The Influence of Type 2 Diabetes Mellitus on the Osseointegration of Titanium Implants With Different Surface Modifications-A Histomorphometric Study in High-Fat Diet/Low-Dose Streptozotocin-Treated Rats.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) is a systemic disease that also compromises the bone healing capacity. In healthy individuals, surface modifications of dental implants are proven to increase bone response and implant success. The aim of this study was to clarify if the surface modifications also improve osseointegration in a setting with diabetes mellitus. METHODS: T2DM was induced in 7 rats by a high-fat diet/low-dose streptozotocin injection. All animals received a hydroxyapatite (HA) implant, a sandblasted and acid-etched (SLA) implant, and a standard machined titanium implant for control in the tibia. After 4 weeks, thin-ground sections were produced, and the volume of new bone formation (nBV/TV) and bone-to-implant contact (nB.I/Im.I) were histomorphometrically analyzed. RESULTS: Both surface modifications led to an increase of osseointegration compared with the machined surface implant in rats with T2DM. nBV/TV was highest in the SLA implants, whereas nB.I/Im.I was highest in the HA group. Regardless of the surface modification, a superordinate regional pattern of new bone formation over the length of the implant was observed. CONCLUSIONS: Implants with HA coating and SLA surface modifications seem to have the potential to increase osseointegration also in T2DM rats when compared with a conventional machined surface.

A quantification of regenerated bone tissue in human sinus biopsies: influences of anatomical region, age and sex.

OBJECTIVES: Sinus augmentation is a standard procedure to increase vertical bone supply for dental implants in the atrophic posterior maxilla. Despite the longstanding application of this method, information about some basic factors that could potentially influence bone regeneration after sinus augmentation is rare. The objective of this study was therefore to quantify the impact of the maxillary region (premolar/molar) and patients' age and sex on bone regeneration after sinus grafting. MATERIAL AND METHODS: Sinus augmentation procedures were performed in 107 patients (66 female: 52.8 ± 11.0 years, 41 male: 50.6 ± 11.3 years). After 6 ± 1 months, 201 sinus biopsies were harvested and histomorphometrically analysed. Height (oldHt) and bone volume fraction of pristine bone (oldBV/TV), as well as the amount of new bone (newBV/TV) and bone-to-bone substitute contact (BBSC) in the augmentation area, were assessed. RESULTS: In women, newBV/TV in the augmented sinus decreased significantly by 0.22 ± 0.08% per year. In men, no similar trend was observed. There were strong influences of the maxillary region and the dimensions of the host bone. In the premolar region, newBV/TV was 23.1 ± 7.9% and 25.1 ± 10.1%; in the molar region, newBV/TV averaged 20.4 ± 9.4% and 17.8 ± 8.8% for women and men, respectively. The greater the thickness of the wall of the sinus floor (mainly in the former premolar region), the greater was the amount of new bone tissue formed in the spaces in-between bone substitute particles. CONCLUSIONS: These empirical results derived from a large human sample, link factors that influence the quality of biomaterial integration to the known clinical risks for the success of dental implants.

Effect of recombinant PDGF-BB on bone formation in the presence of ß-tricalcium phosphate and bovine bone mineral matrix: a pilot study in rat calvarial defects.

BACKGROUND: Supplementation of bone substitutes with recombinant platelet-derived growth factor-BB (PDGF-BB) can enhance bone regeneration. The aim of the study was to evaluate the effect of PDGF-BB on bone formation in the presence of ß-tricalcium phosphate and bovine bone mineral matrix in a rat calvaria defect model. METHODS: The authors examined 5 mm rat calvarial defects treated with ß-tricalcium phosphate (TCP) or demineralized bovine bone mineral (DBBM) with and without 0.3 mg/ml recombinant PDGF-BB. Calvaria defects were randomly divided into the following treatment groups (n = 5); TCP; TCP plus PDGF-BB; DBBM; DBBM plus PDGF-BB; and untreated empty control. After 45 days, bone formation was evaluated by histomorphometry and fluorescence microscopy. RESULTS: The authors report that the area of newly formed bone was similar between the empty controls and the two bone substitutes, TCP and DBBM. Supplementation of TCP and DBBM with PDGF-BB had no significant impact on bone formation. Fluorochrome staining revealed no visible changes in the pattern of bone formation in defects filled with TCP and DBBM, irrespective of PDGF-BB. Furthermore, supplementation with PDGF-BB did not influence biomaterial degradation. CONCLUSIONS: The authors concluded that PDGF-BB had no impact on bone formation and degradation of bone substitutes in the respective rodent models. Thus, possible beneficial effects of PDGF-BB may require other model situations.

Effects of directly autotransplanted tibial bone marrow aspirates on bone regeneration and osseointegration of dental implants.

OBJECTIVES: Aim of the pilot trial was to evaluate applicability and effects of directly autotransplanted tibial bone marrow (BM) aspirates on the incorporation of porous bovine bone mineral in a sinus lift model and on the osseointegration of dental implants. MATERIAL AND METHODS: Six edentulous patients with bilaterally severely resorbed maxillae requiring sinus augmentation and implant treatment were included. During surgery, tibial BM was harvested and added to bone substitute material (Bio-Oss(®) ) at the randomly selected test site. At control sites, augmentation was performed with Bio-Oss(®) alone. The cellular content of each BM aspirate was checked for multipotency and surface antigen expression as quality control. Histomorphometric analysis of biopsies from the augmented sites after 3 and 6 months (during implantation) was used to evaluate effects on bone regeneration. Osseointegration of implants was evaluated with Periotest(®) and radiographic means. RESULTS: Multipotent cellular content in tibial BM aspirates was comparable to that in punctures from the iliac crest. No significant difference in amount of new bone formation and the integration of bone substitute particles was detected histomorphometrically. Periotest(®) values and radiographs showed successful osseointegration of inserted implants at all sites. CONCLUSION: Directly autotransplanted tibial BM aspirates did not show beneficial regenerative effects in the small study population (N = 6) of the present pilot trial. However, the proximal tibia proved to be a potential donor site for small quantities of BM. Future trials should clarify whether concentration of tibial BM aspirates could effect higher regenerative potency.

A histomorphometric analysis of the nature of the mandibular canal in the anterior molar region.

OBJECTIVES: Knowledge of the position and configuration of the mandibular canal is a basic requirement before implant placement in the mandible. Radiological studies suggest a positive correlation between alveolar trabecular bone quality and mandibular canal corticalization. The aim of this study was to test this assumption histomorphometrically in the anterior molar region, which is one of the most frequent places for implantation. MATERIALS AND METHODS: Fifty thin ground sections (from 28 male and 22 female cadavers) of the first molar region were investigated for trabecular bone volume and thickness and the presence of a mandibular canal wall. RESULTS: Trabecular bone volume was significantly higher in males (p = 0.009). Further, it correlated significantly with the presence of a canal wall (rho = 0.585, p < 0.001), indicating that a reduced trabecular bone volume is associated with a reduced amount of bone surrounding the alveolar nerve. The cranial aspects of the canal wall were present at a significantly lower frequency (64.64 %) than the buccal, lingual, or caudal sides (p < 0.006). CONCLUSION: The present study demonstrated that low trabecular bone volume correlates with only a fragmentarily present mandibular canal wall. This suggests that bone surrounding the alveolar nerve is of trabecular, not cortical, origin and possibly affected by reduction of the trabecular bone. CLINICAL RELEVANCE: These results imply that oral surgeons should pay particular attention to implant placement in patients with low alveolar bone quality. The cranial aspects of the mandibular canal might be only fragmentarily or even completely missing. Consequently, they hardly present resistance during implant site preparation, and the risk for nerve injury, e.g., due to post-surgery hematoma, could be increased.

Osteocyte lacunar density and area in newly formed bone of the augmented sinus.

OBJECTIVES: Osteocytes, the most common cells of the bone, are buried in lacunae. Density and area of the osteocyte lacunae change with increasing maturation of the newly formed bone. Evaluation of osteocyte lacunae can therefore provide insights into the process of graft consolidation. MATERIALS AND METHODS: Here, we determined the osteocyte lacunar density (number of osteocyte lacunae per bone area; N.Ot/BAr) and the osteocyte lacunar area in µm(2) (Lac.Ar) in histological specimens 6 and 12 weeks after the sinuses of 10 minipigs were augmented with Bio-Oss(®) , a deproteinized bovine bone mineral, and Ostim(®) , an aqueous paste of synthetic nanoparticular hydroxyapatite. The region of interest was defined by the following criteria: (i) >1 mm from the host bone, (ii) >0.5 mm from the sinus mucosa, (iii) minimum area of 0.2 mm(2) , and (iv) bone tissue spanning at least two bone substitute particles. RESULTS: The overall osteocyte lacunar density was significantly higher in the Bio-Oss(®) group than in the Ostim(®) group and decreased during the observation period at a similar range in both groups. The osteocyte lacunar area was smaller in the Bio-Oss(®) group than the Ostim(®) group but there was no significant change within the groups over time. CONCLUSIONS: These results suggest that bone substitutes affect the osteocyte lacunar density and the osteocyte lacunar area in the newly formed bone within the augmented sinus in this particular model situation. These measures can provide insights into the maturation of newly formed bone in the augmented sinus.

Bone Graft Packing and Its Association with Bone Regeneration in Maxillary Sinus Floor Augmentations: Histomorphometric Analysis of Human Biopsies.

Research in maxillary sinus floor augmentation (MSFA) focussed on the optimisation of microstructural parameters such as microporosity and particle size of bone substitute particles (BS). However, little is known about the impact of BS packing and the corresponding (void) interparticular space on bone regeneration. The aim of this study was to characterise the spatial distribution of BS and its association with BS integration 6 ± 1 months after MSFA. Histological thin-ground sections of 70 human sinus biopsies were histomorphometrically analysed: In serial zones of 100 µm proceeding from the sinus floor (SF) up to the apical end of the biopsy, we measured the distribution of BS particles within these zones in terms of volume (BSV/TV), number and size of BS particles, interparticle spacing (BS.Sp) and bone-to-BS contact. BS particles were not homogeneously distributed over the length of biopsies: The first 200 µm directly adjacent to the SF represented a zone poor in BS particles but with high osteogenic potential. Graft packing density increased from the SF towards the apical part of the AA. Integration of BS particles was inversely associated with the distance to the SF and the graft packing density. A high packing density through excessive compaction of BS particles should be avoided to optimise the macrostructural environment for bone regeneration.

Cortical porosity of the mandible in an osteoporotic sheep model.

OBJECTIVES: Cortical porosity and thickness of the axial and the appendicular skeleton are predictors of osteoporotic fractures. In the jawbone, however, cortical porosity and thickness may affect the mechanical stability of dental implants. We have shown previously that the jawbone of osteoporotic sheep has impaired trabecular structures, but whether catabolic bone turnover also accounts for the cortical bone porosity remains unknown. MATERIAL AND METHODS: We compared mandibular bone from six geriatric sheep subjected to ovariectomy, calcium/vitamin D restriction, and methylprednisolone administration to those of six healthy adult control sheep. Histological ground sections were prepared from the diastema, first and second premolars, and postmolar region. Cortical porosity and thickness were assessed by histomorphometry. RESULTS: Cortical porosity was higher in osteoporotic sheep than in adult controls in the diastema and in the first and second premolar region. In the postmolar region, the difference failed to reach the level of significance. The changes were even more prominent when histomorphometry was restricted to the inner millimeter of the mandibular cortex. In contrast, induction of osteoporosis did not have a discernable effect on cortical thickness. CONCLUSION: These results demonstrate that cortical porosity of mandibles is more pronounced in geriatric osteoporotic sheep than in adult controls.

The vertical course of bone regeneration in maxillary sinus floor augmentations: A histomorphometric analysis of human biopsies.

BACKGROUND: Maxillary sinus floor augmentation (MSFA) is a well-established and predictable augmentation method in severely resorbed maxillae. However, data on the vertical course of bone graft consolidation within the maxillary sinus are rare. The aim of the present study was to quantify the vertical distribution of new bone formation (nBF) in MSFA and to characterize the vertical gradient of bone graft consolidation. METHODS: Eighty-five human sinus biopsies were harvested 6 ± 1 months after MSFA. Histological thin-ground sections were prepared and histomorphometrically analyzed. The volume of newly formed bone (nBV/TV) was measured in serial zones of 100 µm proceeding from the bottom of the sinus floor (SF) up to the apical top of the biopsy. The gradient of nBV/TV within the augmentation area was determined by the vertical distribution of nBV/TV along these zones. RESULTS: In the premolar region, nBV/TV slightly declined from 20.4% in the zone adjacent to the SF to 17.7% at a distance of 8 mm. The gradient was steeper in the molar region: nBV/TV decreased from 18.7% to 12.8%. This decline was even more distinct when the volume fraction and the height of the residual bone of the SF were low. CONCLUSIONS: nBF follows a gradient from native bone of the SF towards the apical part of the augmentation area. The distance to primordial bone thus plays a critical role for bone regeneration in MSFA, particularly in the molar region.

The Effect of Diclofenac Sodium-Loaded PLGA Rods on Bone Healing and Inflammation: A Histological and Histomorphometric Study in the Femur of Rats.

Implants made of poly(lactide-co-glycolide) (PLGA) are biodegradable and frequently provoke foreign body reactions (FBR) in the host tissue. In order to modulate the inflammatory response of the host tissue, PLGA implants can be loaded with anti-inflammatory drugs. The aim of this study was to analyze the impact of PLGA 80/20 rods loaded with the diclofenac sodium (DS) on local tissue reactions in the femur of rats. Special emphasis was put on bone regeneration and the presence of multinucleated giant cells (MGCs) associated with FBR. PLGA 80/20 alone and PLGA 80/20 combined with DS was extruded into rods. PLGA rods loaded with DS (PLGA+DS) were implanted into the femora of 18 rats. Eighteen control rats received unloaded PLGA rods. The follow-up period was of 3, 6 and 12 weeks. Each group comprised of six rats. Peri-implant tissue reactions were histologically and histomorphometrically evaluated. The implantation of PLGA and PLGA+DS8 rods induced the formation of a layer of newly formed bone islands parallel to the contour of the implants. PLGA+DS rods tended to reduce the presence of multi-nucleated giant cells (MGCs) at the implant surface. Although it is known that the systemic administration of DS is associated with compromised bone healing, the local release of DS via PLGA rods did not have negative effects on bone regeneration in the femora of rats throughout 12 weeks.

Minimally invasive mandibular bone augmentation using injectable hydrogels.

Hyaluronic acid-based hydrogels are proven biocompatible materials and excellent carriers of bone morphogenetic protein-2 (BMP-2) that have been successfully tested for bone generation in vivo. Different formulations, with or without nanohydroxyapatite, have shown promise for craniofacial applications. In this study, 28 rats were used to investigate whether it is possible to achieve mandibular bone augmentation upon injection of novel hyaluronic acid-based hydrogels containing nanohydroxyapatite and different concentrations of BMP-2 (0, 5 and 150 µg/ml). The biomaterials were injected subperiosteally through fine needles into the innate mandibular diastema, imitating a clinical procedure for resorbed mandibles. No incisions, flaps or sutures were necessary. After 8 weeks the mandibles were evaluated by peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT), histology, immunohistochemistry and fluorochrome labelling. As a result, engineered bone was observed in all treated mandibles, with a statistically significant increase in mandibular bone volume correlated with the amount of BMP-2 loaded in the hydrogel formula. We therefore demonstrated that minimally invasive mandibular bone augmentation is possible upon injection in rats, when using the appropriate injectable scaffolds. This represents an attractive clinical alternative for oral implantology patients.