Improvement of osseointegration: Guiding cells with external factors including a novel surface microstructure and recognizing bacterial infections

Emilia Kaivosoja

    Research output: ThesisDoctoral ThesisCollection of Articles

    Abstract

    The aim of this study was to find methods that could potentially improve the osseointegration of an implant. The prerequisites for implant integration into bone are the adhesion of the osteoblastic cells and the ability of the progenitor cells (stem cells) to differentiate into bone cells on the surface of the implant. It was found that patterning with diamond-like carbon, Cr, Ta or Ti improved the cytocompatibility of Si substrates with osteoblastic cells and mesenchymal stem cells (MSC). The patterns affected the density of the cells, causing local cellular spots on the patterns initiating the clustering of the cells and the cell–cell contacts, which are considered necessary for osteogenesis. Indeed, patterning improved the osteogenic differentiation of MSCs compared to planar non-patterned surfaces. With three-dimensional surfaces, the aim was to promote tissue-like growth and activationof the cytoskeleton; many previous studies have shown that this improves osteogenesis. However, this work showed that activation of the cytoskeleton alone is not osteoinductive. The osteoblastic differentiation of MSCs on 20 μm high pillars was studied, and it was found that the cytoskeleton of the cells was highly activated, but that osteogenesis was not stimulated; in fact, it was suppressed. The likely reason for this behaviour was the failure of adequate osteoinductive cell–cell contacts. In addition to growth substrate variables, the fate of the stem cells is regulated by physicalforces and soluble factors. It was found that pulsed electromagnetic fields improved the viability of the MSCs, but that they had no significant effect on their osteogenic differentiation at the relatively low seeding density used here. In contrast, a prohormone (dehydroepiandrosterone, DHEA) improved osteogenesis at least in part due to an intracrine conversion of DHEA into a sex steroid (dihydrotestosterone), but also via some other as yet undefined mechanisms. In addition to the integration of implants with tissues via contact with other cells and extracellular matrix, another important factor regulating implant integration and the lifetime of the implant is the amount of contact it has with commensials and pathogenic microbes, in particular bacteria. Diagnostics of peri-implant infections is usually based on the bacterial culture, neutrophil infiltrates and other methods. Nonetheless, the current methods are not reliable enough. In the final part of this thesis, two methods that could potentially be utilised to diagnose implant infections were evaluated. It was found that time-of-flight secondary ion mass spectrometry is a potential tool for differentiating of acellular bacterial from eukaryotic footprints (i.e. extracellular polymeric substance and extracellular matrix produced by the respective cells) and may have potential for the post-hoc diagnosis of colonisation, biofilm formation and implant-related infections even in culture negative cases.
    Translated title of the contributionOsseointegraation edistäminen
    Original languageEnglish
    QualificationDoctor's degree
    Awarding Institution
    • Aalto University
    Supervisors/Advisors
    • Paulasto-Kröckel, Mervi, Supervising Professor
    • Konttinen, Yrjö T., Thesis Advisor, External person
    Publisher
    Print ISBNs978-952-60-5038-6
    Electronic ISBNs978-952-60-5037-9
    Publication statusPublished - 2013
    MoE publication typeG5 Doctoral dissertation (article)

    Keywords

    • osseointegration
    • microfabrication
    • pulsed electromagnetic fields
    • dehydroepiandrosterone
    • ToF-SIMS

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