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Silicon nitride-based materials for spinal and antipathogenic applications
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering, Applied Material Science.
2023 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

Silicon nitride (Si3N4) is a ceramic material that is well-established in industrial applications due to its stability in demanding environments. The mechanical properties and biocompatibility of the material have led to its approval for clinical use in spinal implants. The unique surface chemistry of Si3N4 has been shown to create a chemical environment that is supportive to bone regeneration while simultaneously reducing bacterial viability, both in vitro and in animal models in vivo. Thus, Si3N4 can be used in the spine to reduce patient recovery times while protecting the implant site from damaging and costly infections. However, results from clinical studies have not shown significant differences between silicon nitride and other spinal implant materials in terms of patient outcomes.   

Thus, the first aim of this thesis was to find ways to optimise the biological properties of the material and in turn create spinal implants that would exhibit significantly higher osteointegration while reducing the incidence of infections. To this end, a thermochemical surface modification was developed that changed the surface chemistry and roughness of the material resulting in increased in vitro bioactivity without affecting its antibacterial behaviour. Furthermore, the possibility of creating an osteoconductive, antibacterial bone cement to be used in vertebroplasties in the spine was explored. By adding up to 20%wt of a Si3N4 powder to poly methyl methacrylate (PMMA) cements, a significant (>90%) reduction of bacterial biofilm formation was achieved without affecting the compressive strength or biocompatibility of the modified bone cements in a negative way.

A secondary objective of the study was to explore the antipathogenic properties of the material, fulfilling the growing need for a world where the spread of dangerous pathogens will be limited. The efficiency of the material against one of the most resilient DNA-viruses, the human adenovirus, was tested. It was found that contact with Si3N4 in both powder and bulk form rapidly reduced infectivity (>98% and >73%, respectively). Based on these results, a thermal modification of silicon nitride powders was developed, that would enhance their antiviral efficiency against SARS-CoV-2 and thus the applicability of the material. It was found that 10%wt modified-Si3N4 slurries rendered the coronavirus non-infectious after less than a minute of contact. The results of these studies proved that silicon nitride can also be used as an antipathogenic agent in environmental applications.

Overall, in this thesis, steps were taken towards the development of Si3N4-based materials that can lead to faster healing, lower infection rates and that can be used to limit the spread of disease.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2023. , p. 44
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 2284
National Category
Materials Engineering
Identifiers
URN: urn:nbn:se:uu:diva-506364ISBN: 978-91-513-1846-2 (print)OAI: oai:DiVA.org:uu-506364DiVA, id: diva2:1775396
Public defence
2023-09-15, Siegbahnshalen, Ångströmslaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2023-08-25 Created: 2023-06-27 Last updated: 2023-08-25
List of papers
1. Bioactive Silicon Nitride Implant Surfaces with Maintained Antibacterial Properties
Open this publication in new window or tab >>Bioactive Silicon Nitride Implant Surfaces with Maintained Antibacterial Properties
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2022 (English)In: Journal of Functional Biomaterials, E-ISSN 2079-4983, Vol. 13, no 3, article id 129Article in journal (Refereed) Published
Abstract [en]

Silicon nitride (Si3N4) is a promising biomaterial, currently used in spinal fusion implants. Such implants should result in high vertebral union rates without major complications. However, pseudarthrosis remains an important complication that could lead to a need for implant replacement. Making silicon nitride implants more bioactive could lead to higher fusion rates, and reduce the incidence of pseudarthrosis. In this study, it was hypothesized that creating a highly negatively charged Si3N4 surface would enhance its bioactivity without affecting the antibacterial nature of the material. To this end, samples were thermally, chemically, and thermochemically treated. Apatite formation was examined for a 21-day immersion period as an in-vitro estimate of bioactivity. Staphylococcus aureus bacteria were inoculated on the surface of the samples, and their viability was investigated. It was found that the thermochemically and chemically treated samples exhibited enhanced bioactivity, as demonstrated by the increased spontaneous formation of apatite on their surface. All modified samples showed a reduction in the bacterial population; however, no statistically significant differences were noticed between groups. This study successfully demonstrated a simple method to improve the in vitro bioactivity of Si3N4 implants while maintaining the bacteriostatic properties.

Place, publisher, year, edition, pages
MDPI, 2022
Keywords
bioactivity, silicon nitride, surfaces, antibacterial, biomedical
National Category
Biomaterials Science Medical Materials Nano Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-486395 (URN)10.3390/jfb13030129 (DOI)000857670200001 ()36135564 (PubMedID)
Funder
EU, Horizon 2020, 812765
Available from: 2022-10-10 Created: 2022-10-10 Last updated: 2025-02-09Bibliographically approved
2. The addition of silicon nitride to PMMA bone cements reduces bacterial attachment while supporting pre-osteoblast viability
Open this publication in new window or tab >>The addition of silicon nitride to PMMA bone cements reduces bacterial attachment while supporting pre-osteoblast viability
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2024 (English)In: Next Materials, E-ISSN 2949-8228, Vol. 3, article id 100106Article in journal (Refereed) Published
Abstract [en]

Injectable poly (methyl methacrylate) (PMMA) bone cements are widely used in orthopaedics to stabilize fractures and for implant fixation. However, bacterial attachment to bone cements leads to significant complications that can create a need for implant revision. Common attempts at reducing bacterial attachment are through the addition of antibiotics or antibacterial nanometals to the bone cements. However, clinical data is inconclusive on the effectiveness of antibiotic-loaded bone cements and a negative osteoblastic response has been reported for certain additive concentrations. There is therefore a need for an additive that can positively affect osteoblastic behaviour while inhibiting bacterial attachment. Silicon nitride (Si3N4) could be such an additive, with initial studies showing promise in achieving antipathogenic properties. The aim of this study was hence to investigate the possibility of creating a bone cement that can support osteoblast growth while reducing bacterial attachment by introducing silicon nitride powders into an injectable PMMA cement. To this end, commercially available bone cements were doped with 5%, 10% and 20% weight/weight (w/w) of Si3N4. Their mechanical properties were examined through compression testing and their radiopacity was evaluated through fluoroscopy imaging. The samples that fulfilled compressive strength requirements had their biological properties tested using Staphylococcus epidermidis bacteria for antibacterial properties and MC3T3-E1 preosteoblasts for the examination of cytotoxicity. Bone cements that were doped with up to 20% w/w Si3N4 were radiopaque (only 13% reduction in optical density compared to radiopaque controls) and retained their compressive strength (85.35 ± 2.1 MPa compared to 83.4 ± 1.9 MPa for the commercial cements), while significantly reducing bacterial attachment by more than 90% compared to commercial cements and achieving a similar level of preosteoblast metabolic activity. This study supports further evaluation of Si3N4 as an additive to injectable bone cements as a way to create mechanically stable, radiopaque, bacteriostatic bone cements that could improve osteointegration.

Place, publisher, year, edition, pages
Elsevier, 2024
National Category
Materials Engineering
Identifiers
urn:nbn:se:uu:diva-506362 (URN)10.1016/j.nxmate.2024.100106 (DOI)001466558000001 ()2-s2.0-85202208020 (Scopus ID)
Note

De två sista författarna delar sistaförfattarskapet

Available from: 2023-06-27 Created: 2023-06-27 Last updated: 2025-06-17Bibliographically approved
3. Contact inactivation of human adenovirus type 5 by silicon nitride ceramics
Open this publication in new window or tab >>Contact inactivation of human adenovirus type 5 by silicon nitride ceramics
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Containing the spread of pathogens and treating the diseases they cause have become topics of high importance and urgency for researchers. Recent epidemics and pandemics, key amongst them being the pandemic caused by the coronavirus disease (COVID-19), have highlighted the devastating results virus infections can have on our society. Uncovering and utilising materials for the protection from and treatment of virus-induced diseases can considerably alleviate the load imposed on healthcare systems worldwide. Silicon nitride is a biocompatible ceramic material used in orthopedic implants that is effective in the inactivation of single-stranded RNA viruses. However, the effect of the material on the more resilient DNA viruses remains unknown. This study aimed to investigate the antiviral behaviour of the material, in powder and bulk form, against DNA viruses, and more specifically the human adenovirus. The results of the study indicated that silicon nitride dramatically reduces adenoviral infectivity in powder (>98% reduction in infective virus compared to untreated samples) and bulk form (>73% reduction in infective virus compared to negative control). In both cases, inactivation was achieved rapidly, in one minute for powders and 10 minutes for bulk surfaces. The findings of this study strengthen the potential of silicon nitride to be used as an antiviral agent, aiding the fight against the spread of both DNA and RNA virus diseases.

Keywords
Silicon nitride, viral inactivation, surfaces, adenovirus
National Category
Materials Engineering
Identifiers
urn:nbn:se:uu:diva-506361 (URN)
Available from: 2023-06-27 Created: 2023-06-27 Last updated: 2023-06-27Bibliographically approved
4. Antiviral Properties of Oxidized Silicon Nitride Against SARS-CoV-2
Open this publication in new window or tab >>Antiviral Properties of Oxidized Silicon Nitride Against SARS-CoV-2
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The spread of SARS-CoV-2 led to a global pandemic that caused several million deaths. The severity of this pandemic created challenges for scientists worldwide regarding the prevention of the spread of COVID-19, the disease the virus causes. While the use of personal protective equipment and social distancing limited the spread of the virus, high transmission rates were noted. A solution to the issue of viral spread can be partially given by the utilization of antiviral materials for long-term protection against pathogens on environmental surfaces. To this end, nitrides are materials of high interest due to their proven efficiency in inactivating bacteria and viruses. Silicon nitride (Si3N4) is a ceramic material that possesses an inactivation mechanism termed ‘catch and kill’. In this study we hypothesized that a surface-modified Si3N4 material whose hydrophilicity has been increased through a heat treatment could lead to high attachment and inactivation of SARS-CoV-2 virions. Si3N4 powders were oxidized, characterized and the inactivation of SARS-CoV-2 by them was tested. The results showed that oxidized Si3N4 was highly effective in binding and inactivating SARS-CoV-2 after as little as one minute of contact and can be used to inhibit the spread of COVID-19 under certain circumstances.

National Category
Materials Engineering
Identifiers
urn:nbn:se:uu:diva-506359 (URN)
Note

De två första författarna delar förstaförfattarskapet

Available from: 2023-06-27 Created: 2023-06-27 Last updated: 2023-06-27Bibliographically approved

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