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

Teotia, Arun Kumar ; Raina, Deepak Bushan LU ; Singh, Chandan ; Sinha, Neeraj ; Isaksson, Hanna LU orcid ; Tägil, Magnus LU ; Lidgren, Lars LU and Kumar, Ashok LU (2017) In ACS Applied Materials and Interfaces 9(8). p.6816-6828
Abstract

The aim of this study was to synthesize and characterize a nano-hydroxyapatite (nHAP) and calcium sulfate bone substitute (NC) for cranioplasty. The NC was functionalized with low concentrations of bone morphogenetic protein-2 (BMP-2) 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... (More)

The aim of this study was to synthesize and characterize a nano-hydroxyapatite (nHAP) and calcium sulfate bone substitute (NC) for cranioplasty. The NC was functionalized with low concentrations of bone morphogenetic protein-2 (BMP-2) 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 mm3) compared to the NC + ZA group (9.0 ± 3.2 mm3), NC group (6.4 ± 1.9 mm3), and control group (3.4 ± 1.0 mm3) 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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bisphosphonates, bone morphogenetic proteins, cranial model, nano-hydroxyapatite, osteoinductive, solid state NMR
in
ACS Applied Materials and Interfaces
volume
9
issue
8
pages
13 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • scopus:85014209918
  • pmid:28171719
ISSN
1944-8244
DOI
10.1021/acsami.6b14782
language
English
LU publication?
yes
id
914e9cb4-8bf1-48ff-b742-35e1195fba62
date added to LUP
2017-03-15 07:40:22
date last changed
2024-04-14 07:46:34
@article{914e9cb4-8bf1-48ff-b742-35e1195fba62,
  abstract     = {{<p>The aim of this study was to synthesize and characterize a nano-hydroxyapatite (nHAP) and calcium sulfate bone substitute (NC) for cranioplasty. The NC was functionalized with low concentrations of bone morphogenetic protein-2 (BMP-2) 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<sup>3</sup>) compared to the NC + ZA group (9.0 ± 3.2 mm<sup>3</sup>), NC group (6.4 ± 1.9 mm<sup>3</sup>), and control group (3.4 ± 1.0 mm<sup>3</sup>) 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.</p>}},
  author       = {{Teotia, Arun Kumar and Raina, Deepak Bushan and Singh, Chandan and Sinha, Neeraj and Isaksson, Hanna and Tägil, Magnus and Lidgren, Lars and Kumar, Ashok}},
  issn         = {{1944-8244}},
  keywords     = {{bisphosphonates; bone morphogenetic proteins; cranial model; nano-hydroxyapatite; osteoinductive; solid state NMR}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{8}},
  pages        = {{6816--6828}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{ACS Applied Materials and Interfaces}},
  title        = {{Nano-Hydroxyapatite Bone Substitute Functionalized with Bone Active Molecules for Enhanced Cranial Bone Regeneration}},
  url          = {{http://dx.doi.org/10.1021/acsami.6b14782}},
  doi          = {{10.1021/acsami.6b14782}},
  volume       = {{9}},
  year         = {{2017}},
}