Radiographic and histological evaluation of bone formation induced by rhBMP-2-incorporated biomimetic calcium phosphate material in clinical alveolar sockets preservation

Abstract

Purpose: We assessed the efficiency of low-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) incorporated biomimetic calcium phosphate on β-tricalcium phosphate (β-TCP) (rhBMP-2/BioCaP/β-TCP) on bone formation in a model of socket preservation using cone beam computed tomography (CBCT) scanning and histological examination.

Methods: Forty patients undergoing minimally invasive single-root tooth extraction for dental implantation were randomized to three groups according to the material used for socket preservation: filling with rhBMP-2/BioCaP/β-TCP, β-TCP, or natural healing (kept unfilled) (controls). The alveolar sockets (including the control group) were covered by two-layer collagen membranes and sutured. Two CBCT scans were taken, one immediately after socket preservation procedure (baseline) and another 6 weeks later. Gray values (GVs) obtained from CBCT were recorded. During insertion of the dental implant, biopsies were taken and analyzed histologically for new bone formation, residual material, and unmineralized bone tissue at the core of the biopsy.

Results: The mean (± standard deviation) changes of GVs of the CBCT scans at the central area of filled materials were as follows: 373.19 ± 157.16 in the rhBMP-2/BioCaP/β-TCP group, 112.26 ± 197.25 in the β-TCP group, and -257 ± 273.51 in the control group. The decrease of GVs in the rhBMP-2/BioCaP/β-TCP group as compared with the β-TCP group was statistically significant (P < 0.001). Differences in new bone formation (P = 0.006) were also found: 21,18% ± 7.62% in the rhBMP-2/BioCaP/β-TCP group, 13.44% ± 6.03% in the β-TCP group, and 9.49% ± 0.08% in controls. The residual material was10.04% ± 4.57% in the rhBMP-2/BioCaP/β-TCP group vs. 20.60% ± 9.54%) in the β-TCP group (P < 0.001). Differences in unmineralized bone tissue (P < 0.001) were also found (68.78% ± 7.67%, 65.96% ± 12.64%, and 90.38% ± 7.5% in the rhBMP-2/BioCaP/β-TC, β-TCP, and control groups, respectively).

Conclusions: This study shows that rhBMP-2/BioCaP/β-TCP is a promising bone substitute with fast degradation and potent pro-osteogenic capacity that can be useful for socket preservation in implant dentistry.

Trial registration: ChiCTR, ChiCTR2000035263. Registered 5 August 2020, https://www.chictr.org.cn/ChiCTR2000035263 .

Keywords: Biomimetic; Biopsy; Bone regeneration; CBCT; Gray values; Histomorphometry; rhBMP-2.

Fig. 1

Schematic of clinical trial procedure. A The patients were randomly divided into rhBMP-2/BioCaP/β-TCP, β-TCP, and natural healing groups; B tooth extraction, C the tooth socket filled with either rhBMP-2/BioCaP/β-TCP or β-TCP in relative groups, D the first layer of collagen membrane covered the alveolar sockets and 2-3 mm over the socket edge), E the second collagen membranes, F sutured, G 2 weeks later, took out the suture, H after 6 weeks, soft tissue flap releasing, I a trephine drill (outer diameter 3 mm, inter 2.3 mm diameter) is used to obtain the biopsy, J collected biopsy (2.3 mm in diameter × 6 mm in height)

Fig. 2

Intra-oral photographs of socket preservation and dental implant surgery. A The upper left first premolar needed to be removed. B The gingival biotype was a thick tissue biotype. C Tooth extraction. D The tooth socket was filled with rhBMP-2/BioCaP/β-TCP. E Two layers of collagen membrane covered the alveolar socket. F Sutured. G 6 weeks later. H Soft tissue flap releasing. I Obtained the biopsy and inserted an implant. J, K Guided bone regeneration (GBR) for the horizontal bone gain. L Sutured

Fig. 3

Data import. A Panoramic tomography. B Buccal-lingual section of the surgery area. C 3D model

Fig. 4

The measurement point of GV. A Look for the central point of the pulp cavity at the enamel-cementum junction of the mesial and distal adjacent teeth. The connection of the two points helps determine the coronal plane. B The horizontal reference line was taken through the highest alveolar ridge of extraction fossae (crest of the alveolar ridge). C The buccal-lingual section followed the center line of the root of the tooth. Then the tooth-long axis was followed to find the 3 mm point (GV measurement point) from the baseline and measured the GV based on the software function. D 3D view

Fig. 5

Schematic diagram of the identification of measurement point for GV. The GV measurement baseline is on the alveolar ridge’s crest. Following the long axis of the tooth, the red dot is a point for measuring bone density underneath 3 mm of baseline. The center part of the biopsy is the same as the GV-measured point of the CBCT image

Fig. 6

Light micrographs of biopsy slice (diameter 1.1 mm) in the natural healing group (A), rhBMP-2/BioCaP/β-TCPgroup (B), and β-TCP group (C) 6 weeks after implantation. Stained with McNeil’s Tetra chrome basic fuchsine and toluidine blue O. a Residual material, b new bone, c unmineralized tissue