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Investigating the Mechanical Characteristics of Bone-Metal Implant Interface Using in situ Synchrotron Tomographic Imaging.

ABSTRACT: 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 ?m 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.

SUBMITTER: Le Cann S

PROVIDER: S-EPMC6348316 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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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.

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Investigating the Mechanical Characteristics of Bone-Metal Implant Interface Using in situ Synchrotron Tomographic Imaging.

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