Abstract

Large bone defects pose an unsolved challenge for orthopedic surgeons. Our group has previously reported the construction of a barrier membrane made of ammoniomethacrylate copolymer USP (AMCA), which supports the adhesion, proliferation, and osteoblastic differentiation of human mesenchymal stem cells (hMSCs). In this study, we report the use of AMCA membranes to seclude critical segmental defect (~1.0 cm) created in the middle third of rabbit radius and test the efficiency of bone regeneration. Bone regeneration was assessed by radiography, biweekly for 8 weeks. The results were verified by histology and micro-CT at the end of the follow-up. The AMCA membranes were found superior to no treatment in terms of new bone formation in the defect, bone volume, callus surface area normalized to total volume, and the number of bone trabeculae, after eight weeks. Additional factors were then assessed, and these included the addition of simvastatin to the membrane, coating the membrane with human MSC, and a combination of those. The addition of simvastatin to the membranes demonstrated a stronger effect at a similar radiological follow-up. We conclude that AMCA barrier membranes per se and simvastatin delivered in a controlled manner improve bone regeneration outcome.

Highlights

  • Despite the great regenerative potential of the bone, it may sometimes be insufficient and large segmental bone defects are frequently encountered in the treatment of high-energy fractures, osteomyelitis, and revision arthroplasty and following tumor resection

  • In order to test the effectiveness of ammoniomethacrylate copolymer USP (AMCA)-based barrier membrane in accelerating bone defect recovery, a critical-size radial defect was generated in rabbits with both forearms operated

  • Whereas one defect was treated by secluding it with the AMCA membrane, the contralateral defect served as the control

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Summary

Introduction

Despite the great regenerative potential of the bone, it may sometimes be insufficient and large segmental bone defects are frequently encountered in the treatment of high-energy fractures, osteomyelitis, and revision arthroplasty and following tumor resection. Regeneration of bone defects occurs naturally during fracture healing; and yet, clinical management strategies available today for large segmental bone defects suffer from several drawbacks. These strategies include autografts, allografts, distraction osteogenesis, and various osteogenic and osteoconductive substances, including many experimental treatments. Mesenchymal stem cells constitute a heterogeneous multipotent stem cell population with similar characteristics and are distributed in multiple tissues, including periosteum, and they can differentiate into chondroblasts, lipoblasts, and osteoblasts and may generate mature cells typically arising from the endoderm and ectoderm. The role of improved periosteum function was regarded as a model for guided bone regeneration [13]

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