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Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 20 - 20
1 Apr 2018
Kuroda Y Akiyama H Matsuda S
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Introduction

For many years, minimally invasive joint-preserving regenerative therapy has been desired for the early stages of osteonecrosis of the femoral head (ONFH). In an animal study using adult rabbits, we reported that a single local injection of rhFGF-2-impregnated gelatin hydrogel, which has superior slow-release characteristics, suppresses the progression of femoral head necrosis. The purpose of this study was to evaluate the safety and clinical outcomes of a single local administration of rhFGF-2-impregnated gelatin hydrogel for the precollapse stage of ONFH. Patients and Methods: Ten patients with femoral heads up to precollapse stage 2 underwent a single local administration of 800-µg rhFGF-2-impregnated gelatin hydrogel and were followed up for two years. The eligibility criteria were age between 20 and 80 years and presence of ONFH at precollapse stage 1 or 2 according to the classification system for ONFH developed by the Japanese Investigation Committee of Health and Welfare. Primary outcomes included adverse events and complications. Secondary outcomes included changes in Harris Hip Scores (HHS), visual analog scale pain scores (VAS), the University of California, Los Angeles (UCLA) activity rating scores, radiological changes as determined via radiographs, computed tomography (CT) scans, and magnetic resonance imaging (MRI) of the hip joint. Results: We included five men (five hips) and five women (five hips), with a mean age of 39.8 years (range: 29–53 years) at the time of surgery. Eight patients had bilateral ONFH, three had already undergone THA on the contralateral side. Eight patients were receiving treatment with corticosteroid therapy, and two patients overused alcohol. Stage 1 and 2 disease was present in one and nine patients, respectively. One patient each had type A, type B, and type C1 disease, whereas seven patients had a type C2 lesion. All Adverse events were recovered without problem. The surgery was performed with a minimally invasive technique based core decompression (1 cm of skin incision), and walking was allowed from the day after surgery. Mean clinical scores improved significantly after three year compared with before surgery (before vs. after: VAS for pain, 21.2 vs. 5.3 mm; UCLA activity score 5.5 vs. 6.6; HHS, 81.0 vs. 98.4 points, respectively). There was only one case of femoral head collapse, and it had the greatest necrosis volume fraction and was considered to be in the early collapse stage at the time of operation. The other nine cases did not involve ONFH stage progression, and collapse was prevented. CT images and recent MRI postoperatively confirmed bone regeneration and reduction of the necrotic area. Conclusion: Clinical application of rhFGF-2-impregnated gelatin hydrogel for patients with precollapse stage of ONFH was feasible and safe. Our research is ongoing, further phase II multiple center study has been started in January 2016.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_3 | Pages 56 - 56
1 Apr 2018
Nishitani K Ishikawa M de Mesy Bentley K Ito H Matsuda S Daiss J Schwarz E
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INTRODUCTION

Staphylococci species account for ∼80 % of osteomyelitis cases. While the most severe infections are caused by Staphylococcus aureus (S. aureus), the clinical significance of coagulase negative Staphylococcus epidermidis (S. epidermidis) infections remain controversial. In general, S. epidermidis was known to be a protective commensal bacterium. However, recent studies have shown that intra-operative low-grade S. epidermidis contamination prevents bone healing. Thus, the purpose of this study is to compare the pathogenic features of S. aureus and S. epidermidis in an established murine model of implant-associated osteomyelitis.

METHODS

All animal experiments were performed on IACUC approved protocols. USA300LAC (MRSA) and RP62A(S. epidermidis) were used as prototypic bacterial strains. After sterilization, stainless steel pins were implanted into the tibiae of BALB/c mice (n=5 each) with or without Staphylococci. Mice were euthanized on day 14, and the implants were removed for scanning electron microscopy (SEM). Tibiae were fixed for mCT prior to decalcification for histology.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 341 - 341
1 Jul 2014
Ito H Fujii T Kasahara T Ishikawa M Furu M Shibuya H Matsuda S
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Summary Statement

In articular cartilage defects, chemokines are upregulated and potentially induce the migration of bone marrow cells to accelerate the healing processes.

Introduction

The treatment of damaged articular cartilages is one of the most challenging issues in sports medicine and in aging societies. In the microfracture technique for the treatment of articular cartilage defects, bone marrow cells are assumed to migrate from the bone marrow. Bone marrow cells are well-known for playing crucial roles in the healing processes, but how they can migrate from underlying bone marrow remains to be investigated. We have previously shown that SDF-1, one of chemokines, play crucial roles in the recruitment of mesenchymal stem cells in bone healing processes, and the induction of SDF-1 can induce a successful bone repair. If the migration can be stimulated by any means in the cartilage defects, a better result can be expected. The aim of this study was to elucidate the mechanisms of the migration of bone marrow cells and which factors contribute to the processes.


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 209 - 209
1 Jul 2014
Ishikawa M Ito H Yoshitomi H Murata K Shibuya H Furu M Kitaori T Nakamura T Matsuda S
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Summary Statement

MCP-1/ CCR2 axis at the early phase plays a pivotal role in the fracture healing. Inflammation plays a pivotal role in fracture healing. Among them, chemokines play key roles in inflammation. Monocyte chemotactic protein-1 (MCP-1), via its receptor C-C chemokine receptor 2 (CCR2), acts as a potent chemoattractant for various cells to promote migration from circulation to inflammation site. Thus, the importance of MCP-1/CCR2 axis in fracture healing has been suggested. However, the involvement of MCP-1/CCR2 axis tofracture site is not fully elucidated.

Results

PCR Array: The expression of MCP-1 and MCP-3 had increased on day 2 than 0 or 7 in the rib fracture healing. Immunohistochemistry Staining: To verify the localization of MCP-1 expression, we examined the Wild type (WT)-mouse rib fracture healing. We observed high expression of MCP-1 and MCP-3 at the periosteum and the endosteum on post-fracture day 3. In vivo Antagonist Study: To elucidate whether MCP-1/CCR2 axis is involved during the early phase of fracture healing, we continuously administered RS102895, CCR2 antagonist, before or after rib fracture. Micro-CT analysis showed delayed fracture healing in the before-group compared with both the control and after-group. On day 21, the hard callus volume in the before-group was significantly smaller than that in the control-group. Histological analysis showed that fractures in both the control and the after-groups were healed by day 21. In contrast, less of cartilage in the callus was observed in the before-group on day 7. Gain of Function: To examine the roles of MCP-1 at the periosteum and the endosteum during the fracture healing, we created a segmental bone graft exchanging model. The bone grafts were transplanted from MCP-1−/− mice to another MCP-1−/− mice (KO-to-KO). Micro-CT analysis showed that KO-to-KO transplantation led to the delay of fracture healing on day 21. Next, we created exchanging-bone graft models between MCP-1−/− and WT mice, in which a segmental bone derived from a WT mouse was transplanted into a host MCP-1−/− mouse (WT-to-KO). In contrast to KO-to-KO bone graft transplantation, the transplantation of WT-derived graft into host KO mouse resulted in a significant increase of new bone formation on day 21. Histological analysis revealed that marked and localised induction of MCP-1 expression in the periosteum and the endosteum around the WT-derived graft was observed in the host MCP-1−/− mouse. Loss of Function: To validate whether MCP-1 is a crucial chemokine for fracture healing, we created WT-to-WT and KO-to-WT bone graft models. When WT-donor graft was transplanted into WT-host, abundant new bone formation was observed around a WT-derived graft on day 21. In contrast, transplantation of KO-derived graft into WT-host resulted in a marked reduction of periosteal bone formation on a donor graft.