Nano-Hydroxyapatite Bone Substitute Functionalized with Bone Active Molecules for Enhanced Cranial Bone Regeneration

作者:Teotia Arun Kumar; Raina Deepak Bushan; Singh Chandan; Sinha Neeraj; Isaksson Hanna; Tagil Magnus; Lidgren Lars; Kumar Ashok*
来源:ACS Applied Materials & Interfaces, 2017, 9(8): 6816-6828.
DOI:10.1021/acsami.6b14782

摘要

The aim of this study was to synthesize and characterize a nano-hydroxya.patite (nHAP) and calcium sulfate bone substitute (NC) for cranioplasty. The NC was functionalized with low concentrations of bone morphogenetic protein-2 (EMP2) and zoledronic acid (ZA) and characterized both in vitro and in vivo. In vitro studies included MTT, ALP assays, and fluorescent staining of Saos-2 (human osteoblasts) and MC3T3-E1,(murine preosteoblasts) cells cultured on NC. An in vivo study divided 20 male Wistar rats into four groups: control (defect only), NC, NC + ZA, and NC + ZA + rhBMP-2. The materials were implanted in an 8.5 mm critical size defect in the calvarium for 12 weeks. Micro-CT quantitative analysis was carried out in vivo at 8 weeks and ex vivo after 12 weeks. Mineralization was highest in the NC + ZA + rhBMP-2 group (13.0 +/- 2.8 mm(3)) compared to the NC + ZA group (9.0 +/- 3.2 mm(3)), NC group (6.4 +/- 1.9 mm(3)), and control group (3.4 +/- 1.0 mm(3)) after 12 weeks. Histological and spectroscopic analysis of the defect site provided a qualitative confirmation of neo-bone, which was in agreement with the micro-CT results. In conclusion, NC can be used as a carrier for bioactive molecules, and functionalization with rhBMP-2 and ZA in low doses enhances bone regeneration.

  • 出版日期2017-3-1