Key Points Question Does early surgical treatment yield better motor recovery than delayed surgical treatment for patients with preexisting cervical canal stenosis sustaining acute traumatic spinal cord injury? Findings In this randomized clinical trial that included 72 patients with motor-incomplete cervical spinal cord injury, there was no statistically significant difference between groups in mean improvement in American Spinal Injury Association motor score, total score in the spinal cord independence measure, or patients’ ability to walk at 1 year. Early surgical treatment was associated with higher motor scores than delayed surgical treatment in the first 6 months. Meaning These findings suggest that among patients with motor-incomplete cervical spinal cord injury, early surgical treatment did not significantly improve motor recovery at 1 year compared with delayed surgical treatment but showed accelerated recovery.

BACKGROUND:Chronic low back pain (CLBP) is a major cause of chronic pain with nociceptive, neuropathic or both pain components, and a leading cause of disability. The objectives of this study were to determine the impact of background factors including previous use of drugs on outcomes of pharmacological therapy for CLBP in a nationwide multicenter prospective study. METHODS:The subjects were 474 patients (male: 41.9%, median age: 73.0) with CLBP. Background factors that could influence outcomes after pharmacological treatment for 6 months were examined: age, gender, body mass index (BMI), duration of CLBP, osteoporosis, history of spinal surgery, history of malignant tumor, smoking habit, employment status (yes or no), exercise habit (frequency), number of live-in family members, having something to do for pleasure, Center for Epidemiologic Studies depression scale (CES-D) score, and medication at baseline. Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS) for LBP, JOA Back Pain Evaluation Questionnaire (JOABPEQ), Roland-Morris Disability Questionnaire (RDQ), Short-form 8-item health survey (SF-8), and EQ-5D were used for evaluation at baseline and after 6 months. Multivariate linear regression models were used in statistical analysis. RESULTS:Drugs for neuropathic pain at baseline (p < 0.001), Tramacet® at baseline (p < 0.05), weak opioids at baseline (p < 0.05), older age (p < 0.001), long disease duration (p < 0.005), history of spinal surgery (p < 0.001), and smoking habit (p < 0.001) had significant negative effects on outcomes. Employment (p < 0.05), exercise habit (p < 0.05), and CED-D at baseline (p < 0.001) had positive effects on outcomes. CONCLUSIONS:This is the first study to identify significant prognostic factors for outcomes of pharmacological treatment of CLBP. The neuropathic pain component of CLBP at baseline is a major significant negative factor for most outcomes involving improved pain, activities of daily life, and quality of life. Treatment strategies developed with consideration of these factors may be advantageous for recovery from CLBP.

Background There is considerable interest in using cell sheets for the treatment of various lesions as part of regenerative medicine therapy. Cell sheets can be prepared in temperature-responsive culture dishes and applied to injured tissue. For example, cartilage-derived cell sheets are currently under preclinical testing for use in treatment of knee cartilage injuries. The additional use of cryopreservation technology could increase the range and practicality of cell sheet therapies. To date, however, cryopreservation of cell sheets has proved impractical. Results Here we have developed a novel and effective method for cryopreserving fragile chondrocyte sheets. We modified the vitrification method previously developed for cryopreservation of mammalian embryos to vitrify a cell sheet through use of a minimum volume of vitrification solution containing 20% dimethyl sulfoxide, 20% ethylene glycol, 0.5 M sucrose, and 10% carboxylated poly-L-lysine. The principal feature of our method is the coating of the cell sheet with a viscous vitrification solution containing permeable and non-permeable cryoprotectants prior to vitrification in liquid nitrogen vapor. This method prevented fracturing of the fragile cell sheet even after vitrification and rewarming. Both the macro- and microstructures of the vitrified cell sheets were maintained without damage or loss of major components. Cell survival in the vitrified sheets was comparable to that in non-vitrified samples. Conclusions We have shown here that it is feasible to vitrify chondrocyte cell sheets and that these sheets retain their normal characteristics upon thawing. The availability of a practical cryopreservation method should make a significant contribution to the effectiveness and range of applications of cell sheet therapy.

Introduction: Chronic low back pain (CLBP) is a leading cause of disability, yet there is limited high-quality evidence to identify the most suitable pharmacological therapy. The purpose of this Japanese nationwide, multicenter, prospective study was to compare the effectiveness of four representative drug therapies―acetaminophen, celecoxib, loxoprofen, and a tramadol and acetaminophen (T+A) combination drug―to establish evidence for a drug of choice for CLBP. Methods: Patients with CLBP (N=471) received one of the four treatments and were evaluated, prospectively and comprehensively, once every month for six months using a visual analog scale (VAS) for LBP, the Japanese Orthopedic Association (JOA) score, the JOA Back Pain Evaluation Questionnaire (JOABPEQ), the Roland-Morris Disability Questionnaire (RDQ), the EuroQol five-dimensions three-levels (EQ-5D-3L), and the Short Form-8 item health survey (SF-8). We conducted multivariable linear regression analyses of the four drugs at 1 and 6 months after drug allocation. Differences with P<0.05 were considered statistically significant. Results: Patients who received acetaminophen showed a significant improvement from baseline in the mental health subscale of the JOABPEQ at one month (P=0.02) and the JOA score at six months (P<0.01). None of the other outcome measures among the four drugs differed significantly. Across groups, all outcome measures, except the mental component summary (MCS) score of the SF-8, improved equivalently, although most measurements showed no obvious cumulative effect over six months. The MCS score of the SF-8 decreased gradually over six months in all groups. Conclusions: Most of the outcome measures among the treated groups were not significantly different, indicating similar treatment effects of the four drugs for CLBP. Our study indicated the limit of each outcome measure for evaluating the patient status, suggesting that a single outcome measure is insufficient to reflect treatment effectiveness.

Introduction Chronic low back pain (CLBP) is a major health burden worldwide and requires patient satisfaction with treatment. Consultation length can be an important factor in patient satisfaction, but few studies have investigated the impact of consultation length on satisfaction in patients with CLBP. This study tried to elucidate the impact of consultation length on clinical outcomes in patients with CLBP. Methods This study is part of an analysis using the database of the nationwide, multicenter cohort for CLBP performed by the Project Committee of the Japanese Society for Spine Surgery and Related Research. A total of 427 patients aged 20-85 years (median age, 73.0 years; female, 58.6%) with CLBP were prospectively followed-up monthly for 6 months. Multivariable nonlinear regression analyses were performed to assess the effect of consultation length on outcome measures including subjective satisfaction score, EuroQol 5-dimension, Japanese Orthopaedic Association (JOA) score, Roland-Morris Disability Questionnaire, JOA Back Pain Evaluation Questionnaire, visual analog scale (VAS) and Medical Outcome Survey short-form 8-item health survey that evaluated at the next phase. Furthermore, we assessed whether the effect of consultation length on patient satisfaction was modified by the baseline Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP) score for patient and physician versions. Results VAS for CLBP was the only score that correlated significantly with consultation length (P = 0.018). Satisfaction score showed a significant positive correlation with consultation length in patients with the highest baseline BS-POP scores (P < 0.2). Moreover, consultation lengths more than 7.6 min and 15.1 min offered increase of satisfaction if patients show the highest BS-POP scores on patient and physician versions, respectively. Conclusions These findings suggest that a sufficiently long consultation is an important factor for subjective satisfaction in the patients with CLBP, particularly in patients with psychological problems.

Current cartilage regenerative therapies are not fully effective in treating osteoarthritis of the knee (OAK). We have developed chondrocyte sheets for autologous transplantation and tested these in in vitro and in vivo preclinical studies, and have reported that the transplantation of chondrocyte sheets promoted hyaline cartilage repair in rat, rabbit, and minipig models. However, autologous transplantation of chondrocyte sheets has yet to be reported in humans. Here, we report our combination therapy in which conventional surgical treatment for OAK, is followed by autologous chondrocyte sheet transplantation for cartilage repair. Eight patients with OAK and cartilage defects categorized arthroscopically as Outerbridge grade III or IV receive the therapy. Patients are thoroughly assessed by preoperative and postoperative X-rays, magnetic resonance imaging (MRI), arthroscopy, Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score (LKS), and a laser-induced photoacoustic method to assess cartilage viscoelasticity. Arthroscopic biopsies of all patients are performed 12 months after transplantation for histological evaluation. The properties of the chondrocyte sheets are evaluated using gene expression analysis to investigate the ability to predict the clinical and structural outcomes of the therapy. For this small initial longitudinal series, combination therapy is effective, as assessed by MRI, arthroscopy, viscoelasticity, histology, and the clinical outcomes of KOOS and LKS. Gene marker sets identified in autologous chondrocyte sheets may be predictive of the overall KOOS, LKS, and histological scores after therapy. These predictive gene sets may be potential alternative markers for evaluating OAK treatment.

BACKGROUND:Chronic low back pain is a major health problem that has a substantial effect on people's quality of life and places a significant economic burden on healthcare systems. However, there has been little cost-effectiveness analysis of the treatments for it. Therefore, the purpose of this prospective observational study was to evaluate the cost-effectiveness of the pharmacological management of chronic low back pain. METHODS:A total of 474 patients received pharmacological management for chronic low back pain using four leading drugs for 6 months at 28 institutions in Japan. Outcome measures, including EQ-5D, the Japanese Orthopaedic Association (JOA) score, the JOA back pain evaluation questionnaire (BPEQ), the Roland-Morris Disability Questionnaire, the Medical Outcomes Study SF-8, and the visual analog scale, were investigated at baseline and every one month thereafter. The incremental cost-utility ratio (ICUR) was calculated as drug cost over the quality-adjusted life years. An economic estimation was performed from the perspective of a public healthcare payer in Japan. Stratified analysis based on patient characteristics was also performed to explore the characteristics that affect cost-effectiveness. RESULTS:The ICUR of pharmacological management for chronic low back pain was JPY 453,756. Stratified analysis based on patient characteristics suggested that the pharmacological treatments for patients with a history of spine surgery or cancer, low frequency of exercise, long disease period, low scores in lumbar spine dysfunction and gait disturbance of the JOA BPEQ, and low JOA score at baseline were not cost-effective. CONCLUSIONS:Pharmacological management for chronic low back pain is cost-effective from the reference willingness to pay. Further optimization based on patient characteristics is expected to contribute to the sustainable development of a universal insurance system in Japan.

We have reported the usefulness of chondrocyte sheets on articular cartilage repair in animal experiments. Here, we investigated the regenerative effects of EP2 signalling with or without chondrocyte sheets. Forty-five rabbits were used, with six rabbits in each of the six groups and nine rabbits for chondrocytes and synovial cells harvesting to fabricate triple-layered chondrocyte sheets: osteochondral defect only (control, Group A), EP2 agonist (Group B), EP2 antagonist (Group C), chondrocyte sheets (Group D), EP2 agonist and chondrocyte sheets (Group E), and EP2 antagonist and chondrocyte sheets (Group F). After surgery, the weight distribution ratio was measured as an indicator of pain alleviation. Injections of the EP2 agonist or EP2 antagonist were given from 4 weeks after surgery. The rabbits were sacrificed at 12 weeks, and the repaired tissues were evaluated for histology. The weight distribution ratio and International Cartilage Repair Society grading were as follows: Group A: 40.5% ± 0.2%, 14.8 ± 0.5; Group B: 43.4% ± 0.7%, 25.4 ± 0.8; Group C: 38.7% ± 0.7%, 13.7 ± 0.3; Group D: 48.6% ± 0.6%, 40.2 ± 0.5; Group E: 49.1% ± 0.3%, 40.5 ± 0.4; and Group F; 46.8% ± 0.4%, 38.7 ± 0.5. Significant differences in histology and pain alleviation were observed between groups except between Groups A and C, between Groups D and E, and between Groups D and F. These findings show that the intra-articular administration of an EP2 agonist achieved pain alleviation and tissue repair. However, no synergistic effect with chondrocyte sheets was observed.

The effect of using vitrified–thawed chondrocyte sheets on articular cartilage repair was examined because the methods for storing chondrocyte sheets are essential for allogeneic chondrocyte sheet transplantation. Six Japanese white rabbits were used as sources of articular chondrocytes and synovial cells. Chondrocytes were harvested from the femur, and synovial cells were harvested from inside the knee joints. After coculture of the chondrocytes with synovial cells, triple‐layered chondrocyte sheets were fabricated. Eighteen rabbits were used, with six rabbits in each of three groups: osteochondral defect only (control, group A); chondrocyte sheets (group B); and vitrified–thawed chondrocyte sheets (group C). An osteochondral defect was created on the femur. After transplantation, the weight distribution ratio of the undamaged and damaged limbs was measured as a pain‐alleviating effect. The rabbits were euthanized at 12 weeks, and the transplanted tissues were evaluated for histology (Safranin O staining and immunostaining) using the International Cartilage Repair Society grading system. For both evaluations, significant differences were observed between groups A and B, and between groups A and C (p < 0.05). No significant differences were observed between groups B and C. Thus, pain‐alleviating effects and tissue repair were achieved using vitrified–thawed chondrocyte sheets. Copyright © 2017 John Wiley & Sons, Ltd.

Platelet-activated serum (PAS) was collected from rabbits. This contains high concentrations of growth factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-BB, and transforming growth factor-beta (TGF-). PAS was injected into the knee joints of Japanese White rabbits subjected to anterior cruciate ligament transection (ACL-T) to investigate its therapeutic effects on articular cartilage. The effect of Avastin (an anti-VEGF monoclonal antibody) on VEGF expression was also investigated. The levels of VEGF, PDGF-BB, and TGF- in PAS, platelet-rich plasma (PRP) and autologous serum from untreated rabbits were analysed by enzyme-linked immunosorbent assays. The samples (n=24 rabbits) were divided into control (C), PAS (S), Avastin (A) and PAS+Avastin (S+A) treatment groups. Intra-articular injections were administered weekly for 7weeks after ACL-T, during which the weight distribution ratios of the damaged limbs were evaluated. Histological evaluation was performed 12weeks after ACL-T using Mankin score. The VEGF, PDGF-BB and TGF- expression levels were significantly higher (P<0.05) in the PAS than in the PRP or autologous serum samples. The weight distribution ratios of damaged limbs improved significantly after ACL-T in all treatment groups (P<0.05). The proximal medial, distal medial and lateral aspects of joints in the treatment groups showed significant differences in Mankin scores compared with controls (P<0.05). The damaged limb weight distribution ratios, Mankin scores and articular cartilage structure did not differ significantly among the three treatment groups, which all showed significant improvements in structure compared with controls. Copyright (c) 2017 John Wiley & Sons, Ltd.

We report on a case of a mobile schwannoma of the cauda equina. The patient was a 24-year-old woman who visited our hospital with the chief complaints of low back pain and numbness of the right leg. A tumor was noted from the L2 midbody level to the L3 upper endplate on preoperative MRI and myelogram. During the surgery, a right L2 hemilaminectomy was performed, and the dura was incised, but no tumor was founded in the surgical field, and this was noted as a missing tumor. Intraoperative myelography showed that the tumor had moved to the adjacent vertebra on the caudal side. Myelography applied again to the caudal side of the mobile tumor. Then, the tumor had moved upward, and could be excised without an additional laminectomy.

Transplantation of activated nucleus pulposus (NP) cells obtained by coculturing NP cells and bone marrow mesenchymal stromal cells having cell-to-cell contact has been shown to be effective in animal models and, more recently, in human clinical trials. If the NP cells can be cryopreserved, then autologous cell transplantation could be offered to patients as and when required. In a previous study, we confirmed that activated NP cells can be obtained by coculturing with mesenchymal cells after cryopreservation. However, the in vivo effects of cell transplantation therapy using activated NP cells prepared from cryopreserved cells are not known. In this in vivo canine model, we compared indicators of disc degeneration in animals that received transplanted activated normal NP cells, transplanted cryopreserved NP cells, and no cell transplantation after induction of disc degeneration. The intervertebral disc height on radiographs and T2-weighted magnetic resonance imaging were significantly higher in both cell transplantation groups compared with the degenerated disc group. Macroscopic and histological findings demonstrated attenuated disc degeneration in the two transplanted groups. Intense staining of proteoglycan and collagen type II was seen in green fluorescent protein-labelled transplanted cells, which suggested that the cells had survived and were functioning after transplantation. No significant differences were observed between the two transplanted groups. Transplanted activated cryopreserved NP cells induced a similar attenuation of intervertebral disc degeneration as that of conventionally activated NP cells. These findings suggest that the use of cryopreserved cells specific to a patient's condition has potential in transplantation therapy.

Background: In patients with congenital anomalies of the thumb, the metacarpophalangeal joint often undergoes radial deviation to compensate for a narrow first web space. In this study, we evaluated the relationship between the thumb and index finger in patients with arthrogryposis multiplex congenita (AMC), by measuring the thumb-index angle on radiographs taken while the patient held a styrene foam cone.Methods: Investigation was carried out on nine patients (13 cases: four bilateral and five unilateral) with AMC. The average patient age was 4.4 years (range, 2.6-7.2 years). Overhead radiographs were obtained while the patient held a styrene foam cone. The radiographs were used to evaluate the apparent thumb-index web angle, the thumb to index finger metacarpal angle (1-2MCA), and the first metacarpophalangeal angle (1MPA).Results: In the five unilateral cases, significant differences were seen on the affected versus unaffected sides in 1-2MCA and 1MPA. All 13 cases were treated surgically, and significant differences were observed between the groups before surgery and 2 years after surgery in the 1-2MCA and 1MPA. In addition, the mean postoperative 1MPA in the bilateral cases was significantly smaller compared with the unilateral cases.Conclusions: This radiographic technique enabled us to evaluate the severity of the thumb index web-space narrowing and the radial instability of the thumb metacarpophalangeal joint in patients with AMC. The bilateral cases tended to show better rehabilitative improvement compared with the unilateral ones, probably because the latter patients could use their unaffected hand. (C) 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

BMAL1 and RORα are major regulators of the circadian molecular oscillator. Since previous work in other cell types has shown cross talk between circadian rhythm genes and hypoxic signaling, we investigated the role of BMAL1 and RORα in controlling HIF-1-dependent transcriptional responses in NP cells that exist in the physiologically hypoxic intervertebral disc. HIF-1-dependent HRE reporter activity was further promoted by co-transfection with either BMAL1 or RORα. In addition, stable silencing of BMAL1 or inhibition of RORα activity resulted in decreased HRE activation. Inhibition of RORα also modulated HIF1α-TAD activity. Interestingly, immunoprecipitation studies showed no evidence of BMAL1, CLOCK or RORα binding to HIF-1α in NP cells. Noteworthy, stable silencing of BMAL1 as well as inhibition of RORα decreased expression of select HIF-1 target genes including VEGF, PFKFB3 and Eno1. To delineate if BMAL1 plays a role in maintenance of disc health, we studied the spinal phenotype of BMAL1-null mice. The lumbar discs of null mice evidenced decreased height, and several parameters associated with vertebral trabecular bone quality were also affected in nulls. In addition, null animals showed a higher ratio of cells to matrix in NP tissue and hyperplasia of the annulus fibrosus. Taken together, our results indicate that BMAL1 and RORα form a regulatory loop in the NP and control HIF-1 activity without direct interaction. Importantly, activities of these circadian rhythm molecules may play a role in the adaptation of NP cells to their unique niche.

We reviewed the outcomes of post-traumatic varus deformity treated with modified step-cut osteotomy in 19 patients (average age, 7.4 years; range, 4.3-16.8 years at time of surgery). The average follow-up period was 29.6 months. The mean range of motion was 15.0°/124.7° (extension/flexion) before surgery and 6.8°/132.6° at final follow-up. The humerus-elbow-wrist angle was -21.1° before surgery and 4.2° at final follow-up, with a loss of 4.4° from the value of the humerus-elbow-wrist angle after the surgery. Osteotomy was fixed with Kirschner wires, and, in five cases, chips of excised bone could be inserted to avoid elbow extension. However, in eight cases, usually concerning younger patients, the elbow was fixed in hyperextension higher than 5°. No patient developed postoperative infections or later complications. Only one patient had transient nerve palsy. The modified step-cut osteotomy can precisely and stably correct the varus deformity in the coronal plane, especially in patients under 10 years of age. To avoid radial nerve palsy, we recommend that the retractors be removed sometimes during the operation.

Kyphosis of the cervical spine has been reported in patients with adolescent idiopathic scoliosis (AIS). However, few reports have compared sagittal spine alignment of AIS patients with that of the normal population. The purposes of this study were (1) to analyze the characteristics of sagittal alignment, including the cervical spine, in AIS patients with a single thoracic curve (Lenke type 1) compared with the age-matched normal population and (2) to quantify the changes in sagittal alignment of the cervical spine and thoracic kyphosis following posterior spinal fusion.

Background.Significant and/or complete rupture in the musculotendinous junction (MTJ) is a challenging lesion to treat because of the lack of reliable suture methods. Skeletal muscle-derived multipotent stem cell (Sk-MSC) sheet-pellets, which are able to reconstitute peripheral nerve and muscular/vascular tissues with robust connective tissue networks, have been applied as a “bio-bond”.Methods.Sk-MSC sheet-pellets, derived from GFP transgenic-mice after 7 days of expansion culture, were detached with EDTA to maintain cell–cell connections. A completely ruptured MTJ model was prepared in the right tibialis anterior (TA) of the recipient mice, and was covered with sheet-pellets. The left side was preserved as a contralateral control. The control group received the same amount of the cell-free medium. The sheet-pellet transplantation (SP) group was further divided into two groups; as the short term (4–8 weeks) and long term (14–18 weeks) recovery group. At each time point after transplantation, tetanic tension output was measured through the electrical stimulation of the sciatic nerve. The behavior of engrafted GFP+tissues and cells was analyzed by fluorescence immunohistochemistry.Results.The SP short term recovery group showed average 64% recovery of muscle mass, and 36% recovery of tetanic tension output relative to the contralateral side. Then, the SP long term recovery group showed increased recovery of average muscle mass (77%) and tetanic tension output (49%). However, the control group showed no recovery of continuity between muscle and tendon, and demonstrated increased muscle atrophy, with coalescence to the tibia during 4–8 weeks after operation. Histological evidence also supported the above functional recovery of SP group. Engrafted Sk-MSCs primarily formed the connective tissues and muscle fibers, including nerve-vascular networks, and bridged the ruptured tendon–muscle fiber units, with differentiation into skeletal muscle cells, Schwann cells, vascular smooth muscle, and endothelial cells.Discussion.This bridging capacity between tendon and muscle fibers of the Sk-MSC sheet-pellet, as a “bio-bond,” represents a possible treatment for various MTJ ruptures following surgery.

Many groups have reported good to excellent clinical outcomes of the Elmslie-Trillat (ET) procedure for recurrent dislocation of the patella. However, the mean follow-up period of these studies was no more than 5 years. We hypothesized that the long-term postoperative outcomes of the modified ET procedure for recurrent dislocation of the patella would be acceptable compared with those of other procedures. The long-term postoperative outcomes of patients treated with the modified ET procedure were examined. A total of 31 knees in 27 patients with recurrent dislocation of the patella who underwent amodified ET procedure (without medial capsular plication) were evaluated. The mean follow-up period was 13.0 years. Pre- and postoperative radiographs were examined to determine the Q-angle, tilting angle, lateral shift ratio, sulcus angle, congruence angle, and Insall-Salvati index. Clinical outcomes were evaluated based on the Fulkerson patellofemoral joint evaluation score, Kujala score, and the presence of the apprehension sign. Radiological evaluation revealed significant postoperative improvements in the Q-angle, tilting angle, lateral shift ratio, congruence angle, Kujala score, and Fulkerson score (p < 0.001). Sixty-eight percent of all patients had a "good" or "excellent" Fulkerson score. The apprehension sign continued to be shown for six knees. Progression of osteoarthritic changes was observed in three knees, and one knee was symptomatic. The modified ET procedure provided satisfactory outcomes based on radiological and clinical evaluations. These results show the long-termeffectiveness and safety of the modified ET procedure for recurrent patellar dislocation.

We studied the ability of collagen vitrigel material to repair cartilage in vivo when used alone or with transforming growth factor-β (TGF-β). We measured the time course and quantity of TGF-β1 released from the collagen vitrigel in vitro to quantify the controlled release of TGF-β1. Over 14 days, 0.91 ng of TGF-β was released from the collagen vitrigel. Osteochondral defects were made in the femoral trochlear groove in 36 Japanese white rabbits, which were divided into three groups: untreated group (group A), collagen vitrigel-implanted group (group B), and TGF-β1-incorporated collagen vitrigel-implanted group (group C). The weight distribution ratio between the affected and unaffected limbs served as an indicator of pain. Animals were sacrificed at 4 and 12 weeks after surgery, and their tissues were assessed histologically. The weight distribution ratio increased in all groups and did not differ significantly between groups at 12 weeks. Group A needed 6 weeks to attain maximum improvement, and groups B and C showed near-maximum improvement at 4 and 2 weeks, respectively. The International Cartilage Repair Society II score improved significantly in group C relative to the other groups. These findings suggest that sustained, slow release of TGF-β caused early pain mitigation and cartilage repair. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2592-2602, 2017.

Background: Arthrogryposis is the general term given to conditions characterized by multiple joint contractures resulting in substantial disability most frequently involving a child. Early muscle transfer reconstructive surgery reliably restores elbow flexion. In the present study, we aimed to determine which preoperative condition is best able to restore elbow flexion in patients with arthrogryposis. Methods: We retrospectively reviewed five children (seven cases) who underwent elbow flexor reconstruction (Steindler flexorplasty, four cases; latissimus dorsi transfer, two cases; pectoralis major transfer, one case). Upper-extremity function was assessed on the basis of range of elbow extension and flexion and elbow flexor muscle power pre- and postoperatively. Results: The mean postoperative active flexion and extension range of motion was 82.1° (60° to 100°) and -15.0° (-40° to 0°) respectively. Mean postoperative elbow flexor muscle power was graded as a 3.4 (2 to 4) as measured with the Medical Research Council (MRC) scale. The preoperative passive elbow flexion angle was found to correlate with postoperative muscle power (MRC) (r = 0.830, p = 0.042) and postoperative active elbow flexion angle (r = 0.902, p = 0.027). Age at operation was not found to correlate with postoperative muscle power (MRC) (r = -0.063, p = 0.878) or active elbow flexion angle (r = -0.134, p = 0.743). Conclusions: We found a positive correlation between preoperative passive elbow flexion/range of elbow motion and postoperative results including active range of motion and transferred muscle power. Diminished preoperative elbow flexion appeared to correlate with having a poor outcome. The present results suggest that choosing another muscle, such as the gracilis, may be beneficial for muscle transfer in more severe cases of arthrogryposis.