Immunomodulatory IL-23 receptor antagonist peptide nanocoatings for implant soft tissue healing.

Abstract

OBJECTIVE:

Peri-implantitis, caused by an inflammatory response to pathogens, is the leading cause of dental implant failure. Poor soft tissue healing surrounding implants - caused by inadequate surface properties - leads to infection, inflammation, and dysregulated keratinocyte and macrophage function. One activated inflammatory response, active around peri-implantitis compared to healthy sites, is the IL-23/IL-17A cytokine axis. Implant surfaces can be synthesized with peptide nanocoatings to present immunomodulatory motifs to target peri-implant keratinocytes to control macrophage polarization and regulate inflammatory axises toward enhancing soft tissue healing.

METHODS:

We synthesized an IL-23 receptor (IL-23R) noncompetitive antagonist peptide nanocoating using silanization and evaluated keratinocyte secretome changes and macrophage polarization (M1-like "pro-inflammatory" vs. M2-like "pro-regenerative").

RESULTS:

IL-23R antagonist peptide nanocoatings were successfully synthesized on titanium, to model dental implant surfaces, and compared to nonfunctional nanocoatings and non-coated titanium. IL-23R antagonist nanocoatings significantly decreased keratinocyte IL-23, and downstream IL-17A, expression compared to controls. This peptide noncompetitive antagonistic function was demonstrated under lipopolysaccharide stimulation. Large scale changes in keratinocyte secretome content, toward a pro-regenerative milieu, were observed from keratinocytes cultured on the IL-23R antagonist nanocoatings compared to controls. Conditioned medium collected from keratinocytes cultured on the IL-23R antagonist nanocoatings polarized macrophages toward a M2-like phenotype, based on increased CD163 and CD206 expression and reduced iNOS expression, compared to controls.

SIGNIFICANCE:

Our results support development of IL-23R noncompetitive antagonist nanocoatings to reduce the pro-inflammatory IL-23/17A pathway and augment macrophage polarization toward a pro-regenerative phenotype. Immunomodulatory implant surface engineering may promote soft tissue healing and thereby reduce rates of peri-implantitis.

• Authors: John A Pizarek, Nicholas G Fischer, Conrado Aparicio
• Journal: Dental materials : official publication of the Academy of Dental Materials (Dent Mater) Vol. 39 Issue 2 Pg. 204-216 (02 2023) ISSN: 1879-0097 [Electronic] England
• PMID: 36642687 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2023 The Academy of Dental Materials. Published by Elsevier Inc. All rights reserved.

Chemical References

• Dental Implants
• Interleukin-17
• Interleukin-23
• Titanium
• Receptors, Interleukin

Topics

• Humans
• Dental Implants
• Interleukin-17
• Interleukin-23
• Peri-Implantitis
• Titanium (chemistry)
• Receptors, Interleukin (antagonists & inhibitors)