Nano-Hydroxyapatite Bone Substitute Functionalized with Bone Active Molecules for Enhanced Cranial Bone Regeneration.
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.
Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur , Kanpur 208016, India.
Arun Kumar
AK
Teotia
Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur , Kanpur 208016, India.|Department of Orthopedics, Clinical Sciences Lund, Lund University , Lund 221 85, Sweden.
Deepak Bushan
DB
Raina
Center for Biomedical Research, SGPGIMS Campus , Lucknow 226014, India.
Chandan
C
Singh
Center for Biomedical Research, SGPGIMS Campus , Lucknow 226014, India.
Neeraj
N
Sinha
Department of Orthopedics, Clinical Sciences Lund, Lund University , Lund 221 85, Sweden.|Department of Biomedical Engineering, Lund University , Lund 221 00, Sweden.
Hanna
H
Isaksson
Department of Orthopedics, Clinical Sciences Lund, Lund University , Lund 221 85, Sweden.
Magnus
M
Tägil
Department of Orthopedics, Clinical Sciences Lund, Lund University , Lund 221 85, Sweden.
Lars
L
Lidgren
Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur , Kanpur 208016, India.
Ashok
http://orcid.org/0000-0002-4910-9440
A
Kumar
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D001861:Bone Regeneration; D018786:Bone Substitutes; D017886:Durapatite; D006801:Humans; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D012886:Skull; D016212:Transforming Growth Factor beta
D055396:Bone Morphogenetic Protein 2; D018786:Bone Substitutes; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D017886:Durapatite
bisphosphonates; bone morphogenetic proteins; cranial model; nano-hydroxyapatite; osteoinductive; solid state NMR