effects of reduced loading caused by the absence of weight bearing or joint motion on articular cartilage and subchondral bone is still poorly understood. We aimed to characterize morphological and metabolic responses of articular cartilage and subchondral bone to decreased mechanical stress in vivo.Methods: Mice were subjected to periods of hindlimb unloading by tail suspension or external fixation of the knee joints. The articular surface was observed with digital microscope and the epiphyseal bone was assessed by micro-CT analysis. Articular cartilage and subchondral bone were further evaluated by histomorphometric, histochemical, and immunohistochemical analyses.Results: The joint surface was intact, but thickness of both the total and uncalcified layer of articular cartilage were decreased both after joint unloading and immobilization. Subchondral bone atrophy with concomitant marrow expansion predisposed osteoclast activity at bone surface to invade into cartilaginous layer. Uncalcified cartilage showed decreased aggrecan content and increased aggrecanase expression. Alkaline phosphatase (ALP) activity was increased at uncalcified cartilage, whereas decreased at calcified cartilage. The distributions of hypertrophic chondrocyte markers remained unchanged.Conclusion: Thinning of articular cartilage induced by mechanical unloading may be mediated by metabolic changes in chondrocytes, including accelerated aggrecan catabolism and exquisitely modulated matrix mineralization, and cartilage matrix degradation and resorption by subchondral osteoclasts. Cartilage degeneration without chondrocyte hypertrophy under unloading condition indicate the possible existence of mechanism which is different from osteoarthritis pathogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Autogenous osteochondral grafts have recently become popular for use in small, isolated, contained articular cartilage defects. We treated a 26-year-old man who had a cartilage defect measuring 10 × 20 mm in the anteromedial area of the right talus. We performed multiple osteochondral grafting of the lesion with medial malleolar osteotomy from a donor site in the ipsilateral knee joint. Two years after the operation, the patient’s ankle pain recurred and the bony lesion in the talus also became osteolytic. Because we believed that only the cartilaginous portions of the osteochondral plugs grafted 2 years previously were fully fixed and viable, and that recurrence had occurred at the bony portions, at reoperation we performed curettage of the bony lesions and grafted iliac bone into the lesions with fenestration of the inferomedial ankle joint cartilage, not grafted plug cartilage. Therefore, probably because of overuse, the bony lesion in the talus had recurred 2 years after the first operation, but the grafted hyaline cartilage had survived. Autogenous osteochondral grafting into the talus, unlike the knee joint, should be done with care to ensure there is no sclerotic bone surrounding the lesion in patients with long-standing symptoms and recurrence of bony lesions. [Copyright &y& Elsevier]

The aim of this study was to verify the effects of ultrasound on dorsal root ganglion (DRG) neurons at the injury site in a rat model of sciatic nerve crush injury. We evaluated the mRNA expression of neurotrophic and pro-inflammatory factors by quantitative reverse transcription polymerase chain reaction 7 and 14 d post-injury. We also evaluated the protein levels of brain-derived neurotrophic factor (BDNF) 7 and 14 d post-injury. Axon regeneration and motor function analyses were performed 21 days after injury to confirm the facilitative effect of ultrasound on nerve regeneration. In the ultrasound group, BDNF and interleukin-6 mRNA expression of the DRG was significantly reduced 7 d post-injury. Compared with the sham group, the BDNF protein expression of the DRG in the ultrasound group remained at a higher level 14 d post-injury. Motor function, myelinated fiber density and myelin sheath thickness were significantly higher in the ultrasound group than in the sham group 21 d post-injury. These results indicate that ultrasound therapy at the injury site promotes nerve regeneration and modulates gene and protein expression in the DRG of a rat model of a sciatic nerve crush injury. [ABSTRACT FROM AUTHOR]

This study was aimed at identifying the optimal initiation time of ultrasound (US) therapy for peripheral nerve regeneration after axonotmesis. Thirty-six rats with sciatic nerve crush injury were divided into four groups that received US irradiation initiated 1, 7 or 14 d after injury, or sham stimulation for 4 wk. Motor function analysis was conducted weekly; however, there was no significant improvement attributed to US treatment. Four weeks after injury, compound muscle action potential amplitude values of the group in which US irradiation was initiated 1 d after the injury exhibited significant improvement compared with the sham stimulation group. In addition, myelin sheath thickness was significantly greater in the 1-d group than in other groups. These results indicate that US treatment initiated 1 d after peripheral nerve injury promotes maximum regeneration. [ABSTRACT FROM AUTHOR]

Abstract: This study investigated the method of estimating the fatigue strength of small notched Ti–6Al–4V specimen using the theory of critical distance that employs the stress distribution in the vicinity of the notch root. Circumferential-notched round-bar fatigue tests were conducted to quantify the effects of notch radius and notch depth on fatigue strength. The fatigue tests show that the larger notch radius increases the fatigue strength and the greater notch depth decreases the fatigue strength. The theory of critical distance assumes that fatigue damage can be correctly estimated only if the entire stress field damaging the fatigue fracture process zone is taken into account. Critical distance stress is defined as the average stress within the critical distance from notch root. The region from the notch root to the critical distance corresponds to the fatigue fracture process zone for crack initiation. It has been found that a good correlation exists between the critical distance stress and crack initiation life of small notched specimens if the critical distance is calibrated by the two notched fatigue failure curves of different notch root radii. The calibrated critical distances did not vary clearly over a wide range of fatigue failure cycles from medium-cycle low-cycle fatigue regime to high-cycle fatigue regime and have an almost constant value. This critical distance corresponds to the size of crystallographic facet at the fatigue crack initiation site for the wide range of fatigue cycles. [Copyright &y& Elsevier]

The aim of this study was to determine that low-intensity pulsed ultrasound (LIPUS) at an intensity of 140 mW/cm2 promotes functional and histologic improvements in sciatic nerve crush injury in a rat model and to investigate changes over time in relevant growth factors and receptors, exploring the mechanism of LIPUS in the recovery process after injury. Toe angle in the toe-off phase, regenerative axonal length, myelinated nerve fiber density, diameter of myelinated nerve fiber, axon diameter and myelin sheath thickness were significantly higher in the LIPUS group than in the sham group. Gene and protein expression of brain-derived neurotrophic factor (BDNF) was upregulated in the LIPUS group. In conclusion, LIPUS contributed to rapid functional and histologic improvement and upregulated BDNF expression after sciatic nerve crush injury in rats. [ABSTRACT FROM AUTHOR]

This study was aimed at investigating the use of ultrasound parameters obtained non-invasively through soft tissue (ST) to evaluate degeneration in cartilage and subchondral bone (SB) in the human knee. We developed a 3-D ultrasound system and introduced the ratio parameters Rcb and RcbT to suppress the attenuation effect in the ST or in both the ST and cartilage. As reference measurements, the grade for cartilage by visual judgment (Gsum) and ultrasound parameters for the cartilage and the SB were directly evaluated under arthroscopy. Rcb correlated significantly with Gsum (rs = -0.63) and with the corresponding parameter obtained directly under arthroscopy (r = 0.55). RcbT also correlated significantly with Gsum (rs = -0.46) but was not superior to Rcb. Rcb is considered to be an efficient parameter that reflects the total degeneration in both the cartilage and SB, including the information on cartilage thickness. [ABSTRACT FROM AUTHOR]

Osteoporosis-related fractures are a major public health problem. Mechanobiological stimulation utilizing low-intensity pulsed ultrasound (LIPUS) is the most widely accepted modality for accelerating fracture healing. However, recent evidence has demonstrated the ineffectiveness of LIPUS, and the biophysical mechanisms of ultrasound-induced bone formation also remain elusive. Here, we demonstrate that ultrasound at a higher intensity than LIPUS effectively accelerates fracture healing in a mouse osteoporotic fracture model. Higher-intensity ultrasound promoted chondrogenesis and hypertrophic differentiation of chondrocytes in the fracture callus. Higher-intensity ultrasound also increased osteoblasts and newly formed bone in the callus, resulting in accelerated endochondral ossification during fracture healing. In addition, we found that accelerated fracture healing by ultrasound exposure was attenuated when the mechanosensitive ion channel Piezo1 was inhibited by GsMTx4. Ultrasound-induced new bone formation in the callus was attenuated in fractured mice treated with GsMTx4. Similar results were also confirmed in a 3D osteocyte-osteoblast co-culture system, where osteocytic Piezo1 knockdown attenuated the expression of osteoblastic genes after ultrasound exposure. Together these results demonstrate that higher-intensity ultrasound than clinically used LIPUS can accelerate endochondral ossification after fractures. Furthermore, our results suggest that mechanotransduction via Piezo1 mediates ultrasound-stimulated fracture healing and bone formation. • Higher-intensity ultrasound than low-intensity pulsed ultrasound accelerates fracture healing. • Higher-intensity ultrasound promotes chondrogenesis and osteogenesis in fracture callus. • Mechanosensitive ion channel Piezo1 in osteocytes senses ultrasound acoustic waves. • Piezo1 mediates ultrasound-stimulated fracture healing and bone formation. [ABSTRACT FROM AUTHOR]

The aim of this study was to identify ultrasound parameters reflecting subchondral porosity (Po), subchondral plate thickness (Tpl) and bone volume fraction at the trabecular bone region (BV/TVTb). Sixteen osteoarthritic human lateral femoral condyles were evaluated ex vivo using a 15-MHz pulsed-echo ultrasound 3-D scanning system. The cartilage-subchondral bone (C-B) surface region (layer 1) and inner subchondral bone region (layer 2) were analyzed; we newly introduced entropy (ENT) and correlation (COR) of ultrasound texture parameters of the parallel (x) or perpendicular (z) direction to the C-B interface for this analysis. Po, Tpl and BV/TVTb were evaluated as reference measurements using micro-computed tomography. ENTL1x (ENT of layer 1, x-direction) and ENTL1z were significantly correlated with Po (both r values = 0.58), CORL2x with Tpl (r = -0.73) and CORL2z with BV/TVTb (r = -0.66). These are efficient indicators of the characteristics of osteoarthritis-related subchondral bone; the other texture parameters were not significant. [ABSTRACT FROM AUTHOR]

This cross-sectional study investigated (i) the association of varus thrust during gait with the presence of patellofemoral osteoarthritis (PFOA) in patients with medial knee osteoarthritis (OA) and (ii) patellar alignment in the knees with varus thrust. Participants from orthopedic clinics (n=171; mean age, 73.4 years; 71.9% female) diagnosed with radiographic medial knee OA (Kellgren/Lawrence [K/L] grade ≥1) were included in this study, and underwent gait observation for varus thrust assessment using 2D video analysis. A radiographic skyline view was used to assess the presence of medial PFOA using the grading system from the Osteoarthritis Research Society International Atlas. The tibiofemoral joint K/L grade, patellar alignment (i.e., lateral shift and tilting angle), and knee pain intensity were also evaluated as covariates. Thirty-two (18.7%) of 171 patients exhibited varus thrust and they presented significantly higher knee pain (46.0±3.04mm vs. 32.4±2.73mm; P=0.024), a lower patellar tilting angle (P=0.024), and a higher prevalence of PFOA compared with those without varus thrust. A logistic regression analysis with adjustment of covariates showed that varus thrust was significantly associated with higher odds of the presence of mixed and medial PFOA, and trended to significantly associate with any PFOA, including lateral PFOA. This indicates that varus thrust was associated with PFOA in a compartment-nonspecific manner in patients with medial knee OA. Varus thrust may represent a clinical disease feature of more advanced and multicompartmental disease. [ABSTRACT FROM AUTHOR]

We aimed to quantitatively investigate the relationship between amplitude-based pulse-echo ultrasound parameters and early degeneration of the knee articular cartilage. Twenty samples from six human femoral condyles judged as grade 0 or 1 according to International Cartilage Repair Society grading were assessed using a 15-MHz pulsed-ultrasound 3-D scanning system ex vivo. Surface roughness (Rq), average collagen content (A1) and collagen orientation (A12) in the superficial zone of the cartilage were measured via laser microscopy and Fourier transform infrared imaging spectroscopy. Multiple regression analysis with a linear mixed-effects model (LMM) revealed that a time-domain reflection coefficient at the cartilage surface (Rc) had a significant coefficient of determination with Rq and A12 (RLMMm2=0.79); however, Rc did not correlate with A1. Concerning the collagen characteristic in the superficial zone, Rc was found to be a sensitive indicator reflecting collagen disorganization, not collagen content, for the early degeneration samples. [ABSTRACT FROM AUTHOR]

We investigated the effect of low-intensity pulsed ultrasound (LIPUS) treatment combined with mesenchymal stromal cell (MSC) injection for cartilage repair and subchondral bone reconstitution for treatment of osteochondral defects. An osteochondral defect was created on both femur grooves of Wistar rats. Four weeks later, bone marrow MSCs were injected into the right knee joint. The rats were divided into two intervention groups: without or with LIPUS irradiation. Cartilage repair was evaluated histologically based on the Wakitani cartilage repair score. Subchondral bone reconstitution was evaluated as bone volume (BV)/tissue volume (TV) by micro-computed tomography analysis. MSC injection improved the cartilage repair score, and LIPUS irradiation improved BV/TV. Combination treatment promoted both cartilage repair and BV/TV improvement. Thus, MSC injection combined with LIPUS irradiation is more effective than either treatment alone in promoting concurrent cartilage repair and subchondral reconstitution. [ABSTRACT FROM AUTHOR]

The effects of intermittent hypergravity on gait alterations and hindlimb muscle atrophy in rats induced by 2 weeks of simulated microgravity were investigated. Rats were submitted to hindlimb unloading for 2 weeks (unloading period), followed by 2 weeks of reloading (recovery period). During the unloading period, animals were subjected to the following treatments: (1) free in cages (Control); (2) continuous unloading (UL); (3) released from unloading for 1 hour per day (UL + 1G); (4) hypergravity for 1 h per day using a centrifuge for small animals (UL + 2G). The relative weights of muscles to the whole body weight and kinematics properties of hindlimbs during gait were evaluated. UL rats walked with their hindlimbs overextended, and the oscillation of their limb motion had become narrowed and forward-shifted after the unloading period, and this persisted for at least 2 weeks after the termination of unloading. However, these locomotor alterations were attenuated in rats subjected to UL + 2G centrifugation despite minor systematic changes in muscle recovery. These findings indicate hypergravity application could counteract the adverse effects of simulated or actual microgravity environments. [ABSTRACT FROM AUTHOR]

Abstract: The effect of low-intensity pulsed ultrasound (LIPUS) on articular cartilage metabolism has been characterized. However, the effect of LIPUS intensity on articular cartilage degradation factors remains unknown. This study aimed to investigate the immediate effect of LIPUS at several intensities on cultured chondrocytes treated with interleukin-1β (IL-1β) to induce an inflammatory response and on articular cartilage explants. Cultured chondrocytes and articular cartilage explants were treated by LIPUS at intensities of 0, 7.5, 30 and 120 mW/cm2 or 0, 27 and 67 mW/cm2, respectively. mRNA analysis revealed that LIPUS inhibited induction of MMP13 mRNA expression by 100 pg/mL IL-1β in cultured chondrocytes in an intensity-dependent manner. LIPUS also inhibited MMP13 and MMP1 mRNA expression in articular cartilage explants. Our results indicate that LIPUS may potentially protect articular cartilage by inhibiting MMP mRNA expression in an intensity-dependent manner and should thus be considered a useful candidate for daily treatment of OA. [Copyright &y& Elsevier]