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Biological response to spinal implant degradation products
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science and Engineering.ORCID iD: 0000-0003-2018-3409
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
Abstract [en]

Back pain, affecting 80% of the population, significantly strains the healthcare system. In European countries, spine-related hospital discharges account for 14.2% to 45.6% of all musculoskeletal disease discharges. Conservative treatments like medication and physical therapy are generally preferred, but surgical intervention may be necessary for some. Spinal surgeries often involve implants, such as spinal cages, spinal instrumentation, or total disc replacements, used to treat abnormal spinal curvatures or intervertebral disc degeneration.

Despite their widespread use, spinal implants face challenges such as failed vertebral fusion, infections, and implant failure, which can release harmful ions and particles. Researchers are developing new materials with antibacterial properties and improved interaction with bone tissue. Innovations include wear-resistant coatings to prevent metal ion release and biodegradable materials that the body gradually replaces, reducing infection risks and the need for revision surgeries. However, these advances present challenges. Degradation by-products can migrate more easily to other parts of the body and may elicit unwanted biological responses.

The primary aim of this thesis was to investigate the biological effects of these degradation products from an in vitro perspective. This involved using several relevant cell types and examining morphological and functional changes. A composite of calcium phosphate and polylactic acid was initially examined for spinal fusion. The cell response to the degradation products was comparable to those of a clinically successful calcium phosphate, showing no negative impact on preosteoblast cells. Additionally, silicon nitride (SiN) coatings, known for their wear resistance properties, were explored. The incorporation of additional elements into SiN coatings was studied to enhance stability and durability. It was found that fibroblast and microglial cells tolerated the ions and particles released during degradation similarly to current orthopedic materials. Lastly, the effects of particles from spinal implants on glial cells were evaluated. While most particles did not trigger inflammation, high doses of SiN particles negatively affected microglial cells, reducing their ability to neutralize infectious agents. This highlights the need for further research to fully understand the biological safety of silicon nitride in spinal implants.

In summary, this thesis expands the understanding of the biological responses to spinal implant degradation products, aiding the development of safer and more effective implants.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2024. , p. 77
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 2415
Keywords [en]
Spinal implants, degradation products, biological characterization, wear debris, calcium phosphate, monetite, PLLA, silicon nitride, cell behavior, glial cells
National Category
Biomaterials Science
Research subject
Engineering Science with specialization in Biomedical Engineering
Identifiers
URN: urn:nbn:se:uu:diva-532914ISBN: 978-91-513-2167-7 (print)OAI: oai:DiVA.org:uu-532914DiVA, id: diva2:1875725
Public defence
2024-09-06, Siegbahnsalen, Ångströmslaboratoriet, Lägerhyddsvägen 1, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2024-08-16 Created: 2024-06-24 Last updated: 2024-08-16
List of papers
1. Osteogenic potential of a calcium phosphate-PLLA composite structure
Open this publication in new window or tab >>Osteogenic potential of a calcium phosphate-PLLA composite structure
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(English)Manuscript (preprint) (Other academic)
National Category
Biomaterials Science
Research subject
Engineering Science with specialization in Biomedical Engineering
Identifiers
urn:nbn:se:uu:diva-532912 (URN)
Available from: 2024-06-24 Created: 2024-06-24 Last updated: 2024-07-27
2. Tailoring the dissolution rate and in vitro cell response of silicon nitride coatings through combinatorial sputtering with chromium and niobium
Open this publication in new window or tab >>Tailoring the dissolution rate and in vitro cell response of silicon nitride coatings through combinatorial sputtering with chromium and niobium
2022 (English)In: Biomaterials Science, ISSN 2047-4830, E-ISSN 2047-4849, Vol. 10, no 14, p. 3757-3769Article in journal (Refereed) Published
Abstract [en]

Ceramic coatings have been widely investigated as a means to reduce wear and metallic ion release from joint implants. Silicon nitride-based coatings have been a topic of interest specifically due to their solubility in aqueous solutions. This could imply a reduced adverse immune response since the generated debris would dissolve. However, there are concerns regarding the dissolution rate and adhesion of these silicon nitride-based coatings. This study attempts to address the concern of dissolution rate as well as coating adhesion of silicon nitride coatings. We hypothesized that alloying with chromium and niobium would affect the adhesion, dissolution rate, and the resulting ion release and cell response to the coatings. A combinatorial approach was used to deposit sputtered coatings with compositional gradients both with and without a CrN interlayer. Compositional gradients were achieved for all the investigated elements: Si (38.6-46.9 at%), Nb (2.2-4.6 at%) and Cr (1.9-6.0 at%). However, while the presence of an interlayer reduced the delamination during adhesion testing, the differences in composition in the top coating did not affect the adhesion. Nor did the top coating's composition affect the surface roughness or the coatings' inherent mechanical properties (elastic modulus and hardness). All coating compositions were associated with a low Co release from the underlying metal and points with a higher Cr content (4.3-6.0 at%) gave an overall lower release of Si, Cr and Nb ions, possibly due to the formation of a stable oxide, which reduced the dissolution rate of the coating. Optimum chromium contents were furthermore found to give an enhanced in vitro fibroblast cell viability. In conclusion, the results indicate a possibility to tailor the ion release rate, which lends promise to further investigations such as tribocorrosive tests towards a future biomedical application.

Place, publisher, year, edition, pages
Royal Society of Chemistry (RSC), 2022
National Category
Corrosion Engineering
Identifiers
urn:nbn:se:uu:diva-483686 (URN)10.1039/d1bm01978c (DOI)000802297900001 ()35622079 (PubMedID)
Available from: 2022-09-01 Created: 2022-09-01 Last updated: 2024-06-24Bibliographically approved
3. Fe and C additions decrease the dissolution rate of silicon nitride coatings and are compatible with microglial viability in 3D collagen hydrogels
Open this publication in new window or tab >>Fe and C additions decrease the dissolution rate of silicon nitride coatings and are compatible with microglial viability in 3D collagen hydrogels
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2023 (English)In: Biomaterials Science, ISSN 2047-4830, E-ISSN 2047-4849, Vol. 11, no 9, p. 3144-3158Article in journal (Refereed) Published
Abstract [en]

Silicon nitride (SiN) coatings may reduce unwanted release of metal ions from metallic implants. However, as SiN slowly dissolves in aqueous solutions, additives that reduce this dissolution rate would likely increase the lifetime and functionality of implants. Adding iron (Fe) and carbon (C) permits tuning of the SiN coatings’ mechanical properties, but their effect on SiN dissolution rates, and their capacity to reduce metal ion release from metallic implant substrates, have yet to be investigated. Such coatings have recently been proposed for use in spinal implants; therefore, it is relevant to assess their impact on the viability of cells expected at the implant site, such as microglia, the resident macrophages of the central nervous system (CNS). To study the effects of Fe and C on the dissolution rate of SiN coatings, compositional gradients of Si, Fe and C in combination with N were generated by physical vapor deposition onto CoCrMo discs. Differences in composition did not affect the surface roughness or the release of Si, Fe or Co ions (the latter from the CoCrMo substrate). Adding Fe and C reduced ion release compared to a SiN reference coating, which was attributed to altered reactivity due to an increase in the fraction of stabilizing Si–C or Fe–C bonds. Extracts from the SiN coatings containing Fe and C were compatible with microglial viability in 2D cultures and 3D collagen hydrogels, to a similar degree as CoCrMo and SiN coated CoCrMo reference extracts. As Fe and C reduced the dissolution rate of SiN-coatings and did not compromise microglial viability, the capacity of these additives to extend the lifetime and functionality of SiN-coated metallic implants warrants further investigation.

Place, publisher, year, edition, pages
Royal Society of Medicine Press, 2023
National Category
Biomaterials Science
Research subject
Engineering Science with specialization in Biomedical Engineering
Identifiers
urn:nbn:se:uu:diva-509390 (URN)10.1039/d2bm02074b (DOI)000949773600001 ()
Funder
Swedish Research Council, 2020-04715EU, FP7, Seventh Framework Programme, GA-310477(Life-Long Joints)Swedish Cancer Society, grant number 20 1285 PjFEU, Horizon 2020, grant agreement no. 812765
Available from: 2023-08-18 Created: 2023-08-18 Last updated: 2024-06-24Bibliographically approved
4. Impact of particles derived from spinal implant materials on glial survival and activation
Open this publication in new window or tab >>Impact of particles derived from spinal implant materials on glial survival and activation
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(English)Manuscript (preprint) (Other academic)
National Category
Biomaterials Science
Research subject
Engineering Science with specialization in Biomedical Engineering
Identifiers
urn:nbn:se:uu:diva-532909 (URN)
Available from: 2024-06-24 Created: 2024-06-24 Last updated: 2024-06-24

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Echeverri Correa, Estefanía

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