Bisphosphonate-adsorbed ceramic nanoparticles increase bone formation in an injectable carrier for bone tissue engineering

J Tissue Eng. 2015 Oct 22:6:2041731415609448. doi: 10.1177/2041731415609448. eCollection 2015 Jan-Dec.

Abstract

Sucrose acetate isobutyrate (SAIB) is a sugar-based carrier. We have previously applied SAIB as a minimally invasive system for the co-delivery of recombinant human bone morphogenetic protein-2 (rhBMP-2) and found synergy when co-delivering zoledronic acid (ZA) and hydroxyapatite (HA) nanoparticles. Alternative bioceramics were investigated in a murine SAIB/rhBMP-2 injection model. Neither beta-tricalcium phosphate (TCP) nor Bioglass (BG) 45S5 had a significant effect on bone volume (BV) alone or in combination with the ZA. (14)C-labelled ZA binding assays showed particle size and ceramic composition affected binding with nano-HA > micro-HA > TCP > BG. Micro-HA and nano-HA increased BV in a rat model of rhBMP-2/SAIB injection (+278% and +337%), and BV was further increased with ZA-adsorbed micro-HA and nano-HA (+530% and +889%). These data support the use of ZA-adsorbed nanoparticle-sized HA as an optimal additive for the SAIB/rhBMP-2 injectable system for bone tissue engineering.

Keywords: Bioglass 45S5; Bone tissue engineering; bisphosphonate; hydroxyapatite; recombinant human bone morphogenetic protein-2; sucrose acetate isobutyrate; tricalcium phosphate.