Synergy between Rhbmp-2 and IKK-Inhibitor PS-1145 Delivered via a Porous Biodegradable Polymer ImplantDavid Carr1,2, Nicole Y.C Yu1,2, Jane Fitzpatrick4, Lauren Peacock1, Kathy Mikulec1, Andrew J. Ruys2, Justin C. Cooper-White4, David G. Little1,3 and Aaron Schindeler1,3*
- Corresponding Author:
- Aaron Schindeler
Department of Orthopaedic Research & Biotechnology
The Children’s Hospital at Westmead, Locked Bag 4001
Westmead, NSW 2145, Australia
E-mail: [email protected]
Received date: April 03, 2012; Accepted date: April 24, 2012; Published date: April 26, 2012
Citation: Carr D, Yu NYC, Fitzpatrick J, Peacock L, Mikulec K, et al. (2012) Synergy between rhBMP-2 and IKK-Inhibitor PS-1145 Delivered via a Porous Biodegradable Polymer Implant. J Tissue Sci Eng S1:003. doi:10.4172/2157-7552.S1-003
Copyright: © 2012 Carr D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits nrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Critical-sized bone defects, whether caused by congenital malformation, tumor resection, trauma, or implant loosening, remain a major challenge for orthopaedic management. In this study we describe a bone tissue engineering approach in mice for the co-delivery of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2) and the IKK inhibitor PS-1145.
Scaffold implants were manufactured from poly(lactide-co-glycolide)(PLGA) by Thermally-Induced Phase Separation (TIPS), with rhBMP-2 (10 μg) and the IKK inhibitor PS-1145 (0 μg, 40 μg or 80 μg) incorporated into the polymer. These scaffolds were then surgically implanted into the hind limb muscle of C57BL6/J mice. One group of mice also received systemic 50 mg/kg PS-1145 (days 11-20). Specimens were harvested at week 3 for X-ray and microCT analyses and descriptive histology.
Local and systemic delivery PS-1145 both significantly increased the net rhBMP-2 induced bone at 3 weeks. A maximal response was seen with the 40 μg PS-1145 group, although there was no significant difference between the 40 μg and 80 μg PS-1145 regimens. No local cytotoxicity was seen with either dose of PS-1145. In summary, local co-delivery of rhBMP-2 and PS-1145 via a porous PLGA scaffold represents a new tissue engineering approach for maintaining new bone in an unloaded environment.