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Featured researches published by Issei Nagura.


Arthroscopy | 2010

Electrospun Synthetic Polymer Scaffold for Cartilage Repair Without Cultured Cells in an Animal Model

Narikazu Toyokawa; Hiroyuki Fujioka; Takeshi Kokubu; Issei Nagura; Atsuyuki Inui; Ryosuke Sakata; Makoto Satake; Hiroaki Kaneko; Masahiro Kurosaka

PURPOSE The purpose of our study was to explore the possibility that an electrospun bioabsorbable scaffold could be used in the treatment of a full-thickness articular defect without the addition of exogenous cells in a rabbit model. METHODS Two types of poly(D,L-lactide-co-glycolide) (PLG) scaffolds, a solid cylindrical type and a cannulated tubular type, were made with the electrospinning method. Osteochondral defects, 5 mm in diameter and 5 mm in depth, made on the femoral condyles of rabbits were filled with these scaffolds, and the repair process was investigated histologically. RESULTS In the groups in which the defect was filled with the scaffold, fibrous tissue at the articular surface of the scaffold was observed at postoperative week 2. Thereafter cartilage at the articular surface and bone at the subchondral zone were regenerated, and the repaired cartilage was maintained through postoperative week 24. By contrast, the untreated defect was filled with hematoma at postoperative week 2; thereafter regenerated cartilage and bone were observed. However, the surface of the articular cartilage was not regular, and regenerated cartilage was not well organized. The histologic scores of the groups in which the defect was filled with cannulated tubular electrospun PLG scaffolds were significantly higher than those of the untreated defect group at postoperative weeks 12 and 24 (P < .01). CONCLUSIONS The electrospun PLG scaffold could repair a 5-mm osteochondral defect created in the rabbit model without exogenous cultured cells. CLINICAL RELEVANCE The electrospun PLG scaffold could repair full-thickness osteochondral defects. The cannulated type of PLG scaffold has the possibility to lead not only to good regeneration of cartilage but also to easy transplantation by use of a guidewire through the cannulas in the scaffold.


Journal of Bone and Joint Surgery-british Volume | 2007

Repair of osteochondral defects with a new porous synthetic polymer scaffold

Issei Nagura; Hiroyuki Fujioka; Takeshi Kokubu; Takeshi Makino; Y. Sumi; Masahiro Kurosaka

We developed a new porous scaffold made from a synthetic polymer, poly(DL-lactide-co-glycolide) (PLG), and evaluated its use in the repair of cartilage. Osteochondral defects made on the femoral trochlear of rabbits were treated by transplantation of the PLG scaffold, examined histologically and compared with an untreated control group. Fibrous tissue was initially organised in an arcade array with poor cellularity at the articular surface of the scaffold. The tissue regenerated to cartilage at the articular surface. In the subchondral area, new bone formed and the scaffold was absorbed. The histological scores were significantly higher in the defects treated by the scaffold than in the control group (p<0.05). Our findings suggest that in an animal model the new porous PLG scaffold is effective for repairing full-thickness osteochondral defects without cultured cells and growth factors.


Journal of Orthopaedic Research | 2013

Platelet-rich plasma protects rotator cuff-derived cells from the deleterious effects of triamcinolone acetonide.

Tomoyuki Muto; Takeshi Kokubu; Yutaka Mifune; Ryosuke Sakata; Issei Nagura; Hanako Nishimoto; Yoshifumi Harada; Kotaro Nishida; Ryosuke Kuroda; Masahiro Kurosaka

Triamcinolone acetonide (TA) injections are widely used to treat enthesopathy, but they may induce adverse effects such as tendon impairment and rupture. Platelet‐rich plasma (PRP) is a blood fraction containing high platelet concentrations and various growth factors that play a role in tissue repair processes. The purpose of this study is to investigate whether TA has deleterious effects on human rotator cuff‐derived cells, and if PRP can protect these cells from the effects of TA. Human rotator cuff‐derived cells were cultured with and without TA and PRP, and the culture without any additive served as the control. Cell morphology was assessed at days 7 and 21. Cell viability was evaluated at days 1, 7, 14, and 21 by a water‐soluble tetrazolium salt assay. Induction of apoptosis was measured by immunofluorescence staining and flow cytometry at day 7. Induction of cleaved caspase‐3 was measured by immunofluorescence staining at day 7. The cells cultured with TA had a flattened and polygonal shape at day 7. The cells cultured with both TA and PRP were similar in appearance to control cells. Exposure to TA also significantly decreased cell viability, but cell viability did not decrease when PRP was added along with TA. The number of apoptotic cells increased with TA exposure, while addition of PRP prevented cell apoptosis. In conclusion, the deleterious effect of TA was prevented by PRP, which can be used as a protective agent for patients receiving local TA injections.


Sports Medicine, Arthroscopy, Rehabilitation, Therapy & Technology | 2011

Application of layered poly (L-lactic acid) cell free scaffold in a rabbit rotator cuff defect model

Atsuyuki Inui; Takeshi Kokubu; Hiroyuki Fujioka; Issei Nagura; Ryosuke Sakata; Hanako Nishimoto; Masaru Kotera; Takashi Nishino; Masahiro Kurosaka

BackgroundThis study evaluated the application of a layered cell free poly (L-lactic acid) (PLLA) scaffold to regenerate an infraspinatus tendon defect in a rabbit model. We hypothesized that PLLA scaffold without cultivated cells would lead to regeneration of tissue with mechanical properties similar to reattached infraspinatus without tendon defects.MethodsLayered PLLA fabric with a smooth surface on one side and a pile-finished surface on the other side was used. Novel form of layered PLLA scaffold was created by superimposing 2 PLLA fabrics. Defects of the infraspinatus tendon were created in 32 rabbits and the PLLA scaffolds were transplanted, four rabbits were used as normal control. Contralateral infraspinatus tendons were reattached to humeral head without scaffold implantation. Histological and mechanical evaluations were performed at 4, 8, and 16 weeks after operation.ResultsAt 4 weeks postoperatively, cell migration was observed in the interstice of the PLLA fibers. Regenerated tissue was directly connected to the bone composed mainly of type III collagen, at 16 weeks postoperatively. The ultimate failure load increased in a time-dependent manner and no statistical difference was seen between normal infraspinatus tendon and scaffold group at 8 and 16 weeks postoperatively. There were no differences between scaffold group and reattach group at each time of point. The stiffness did not improve significantly in both groups.ConclusionsA novel form of layered PLLA scaffold has the potential to induce cell migration into the scaffold and to bridge the tendon defect with mechanical properties similar to reattached infraspinatus tendon model.


Journal of Orthopaedic Research | 2012

Localization of vascular endothelial growth factor during the early stages of osteochondral regeneration using a bioabsorbable synthetic polymer scaffold.

Ryosuke Sakata; Takeshi Kokubu; Issei Nagura; Narikazu Toyokawa; Atsuyuki Inui; Hiroyuki Fujioka; Masahiro Kurosaka

Vascular endothelial growth factor (VEGF) plays a critical role in chondrogenic differentiation in the growth plate of the epiphysis. This function is necessary for chondrocyte survival in cartilage development. We investigated the localization of VEGF in the osteochondral regeneration process using a bioabsorbable polymer scaffold. Osteochondral defects (5 mm in diameter and 5 mm in depth) were made on the femoral condyle of forty‐eight skeletally mature female Japanese white rabbits. In total, twenty‐four defects were filled with poly(DL‐lactide‐co‐glycolide) scaffolds and the others were left untreated. The regeneration process was investigated macroscopically, histologically, immunohistochemically, and by gene expression analysis. In the early stages of osteochondral regeneration, bone ingrowth was observed in the deep zone of the scaffold with continuous VEGF expression; cartilage regeneration was observed in the superficial zone of the scaffold with decreased VEGF expression. In contrast, when the defect was left untreated, VEGF localization was observed throughout the entire defect area, and cartilage regeneration at the articular surface was delayed. We conclude that decrease in localization of VEGF at the articular surface in the postoperative early stage is closely related to the progression of cartilage regeneration in osteochondral defects.


Journal of Clinical Neurophysiology | 2013

Delayed electrophysiological recovery after carpal tunnel release for advanced carpal tunnel syndrome: a two-year follow-up study.

Takako Kanatani; Hiroyuki Fujioka; Masahiro Kurosaka; Issei Nagura; Masatoshi Sumi

Summary: Advanced carpal tunnel syndrome presents severe thenar atrophy with the absence of electrophysiological motor and sensory responses. Because of severity of these conditions, a substantial period of recovery after surgery is required before improvement becomes evident. In this electrophysiological-based study, the reappearance of distal motor latency (DML) at the abductor pollicis brevis and/or sensory nerve conduction velocity (SCV) after wrist stimulation were evaluated 1 year and 2 years after carpal tunnel release . To categorize outcomes, the following grading scale was used: stage I, normal DML and SCV; stage II, DML ≥ 4.5 ms and normal SCV; stage III, DML ≥ 4.5 ms and SCV < 40.0 ms; stage IV, DML ≥ 4.5 ms and nonmeasurable SCV; stage V: nonmeasurable DML and SCV. The authors found measurable DML and/or SCV and significant improvement both 1 year and 2 years postoperatively. Furthermore, the percentage of patients who recovered to the extent that they presented as mild carpal tunnel syndrome (stage I or II) increased significantly. They conclude that electrophysiological assessment of DML and SCV of advanced carpal tunnel syndrome using the above grading scale was effective as an objective evaluation tool of recovery after carpal tunnel release.


Journal of Foot & Ankle Surgery | 2012

Modified Tension Band Wiring Fixation for Avulsion Fractures of the Calcaneus in Osteoporotic Bone: A Review of Three Patients

Issei Nagura; Hiroyuki Fujioka; Masahiro Kurosaka; Hiroyuki Mori; Makoto Mitani; Akihiro Ozaki; Hideo Fujii; Yuji Nabeshima

Calcaneal avulsion fractures are not uncommon, and they are probably more likely in patients with osteoporosis. Closed manipulation for this type of fracture often fails to achieve acceptable reduction, and open reduction and internal fixation are usually required. However, open reduction and internal fixation with either a lag screw or Steinmann pins do not provide satisfactory fixation in patients with diabetes and elderly patients because of the presence of porotic bone. Levi described a tension band fixation system used to treat a calcaneal avulsion fracture using a simple technique performed with a transverse Kirschner wire through the os calcaneus, securing a figure-of-8 metal tension band wiring to the fragment. We report the successful treatment of 3 patients with calcaneal avulsion fractures using a modified tension band wiring technique, resulting in satisfactory recovery. Re-displacement of the fragment during the initial follow-up period was not reported, and bony union was achieved in all patients. We believe this technique is a useful surgical option for the treatment of calcaneal avulsion fractures.


Journal of Hand Surgery (European Volume) | 2014

Electrophysiological Assessment of Carpal Tunnel Syndrome in Elderly Patients: One-Year Follow-Up Study

Takako Kanatani; Issei Nagura; Masahiro Kurosaka; Takeshi Kokubu; Masatoshi Sumi

PURPOSE To objectively assess elderly patients with carpal tunnel syndrome to characterize their preoperative severity and prognosis after carpal tunnel release using a electrophysiological severity scale. METHODS Electrophysiologic assessment was performed preoperatively and 1 year postoperatively following carpal tunnel release in 112 hands in patients over 70 years of age prospectively by the use of the following electrophysiological severity scale: stage 1, normal distal motor latency (DML) and normal sensory conduction velocity (SCV); stage 2, DML ≥ 4.5 milliseconds and normal SCV; stage 3, DML ≥ 4.5 milliseconds and SCV < 40.0 m/s; stage 4, DML ≥ 4.5 milliseconds and non-measurable SCV; stage 5; non-measurable DML and non-measurable SCV. Additionally, the outcomes of clinical symptoms of pain, nocturnal symptoms, numbness, loss of 2-point discrimination in the median nerve territory, and thenar atrophy were assessed. RESULTS The mean age of patients was 77 years at the time of the operation. Preoperatively, the most common severity was stage 5 (70 of 112 hands, 63%), and clustering stage 4 and 5 together as severe resulted in 103 hands (92%). One year postoperatively, 97 hands (87%) demonstrated at least one stage improvement, and the numbers of mild (stage 1 or 2) increased from 3 (3%) to 45 hands (40%). Parallel with the electrophysiological improvement, pain and nocturnal symptoms resolved in 17 of 17 hands and 11 of 11 hands, respectively, in whom they were present preoperatively. Numbness, loss of 2-point discrimination, and thenar atrophy demonstrated the improvement in 96 of 112 (86%) hands, in 58 of 112 (52%) hands, and in 80 of 96 (83%) hands. CONCLUSIONS We observed electrophysiologic improvement in 86% of elderly patients following carpal tunnel release. Electrophysiologic outcomes correlated with improvement in clinical variables. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic IV.


Journal of Orthopaedic Science | 2009

Monteggia fracture managed by intramedullary kirschner wire fixation with pyknodysostosis

Issei Nagura; Hiroyuki Fujioka; Yuji Nabeshima; Takeshi Kokubu; Minoru Doita; Masahiro Kurosaka

Pyknodysostosis was fi rst described by Maroteaux and Lamy in 1962 as an unusual variant of achondroplasia. The patients’ bone abnormalities are manifested in short stature, hypoplasia of the mandible and the distal phalanges of the fi ngers, and open sutures of the skull. Pyknodysostosis is a rare hypoplastic, osteosclerotic condition that often presents with pathological fractures in the long bone. Recent reports have shown genetic abnormalities characterized by mutation in cathepsin K, an important cysteine protease gene for bone metabolism that is highly expressed in osteoclasts. The defi ciency of this enzyme has been proved to be responsible for pyknodysostosis. Up to now, more than 100 cases of pyknodysostosis have been reported. Most of the case reports describe fractures of the lower extremities, the tibia, and the femur. By contrast, fractures of the upper extremities have rarely been described for this disease. In the present report, Monteggia fracture was successfully treated using percutaneous Kirschner wire fi xation. This is a rare report of Monteggia fracture with pyknodysostosis caused by injury in a patient who has age-related bone fragility.


Journal of Medical Case Reports | 2014

Assessment of vascularized free fibula transplantation revealing a congenital aplastic posterior tibial artery: a case report

Takako Kanatani; Issei Nagura; Ikuo Fujita; Takuya Fujimoto; Masatoshi Sumi

IntroductionAnatomical abnormalities in the lower limb vessels are uncommon. However, the preoperative evaluation of the anatomical variations is very important for planning the operation procedure to prevent jeopardizing the donor leg.Case presentationIn this case report, a 23-year-old Asian woman who was scheduled to have vascularized free fibula transplantation for reconstruction of her wrist after excision of bone tumor in her distal radius, was found to have congenital aplastic posterior tibial arteries in both legs. These findings were found on magnetic resonance angiography (our preferred methodology due to its simplicity). We planned testing the sufficiency of her pedal pulses after temporarily clamping her peroneal artery but prior to harvesting, to ensure minimal risk to the longevity of her donor leg. During the operation, after dissection of a 10cm segment of her fibula with the peroneal artery, the peroneal artery proximal to the graft was temporarily clamped and the tourniquet was released. As adequate sustainable pedal pulses were confirmed, the graft was harvested and transplanted to her wrist. There was no morbidity in her right leg postoperatively and the union of the grafted fibula was substantiated 10 months postoperatively.ConclusionsWe concluded two findings: firstly, for accurate preoperative planning of a vascularized free fibula procedure, examination of the bilateral lower leg vasculature either by angiography or other imaging should be performed. Secondly, abnormalities are not in themselves reason to abandon the vascularized free fibula procedure. We contend that pedal pulses should be evaluated preoperatively and provided that adequate foot circulation can be confirmed (by temporarily clamping the vessels and releasing the tourniquet during the operation prior to harvesting the free vascularized fibula) the procedure should be successful without jeopardizing the donor leg.

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Ryosuke Sakata

Wakayama Medical University

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