Modulation of anabolic and catabolic responses via a porous polymer scaffold manufactured using thermally induced phase separation

Yu, Nicole Y. C., Schindeler, Aaron, Peacock, Lauren, Mikulec, Kathy, Fitzpatrick, Jane, Ruys, Andrew J., Cooper-White, Justin J. and Little, David G. (2013) Modulation of anabolic and catabolic responses via a porous polymer scaffold manufactured using thermally induced phase separation. European Cells and Materials, 25 190-203.

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Author Yu, Nicole Y. C.
Schindeler, Aaron
Peacock, Lauren
Mikulec, Kathy
Fitzpatrick, Jane
Ruys, Andrew J.
Cooper-White, Justin J.
Little, David G.
Title Modulation of anabolic and catabolic responses via a porous polymer scaffold manufactured using thermally induced phase separation
Journal name European Cells and Materials   Check publisher's open access policy
ISSN 1473-2262
Publication date 2013-02-27
Year available 2013
Sub-type Article (original research)
Volume 25
Start page 190
End page 203
Total pages 14
Place of publication Switzerland
Publisher Swiss Society for Biomaterials
Collection year 2014
Language eng
Formatted 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 vivo ectopic 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 10 µg rhBMP-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
Bone morphogenetic protein-2
In-vivo
Biodegradable polymers
Mechanical-properties
Composite scaffolds
Local-delivery
Bisphosphonate
Resorption
Vitro
Zoledronate
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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