A sugar-based phase-transitioning delivery system for bone tissue engineering
1 Orthopaedic Research and Biotechnology Unit, The Children’s Hospital at Westmead, Sydney, Australia
2 Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Sydney, Australia
3 School of Chemical and Biomolecular Engineering, University of Sydney, Sydney, Australia
4 Microscopy Services at The Kids Research Institute, The Children’s Hospital at Westmead, Sydney, Australia
Abstract
Bone tissue engineering approaches commonly involve the delivery of recombinant human bone morphogenetic proteins (rhBMPs). However, there are limitations associated with the currently used carriers, including the need for surgical implantation and the associated increase in infection risk. As an alternative to traditional porous collagen sponge, we have adopted a solution of the injectable sucrose acetate isobutyrate (SAIB) as a carrier for rhBMP-2. The ability to deliver rhBMP-2 and other agents by injection reduces the infection risk and lesion size whilst in surgery, with the potential to avoid open surgery altogether in some indications.The primary methodology used for thisin vivostudy was a C57BL6/J mouse ectopic bone formation model. Specimens were examined by x-ray, microCT, and histology at 3 weeks. SAIB was delivered non-invasively and produced up to 3-fold greater bone volume compared to collagen. To further refine and improve upon the formulation, SAIB containing rhBMP-2 was admixed with candidate compounds including ceramic microparticles, anti-resorptives, and cell signalling inhibitors and further testedin vivo.The formulation combining SAIB/rhBMP-2, the bisphosphonate zoledronic acid (ZA), and hydroxyapatite (HA) microparticles yielded a 10-fold greater bone volume than SAIB/rhBMP-2 alone. To investigate the mechanism underlying the synergy between ZA and HA, we usedin vitrobinding assays andin vivofluorescent biodistribution studies to demonstrate that ceramic particles could bind and sequester the bisphosphonate. These data show the utility of SAIB as a non-invasive rhBMP delivery system as well as describing an optimised formulation for bone tissue engineering.
Keyword
- Sucrose acetate isobutyrate; injectable scaffold; bisphosphonate; hydroxyapatite; bone tissue engineering
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