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Supporting data for the Design and Synthesis of Novel Bismuth-based Materials as Promising Antimicrobials for Tackling Periodontopathogens and Potential Agents  for Modulating Oral Ecological Conditions

posted on 2023-05-19, 07:40 authored by Regina HuangRegina Huang

The following file contains all the data (Folder 01 to Folder 05) generated during this study period, including SEM and TEM images (morphologies and topographies), XRD (crystallinity), BET (porosity and surface area), FTIR & XPS (elemental compositions) of the as-synthesized bismuth-based particles. Additionally, all biological data (antimicrobial activities on pathogens in both planktonic and biofilm modes) and cytotoxicity on host cells were also included in Folder 06 to Folder 09.

Project description

Bismuth drugs, commonly used for treating Helicobacter pylori-associated gastrointestinal infections, have been considerably repositioned to tackle the key oral/periodontal pathogen Porphyromonas gingivalis (Pg). Combining these metallodrugs and classical antibiotics can synergistically eliminate the recalcitrant Pg persisters. However, current bismuth drug formulations exhibit poor water solubility and low bioavailability, and therefore precise delivery of co-administrated drugs is highly challenging.

Essentially, bismuth ions with high affinities towards oxygen, nitrogen and sulfur can be facilely constructed into metal-organic frameworks (MOFs) and other materials by optimizing various synthetic parameters and routes. These resultant particles with antimicrobial effects acquired from the metals act as an adjunct to improve the efficacy of the original drugs. Moreover, they enable the progressively controlled release of drugs and generate synergistic effects after co-administration with antibiotics. Indeed, these materials have emerged as promising therapeutic approaches to tackling current biomedical challenges, such as overcoming the antibiotic resistance crisis for better oral and general healthcare.

In this work, various bismuth-based particles were synthesized, and their morphological and size changes were analyzed with electron microscopy images. Amongst, highly uniformed particles with ellipsoid- (Ellipsoids) and rod-like (Rods) shapes were selected and fully characterized. Specifically, Rods containing a porous structure were confirmed as MOF with an aligned crystallinity of CAU-17. Notably, Rods could be formed within a ‘two-step’ crystallization process by stacking up almond-flake-like intermediates and yet precisely controlled from micro- to nanoscales by varying concentrations of metal ions and their ratio to the ligands. Regarding the biological activities, both particles showed excellent biocompatibility with human gingival fibroblasts and oral epithelial cells and possessed potent antimicrobial effects on the Gram-negative oral pathogens like Aggregatibacter actinomycetemcomitans, Pg and Fusobacterium nucleatum. Particularly, both particles at 50 μg/mL effectively

disrupted the bacterial membranes and eliminated 3-day-old Pg biofilms.

Next, the antimicrobial effects of nanoscale Rods (Bi-MOFsNano) and emodin (an active component of several plants used in Chinese medicine) were evaluated against selected periodontopathogens. Further experiments were undertaken to investigate whether the co-administration of Bi-MOFsNano and emodin could eliminate the noxious intracellular Pg in the host cells. A checkerboard assay was carried out to determine the fractional inhibitory concentration (FIC) index of Bi-MOFsNano and emodin. The co-administration could synergistically suppress the growth of planktonic Pg cells (FIC ≤ 0.5), while both agents at low concentrations exhibited no detectable cytotoxicity of host cells (HGECs) as demonstrated in the cell viability assay. Remarkably, the synergistic pairs of Bi-MOFsNano and emodin could inhibit the intracellular Pg in HGECs.

The present study presents two novel highly efficient and facile approaches to synthesizing bismuth-based particles. Importantly, Bi-MOFs as a bismuth reservoir exhibit potent antimicrobial effects against the keystone periodontopathogen Pg. In synergistic combination with emodin, these particles can serve as an innovative platform to precisely deliver drugs via topical administrations while simultaneously tackling various pathogens and modulating the resultant immunoinflammatory responses. This work may shed light on enriching the administration modalities of metallic drugs for better antibiotic-free oral and general healthcare in the near future.


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