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

Abstract

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.

Keywords: dental implants; metabolic diseases; osseointegration.

Figure 1.

A and B. Implant macrogeometry. Internal conical implants with internal and external trapezoidal threads and a tapered apex, which allow for the formation of healing chambers.

Figure 2.

Schematic of the implant placement site and distribution. Implants with different surface treatment, NANO and DAE, were installed in the right ilium of the animals in an interpolated distribution (2-cm apart in a mesial-distal fashion), so that the same animal received both implant surface types.

Figure 3.

%BIC and %BAFO illustration, where %BIC was determined by the ratio between the perimeter of the implant surface with new bone (depicted in A-2) and perimeter of the entire implant (depicted in A-1). %BAFO was determined by the ratio between the bone fraction area within the threads (depicted in A-4) and the total area of the threads (depicted in A-4).

Figure 4.

A, B, C, D and E. SEM micrographs at A) 100 X, B) 1,000 x, C) 5,000 x, and D) 10,000 x. A-C. surface shows a homogeneous pattern of micropores, with larger craters embracing smaller groves for both implants, which is usually consistent with patterns observed in acid etched DAE implants. D. The regular homogeneously distributed nanotopography can be observed for the NANO implant. E. Chemical element analysis depicts the presence of Ca and P on the surface of the NANO implants.

Figure 5.

A, B, C, D and E. Parameters used to characterize and validate disease induction A. Weight increase. B. Glucose level. C. Cholesterol. D. Triglycerides. E. Cortisol. Identical letters indicate no significant difference among groups. ‘□’ indicates the mean and ‘♦’ indicates an outlier.

Figure 6.

A, B and C. Percentage of bone to implant contact (%BIC). A. Regarding to surface treatment, NANO coated implants depicted higher levels of bone to implant contact than DAE. B. Concerning to systemic condition, control group presented significant more %BIC when compared to O/MS and T2DM; without significant difference between them. C. All NANO coated groups demonstrated higher %BIC when compared to their DAE counterparts. Identical letters indicate no significant difference among groups. ‘□’ indicates the mean and ‘♦’ indicates an outlier.

Figure 7.

A, B and C. Percentage of bone area fraction occupancy (%BAFO). A. Regarding to surface treatment, NANO coated implants depicted higher levels of bone area fraction occupancy within healing chambers. B. Control group presented significant more %BAFO when compared to O/MS and T2DM conditions, without significant difference between them. C..Higher %BAFO for control groups when compared to O/MS and T2DM. All NANO coated groups demonstrated higher %BAFO when compared to their DAE counterparts, with significant difference for O/MS group. Identical letters indicate no significant difference among groups. ‘□’ indicates the mean and ‘♦’ indicates an outlier.

Figure 8.

Histological sections of control (A and D), O/MS (B and E) and T2DM groups (C and F) for NANO coated (A, B and C) and DAE treated (D, E and F) implant surface treatments. More pronounced bone formation in direct contact and in proximity with the implant is evidenced for NANO surface treatment, regardless group. Also, control group presented higher amount of woven bone when compared to O/MS and T2DM systemic conditions.

Figure 9.

Histological micrographs of control group healing chambers for NANO coated (A) and DAE treated (B) surfaces. The green arrows depicted new bone formation in direct contact and in proximity with the implant surface, which was more pronounced for NANO surface. Bone remodeling units were observed (yellow arrow) replacing previously formed bone.

Figure 10.

Histological micrographs of obesity/metabolic syndrome (O/MS) group healing chambers for NANO coated (A) and DAE (B) treated surfaces. The green arrows depicted new bone formation in direct contact and in proximity with the implant surface, which was more pronounced for NANO surface when compared to DAE. Bone remodeling units were observed (yellow arrow) replacing previously formed bone.

Figure 11.

Histological micrographs of obesity/metabolic syndrome (T2DM) group healing chambers for NANO coated (A) and DAE (B) treated surfaces. The green arrows depicted new bone formation in direct contact and in proximity with the implant surface, which was more pronounced for NANO surface when compared to DAE. Bone remodeling units were observed (yellow arrow) replacing previously formed bone.