Toshihiro Akisue

Enhancement of Tendon-Bone Osteointegration of Anterior Cruciate Ligament Graft Using Granulocyte Colony-Stimulating Factor

Background Whereas anterior cruciate ligament rupture usually requires reconstruction, the attachment between the tendon and the bone is the weakest region in the early posttransplantation period. In this process, the acquisition of appropriate vascularity is a key for early bone-tendon healing. Hypothesis Granulocyte colony-stimulating factor has an effect on the maturation of bone-tendon integration of anterior cruciate ligament reconstruction. Study Design Controlled laboratory study. Methods Twenty-eight healthy adult beagle dogs underwent bilateral anterior cruciate ligament reconstruction using the ipsilateral flexor digitorum superficialis tendon and were divided into 2 groups. A granulocyte colony-stimulating factor-incorporated gelatin surrounded the graft in the granulocyte colony-stimulating factor group, and the same gelatin without granulocyte colony-stimulating factor was used as the control group. Assessment was done at 2 and 4 weeks. Results Histological analysis at week 2 demonstrated that, in addition to more Sharpey fibers, microvessels were significantly enhanced in the granulocyte colony-stimulating factor groups grafts. Computed tomography at week 4 showed a significantly smaller tibial bone tunnel in the granulocyte colony-stimulating factor group. Real-time polymerase chain reaction revealed significantly elevated messenger ribonucleic acid expression levels of vascular endothelial growth factor and osteocalcin in the tibial bone tunnel and graft compared with controls. Furthermore, biomechanical testing of force during loading to ultimate failure at week 4 demonstrated a significant increase in strength in the granulocyte colony-stimulating factor group. Conclusion This study demonstrated that a local application of granulocyte colony-stimulating factor-incorporated gelatin significantly accelerates bone-tendon interface strength via enhanced angiogenesis and osteogenesis. Clinical Relevance Granulocyte colony-stimulating factor has therapeutic potential in promoting an environment conductive to angiogenesis and osteogenesis in bone tunnels.

Bone Regeneration Properties of Granulocyte Colony-Stimulating Factor via Neovascularization and Osteogenesis

OBJECTIVES It has been well recognized that appropriate vascularization is emerging as a prerequisite for bone development and regeneration. The aim of this study was to test the hypothesis that locally applied granulocyte colony-stimulating factor (G-CSF) enhances bone regeneration via revascularization and osteogenesis. METHODS A segmental bone defect (20mm) was created at the diaphysis of the rabbit ulna. The defects were treated with cationized gelatin hydrogel, which was the drug delivery system, with G-CSF, and then bone regeneration, neovascularization, and osteogenesis properties with G-CSF were assessed. RESULTS Radiographic, computed tomography, and histological findings revealed that bone formation was significantly promoted in G-CSF-treated group as early as 2 weeks. Immunohistochemistry, real-time reverse transcription-polymerase chain reaction, and flow cytometry studies indicated that angiogenesis/vasculogenesis, which are regulated by mobilization and incorporation of CD34+/G-CSF receptor (CSFR+) cells, and osteogenesis, which is regulated by osteocalcin+/G-CSFR+ cells, were also significantly enhanced in the G-CSF group. CONCLUSIONS This study suggests that locally applied G-CSF contributes to an ideal local environment for fracture healing by supplying adequate blood flow and stimulating osteogenesis. G-CSF may have the therapeutic potential for bone regeneration.

Solitary fibrous tumor in the extremity: case report and review of the literature.

A solitary fibrous tumor is a relatively unusual neoplasm first described as a distinctive tumor arising from pleura. Some reports have shown that solitary fibrous tumors also affect extrathoracic regions. The current study presents a literature review with four additional patients with solitary fibrous tumor arising from the extremities to clarify clinicopathologic features. The current four patients were two males and two females, ranging from 17 to 60 years of age. Magnetic resonance imaging scans of the current patients showed inhomogeneous low to intermediate intensity signal on T1-weighted images and inhomogeneous intermediate to high intensity signal on T2-weighted images. Histologically, the tumors were composed of a haphazard proliferation of spindle cells, although cellularity was variable in each case. Two of the four tumors showed hypercellularity of spindle cells with focally myxomatous or hyaline changes, whereas myxomatous patterns with scattered spindle cells throughout the specimens were observed in the other two tumors. Immunohistochemically, all four patients showed positive immunoreactivity for CD34, and two tumors showed focally positive immunoreactivity for bcl-2 protein. During the followup of 12 to 54 months, neither local recurrence nor distant metastasis was detected after wide resection. Examination of the literature and the current patients suggests that solitary fibrous tumors in the extremities are likely to have a malignant potential, although most patients have a benign clinical course. Local wide resection and careful long-term followup are necessary for patients with solitary fibrous tumor in the extremities.

Regeneration of rotator cuff tear using electrospun poly(d,l-Lactide-Co-Glycolide) scaffolds in a rabbit model.

PURPOSE The purpose of this study was to evaluate an application of poly(d,l-lactide-co-glycolide) (PLG) scaffold created by electrospinning in a rabbit rotator cuff defect model. METHODS Forty-two Japanese white rabbits were used in this study. Defects of the infraspinatus tendon were created, and the PLG scaffolds were implanted. Contralateral infraspinatus tendons were reattached without creating defects. Histologic analyses were performed 4, 8, and 16 weeks after the operation, and mechanical evaluations were performed 0, 4, 8, and 16 weeks after the operation. RESULTS Scaffold fibers remained without dissolution and spindle-shaped cells were observed inside of the scaffold at 4 weeks postoperatively. At 8 weeks, the PLG scaffold had dissolved and bone formation was observed at the scaffold-bone interface. At 16 weeks, the scaffold-bone interface matured and expression of type II collagen was observed. A statistical difference in ultimate failure load was not seen between the scaffold group and reattachment group or normal tendon after 8 weeks postoperatively. The stiffness in the scaffold group was not significantly different from that in the reattachment group at each time point. However, it was significantly weaker than normal tendon at each time point. CONCLUSIONS Transplantation of cell-free PLG scaffold showed cell migration and type II collagen and proteoglycan expression at the scaffold-bone junction by 16 weeks postoperatively with a sufficient ultimate failure load in a rabbit rotator cuff defect model. CLINICAL RELEVANCE The PLG scaffold could be applied to bridge rotator cuff defects. The results showed that bridging with scaffold can be equivalent to reattachment.

Alendronate does not inhibit early bone apposition to hydroxyapatite-coated total joint implants: a preliminary study.

Background: Alendronate is a pyrophosphate analogue of bisphosphonate that has been shown to inhibit osteoclastic bone resorption. Bone formation and remodeling are necessary to establish initial fixation of uncemented implants, especially those coated with a bioactive surface such as hydroxyapatite. Because the process of bone-remodeling that culminates in new-bone formation is thought to be initiated by osteoclastic bone resorption, it is appropriate to test the influence of osteoclast-inhibiting medications on bone apposition to hydroxyapatite-coated implants.Methods: Twelve dogs underwent staged bilateral total hip arthroplasty, with twenty weeks between the first and second operations, with use of a titanium-alloy femoral stem that had a proximal macrotextured surface and a plasma-sprayed hydroxyapatite coating. Six of the dogs received oral alendronate therapy from the time of the surgery until they were killed; the other six dogs were untreated controls. The animals were killed four weeks after the second operation. Sections from matched implant sites (proximal, middle, and distal) were histologically analyzed. The linear extent of bone apposition, the linear extent and the thickness of the hydroxyapatite coating, and the total amount of cortical and trabecular bone were measured with the use of an interactive image analysis system.Results: There were no significant differences in radiographic or histologic findings between the two groups at either four or twenty-four weeks. Although the extent of the hydroxyapatite coating decreased significantly with time in both groups (p < 0.01), we identified no significant influence of alendronate on the extent of bone apposition, the extent or thickness of the hydroxyapatite coating, or the cortical or trabecular bone area around the implants.Conclusions: Many patients who are receiving alendronate for osteoporosis or other disorders may also be candidates for cementless total joint arthroplasty. Although bone formation is generally thought to be initiated by and coupled with bone resorption, our results suggest that alendronate has no discernible effect on the initial fixation of or the short-term bone-remodeling around hydroxyapatite-coated femoral total joint implants.

Fibroma of tendon sheath originating from the knee joint capsule

We present a rare case of fibroma of the tendon sheath originating from the posterior joint capsule of the knee in a 50-year-old man. Magnetic resonance (MR) imaging revealed a lesion posterior to the medial femoral condyle. The lesion showed hypointensity on all T1-weighted, T2-weighted, short tau inversion recovery (STIR), and contrast-enhanced T1-weighted images. Plain computed tomographic (CT) scans showed a lesion with isodensity to muscle. The lesion showed no enhancement on postcontrast CT scans.

Neural fibrolipoma of the superficial peroneal nerve in the ankle: A case report with immunohistochemical analysis

This report presents a case of neural fibrolipoma arising from the superficial peroneal nerve in the ankle. A 28‐year‐old woman was referred with a soft tissue mass in the anterior aspect of the right ankle, which had been gradually enlarging for the past 10 years. Magnetic resonance imaging showed a mass lesion, measuring approximately 8 × 3 × 2 cm, with high to partially low signal intensity on both T1‐ and T2‐weighted images. A band of low signal intensity within the lesion, which is indicative of coexistence with the tumor and the superficial peroneal nerve, could be detected on both T1‐ and T2‐weighted images. The patient underwent an excisional biopsy. The specimen microscopically consisted of nerve bundles and fibro‐fatty proliferation with abundant collagen fibers. Immunoreactivity for CD34 antigen antibody was detected in fibrous spindle cells. This is the first report to present an immunohistochemical profile of neural fibrolipoma. Neural fibrolipoma should be considered as a differential diagnosis when a lipomatous lesion is encountered in the foot or ankle as well as in the upper extremities.

Early Osteolysis Following Total Hip Arthroplasty with Use of a Hylamer Liner in Combination with a Modular Ceramic Femoral Head. A Case Report

In an effort to improve the surface and wear characteristics of ultra-high molecular weight polyethylene, an enhanced ultra-high molecular weight polyethylene (Hylamer; DePuy-DuPont Orthopaedics, Wilmington, Delaware)6 was introduced in 1991. It was anticipated that the wear characteristics of a Hylamer acetabular surface in combination with a ceramic modular femoral head would improve the long-term performance of prostheses in young, active patients4,25. Several recent reports, however, have described wear and early osteolysis in association with Hylamer acetabular liners coupled with cobalt-chromium modular femoral heads manufactured by various companies3,15. The purpose of the current report is to describe rapid wear and early osteolysis following use of a Hylamer acetabular liner in combination with a ceramic femoral head made by the same manufacturer. In April 1994, a total hip arthroplasty was performed on a thirty-three-year-old woman (height, 167 centimeters; weight, fifty-two kilograms) who had arthritis due to congenital dysplasia of the left hip. The patients preoperative work activities as an accountant had required frequent climbing and descending of multiple sets of stairs, which had greatly aggravated the problems with the hip. The work environment subsequently was modified to better accommodate the patient. The arthroplasty was performed with use of components from the same manufacturer. These included a femoral component (Stability; DePuy Orthopaedics, Warsaw, Indiana) measuring twelve by 150 millimeters, which was inserted without cement; an acetabular shell (Duraloc; DePuy Orthopaedics) with a diameter of fifty-two millimeters, also inserted without cement; a Ti-6Al-4V bone-screw (Low Profile; DePuy Orthopaedics) with a diameter of 6.5 millimeters and a length of thirty millimeters, for augmentation of the cup; and a neutral Hylamer liner measuring fifty-two by twenty-eight millimeters with a thickness of eight millimeters. Because of the patients young age, activity level, and life expectancy, an aluminum-oxide-ceramic modular …

A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype

The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types—notochordal cells (NCs) and non‐notochordal chondrocyte‐like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI‐positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin‐8‐ and galectin‐3‐co‐positive cells, identified as NCs. The proportion of TUNEL‐positive cells, which predominantly comprised non‐NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up‐regulation of ADAMTS‐5 in the 1‐day loaded group and MMP‐3 in the 7‐day loaded group. Aggrecan‐1 and collagen type 2α‐1 mRNA levels were down‐regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration.

Satisfactory results at 8 years mean follow-up after ADVANCE® medial-pivot total knee arthroplasty.

BACKGROUND Although good overall results have been reported with TKA, certain problems and limitations remain, primarily due to postoperative differences in joint kinematics, when compared with the normal knee. ADVANCE® Medial-Pivot TKA involves replicating the medial pivoting behavior observed in normal knees. Here, we aimed to investigate the clinical and radiological results and complications of TKA using this implant, at mid-term follow-up. METHODS From January 2001 to March 2012, we retrospectively selected 76 patients (85 knees; mean age at operation, 70.2±8.1 years; range, 51-88 years) with a mean follow-up period of 93.1±14.3 months (range, 72-132 months). Indications for TKA included primary degenerative osteoarthritis (60 knees), rheumatoid arthritis (22 knees), osteonecrosis (two knees), and osteoarthritis following high tibial osteotomy (one knee). The clinical and radiographic results were evaluated. RESULTS Kaplan-Meier survivorship analysis indicated a success rate of 98.3% (95% confidence interval, 96.6-99.9%). Comparison of pre- and postoperative knee extension angles and ranges of motion showed significant improvement postoperatively, in both the Knee Society Scores (KSS) and Knee Society Functional Scores (KSFS) (p<0.05). In one case, radiographic assessment indicated implant loosening due to infection; however, despite this complication, significant improvement of postoperative varus or valgus deformity angles were noted in all cases (p<0.05). CONCLUSION Patients undergoing ADVANCE® Medial-Pivot TKA achieved excellent clinical and radiographic results without any implant-related failures at mid-term follow-up. LEVEL OF EVIDENCE Level IV.