J Tissue Sci Eng Bone Tissue Engineering ISSN: 2157-7552 JTSE an open access journal Research Article Open Access Carr et al., J Tissue Sci Eng 2012, S:1 DOI: 10.4172/2157-7552.S1-003 Keywords: PS1145; IKK inhibitor; rhBMP-2; Bone morphogenetic protein; Bone tissue engineering; Biodegradable polymer scaffold; ermally induced phase separation Introduction Treatment of critical-sized bone defects remains a challenge for orthopaedic medicine. Such defects require exogenous osteogenic stimulation in order for them to heal [1], autograſt being the current gold standard. Autograſt is not without its limitations, including its availability and complications associated with donor site morbidity [2-8]. Other alternatives, such as allograſt or bone transport using the Ilizarov technique, have utility but key limitations. Allograſt has a reduced osteoinductive capacity and has an intrinsic disease and rejection risk [4,6,8], while bone transport can be prolonged and uncomfortable [9-11]. Bone tissue engineering is a developing field of research that shows many promising possibilities for the treatment of critical size bone defects [6]. Giannoudis et al.[12] have described four essential components required to facilitate engineered bone as being (1) an osteoconductive matrix scaffold; (2) osteoinductive growth factors; (3) a cell population with osteogenic capacity; and (4) a mechanically stable environment. In this study, we aimed to create a biocompatible porous scaffold for the delivery of osteoinductive growth factors. In mice, new bone was induced within the muscle compartment; this tissue contains cells with osteogenic potential [13], but represents a mechanically unloaded environment. To compensate for the biomechanical insufficiency, we have trialed local delivery of an IKK inhibitor to prevent osteoclast-mediated bone loss. A range of materials have been proposed for scaffolds including metals, ceramics and polymers, both natural and synthetic. Synthetic polymers have become the most commonly used material for bone tissue engineering, particularly the poly(α-hydroxyacids),which have great chemical versatility [8,14-16]. Numerous methods have been used to fabricate poly(α-hydroxyacids) scaffolds to optimize the essential properties of a scaffold (porosity, pore size, surface properties, osteoinductivity, mechanical properties, and biodegradability). Solvent-casting and particulate leaching [17], emulsion freeze-drying [18], electrospinning [19], gas foaming [20], the various types of rapid prototyping [21] and most recently thermally induced phase separation (TIPS) [22] have all been described. We have utilized a TIPS-based method that allows for rapid fabrication of high porosity scaffolds with defined pore sizes. Poly(lactide-co-glycolide) (PLGA) was used as a copolymer of poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) to generate a material capable of degrading into non-toxic, natural metabolites [14]. Osteoinductive growth factors are an integral component of bone tissue engineering. Recombinant human BMP-2 and BMP-7 are potent anabolic agents that are reported to have an efficacy comparable to autograſt and act to potently stimulate the differentiation of *Corresponding author: Aaron Schindeler, Department of Orthopaedic Research & Biotechnology, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia, Tel: +61-2-98451451; Fax: +61-2-98453078; E-mail: aaron.schindeler@sydney.edu.au Received April 03, 2012; Accepted April 24, 2012; Published April 26, 2012 Citation: Carr D, Yu NYC, Fitzpatrick J, Peacock L, Mikulec K, et al. (2011) 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: © 2011 Carr D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Synergy between rhBMP-2 and IKK-Inhibitor PS-1145 Delivered via a Porous Biodegradable Polymer Implant David Carr 1,2 , Nicole Y.C Yu 1,2 , Jane Fitzpatrick 4 , Lauren Peacock 1 , Kathy Mikulec 1 , Andrew J. Ruys 2 , Justin C. Cooper-White 4 , David G. Little 1,3 and Aaron Schindeler 1,3 * 1 Department of Orthopaedic Research & Biotechnology, The Children’s Hospital at Westmead, Locked Bag 4001, Westmead, NSW 2145, Australia 2 School of Aerospace, Mechanical and Mechatronic Engineering, J07 University of Sydney, NSW 2006, Australia 3 Discipline of Paediatrics and Child Health, Faculty of Medicine, A27 University of Sydney, NSW 2006, Australia 4 Tissue Engineering and Microfluidics Laboratory, Australian Institute for Nanotechnology and Bioengineering, University of Queensland, Brisbane, QLD, Australia Abstract 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. Journal of Tissue Science & Engineering J o u r n a l o f T i s s u e S c i e n c e & E n g i n e e r i n g ISSN: 2157-7552