Functional biomaterials for comprehensive periodontitis therapy

Abstract

Periodontitis is an inflammatory disease caused by bacterial infection directly, and the dysregulation of host immune-inflammatory response finally destroys periodontal tissues. Current treatment strategies for periodontitis mainly involve mechanical scaling/root planing (SRP), surgical procedures, and systemic or localized delivery of antimicrobial agents. However, SRP or surgical treatment alone has unsatisfactory long-term effects and is easy to relapse. In addition, the existing drugs for local periodontal therapy do not stay in the periodontal pocket long enough and have difficulties in maintaining a steady, effective concentration to obtain a therapeutic effect, and continuous administration always causes drug resistance. Many recent studies have shown that adding bio-functional materials and drug delivery systems upregulates the therapeutic effectiveness of periodontitis. This review focuses on the role of biomaterials in periodontitis treatment and presents an overview of antibacterial therapy, host modulatory therapy, periodontal regeneration, and multifunctional regulation of periodontitis therapy. Biomaterials provide advanced approaches for periodontal therapy, and it is foreseeable that further understanding and applications of biomaterials will promote the development of periodontal therapy.

Keywords: Anti-inflammation; Anti-oxidant; Antibacterial effect; Biomaterial; Drug delivery; Host modulation; Periodontal regeneration; Periodontitis therapy.

Graphical abstract

Scheme 1

Functional biomaterials for comprehensive treatment of periodontitis, , , . Reprinted with the permission from Ref. 35. Copyright © 2016 American Chemical Society; Ref. 36. Copyright © 2021 Wiley-VCH GmbH; Ref. 37. Copyright © 2019, American Chemical Society. Ref. 38. Copyright © 2021 The Authors.

Figure 1

Double-layer nanofiber mat as sustained release system of antibiotics for periodontitis therapy. (A) In vitro microflow-through apparatus to simulate periodontal pocket microenvironments in vivo. (B) Cumulative drug release of CIP and MTZ from double-layer nanofiber mats. (C) Drug concentration of CIP and MTZ released from double-layer nanofiber mat into dissolution medium. (D) In vitro testing on growth inhibition of Gram-negative bacteria using antimicrobial nanofiber mat. D-CIP, double-layer mat of MTZ-loaded PCL layer and CIP-loaded CS/PEG layer opposite agar medium; D-MTZ, double-layered mat as described above with the PCL layer loaded with MTZ facing the agar medium; E. coli, Escherichia coli. Reprinted with the permission from Ref. 52. Copyright © 2019 Elsevier B.V.

Figure 2

Dual crown vesicle as an antibiotic delivery system enhanced the anti-biofilm activity for treatment of periodontitis. (A) Synthesis, structure, and action mechanism of dual crown vesicles. (B, C) In vitro anti-biofilm activity of dual crowned vesicle. Considering the untreated cases as 100%, the biomass percentage of treated cases over 24 h was calculated. (B) E. coli biofilm. (C) S. aureus biofilm. In vivo antibacterial activity of double-crowned vesicle. (D) Experimental design and processing flow. S. aureus, Staphylococcus aureus. Reprinted with the permission from Ref. 37. Copyright © 2019 American Chemical Society.

Figure 3

2D MOF for aPDT with enhanced antibacterial activity and reduced periodontal inflammation. (A) Ointment for effective treatment of periodontitis based on 2D MOF heterojunction. (B) In vitro antibacterial effect of photodynamic ion therapy. (C‒F) Evaluation of therapeutic effect of 2D MOF photodynamic ion therapy on rat periodontitis model by (C) H&E staining, (D) Masson's trichrome staining (scale bars = 500 and 50 μm for low-magnification and high-magnification images, respectively), (E) immunohistochemical staining (scale bars = 50 μm for all images), and (F) micro-CT. Scale bar, 1 mm. P. g., Porphyromonas gingivalis; F. n., Fusobacterium nucleatum; S. a., Staphylococcus aureus. Reprinted with the permission from Ref. 146. Copyright © 2021 American Chemical Society.

Figure 4

CS hydrogel combined with exosomes derived from hDP-MSCs to treat periodontitis by regulating macrophage polarization. (A) Schematic diagram of material design, experiment process, and therapeutic mechanisms. (B, C) hDP-MSC Exo/CS promoted the phenotypic transformation of macrophages in vitro. (B) Representative density plots and (C) mean fluorescence intensity of phenotypic characterization of BMDMs co-cultured with Exo/CS and CS. (D−E) hDP-MSC Exo/CS promoted the phenotypic transformation of macrophages in periodontitis rats. (D) Density of CD206⁺ cells, (E) density of CD86⁺ cells. Reprinted with the permission from Ref. 171. Copyright © 2020 The Authors.

Figure 5

PDA NP scavenged ROS for treatment of periodontitis. (A) Synthesis and therapy effect of PDA NP toward periodontitis. Scavenging efficiencies of PDA NP for (B) HO· and (C) ·O₂⁻in vitro. Expression of (D) TNF-α and (E) IL-1β in human gingival epithelial cells treated with LPS. Reprinted with the permission from Ref. 210. Copyright © 2018, American Chemical Society.