%0 Journal Article
%T Modulation of anabolic and catabolic responses via a porous polymer scaffold manufactured using thermally induced phase separation
%A NYC Yu
%A A Schindeler
%A L Peacock
%A K Mikulec
%J European Cells and Materials (ECM)
%D 2013
%I 
%X 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 vivo ectopic bone formation studies were performed in C57BL6/J mice. Polymer scaffolds containing 0, 5, 10 or 20 ¦Ìg 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 10 ¦Ìg rhBMP-2 ¡À 0.2, or 2 ¦Ìg zoledronic acid (ZA) were inserted into the hind-limb musculature. Co-delivery of local 10 ¦Ìg rhBMP-2/2 ¦Ìg 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 ¦Ìg rhBMP-2/0.2 ¦Ìg 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.
%K Zoledronic acid
%K bisphosphonate
%K rhBMP-2
%K bone morphogenetic protein
%K bone tissue engineering
%K biodegradable polymer scaffold
%K thermally induced phase separation
%U http://www.ecmjournal.org/journal/papers/vol025/pdf/v025a14.pdf