Modulation of anabolic and catabolic responsesviaa porous polymer scaffold manufactured using thermally induced phase separation
, Aaron Schindeler 1,3,*, Lauren Peacock 1, Kathy Mikulec 1, Jane Fitzpatrick 4, Andrew J. Ruys 2, Justin J. Cooper-White 4, David G. Little 1,31 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 and the School of Chemical Engineering, University of Queensland, Brisbane, QLD, Australia
* These authors contributed equally as corresponding authors
Abstract
We describe two studies encompassing the iterative refinement of a polymer-based rhBMP-2 delivery system for bone tissue engineering. Firstly, we compared the bone-forming capacity of porous poly(D,L-lactic-co-glycolic acid) (PLGA) scaffolds produced by thermally induced phase separation (TIPS) with non-porous solvent cast poly(D,L-lactic acid) (PDLLA) used previously. Secondly, we examined the potential synergy between rhBMP-2 and local bisphosphonate in the PLGA scaffold system.In vivoectopic bone formation studies were performed in C57BL6/J mice. Polymer scaffolds containing 0, 5, 10 or 20 µg rhBMP-2 were inserted into the dorsal musculature. At all rhBMP-2 doses, porous PLGA produced significantly higher bone volume (BV, mm3) than the solid PDLLA scaffolds. Next, porous PLGA scaffolds containing 10µgrhBMP-2 ± 0.2, or 2 µg zoledronic acid (ZA) were inserted into the hind-limb musculature. Co-delivery of local 10 µg rhBMP-2/2 µg ZA significantly augmented bone formation compared with rhBMP-2 alone (400 % BV increase,p< 0.01). Hydroxyapatite microparticle (HAp) addition (2 % w/w) to the 10 µg rhBMP-2/0.2 µg ZA group increased BV (200 %,p< 0.01). We propose that this was due to controlled ZA release of HAp-bound ZA. Consistent with this, elution analyses showed that HAp addition did not alter the rhBMP-2 elution, but delayed ZA release. Moreover, 2 % w/w HAp addition reduced the scaffold’s compressive properties, but did not alter ease of surgical handling.In summary, our data show that refinement of the polymer selection and scaffold fabrication can enhance rhBMP-2 induced bone formation in our bone tissue engineering implant, and this can be further optimised by the local co-delivery of ZA/HAp.
Keyword
- Zoledronic acid; bisphosphonate; rhBMP-2; bone morphogenetic protein; bone tissue engineering; biodegradable polymer scaffold; thermally induced phase separation
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