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. 2021 Dec 31;47(6):454-464.
doi: 10.5125/jkaoms.2021.47.6.454.

Effects of the combination of bone morphogenetic protein-2 and nano-hydroxyapatite on the osseointegration of dental implants

KangMi Pang  1 , Young-Kwon Seo  2 , Jong-Ho Lee  3   4
Affiliations
Free PMC article

Effects of the combination of bone morphogenetic protein-2 and nano-hydroxyapatite on the osseointegration of dental implants

KangMi Pang et al. J Korean Assoc Oral Maxillofac Surg. .
Free PMC article

Abstract

Objectives: This study aimed to investigate the in vitro osteoinductivity of the combination of bone morphogenetic protein-2 (BMP-2) and nanohydroxyapatite (nHAp) and the in vivo effects of implants coated with nHAp/BMP-2.

Materials and methods: To evaluate the in vitro efficacy of nHAp/BMP-2 on bone formation, bone marrow-derived mesenchymal stem cells (BMMSCs) were seeded onto titanium disks coated with collagen (Col), Col/nHAp, or Col/nHAp/BMP-2. Protein levels were determined by a biochemical assay and reverse transcriptase-polymerase chain reaction. Stem cell differentiation was analyzed by flow cytometry. For in vivo studies with mice, Col, Col/nHAp, and Col/nHAp/BMP-2 were injected in subcutaneous pockets. Titanium implants or implants coated with Col/nHAp/BMP-2 were placed bilaterally on rabbit tibias and evaluated for 4 weeks.

Results: In the in vitro study, BM-MSCs on Col/nHAp/BMP-2 showed reduced levels of CD73, CD90, and CD105 and increased levels of glycosaminoglycan, osteopontin, and alkaline phosphatase activity. After 4 weeks, the Col/nHAp/BMP-2 implant showed greater bone formation than the control (P=0.07), while no differences were observed in bone implant contact and removal torque.

Conclusion: These results suggest that a combination of BMP-2 and an nHAp carrier would activate osseointegration on dental implant surfaces.

Keywords: Bone morphogenetic protein 2; Collagen; Dental implant; Hydroxyapatite; Osseointegration.

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Conflict of interest statement

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Figures

Fig. 1
Fig. 1
Topographic and three-dimensional atomic force microscopic images of the coatings. Titanium: untreated titanium disk, Col: collagen-coated titanium surface, Col/BMP-2: collagen/bone morphogenetic protein-2 (BMP-2)-coated titanium surface, Col/nHAp/BMP-2: collagen/nano-hydroxyapatite/BMP-2-coated titanium surface. (RMS: root mean square)
Fig. 2
Fig. 2
Static water contact angle on titanium surface. A. Negative control (resorbable blasted media surface titanium). B. Collagen-coated surface. C. Collagen/BMP-2-coated surface. D. Collagen/nHAp/BMP-2-coated surface. (BMP-2: bone morphogenetic protein-2, nHAp: nano-hydroxyapatite)
Fig. 3
Fig. 3
In vitro release curve of bone morphogenetic protein-2 (BMP-2) from various surface-treated titanium disks. The results are shown as mean±standard deviation values (n=3). An increase in BMP-2 release was observed within 24 hours. A sustained release in the Col/nHAp/BMP-2 group was observed between 1-5 days. (Col: collagen, nHAp: nano-hydroxyapatite)
Fig. 4
Fig. 4
Bone marrow-derived mesenchymal stem cell (BM-MSC) differentiation on differently treated titanium disks. A. Flow cytometry of typical CD markers present on BM-MSCs cultured on the Col-, Col/nHAp-, or Col/nHAp/BMP-2-coated titanium disks. CD73+, CD90+, and CD105+ cells were observed prior to differentiation. Reduction in mesenchymal CD73+, CD90+, and CD105+ cells was observed in the Col/nHAp/BMP-2 group. B. Biochemical assays for alkaline phosphatase (ALP) activity and intracellular glycosaminoglycan (GAG) and osteopontin expression in BM-MSCs. Cells on Col/nHAp/BMP-2 exhibited the highest expression. C. mRNA expression of different osteoblastic markers in BM-MSC. The highest expression was observed for type III collagen (Col III), osteocalcin, and osteoprotegerin in cells grown on Col/nHAp/BMP-2. The levels of type I collagen (Col I), osteopontin, osteonectin, and BMP-2 expression were higher in BM-MSCs on Col/nHAp and Col/nHAp/BMP-2 than in those with Col enrichment. (Col: collagen, nHAp: nano-hydroxyapatite, BMP-2: bone morphogenetic protein-2)
Fig. 5
Fig. 5
Histological images of the mouse subcutaneous pocket injection model. Col (A, D, G, J, M, P), Col/nHAp (B, E, H, K, N, Q), and Col/nHAp/BMP (C, F, I, L, O, R). Macroscopic images (A-C), H&E staining (D-F), Masson’s trichrome (MT) staining (G-I), von Kossa staining (J-L), osteonectin staining (M-O), and CD31 staining (P-R) (D-O: ×100, P-R: ×200, scale bars=200 µm). (Col: collagen, nHAp: nano-hydroxyapatite, BMP-2: bone morphogenetic protein-2)
Fig. 6
Fig. 6
Implant installation on rabbit tibia. A. Photograph of titanium implant (left) and Col/nHAp/BMP-2-coated implant (right). B-D. Bone implant contact, new bone area, and removal torque. At 4 weeks after implant installation on rabbit tibia, Col/nHAp/BMP-2 exhibited increased new bone area compared with the negative control (P=0.07), whereas bone implant contact and removal torque exhibited no significant difference, although the mean values were higher. (Col: collagen, nHAp: nano-hydroxyapatite, BMP-2: bone morphogenetic protein-2)
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