Analysis of Implant Osseointegration, Bone Repair, and Sinus Mucosa Integrity Using Bio-Oss® and Hyaluronic Acid-Polynucleotide Gel (Regenfast®) in Maxillary Sinus Augmentation in Rabbits

Abstract

Background: The combination of polynucleotides and hyaluronic acid with bovine bone grafts in maxillary sinus lift procedures appears to be a promising strategy to enhance bone regeneration. This study aimed to analyze implant osseointegration, bone repair and sinus mucosa integrity using Bio-Oss^® and Hyaluronic Acid-Polynucleotide Gel (Regenfast^®) in maxillary sinus augmentation in rabbits. Methods: Sinus floor elevation was performed in 12 rabbits, with one implant placed per sinus simultaneously. In the control group, sinuses were grafted with deproteinized bovine bone mineral (Bio-Oss^®) alone; in the test group, Bio-Oss^® was combined with Regenfast^®. Two histological slides were obtained per sinus after 2 weeks (six animals) and 10 weeks (six animals): one from the grafted area alone (non-implant sites), and one from the implant site. Primary outcome variables included the percentage of newly formed bone, the extent of implant osseointegration, and the number of sinus mucosa perforations caused by contact with graft granules. Results: After 10 weeks of healing, the test group showed a significantly higher percentage of new bone formation (37.2 ± 6.7%) compared to the control group (26.8 ± 10.0%; p = 0.031); osseointegration extended to the implant apex in both groups; fewer sinus mucosa perforations were observed in the test group (n = 5) than in the control group (n = 14). Conclusions: The addition of Regenfast^® to Bio-Oss^® granules promoted enhanced bone regeneration within the elevated sinus area and was associated with a lower incidence of sinus membrane perforations compared to the use of Bio-Oss^® alone.

Keywords: animal study; bone healing; dental implants; histology; hyaluronic acid; osseointegration; osteoinduction; resorbable polynucleotides; sinus augmentation; sinus membrane perforation; xenogeneic bone substitute.

Figure 1

Clinical procedures. (A) Preparation of the osteotomies laterally to the naso-incisal suture. (B) Bio-Oss® granules were dispensed into a glass dish using a measuring spoon. Regenfast® was added and mixed to the xenograft. (C) After sinus mucosa elevation, the graft was inserted into the elevated space. (D) In this study, 3 mm × 4 mm implants (S.I.N.® Implant System) were used. (E) The implants were installed in each osteotomy at bone level. (F) Final trans-operative view.

Figure 2

Photomicrograph of ground section illustrating the six areas evaluated: sub-mucosa (two areas); central; sub-window; medial and lateral walls. Stevenel’s blue and Alizarin Red staining.

Figure 3

Landmarks for histomorphometric analysis. (A) Linear measurements indicating the distances between the native marginal bone (NMB) to the coronal level of osseointegration (first newly formed bone contact; FNBC) and between NMB and the apical level of osseointegration (Apx). (B) Bone-to-implant percentage in three implant areas: coronal, medial and apical. Stevenel’s blue and alizarin red staining.

Figure 4

Photomicrographs of ground sections after 2 weeks of healing. The elevated area was predominantly occupied by xenograft particles and soft tissue both in the test (A) and control sites (B). (C) Photomicrograph showing the open osteotomy window after two weeks of healing. (D) New bone formation observed from the adjacent cortical bone layers. Yellow arrows indicate residual graft material, while red arrows highlight areas of new bone formation. The red square outlines the antrostomy site. Stevenel’s blue and alizarin red staining.

Figure 5

Photomicrograph of ground section indicating an increase in the fraction of new bone after ten weeks of healing, compared to the earlier time point, and an initial corticalization of the osteotomy. Stevenel’s blue and alizarin red staining.

Figure 6

Photomicrographs of ground sections indicating a limited amount of marginal bone resorption in two weeks of healing at both control (A) and test (B) sides, and in ten weeks of healing for control (C) and test (D) sides. Stevenel’s blue and alizarin red staining.

Figure 7

Photomicrographs of ground sections illustrating the differences in the mean apical extension of osseointegration from native marginal bone (NMB-Apx) in the control (A) and test (B) sides in two weeks of healing. Stevenel’s blue and alizarin red staining.

Figure 8

Photomicrograph of ground sections indicating that in ten weeks of healing the apical extension of native marginal bone (NMB-Apx) became equivalent in both control (A) and test groups (B). Stevenel’s blue and alizarin red staining.

Figure 9

The yellow arrows indicate the sinus mucosa pattern. (A) Smooth mucosa in two weeks of healing. (B) Corrugated configuration following the contours of adjacent granules. A rectangle indicates the specific area of interest within the histological section. Stevenel’s blue and Alizarin Red staining.

Figure 10

(A) Photomicrograph showing thinned epithelium limited to the lamina propria, with blood vessels and mucosal glands near the xenograft. (B) Epithelial thinning became evident, with reduction of goblet cells and cilia. (C) Connective tissue layer remnant between granules and the sinus cavity in most severe cases. (D) Epithelial perforation associated with angular granule surface. (E) Reparative response, with signs of displacement of granules from the augmented space. (F) Tapered morphology of the surrounding epithelium, indicating the attempt to re-establish separation from the sinus lumen. Stevenel’s blue and alizarin red staining.