Immunomodulation of oral keratinocytes through titanium surface peptide coatings of cell adhesion oligopeptide motifs and IL-23 Receptor antagonist
2021-11
Loading...
View/Download File
Persistent link to this item
Statistics
View StatisticsJournal Title
Journal ISSN
Volume Title
Title
Immunomodulation of oral keratinocytes through titanium surface peptide coatings of cell adhesion oligopeptide motifs and IL-23 Receptor antagonist
Authors
Published Date
2021-11
Publisher
Type
Thesis or Dissertation
Abstract
Objectives: Peri-implantitis is the leading cause of implant failure with a prevalence of 8-34%. The dysbiotic bacterial invasion of the peri-implant surface leads to an inflammatory reaction of oral keratinocytes (OK) that attach to the implant surface via the junctional epithelium. During stages of inflammation, the attachment of keratinocytes to bound surfaces decreases. We evaluated OKs’ cytokine response to cell adhesion motif peptides, shown to increase hemidesmosomes (LamLG3 and Net1), bound to plasma activated glass (pGlass), compared to controls pGlass and activated pGlass (DIBO). Next, the innate inflammatory response of OKs through cytokine production, specifically the IL-17/IL-23 inflammatory axis, can induce activation of neutrophils and Th17 cells that are present in higher levels in peri-implantitis. We evaluated an IL-23 receptor antagonist (IL-23Ra) bound to etched titanium for cell proliferation of OKs, production of IL-17 and 23, and cytokine secretome regulation. By inducing cell adhesion or regulating the IL-17/23 pathway may reduce the induction and recruitment of aforementioned inflammatory cells, promoting integrity of the soft tissue interface of implants at sites of bacterial infection.Methods: Plasma disks were covalently functionalized with Net1 and LamLG3 and titanium disks were covalently functionalized with IL-23Ra using silanization. Disks in the cell adhesion studied had activated pGlass (DIBO), uncoated surface, and an antimicrobial peptide serving as controls, and the IL-23Ra study had disks with a randomized sequence peptide and non-coated disks serving as controls. IL-23Ra-coatings were physicochemically analyzed with water contact angle and X-ray photoelectron spectroscopy. Proliferation of OKs was measured. ELISAs were used to analyze levels of IL-23 and IL-17 in presence and absence of pro-inflammatory Porphyromonas gingivalis lipopolysaccharide (LPS). For both studies, supernatant and cell lysates were collected at 5 days and analyzed using a 20 and 36-target cytokine array. The IL-23Ra study assessed the cytokine array with a functional protein association network analysis (STRING). ANOVA and Tukey post-hoc tests assessed statistical significance (p<0.05)
Results: Physicochemical analysis demonstrated the successful immobilization of the peptide coatings. The cell adhesion peptides showed a decrease in the production of pro-inflammatory cytokines compared to the three controls. On the other hand, the IL-23Ra-coated titanium significantly increased proliferation of OKs. Further, the IL-23Ra significantly decreased secretion of IL-17 and IL-23, both with and without LPS stimulation, compared to controls.
Conclusions: Our results support the use of IL-23Ra-coatings for reduction of the keratinocyte IL17/23 pro-inflammatory pathway and the use of cell adhesion peptides for the reduction of pro-inflammatory cytokine secretion, and may inform immunomodulatory dental implant designs for soft tissue attachment to thereby reduce peri-implantitis rates.
Description
University of Minnesota M.S. thesis. November 2021. Major: Dentistry. Advisors: Flavia Lakschevtiz, Conrado Aparicio. 1 computer file (PDF); viii, 62 pages.
Related to
Replaces
License
Series/Report Number
Funding information
Isbn identifier
Doi identifier
Previously Published Citation
Suggested citation
Pizarek, John. (2021). Immunomodulation of oral keratinocytes through titanium surface peptide coatings of cell adhesion oligopeptide motifs and IL-23 Receptor antagonist. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/225864.
Content distributed via the University Digital Conservancy may be subject to additional license and use restrictions applied by the depositor. By using these files, users agree to the Terms of Use. Materials in the UDC may contain content that is disturbing and/or harmful. For more information, please see our statement on harmful content in digital repositories.