Article
PLGA-fiber reinforcement of injectable calcium phosphate cement enhances bone regeneration in an in vivo vertebral body augmentation model
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Published: | October 10, 2016 |
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Objectives: Injectable calcium phosphate cements (CPC) represent resorbable, bioactive, osteoconductive alternatives to bioinert polymethylmethacrylate cement. However, their low mechanical strength currently makes them unsuitable for the filling/treatment of bone defects in load-bearing areas, e.g. in vertebral body fractures. To improve their mechanical strength, CPC can be reinforced using fibers. The present study assessed the influence of a newly developed, fiber-reinforced, injectable CPC on bone regeneration in a minimally-invasive, in vivo vertebroplasty model in the lumbar spine of sheep.
Methods: An injectable, biodegradable, brushite-forming CPC based on a commercial cement (FDA-approved, JectOS+; Kasios, L'Union, France) with fiber reinforcement was developed for minimally-invasive surgery. The fibers (diameter 25 µm; length 1 mm) were extruded from degradable poly (l-lactide-co-glycolide) acid (PLGA) and added to the CPC (10% (w/w)). Defined bone defects (diameter 5 mm; depth approx. 1/2 of the total vertebral body width; L1 untouched; L2 empty defect; L3 pure CPC (pCPC); L4 fiber-reinforced (F-CPC)) were created by a ventrolateral percutaneous approach in aged, osteopenic, female sheep (20 Merino sheep each group; 6 - 9 years old; 68 - 110 kg body weight). Three and 9 months post-operation, structural/functional effects of the CPC on bone regeneration were documented ex vivo by osteodensitometry, static histomorphometry, micro-CT, and biomechanical testing.
Results: Both pCPC and F-CPC significantly increased the bone mineral density (pCPC > untouched (3 and 9 months); F-CPC > untouched (3 and 9 months), empty (3 months); p < 0.05). The bone volume/total volume (BV/TV; static histomorphometry) was also significantly enhanced by cement augmentation (pCPC and F-CPC > untouched and empty, 3 and 9 months). In addition, F-CPC was significantly more potent than pCPC (9 months). BV/TV analysis with µCT showed that the increase of the BV/TV by F-CPC was particularly prominent at remote distances (at 2.0 mm and 2.5 mm from the defect; 3 months). Furthermore, F-CPC significantly improved the osteoid volume (F-CPC > pCPC; 9 months) and numerically decreased the eroded surface (3 and 9 months). The compression strength was only significantly influenced by F-CPC (F-CPC > untouched and empty; 9 months).
Conclusion: F-CPC (as compared to pCPC) increases bone formation and decreases bone erosion. In particular, F-CPC enhances bone regeneration at remote distances from the defect site. Therefore, F-CPC may be superior to pCPC in bone regeneration and potentially suited for the treatment of bone defects in load-bearing areas, e.g. vertebral body fractures.