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Multiscale analyses of the bone-implant interface.

ABSTRACT: Implants placed with high insertion torque (IT) typically exhibit primary stability, which enables early loading. Whether high IT has a negative impact on peri-implant bone health, however, remains to be determined. The purpose of this study was to ascertain how peri-implant bone responds to strains and stresses created when implants are placed with low and high IT. Titanium micro-implants were inserted into murine femurs with low and high IT using torque values that were scaled to approximate those used to place clinically sized implants. Torque created in peri-implant tissues a distribution and magnitude of strains, which were calculated through finite element modeling. Stiffness tests quantified primary and secondary implant stability. At multiple time points, molecular, cellular, and histomorphometric analyses were performed to quantitatively determine the effect of high and low strains on apoptosis, mineralization, resorption, and collagen matrix deposition in peri-implant bone. Preparation of an osteotomy results in a narrow zone of dead and dying osteocytes in peri-implant bone that is not significantly enlarged in response to implants placed with low IT. Placing implants with high IT more than doubles this zone of dead and dying osteocytes. As a result, peri-implant bone develops micro-fractures, bone resorption is increased, and bone formation is decreased. Using high IT to place an implant creates high interfacial stress and strain that are associated with damage to peri-implant bone and therefore should be avoided to best preserve the viability of this tissue.

SUBMITTER: Cha JY

PROVIDER: S-EPMC4814020 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Multiscale analyses of the bone-implant interface.

Cha J Y JY Pereira M D MD Smith A A AA Houschyar K S KS Yin X X Mouraret S S Brunski J B JB Helms J A JA

Journal of dental research 20150127 3

Implants placed with high insertion torque (IT) typically exhibit primary stability, which enables early loading. Whether high IT has a negative impact on peri-implant bone health, however, remains to be determined. The purpose of this study was to ascertain how peri-implant bone responds to strains and stresses created when implants are placed with low and high IT. Titanium micro-implants were inserted into murine femurs with low and high IT using torque values that were scaled to approximate t ...[more]

PMID: 25628271

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Project description:Histological analysis is considered to be the gold standard method of evaluating osseointegration around a bone-implant. However, this method requires invasive specimen preparation and is capable of representing only one plane. By comparison, micro-computed tomography (μCT) is a fast and convenient method that offers three-dimensional information but is hampered by problems related to resolution and artifacts, making it a supplementary method for osseointegration analysis. To verify the reliability of μCT for osseointegration evaluation, this animal model study compared bone-to-implant contact (BIC) ratios obtained by the gold standard histomorphometric method with those obtained by the μCT method, using a rabbit tibia implant model. A sandblasted, large-grit, acid-etched (SLA) implant and a machined surface implant were inserted into each tibia of two rabbits (giving eight implants in total). Bone-implant specimens were analyzed using μCT with a spiral scan technique (SkyScan 1275) and histological sections were prepared thereafter. Three-dimensional (3D) reconstructed μCT data and four two-dimensional (2D) μCT sections, including one section corresponding to the histologic section and three additional sections rotated 45°, 90°, and 135°, were used to calculate the BIC ratio. The Pearson's test was used for correlation analysis at a significance level of 0.05. The histomorphometric BIC and the 2D-μCT BIC showed strong correlation (r = 0.762, P = 0.046), whereas the histomorphometric BIC and 3D-μCT BIC did not (r = -0.375, P = 0.385). However, the mean BIC value of three or four 2D-μCT sections showed a strong correlation with the 3D-μCT BIC (three sections: r = 0.781, P = 0.038; four sections: r = 0.804, P = 0.029). The results of this animal model study indicate that μCT can be used to complement the histomorphometric method in bone-implant interface analyses. With the limitations of this study, 3D-μCT analysis may even have a superior aspect in that it eliminates random variables that arise as a consequence of the selected cutting direction.

Project description:This study aimed to delineate the cell heterogeneity in the bone-implant interface and investigate the fibroblast responses to implant-associated S. aureus infection. Single-cell RNA sequencing of human periprosthetic tissues from patients with periprosthetic joint infection (PJI, n = 3) and patients with aseptic loosening (AL, n = 2) was performed. Cell type identities and gene expression profiles were analyzed to depict the single-cell landscape in the periprosthetic environment. In addition, 11 publicly available human scRNA-seq datasets were downloaded from GSE datasets and integrated with the in-house sequencing data to identify disease-specific fibroblast subtypes. Furthermore, fibroblast pseudotime trajectory analysis and Single-cell regulatory network inference and clustering (SCENIC) analysis were combined to identify transcription regulators responsible for fibroblast differentiation. Immunofluorescence was performed on the sequenced samples to validate the protein expression of the differentially expressed transcription regulators. Eight major cell types were identified in the human bone-implant interface by analyzing 36,466 cells. Meta-analysis of fibroblasts scRNA-seq data found fibroblasts in the bone-implant interface express a high level of CTHRC1. We also found fibroblasts could differentiate into pro-inflammatory and matrix-producing phenotypes, each primarily presented in the PJI and AL groups, respectively. Furthermore, NPAS2 and TFEC which are activated in PJI samples were suggested to induce pro-inflammatory polarization in fibroblasts, whereas HMX1, SOX5, SOX9, ZIC1, ETS2, and FOXO1 are matrix-producing regulators. Meanwhile, we conducted a CMap analysis and identified forskolin as a potential regulator for fibroblast differentiation toward matrix-producing phenotypes. In this study, we discovered the existence of CTHRC1+ fibroblast in the bone-implant interface. Moreover, we revealed a bipolar mode of fibroblast differentiation and put forward the hypothesis that infection could modulate fibroblast toward a pro-inflammatory phenotype through NPAS2 and TFEC.

Project description:Long-term stability of endosseous implants depends on successful bone formation, ingrowth and adaptation to the implant. Specifically, it will define the mechanical properties of the newly formed bone-implant interface. 3D imaging during mechanical loading tests (in situ loading) can improve the understanding of the local processes leading to bone damage and failure. In this study, titanium screws were implanted into rat tibiae and were allowed to integrate for 4 weeks with or without the addition of the growth factor Bone Morphogenetic Protein and the bisphosphonate Zoledronic Acid. Samples were subjected to in situ pullout using high-resolution synchrotron x-ray tomography at the Tomcat beamline (SLS, PSI, Switzerland) at 30 keV with 25 ms exposure time, resulting in a total acquisition time of 45 s per scan, with a 3.6 μm isotropic voxel size. Using a custom-made loading device positioned inside the beamline, screws were pulled out with 0.05 mm increment, acquiring multiple scans until rupture of the sample. The in situ loading protocol was adapted to ensure short imaging time, which enabled multiple samples to be tested with short loading steps, while keeping the total testing time low and reducing dose deposition. Higher trabecular bone content was quantified in the surrounding of the screw in the treated groups, which correlated with increased mechanical strength and stiffness. Differences in screw implantation, such as contact between threads and cortex as well as minor tilt of the screw were also correlated to the mechanical parameters. In situ loading enabled the investigation of crack propagation during the pullout, highlighting the mechanical behavior of the interface. Three typical crack types were observed: (1) rupture at the interface of trabecular and cortical bone tissues, close to the screw, (2) large crack inside the cortex connected to the implant, and (3) first failure away from the screw with cracks propagating toward the screw-bone interface. Mechanical properties of in vivo integrated bone-metal screws rely on a combination of multiple parameters that are difficult to identify and separate one from the other.

Dataset Information

Multiscale analyses of the bone-implant interface.

Publications

Multiscale analyses of the bone-implant interface.

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