Osseointegration of implant surfaces in metabolic syndrome and type-2 diabetes mellitus.

This in vivo study evaluated the bone healing response around endosteal implants with varying surface topography/chemistry in a preclinical, large transitional model induced with metabolic syndrome (MS) and type-2 diabetes mellitus (T2DM). Fifteen Göttingen minipigs were randomly distributed into two groups: (i) control (normal diet, n = 5) and (ii) O/MS (cafeteria diet for obesity induction, n = 10). Following obesity induction, five minipigs from the obese/metabolic syndrome (O/MS) group were further allocated, randomly, into the third experimental group: (iii) T2DM (cafeteria diet + streptozotocin). Implants with different surface topography/chemistry: (i) dual acid-etched (DAE) and (ii) nano-hydroxyapatite coating over the DAE surface (NANO), were placed into the right ilium of the subjects and allowed to heal for 4 weeks. Histomorphometric evaluation of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO) within implant threads were performed using histomicrographs. Implants with NANO surface presented significantly higher %BIC (~26%) and %BAFO (~35%) relative to implants with DAE surface (%BIC = ~14% and %BAFO = ~28%, p < .025). Data as a function of systemic condition presented significantly higher %BIC (~28%) and %BAFO (~42%) in the control group compared with the metabolically compromised groups (O/MS: %BIC = 14.35% and %BAFO = 26.24%, p < .021; T2DM: %BIC = 17.91% and %BAFO = 26.12%, p < .021) with no significant difference between O/MS and T2DM (p > .05). Statistical evaluation considering both factors demonstrated significantly higher %BIC and %BAFO for the NANO surface relative to DAE implant, independent of systemic condition (p < .05). The gain increase of %BIC and %BAFO for the NANO compared with DAE was more pronounced in O/MS and T2DM subjects. Osseointegration parameters were significantly reduced in metabolically compromised subjects compared with healthy subjects. Nanostructured hydroxyapatite-coated surfaces improved osseointegration relative to DAE, regardless of systemic condition.

The Influence of Implant Design Features on the Bone Healing Pathway: An Experimental Study in Sheep.

This study evaluated how implant design features influence osseointegration. Two implant macrogeometries and surface treatments were evaluated: (1) progressive buttress threads with an SLActive surface (SLActive/BL), and (2) inner and outer trapezoidal threads with a nanohydroxyapatite coating over a dual acid-etched surface (Nano/U). Implants were placed in the right ilium of 12 sheep, and histologic and -metric analyses were conducted after 12 weeks. Percentages of bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) within the threads were quantified. Histologically, the SLActive/BL group showed greater and more intimate BIC than the Nano/U group. In contrast, Nano/U group depicted woven bone formation within the healing chambers, between the osteotomy wall and implant threads, and bone remodeling was evident at the outer thread tip. Significantly higher BAFO was seen in the Nano/U group than the SLActive/BL group at 12 weeks (P < .042). Different implant design features influenced the osseointegration pathway, supporting further investigations to describe the differences and clinical performance.

Histological and Nanomechanical Properties of a New Nanometric Hydroxiapatite Implant Surface. An In Vivo Study in Diabetic Rats.

Implant therapy is a predictable treatment to replace missing teeth. However, the osseointegration process may be negatively influenced by systemic conditions, such as diabetes mellitus (DM). Microtopography and implant surface developments are strategies associated to better bone repair. This study aimed to evaluate, in healthy and diabetic rats, histomorphometric (bone to implant contact = %BIC; and bone area fraction occupancy = %BAFO) and nanomechanical (elastic modulus = EM; and hardness = H) bone parameters, in response to a nanometric hydroxyapatite implant surface. Mini implants (machined = MAC; double acid etched = DAE, and with addition of nano-hydroxyapatite = NANO) were installed in tibias of healthy and diabetic rats. The animals were euthanized at 7 and 30 days. NANO surface presented higher %BIC and %BAFO when compared to MAC and DAE (data evaluated as a function of implant surface). NANO surface presented higher %BIC and %BAFO, with statistically significant differences (data as a function of time and implant surface). NANO surface depicted higher EM and H values, when compared to machined and DAE surfaces (data as a function of time and implant surface). Nano-hydroxyapatite coated implants presented promising biomechanical results and could be an important tool to compensate impaired bone healing reported in diabetics.

Cell Therapy: Effect of Locally Injected Mesenchymal Stromal Cells Derived from Bone Marrow or Adipose Tissue on Bone Regeneration of Rat Calvarial Defects.

Treatment of large bone defects is a challenging clinical situation that may be benefited from cell therapies based on regenerative medicine. This study was conducted to evaluate the effect of local injection of bone marrow-derived mesenchymal stromal cells (BM-MSCs) or adipose tissue-derived MSCs (AT-MSCs) on the regeneration of rat calvarial defects. BM-MSCs and AT-MSCs were characterized based on their expression of specific surface markers; cell viability was evaluated after injection with a 21-G needle. Defects measuring 5 mm that were created in rat calvaria were injected with BM-MSCs, AT-MSCs, or vehicle-phosphate-buffered saline (Control) 2 weeks post-defect creation. Cells were tracked by bioluminescence, and 4 weeks post-injection, the newly formed bone was evaluated by µCT, histology, nanoindentation, and gene expression of bone markers. BM-MSCs and AT-MSCs exhibited the characteristics of MSCs and maintained their viability after passing through the 21-G needle. Injection of both BM-MSCs and AT-MSCs resulted in increased bone formation compared to that in Control and with similar mechanical properties as those of native bone. The expression of genes associated with bone formation was higher in the newly formed bone induced by BM-MSCs, whereas the expression of genes involved in bone resorption was higher in the AT-MSC group. Cell therapy based on local injection of BM-MSCs or AT-MSCs is effective in delivering cells that induced a significant improvement in bone healing. Despite differences observed in molecular cues between BM-MSCs and AT-MSCs, both cells had the ability to induce bone tissue formation at comparable amounts and properties. These results may drive new cell therapy approaches toward complete bone regeneration.

Synergistic Effects of Implant Macrogeometry and Surface Physicochemical Modifications on Osseointegration: An In Vivo Experimental Study in Sheep.

This study evaluates the influence of two surface physicochemical modifications on osseointegration parameters of a healing chamber implant design. We examine dental implants with internal and external trapezoidal threads that have the following surface modifications: dual acid etching (DAE) and nano-hydroxyapatite (HA) coating over DAE surface (Nano). We installed implants in the right ilium of sheep and conducted histologic/metric analyses after 3 and 12 wk in vivo. We quantified the percentage of bone-to-implant contact (%BIC) and bone area fraction occupancy (%BAFO) within implant threads. Histologic micrographs indicate early bone formation within the healing chambers of implants with Nano surface relative to DAE surface. Histomorphometric analysis demonstrates there to be no significant differences in %BIC between 3 and 12 wk (p = 0.298). Compared to DAE, Nano shows more bone formation in contact with implant, regardless of time (p < 0.025). We observe > %BAFO at 12 wk relative to 3 wk, which differs significantly for Nano (p < 0.038). Implant surface treatment affects the amounts of bone formation within healing chambers, with Nano significantly outperforming DAE at 12 wk (p < 0.025). Nano presents a synergistic effect with implant design, improving osseointegration parameters.

Effect of Obesity or Metabolic Syndrome and Diabetes on Osseointegration of Dental Implants in a Miniature Swine Model: A Pilot Study.

PURPOSE: The increasing prevalence of obesity or metabolic syndrome (O/MS) and type 2 diabetes mellitus (DM) remains a global health concern. Clinically relevant and practical translational models mimicking human characteristics of these conditions are lacking. This study aimed to demonstrate proof of concept of the induction of stable O/MS and type 2 DM in a Göttingen minipig model and validate both of these disease-adjusted Göttingen minipig models as impaired healing models for the testing of dental implants. MATERIALS AND METHODS: Nine minipigs were split into 3 groups-control (normal diet), obese (cafeteria diet), and diabetic (cafeteria diet plus low-dosage streptozotocin)-followed by placement of dental implants. Inflammatory markers including tumor necrosis factor α, C-reactive protein, and cortisol were recorded for each study group. Removal torque was measured, and histomorphometric analysis (bone-to-implant contact and bone area fraction occupancy) was performed. RESULTS: O/MS pigs showed, on average, a 2-fold increase in plasma C-reactive protein (P < .05) and cortisol (P < .09) concentrations compared with controls; DM pigs showed, on average approximately, a 40-fold increase in plasma tumor necrosis factor α levels (P < .05) and a 2-fold increase in cortisol concentrations (P < .05) compared with controls. The impact of O/MS and DM on implants was determined. The torque to interface failure was highest in the control group (200 N-cm) and significantly lower in the O/MS (90 N-cm) and DM (60 N-cm) groups (P < .01). Bone formation around implants was significantly greater in the control group than in the O/MS and DM groups (P < .02). CONCLUSIONS: Both O/MS and DM minipigs express a human-like disease phenotype, and both presented bone-healing impairment around dental implants. Our finding of no significant difference between type 2 DM and O/MS in bone formation around implants provides evidence that further investigation of the impact of O/MS is warranted.

Effect of low-level laser on bone defects treated with bovine or autogenous bone grafts: in vivo study in rat calvaria.

OBJECTIVE: The purpose of this study was to histologically evaluate the effect of low-level laser (LLL) on the healing of critical size defects (CSD) in rat calvaria, filled with autogenous or inorganic bovine bone grafts. METHODS: Sixty rats were divided into 6 groups (n = 10): C (control-filled with blood clot), LLL (low-level laser-GaAlAs, λ 780 nm, 100 mW, 210 J/cm(2), Φ 0.05 cm(2); 6 J/point), AB (autogenous bone), ABL (autogenous bone + low-level laser), OB (inorganic bovine bone), and OBL (inorganic bovine bone + LLL). MATERIAL AND METHODS: The animals were killed after 30 days. Histological and histometric analyses were performed by light microscopy. Results. The groups irradiated with laser, LLL (47.67% ± 8.66%), ABL (39.15% ± 16.72%), and OBL (48.57% ± 28.22%), presented greater area of new bone formation than groups C (9.96% ± 4.50%), AB (30.98% ± 16.59%), and OB (11.36% ± 7.89%), which were not irradiated. Moreover, they were significantly better than group C (Kruskal-Wallis test followed by Dunn test, P < 0.05). CONCLUSION: The laser accelerated the healing of bone defects and the resorption of particles of the graft material.

The effect of low-level laser on bone healing in critical size defects treated with or without autogenous bone graft: an experimental study in rat calvaria.

OBJECTIVE: The objective of this study was to evaluate the effect of low-level laser (LLL) on bone healing process in surgically created critical size defects in rat calvaria treated with or without autogenous bone graft (AB). MATERIAL AND METHODS: The study was conducted on 40 male rats (Rattusnorvegicus, albinus, Wistar), weighing 250-300 g. For accomplishment of the experimental procedures, the rats were anesthetized with an intramuscular injection of xylazine (0.02 ml/kg) and ketamine hydrochloride (0.4 ml/kg). Acritical size defect with 5-mm diameter was created. The animals were divided into four groups: Group C (Control- filled with blood clot), Group LLL, Group AB (autogenous bone graft), Group AB + LLL (autogenous bone graft and LLL). The animals treated with LLL received applications of LLL at the infrared spectrum wavelength (λ = 810 nm) and energy density of 6 J/cm(2) per point, 60 s per point, adding up to five points on the entire created defect. The animals were euthanized at 30 days postoperatively. After decalcification, each specimen was longitudinally divided into two blocks, exactly along the center of the original surgical defect, processed and embedded in paraffin. Longitudinal serial sections with 6-µm thickness were made, initiating from the center of the original surgical defect. The sections were stained with hematoxylin and eosin (HE) for light microscopy analysis for histomorphometric analysis. RESULTS: Group C presented smaller quantity of new bone formation than Groups LLL (P < 0.01), AB (P < 0.01), and AB + LLL (P < 0.01). CONCLUSIONS: Utilization of LLL favored the healing process in rat calvaria. The quantity of new bone formation with use of the LLL was similar to the autogenous bone graft.