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. 2025 Jul 30;18(15):3582.
doi: 10.3390/ma18153582.

Assessment of Low-Dose rhBMP-2 and Vacuum Plasma Treatments on Titanium Implants for Osseointegration and Bone Regeneration

Won-Tak Cho  1 , Soon Chul Heo  2 , Hyung Joon Kim  2 , Seong Soo Kang  3 , Se Eun Kim  3 , Jong-Ho Lee  1 , Gang-Ho Bae  1 , Jung-Bo Huh  1
Affiliations

Assessment of Low-Dose rhBMP-2 and Vacuum Plasma Treatments on Titanium Implants for Osseointegration and Bone Regeneration

Won-Tak Cho et al. Materials (Basel). .

Abstract

This study evaluated the effects of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) coating in combination with vacuum plasma treatment on titanium implants, aiming to enhance osseointegration and bone regeneration while minimizing the adverse effects associated with high-dose rhBMP-2. In vitro analyses demonstrated that plasma treatment increased surface energy, promoting cell adhesion and proliferation. Additionally, it facilitated sustained rhBMP-2 release by enhancing protein binding to the implant surface. In vivo experiments using the four-beagle mandibular defect model were conducted with the following four groups: un-treated implants, rhBMP-2-coated implants, plasma-treated implants, and implants treated with both rhBMP-2 and plasma. Micro-computed tomography (micro-CT) and medical CT analyses revealed a significantly greater volume of newly formed bone in the combined treatment group (p < 0.05). Histological evaluation further confirmed superior outcomes in the combined group, showing significantly higher bone-to-implant contact (BIC), new bone area (NBA), and inter-thread bone density (ITBD) compared to the other groups (p < 0.05). These findings indicate that vacuum plasma treatment enhances the biological efficacy of low-dose rhBMP-2, representing a promising strategy to improve implant integration in compromised conditions. Further studies are warranted to determine the optimal clinical dosage.

Keywords: bone regeneration; osseointegration; rhBMP-2; titanium implant; vacuum plasma.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Surgical procedures for implant placement. (A) Intraoral photograph before surgery. (B) Flap elevation and alveolar bone flattening. (C) Marking of implant sites for defect creation. (D) Creation of occlusal cylindrical defects. (E) Allocation of implants according to experimental groups. (F) Suturing of the gingiva.
Figure 2
Figure 2
Medical CT images used for volumetric analysis. (A) Axial view. (B) Coronal view. (C) Sagittal view. (D) 3D rendering. (E) Panoramic view.
Figure 3
Figure 3
μ-CT images used for volumetric analysis of peri-implant bone. (A) Sagittal section showing the vertical and horizontal dimensions of the region of interest (ROI). (B) Axial section indicating the circular ROI around the implant.
Figure 4
Figure 4
Histological images used for histometric analysis. (A) Defined ROI area used to calculate new bone area (NBA), bone-to-implant contact (BIC), and inter-thread bone density (ITBD). (B) Measurement of BIC. (C) Measurement of ITBD.
Figure 5
Figure 5
Morphological images of implant surfaces at ×5000 (left) and ×15,000 (right) magnification. (A) Group NS; non-treated SLA disks. (B) Group BS; SLA disks coated with low-dose rhBMP-2. (C) Group PS; vacuum plasma-treated SLA disks. (D) Group PB; SLA disks treated with vacuum plasma irradiation followed by low-dose rhBMP-2 coating.
Figure 6
Figure 6
Survey XPS spectra of titanium disks from each group. (A) Group NS; non-treated SLA disks. (B) Group BS; SLA disks coated with low-dose rhBMP-2. (C) Group PS; vacuum plasma-treated SLA disks. (D) Group PB; SLA disks treated with both low-dose rhBMP-2 and vacuum plasma.
Figure 7
Figure 7
ALP activity according to treatment time and rhBMP-2 concentration. ns, not significance. ** Indicates statistical significance (p < 0.01). *** Indicates statistical significance (p < 0.001).
Figure 8
Figure 8
Real-time PCR analysis of C2C12 cells. ns, not significance. ** Indicates statistical significance (p < 0.01). *** Indicates statistical significance (p < 0.001).
Figure 9
Figure 9
Cumulative release kinetics of rhBMP-2 from the SLA surface.
Figure 10
Figure 10
Representative sectional medical CT images of each group at baseline (0 weeks) and 8 weeks post-implantation. Left column: coronal views; right column: sagittal views. (A) Group NS at 0 wk. (a) Group NS at 8 wk. (B) Group BS at 0 wk. (b) Group BS at 8 wk. (C) Group PS at 0 wk. (c) Group PS at 8 wk. (D) Group PB at 0 wk. (d) Group PB at 8 wk.
Figure 11
Figure 11
Representative sectional micro-CT images of each group at 8 weeks post-implantation. (A) Group NS; non-treated SLA implants. (B) Group BS; SLA implants coated with low-dose rhBMP-2. (C) Group PS; vacuum plasma-treated SLA implants. (D) Group PB; SLA disks treated with vacuum plasma irradiation followed by low-dose rhBMP-2 coating.
Figure 12
Figure 12
Goldner’s trichrome (GT) stain histological sections of each groups. (A) Group NS; non-treated SLA implants. (B) Group BS; SLA implants coated with low-dose rhBMP-2. (C) Group PS; vacuum plasma-treated SLA implants. (D) Group PB; SLA disks treated with vacuum plasma irradiation followed by low-dose rhBMP-2 coating. NB; new bone. OB; old bone.
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