2010 Volume No 20 – pages 431-442
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Title: In vivo local co-delivery of recombinant human bone morphogenetic protein-7 and pamidronate via poly-D, L-lactic acid |
Author: NYC Yu, A Schindeler, L Peacock, K Mikulec, PA Baldock, AJ Ruys, DG Little |
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Address: The Children's Hospital at Westmead, Orthopaedic Research and Biotechnology Unit, Locked Bag 4001, Westmead, Sydney, NSW 2145, Australia |
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E-mail: nicole.yu at sydney.edu.au or aaron.schindeler at sydney.edu.au |
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Key Words: Anabolism, catabolism, bone tissue engineering, bone morphogenetic protein (BMP), bisphosphonate
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Publication date: December 22nd 2010 |
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Abstract: The effects of bone anabolic agents such as bone morphogenetic proteins (BMPs) have the potential to be augmented by co-treatment with an anti-catabolic such as a bisphosphonate. We hypothesised that the effects of bisphosphonates on BMP-induced bone anabolism would be dose dependent, and we aimed to test this in a small animal model. Agents were delivered locally using a biodegradable poly-d, l-lactic-acid (PDLLA) polymer delivery system. Recombinant human BMP-7 (25 µg) was tested with a range of doses of the bisphosphonate pamidronate (0.02 mg, 0.2 mg and 2 mg local PAM; 0.3 mg/kg and 3 mg/kg thrice-weekly systemic PAM) versus BMP-7 alone. Polymer pellets were surgically implanted in the hind limbs of female C57BL6/J mice (8-10 week) and ectopic bone nodules were harvested at 3 and 8 weeks post-operatively. At 3 weeks, local low dose PAM (0.02 mg) induced a 102% increase in rhBMP-7 induced bone volume (p<0.01) as measured by miroCT, and this was comparable to systemic PAM (0.3 mg/kg thrice-weekly). In contrast, local high dose PAM (2 mg) resulted in a 97% decrease in bone volume (p<0.01). Radiography and histology indicated that the polymer vehicle was still largely present at 8 weeks indicating inefficient biodegradation. This is the first study to validate the utility of local co-delivery of BMP/bisphosphonate via biodegradable polymer and supports the continued refinement of more advanced bioresorbable delivery systems for clinical applications. |
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Article download: Pages
431-442 (PDF file) |
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