Kentaro Yamane

A novel, visible light-induced, rapidly cross-linkable gelatin scaffold for osteochondral tissue engineering

Osteochondral injuries remain difficult to repair. We developed a novel photo-cross-linkable furfurylamine-conjugated gelatin (gelatin-FA). Gelatin-FA was rapidly cross-linked by visible light with Rose Bengal, a light sensitizer, and was kept gelled for 3 weeks submerged in saline at 37°C. When bone marrow-derived stromal cells (BMSCs) were suspended in gelatin-FA with 0.05% Rose Bengal, approximately 87% of the cells were viable in the hydrogel at 24 h after photo-cross-linking, and the chondrogenic differentiation of BMSCs was maintained for up to 3 weeks. BMP4 fusion protein with a collagen binding domain (CBD) was retained in the hydrogels at higher levels than unmodified BMP4. Gelatin-FA was subsequently employed as a scaffold for BMSCs and CBD-BMP4 in a rabbit osteochondral defect model. In both cases, the defect was repaired with articular cartilage-like tissue and regenerated subchondral bone. This novel, photo-cross-linkable gelatin appears to be a promising scaffold for the treatment of osteochondral injury.

Implant Failure of Titanium Versus Cobalt-Chromium Growing Rods in Early-onset Scoliosis.

Study Design. Retrospective case series of one institute database. Objective. To investigate the differences in the metallic strength of rods used for implant failure in the dual growing rod technique and evaluate clinical outcomes. Summary of Background Data. The dual growing rod technique in which implanted rods extend with the growth of the spine is a useful treatment for early onset scoliosis. However, many complications, particularly those associated with rods, exist. Especially, the implant failure of growing rod focused on metallic strength is unknown. Methods. Thirteen patients (42 lengthening surgeries) who underwent surgery by this technique at our hospital from 2007 were divided into a titanium rod plus titanium connector group (T group, n = 4, 26 lengthening surgeries) and cobalt-chromium rod plus titanium connection group (C group, n = 9, 16 lengthening surgeries). The incidence of implant failure and the site of fracture were retrospectively investigated. Results. Implant failure occurred in three patients in the T group, because of rod fracture in two patients and connector fracture in one. In the C group, implant failure occurred in six patients, because of rod fracture in one patient and connector fracture in seven. Fracture occurred twice in two patients. The rod fracture rate decreased with the use of cobalt-chromium rods but the rate of connector fracture increased. We performed a stress distribution analysis using the finite element method to clarify the mechanisms underlying implant failure in both groups. Regardless of the rod type, the greater load was placed on the distal rod. However, differences in the metallic strength caused the rod to fracture when titanium rods were used and connectors (weak metallic strength) to fracture when cobalt-chromium rods were used. Conclusion. Rod fractures occurred more commonly with titanium rods and connector fractures with cobalt-chromium rods. Level of Evidence: 4

Bone engineering by phosphorylated-pullulan and β-TCP composite

A multifunctional biomaterial with the capacity bond to hard tissues, such as bones and teeth, is a real need for medical and dental applications in tissue engineering and regenerative medicine. Recently, we created phosphorylated-pullulan (PPL), capable of binding to hydroxyapatite in bones and teeth. In the present study, we employed PPL as a novel biocompatible material for bone engineering. First, an in vitro evaluation of the mechanical properties of PPL demonstrated both PPL and PPL/β-TCP composites have higher shear bond strength than materials in current clinical use, including polymethylmethacrylate (PMMA) cement and α-tricalcium phosphate (TCP) cement, Biopex-R. Further, the compressive strength of PPL/β-TCP composite was significantly higher than Biopex-R. Next, in vivo osteoconductivity of PPL/β-TCP composite was investigated in a murine intramedular injection model. Bone formation was observed 5 weeks after injection of PPL/β-TCP composite, which was even more evident at 8 weeks; whereas, no bone formation was detected after injection of PPL alone. We then applied PPL/β-TCP composite to a rabbit ulnar bone defect model and observed bone formation comparable to that induced by Biopex-R. Implantation of PPL/β-TCP composite induced new bone formation at 4 weeks, which was remarkably evident at 8 weeks. In contrast, Biopex-R remained isolated from the surrounding bone at 8 weeks. In a pig vertebral bone defect model, defects treated with PPL/β-TCP composite were almost completely replaced by new bone; whereas, PPL alone failed to induce bone formation. Collectively, our results suggest PPL/β-TCP composite may be useful for bone engineering.

Scoliosis correction surgery for patients with McCune–Albright syndrome using pedicle screws: a report of two cases with different characteristics and a review of the literature

PurposeScoliosis can occur secondary to McCune–Albright syndrome (MAS); it can be progressive and sometimes requires surgical treatment. It is still unclear if pedicle screw (PS) fixation in these patients with poor bone quality can be considered an effective treatment for scoliosis. The purpose of this study is to report two MAS patients with spinal fibrous dysplasia (FD) who underwent scoliosis surgeries with the PS system.MethodsCase 1: a 12-year-old girl. Standing posteroanterior radiographs revealed a 58° right curve from T7 to L2. Computed tomography (CT) showed small areas of FD throughout the spine. A posterior spinal arthrodesis from T4 to L3 using PS fixation was performed with a CT-based navigation system. Case 2: a 26-year-old woman. Radiographs in the standing position revealed a right 87° curve from T8 to L2 and a 55° kyphosis from T8 to T12. CT images showed multiple areas of severe spinal FD causing angular deformity and collapse of vertebral bodies. The patient underwent posterior spinal arthrodesis from T8 to her pelvis using a CT-based navigation system for PS fixation.ResultsSuperior scoliosis corrections were obtained using PS instrumentation, attaining complete bony union in both cases without major complications. However, Case 2 had some technical difficulties in treating due to the multiple large FD lesions.ConclusionsPS fixation can be considered an effective treatment for correcting scoliosis and maintaining the correction at follow-up in MAS patients with poor bone quality. However, great care must be taken when performing correction and follow-up.

Collagen-Binding Hepatocyte Growth Factor (HGF) alone or with a Gelatin-furfurylamine Hydrogel Enhances Functional Recovery in Mice after Spinal Cord Injury

The treatment of spinal cord injury (SCI) is currently a significant challenge. Hepatocyte growth factor (HGF) is a multipotent neurotrophic and neuroregenerative factor that can be beneficial for the treatment of SCI. However, immobilized HGF targeted to extracellular matrix may be more effective than diffusible, unmodified HGF. In this study, we evaluated the neurorestorative effects of an engineered HGF with a collagen biding domain (CBD-HGF). CBD-HGF remained in the spinal cord for 7 days after a single administration, while unmodified HGF was barely seen at 1 day. When a gelatin-furfurylamine (FA) hydrogel was applied on damaged spinal cord as a scaffold, CBD-HGF was retained in gelatin-FA hydrogel for 7 days, whereas HGF had faded by 1 day. A single administration of CBD-HGF enhanced recovery from spinal cord compression injury compared with HGF, as determined by motor recovery, and electrophysiological and immunohistochemical analyses. CBD-HGF alone failed to improve recovery from a complete transection injury, however CBD-HGF combined with gelatin-FA hydrogel promoted endogenous repair and recovery more effectively than HGF with hydrogel. These results suggest that engineered CBD-HGF has superior therapeutic effects than naïve HGF. CBD-HGF combined with hydrogel scaffold may be promising for the treatment of serious SCI.

Impact of Rotation Correction after Brace Treatment on Prognosis in Adolescent Idiopathic Scoliosis

Study Design Level 4 retrospective review. Purpose Brace treatment is the standard nonoperative treatment for adolescent idiopathic scoliosis (AIS). Rotation correction is also important, because AIS involves a rotation deformity. The purpose of this study was to evaluate the impact of rotation correction after Osaka Medical College (OMC) brace treatment on clinical outcomes in AIS. Overview of Literature Brace treatment has a significant effect on the progression of AIS. However, few reports have examined rotation correction after brace treatment. Methods A total of 46 patients who wore the OMC brace were retrospectively reviewed. The curve magnitude was determined according to the Cobb method, and the rotation angle of the apical vertebrae was measured by the modified Nash-Moe method. Based on the difference in the rotation angle before and after the initial brace treatment, patients were divided into two groups. Group A (n=33) was defined as no change or improvement of the rotation angle; group B (n=13) was defined as deterioration of the rotation angle. If the patients had curve or rotation progression of 5° or more at skeletal maturity, or had undergone surgery, the treatment was considered a failure. Results Differences of rotation angle between before and after the initial brace treatment were 2°±2° in group A and –3°±2° in group B (p<0.001). The rates of treatment failure were 42% in group A and 77% in group B (p<0.05). This study included 25 patients with Lenke type 1 (54%). Group A (24%) with Lenke type 1 also had a significantly better success rate of brace treatment than group B (75%) (p<0.05). Conclusions Insufficient rotation correction increased brace treatment failure. Better rotation correction resulted in a higher success rate of brace treatment in patients with Lenke type 1.