Dataset Information

Surface Roughness of Titanium Orthopedic Implants Alters the Biological Phenotype of Human Mesenchymal Stromal Cells.

ABSTRACT: Metal orthopedic implants are largely biocompatible and generally achieve long-term structural fixation. However, some orthopedic implants may loosen over time even in the absence of infection. In vivo fixation failure is multifactorial, but the fundamental biological defect is cellular dysfunction at the host-implant interface. Strategies to reduce the risk of short- and long-term loosening include surface modifications, implant metal alloy type, and adjuvant substances such as polymethylmethacrylate cement. Surface modifications (e.g., increased surface rugosity) can increase osseointegration and biological ingrowth of orthopedic implants. However, the localized responses of cells to implant surface modifications need to be better characterized. As an in vitro model for investigating cellular responses to metallic orthopedic implants, we cultured mesenchymal stromal/stem cells on clinical-grade titanium disks (Ti6Al4V) that differed in surface roughness as high (porous structured), medium (grit blasted), and low (bead blasted). Topological characterization of clinically relevant titanium (Ti) materials combined with differential mRNA expression analyses (RNA-seq and real-time quantitative polymerase chain reaction) revealed alterations to the biological phenotype of cells cultured on titanium structures that favor early extracellular matrix production and observable responses to oxidative stress and heavy metal stress. These results provide a descriptive model for the interpretation of cellular responses at the interface between native host tissues and three-dimensionally printed modular orthopedic implants, and will guide future studies aimed at increasing the long-term retention of such materials after total joint arthroplasty. Impact statement Using an in vitro model of implant-to-cell interactions by culturing mesenchymal stromal cells (MSCs) on clinically relevant titanium materials of varying topological roughness, we identified mRNA expression patterns consistent with early extracellular matrix (ECM) production and responses to oxidative/heavy metal stress. Implants with high surface roughness may delay the differentiation and ECM formation of MSCs and alter the expression of genes sensitive to reactive oxygen species and protein kinases. In combination with ongoing animal studies, these results will guide future studies aimed at increasing the long-term retention of widely used titanium materials after total joint arthroplasty.

SUBMITTER: Lewallen EA

PROVIDER: S-EPMC8742309 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Surface Roughness of Titanium Orthopedic Implants Alters the Biological Phenotype of Human Mesenchymal Stromal Cells.

Lewallen Eric A EA Trousdale William H WH Thaler Roman R Yao Jie J JJ Xu Wei W Denbeigh Janet M JM Nair Asha A Kocher Jean-Pierre JP Dudakovic Amel A Berry Daniel J DJ Cohen Robert C RC Abdel Matthew P MP Lewallen David G DG van Wijnen Andre J AJ

Tissue engineering. Part A 20210816 23-24

Metal orthopedic implants are largely biocompatible and generally achieve long-term structural fixation. However, some orthopedic implants may loosen over time even in the absence of infection. <i>In vivo</i> fixation failure is multifactorial, but the fundamental biological defect is cellular dysfunction at the host-implant interface. Strategies to reduce the risk of short- and long-term loosening include surface modifications, implant metal alloy type, and adjuvant substances such as polymethy ...[more]

PMID: 33975459

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Project description:Orthopedic implant failure due to aseptic loosening and mechanical instability remains a major problem in total joint replacement. Improving osseointegration at the bone-implant interface may reduce micromotion and loosening. Bone sialoprotein (BSP) has been shown to enhance bone formation when coated onto titanium femoral implants and in rat calvarial defect models. However, the most appropriate method of BSP coating, the necessary level of BSP coating, and the effect of BSP coating on cell behavior remain largely unknown. In this study, BSP was covalently coupled to titanium surfaces via an aminosilane linker (APTES), and its properties were compared to BSP applied to titanium via physisorption and untreated titanium. Cell functions were examined using primary human osteoblasts (hOBs) and L929 mouse fibroblasts. Gene expression of specific bone turnover markers at the RNA level was detected at different intervals. Cell adhesion to titanium surfaces treated with BSP via physisorption was not significantly different from that of untreated titanium at any time point, whereas BSP application via covalent coupling caused reduced cell adhesion during the first few hours in culture. Cell migration was increased on titanium disks that were treated with higher concentrations of BSP solution, independent of the coating method. During the early phases of hOB proliferation, a suppressive effect of BSP was observed independent of its concentration, particularly when BSP was applied to the titanium surface via physisorption. Although alkaline phosphatase activity was reduced in the BSP-coated titanium groups after 4 days in culture, increased calcium deposition was observed after 21 days. In particular, the gene expression level of RUNX2 was upregulated by BSP. The increase in calcium deposition and the stimulation of cell differentiation induced by BSP highlight its potential as a surface modifier that could enhance the osseointegration of orthopedic implants. Both physisorption and covalent coupling of BSP are similarly effective, feasible methods, although a higher BSP concentration is recommended.

Project description:Tissue response following implantation determines the success of the healing process. This response is not only dependent on the chemical properties of the implant surface but also by the surface topography or its roughness. Although in vitro and in vivo studies show improved results with rough- and fluoride-modified implants, the mechanisms behind these findings are still unknown. Here, we have used a two step procedure to identify novel genes related to the early cell response of primary human osteoblasts to roughness and fluoride-modified titanium implants. 217 genes were identified by microarray analysis as response genes to roughness and 198 genes as response genes to fluoride. 11 of these identified genes have been related to bone and mineralization and were further investigated by real-time RT-PCR. After one day of culture, TLR3, ANKH, DCN, OC and RUNX2 were classified as responsive genes to roughness; DLX2 and TUFT1 as responsive genes to fluoride treatment. COLL-I, PTHLH, HES1, FST, ENPP1 and THRA as responsive genes to both, roughness and fluoride treatment. In conclusion, our strategy was useful for identifying novel genes that might be involved in the early response of osteoblasts to roughness and fluoride treatment of titanium implants. Tissue response following implantation determines the success of the healing process. This response is not only dependent on the chemical properties of the implant surface but also by the surface topography or its roughness. Although in vitro and in vivo studies show improved results with rough- and fluoride-modified implants, the mechanisms behind these findings are still unknown. Here, we have used a two step procedure to identify novel genes related to the early cell response of primary human osteoblasts to roughness and fluoride-modified titanium implants. 217 genes were identified by microarray analysis as response genes to roughness and 198 genes as response genes to fluoride. 11 of these identified genes have been related to bone and mineralization and were further investigated by real-time RT-PCR. After one day of culture, TLR3, ANKH, DCN, OC and RUNX2 were classified as responsive genes to roughness; DLX2 and TUFT1 as responsive genes to fluoride treatment. COLL-I, PTHLH, HES1, FST, ENPP1 and THRA as responsive genes to both, roughness and fluoride treatment. In conclusion, our strategy was useful for identifying novel genes that might be involved in the early response of osteoblasts to roughness and fluoride treatment of titanium implants.

Dataset Information

Surface Roughness of Titanium Orthopedic Implants Alters the Biological Phenotype of Human Mesenchymal Stromal Cells.

Publications

Surface Roughness of Titanium Orthopedic Implants Alters the Biological Phenotype of Human Mesenchymal Stromal Cells.

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