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Long-term stability

The biology behind Geistlich Bio-Oss®

15.01.2019
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Histologic staining properties, adsorption and uptake of proteins, osteoconductivity, and resorbability – an overview of biological data and long-term stability clinical outcomes to better understand Geistlich Bio-Oss®.

Associate Prof. Dieter D. Bosshardt | Switzerland

Geistlich Bio-Oss®, a natural, non-antigenic, porous bone mineral matrix of bovine origin, has been commercially available for regenerative dentistry for more than 30 years. But what are the characteristics of this product that guarantee stable and long-term clinical results? Let us take a step back and examine the biology.


Histologic staining properties

When Geistlich Bio-Oss® is processed in its native form for the production of undecalcified ground sections and stained with toluidine blue, staining is extremely weak (Fig. 1). Nevertheless, an empty Haversian canal is visible forming a macropore surrounded by lamellar bone, generated through the birefringence of hydroxyapatite (Fig. 2). After placement of Geistlich Bio-Oss® in an augmentation site, an undecalcified ground section stained with toluidine blue demonstrates completely different characteristics. The biomaterial is much more intensely stained than the surrounding bone (Fig. 3),1 indicating the presence of organic material. Based on this comparison we can conclude that Geistlich Bio-Oss® has taken up organic components such as endogenous proteins, which could enhance biofunctionality and contribute to biocompatibility. Also, the presence of endogenous proteins can be observed when staining is performed on decalcified sections before embedding and cutting.1 Indeed, both the resin (Fig. 4) and the paraffin sections (Fig. 5) reveal a slightly darker staining of new bone and subtle shades of blue and red for Geistlich Bio-Oss®.


Adsorption and uptake of proteins

Protein adsorption plays a key role in determining the initial cell response to an implanted biomaterial, which is immediately coated with proteins and other molecules from blood and tissue fluids. The uptake of endogenous proteins can be demonstrated using high-resolution immunohistochemistry with an antibody for typical bone-related noncollagenous proteins, the abundance of which is indicated by gold particles that turn into black dots in the image shown in Figure 6. Geistlich Bio-Oss® can also be pre-coated with exogenous proteins with biological activity. In vitro, Geistlich Bio-Oss® retains enamel matrix proteins (Emdogain®, Straumann AG, Switzerland – Fig. 7)2 as well as Osteogain®3 (Straumann AG, Switzerland), a liquid formulation of Emdogain®. These findings demonstrate that Geistlich Bio-Oss® can function not only as a bone substitute biomaterial filling the bone-defect and promoting bone formation through osteoconduction, but also as a carrier delivering exogenous proteins with biologic activity.

 

Osteoconductivity

Numerous studies have demonstrated the osteoconductivity of Geistlich Bio-Oss®.4-6 Indeed, when it is placed close to or into a bony environment, osteoblasts can deposit bone matrix directly onto the biomaterial (Fig. 8).

 

Resorbability

One of the characteristics of Geistlich Bio-Oss® is its resistance to resorption.4-6 The particles are frequently covered by osteoclast-like multinucleated giant cells (MNGCs), and the implication of the MNGCs has been studied.7-9 Osteoclasts can be labeled for tartrate-resistant phosphatase (TRAP), an enzyme typically, but not exclusively, expressed in osteoclasts. MNGCs on Geistlich Bio-Oss® embedded in bone are consistently TRAP-positive (Fig. 9).
The Geistlich Bio-Oss® surface under these MNGCs is predominantly flat and does not reveal signs of resorption (e.g., Howship’s lacunae – Fig. 10). Very rarely, however, shallow concavities reminiscent of Howship’s lacunae can be seen under these MNGCs (Fig. 11), indicating a resorptive activity.10-13 Under which specific conditions resorption of Geistlich Bio-Oss® occurs is still unclear and requires more research. Possible reasons include inflammation and displacement of the particles away from the augmentation site, but other co-factors may be involved as well.10-13 For example, researchers have demonstrated normal resorption and replacement of Geistlich Bio-Oss® with orthodontic tooth movement.14

Long-term stability in the aesthetic area

Human biopsies harvested after sinus floor elevation offer an ideal opportunity for histologic analysis, since they can be collected non-invasively. In a recent article, Jensen et al. have shown histologic and histomorphometric data in 12 biopsies from ten patients harvested 14 to 80 months after dental implant placement with simultaneous contour augmentation.15 Before this publication no human histologic data were available to document the tissue reactions to bone augmentation procedures with autologous bone and Geistlich Bio-Oss®. Most xenogeneic particles were embedded in mature bone, and no inflammatory reaction was observed. On average, 40.6% of the augmented area was occupied by bone, 32.0% by Geistlich Bio-Oss®, and 27.4% by soft tissue (Fig. 12), and there was no tendency toward a decreasing area fraction of Geistlich Bio-Oss® over time. In addition, 70.3% of Geistlich Bio-Oss® particle surface area was covered with bone (i.e., osteoconductivity – Fig. 13). These data demonstrate stable long-term conditions and support previous clinical and radiographic data showing stable peri-implant soft tissues for up to nine-years, with an intact facial bone wall in 95% of the cases.16-19 The data also indicate that neither the presence of MNGCs nor their positive staining for TRAP correlate with resorption rate. Very recently, biopsies with Geistlich Bio-Oss® harvested from a patient 20-years after sinus floor elevation were analyzed histologically (Fig. 14, 15).20 The results show that Geistlich Bio-Oss® particles and MNGCs are still present after 20-years, with the particles embedded in mature trabecular bone exhibiting mature bone marrow.

Associate Prof. Dieter D. Bosshardt

Associate Prof. Dieter D. Bosshardt | Switzerland

Robert K. Schenk Laboratory of Oral Histology
School of Dental Medicine, University of Bern

 

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