Katsuya Aoto

Novel unidirectional porous hydroxyapatite used as a bone substitute for open wedge high tibial osteotomy

Purpose: The purpose of this study was to clinically and radiologically evaluate the availability, osteoconductivity, and resorption of a novel unidirectional porous hydroxyapatite (UDPHAp) used as an artificial substitute for open wedge high tibial osteotomy (OWHTO). Our hypothesis was that UDPHAp is a safe and useful bone substitute for OWHTO. Materials and methods: Seven patients (2 men and 5 women aged 34-72years) who underwent OWHTO and were followed up for more than 12months were retrospectively studied. After the osteotomy, the gap created was filled with UDPHAp(REGENOS® Kuraray Co.Ltd). Radiography and computed tomography(CT) were performed, and gap healing was assessed postoperatively. The Japanese Orthopaedic Association (JOA) knee score was determined pre- and post-operatively for clinical evaluation. Results: Neither gross displacement nor collapse of the UDPHAp block graft was observed within 12 months after surgery. Both radiographs and CT showed attenuation of lucency and increasing sclerosis over time. JOA score improved from 71.2 (65−80) to 95.8 (85−100). Conclusions: Short term results for OWHTO using UDPHAp was satisfactory. Clinical improvement of JOA scores were seen, besides osteogenesis was progressing in and around the artificial bone grafts.

Circadian variation of growth factor levels in platelet-rich plasma.

Objective:The influence of circadian rhythms has recently been considered in advanced studies of chronopharmacology and chronotherapeutics. Although emerging studies have reported the usefulness of platelet-rich plasma (PRP), no reports have described the diurnal variations in PRP growth factor levels. In the present study, we hypothesized that growth factor levels in PRP show a significant diurnal variation. Design:Controlled laboratory study. Setting:Institutional. Participants:Ten adult male volunteers (mean age, 30.0 ± 2.6 years; range, 26-34 years). Interventions:Each subject donated a 20-mL sample of fasting blood, 4 times per day (7 AM, 11 AM, 3 PM, and 7 PM). Main Outcome Measures:Each blood sample was processed to produce PRP. Complete blood counts of peripheral blood (PB) and PRP, as well as quantitative determination of PRP growth factor levels (platelet-derived growth factor and transforming growth factor) were performed. Statistical analyses were conducted using a one-way repeated measures analysis of variance. Results:No significant differences were observed in platelet, white blood cell, and red blood cell counts in the PB or in the PRP samples throughout the course of the day. In addition, there were no significant differences in PRP growth factor levels at the various time points. Conclusions:Significant diurnal variations in platelet counts and growth factor levels were not observed in PRP. Therefore, adjustments for diurnal variation in chronotherapy may not be important when PRP is used in clinical practice.

Fate of bone marrow mesenchymal stromal cells following autologous transplantation in a rabbit model of osteonecrosis

BACKGROUND AIMS Internalizing quantum dots (i-QDs) are a useful tool for tracking cells in vivo in models of tissue regeneration. We previously synthesized i-QDs by conjugating QDs with a unique internalizing antibody against a heat shock protein 70 family stress chaperone. In the present study, i-QDs were used to label rabbit mesenchymal stromal cells (MSCs) that were then transplanted into rabbits to assess differentiation potential in an osteonecrosis model. METHODS The i-QDs were taken up by bone marrow-derived MSCs collected from the iliac of 12-week-old Japanese white rabbits that were positive for cluster of differentiation (CD)81 and negative for CD34 and human leukocyte antigen DR. The average rate of i-QD internalization was 93.3%. At 4, 8, 12, and 24 weeks after transplantation, tissue repair was evaluated histologically and by epifluorescence and electron microscopy. RESULTS The i-QDs were detected at the margins of the drill holes and in the necrotized bone trabecular. There was significant colocalization of the i-QD signal in transplanted cells and markers of osteoblast and mineralization at 4, 8, and 12 weeks post-transplantation, while i-QDs were detected in areas of mineralization at 12 and 24 weeks post-transplantation. Moreover, i-QDs were observed in osteoblasts in regenerated tissue by electron microscopy, demonstrating that the tissue was derived from transplanted cells. CONCLUSION These results indicate that transplanted MSCs can differentiate into osteoblasts and induce tissue repair in an osteonecrosis model and can be tracked over the long term by i-QD labeling.

2. The Effect of Combined Therapy, Percutaneous Autologous Concentrated Bone Marrow Grafting and Low-Intensity Pulsed Ultrasound (LIPUS), on the Treatment of Non-Unions.

We discuss the effect of combined therapy of percutaneous autologous concentrated bone graft and LIPUS on complex non-union treatment. Seventeen of 27 treated patients who had received the therapy at least 1 year before were discussed (10 femurs, 5 tibiae, 1 humerus, and 1 ulna). The average age of the patients was 40.7, and atrophic degeneration was observed in all cases. After 12 months of treatment, bone union was recognized in 76% in all cases, and in 87% of lower long bones. It was reported that LIPUS was effective at improving blood flow, accelerating cytokines which induce angiogenesis, promoting the transport of nutrition and enzymes to living cells, developing the differentiation of osteoblast from mesenchymal stem cells (MSC), inhibiting the differentiation and development of osteoclast, and promoting endochondral ossification. In this study, all patients had been treated with LIPUS for more than 3 months before the grafting was conducted, but the bone union seemed to stop. It was thought that this combined therapy provided a bone marrow cell growth factor sufficient to enable new bone formation to re-start bone union, and then LIPUS worked effectively to promote the initial differentiation, contributing to new bone formation. This combination therapy—less invasive, safe, and low cost—was considered one useful treatment option for non-union.

Mid-term results of concentrated autologous bone marrow aspirate transplantation for corticosteroid-associated osteonecrosis of the femoral head in systemic lupus erythematosus

PurposeWe had previously established concentrated autologous bone marrow aspirate transplantation (CABMAT), a one-step, low-invasive, joint-preserving surgical technique for treating osteonecrosis of the femoral head (ONFH). This study aimed to evaluate the effects of CABMAT as a hip-preserving surgical approach, preventing conversion to total hip arthroplasty (THA) and femoral head collapse in patients with systemic lupus erythematosus (SLE).MethodsSince 2003, 52 SLE patients (8 male, 44 female, 92 hips, mean age 35.3 (16–77) (years) were treated with CABMAT. The mean follow-up period was 5.5 (0.7–14) years. Conversion rate to THA and its predicting factors were analyzed.ResultsThe overall conversion rate to THA was 29% (27/92). Conversion rate to THA was 0% (0/3), 0% (0/4), 22% (9/41), and 41% (18/44) in types A, B, C1, and C2, respectively. Conversion rate to THA was 26% (5/19), 26% (6/23), 28% (11/39), 44% (4/9), and 50% (1/2) in stages 1, 2, 3A, 3B, and 4, respectively. In multivariate logistic regression analysis, sex, body mass index (BMI), pre-operative type, and pre-operative stage were significantly correlated with conversion to THA.ConclusionThe conversion rate to THA was lower than that in the natural course and core decompression, but was higher than that seen in other bone marrow transplantation and osteotomy. Since sex, pre-operative type, and pre-operative stage were significantly correlated with conversion to THA, it is suggested that the higher proportion of women, advanced stage (stage 3A or above), and advanced type (type C or above) in this study affected the THA conversion rate.

Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model

No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30 μg/kg) or saline administration three times per week (n = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy.