Non-invasive monitoring of BMP-2 retention and bone formation in composites for bone tissue engineering using SPECT/CT and scintillation probes

Diederik H.R. Kempen, Michael J. Yaszemski, Andras Heijink, Theresa E. Hefferan, Laura B. Creemers, Jason Britson, Avudaiappan Maran, Kelly L. Classic, Wouter J.A. Dhert, Lichun Lu

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Non-invasive imaging can provide essential information for the optimization of new drug delivery-based bone regeneration strategies to repair damaged or impaired bone tissue. This study investigates the applicability of nuclear medicine and radiological techniques to monitor growth factor retention profiles and subsequent effects on bone formation. Recombinant human bone morphogenetic protein-2 (BMP-2, 6.5 μg/scaffold) was incorporated into a sustained release vehicle consisting of poly(lactic-co-glycolic acid) microspheres embedded in a poly(propylene fumarate) scaffold surrounded by a gelatin hydrogel and implanted subcutaneously and in 5-mm segmental femoral defects in 9 rats for a period of 56 days. To determine the pharmacokinetic profile, BMP-2 was radiolabeled with 125I and the local retention of 125I-BMP-2 was measured by single photon emission computed tomography (SPECT), scintillation probes and ex vivo scintillation analysis. Bone formation was monitored by micro-computed tomography (μCT). The scaffolds released BMP-2 in a sustained fashion over the 56-day implantation period. A good correlation between the SPECT and scintillation probe measurements was found and there were no significant differences between the non-invasive and ex-vivo counting method after 8 weeks of follow up. SPECT analysis of the total body and thyroid counts showed a limited accumulation of 125I within the body. Ectopic bone formation was induced in the scaffolds and the femur defects healed completely. In vivo μCT imaging detected the first signs of bone formation at days 14 and 28 for the orthotopic and ectopic implants, respectively, and provided a detailed profile of the bone formation rate. Overall, this study clearly demonstrates the benefit of applying non-invasive techniques in drug delivery-based bone regeneration strategies by providing detailed and reliable profiles of the growth factor retention and bone formation at different implantation sites in a limited number of animals.

Original languageEnglish (US)
Pages (from-to)169-176
Number of pages8
JournalJournal of Controlled Release
Volume134
Issue number3
DOIs
StatePublished - Mar 19 2009

Keywords

  • Bone morphogenetic protein-2
  • Controlled release
  • Drug delivery
  • Micro-computed tomography
  • Scintillation probes
  • Single photon emission computed tomography

ASJC Scopus subject areas

  • Pharmaceutical Science

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