Potential use of gallium-doped phosphate-based glass material for periodontitis treatment

Abstract

This study aimed at evaluating the potential effect of gallium-incorporated phosphate-based glasses towards periodontitis-associated bacteria, Porphyromonas gingivalis, and matrix metalloproteinase-13. Periodontitis describes a group of inflammatory diseases of the gingiva and supporting structures of the periodontium. They are initiated by the accumulation of plaque bacteria, such as the putative periodontal pathogen Porphyromonas gingivalis, but the host immune response such as elevated matrix metalloproteinases are the major contributing factor for destruction of periodontal tissues. Antibacterial assays of gallium-incorporated phosphate-based glasses were conducted on Porphyromonas gingivalis ATCC 33277 using disc diffusion assay on fastidious anaerobe agar and liquid broth assay in a modified tryptic soy broth. In vitro study investigated the effect of gallium on purified recombinant human matrix metalloproteinase-13 activity using matrix metalloproteinase assay kit. In vivo biocompatibility of gallium-incorporated phosphate-based glass was evaluated in rats as subcutaneous implants. Antibacterial assay of gallium displayed activity against Porphyromonas gingivalis (inhibition zone of 22 ± 0.5 mm compared with 0 mm for control glass, c-PBG). Gallium in the glass contributed to growth inhibitory effect on Porphyromonas gingivalis (up to 1.30 reductions in log ₁₀ values of the viable counts compared with control) in a modified tryptic soy broth. In vitro study showed gallium-incorporated phosphate-based glasses inhibited matrix metalloproteinase activity significantly (p ≤ 0.01) compared with c-PBG. Evaluation of in vivo biocompatibility of gallium-incorporated phosphate-based glasses in rats showed a non-toxic and foreign body response after 2 weeks of implantation. The results indicate that gallium ions might act on multiple targets of biological mechanisms underlying periodontal disease. Moreover, gallium-incorporated phosphate-based glasses are biocompatible in a rat model. The findings warrant further investigation and will have important clinical implications in the future treatment and management of periodontitis.

Keywords

Gallium periodontitis phosphate-based glasses matrix metalloproteinase

Get full access to this article

View all access options for this article.

References

Kaneko

Thoendel

Olakanmi

. The transition metal gallium disrupts Pseudomonas aeruginosa iron metabolism and has antimicrobial and antibiofilm activity. J Clin Invest 2007; 117: 877–888.

Valappil

Ready

Abou Neel

. Antimicrobial gallium-doped phosphate-based glasses. Adv Fun Mater 2008; 18: 732–741.

Chitambar

Narasimhan

. Targeting iron-dependent DNA synthesis with gallium and transferrin-gallium. Pathobiol 1991; 59: 3–10.

Hedley

Tripp

Slowiaczek

. Effect of gallium on DNA synthesis by human T-cell lymphoblasts. Cancer Res 1988; 48: 3014–3018.

Bonchi

Imperi

Minandri

. Repurposing of gallium-based drugs for antibacterial therapy. Biofactors 2014; 40: 303–312.

Bernstein

Tanner

Godfrey

. Chemistry and pharmacokinetics of gallium maltolate, a compound with high oral gallium bioavailability. Met-Based Drugs 2000; 7: 33–47.

Banin

Lozinski

Brady

. The potential of desferrioxamine-gallium as an anti-Pseudomonas therapeutic agent. Proc Natl Acad Sci USA 2008; 105: 16761–16766.

Moore

Murphy

Millar

. Improved cultural selectivity of medically significant fungi by suppression of contaminating bacterial flora employing gallium (III) nitrate. J Microbiol Meth 2009; 76: 201–203.

Vitale-Brovarone

Ciapetti

Leonardi

. Resorbable glass–ceramic phosphate-based scaffolds for bone tissue engineering: synthesis, properties and in vitro effects on human marrow stromal cells. J Biomat Appl 2011; 26: 465–489.

10.

Gentile

Chiono

Thonda-Turo

. Bioresorbable glass effect on the physico-chemical properties of bilayered scaffolds for osteochondral regeneration. Mater Lett 2012; 89: 74–76.

11.

Bretcanu

Baino

Verné

. Novel resorbable glass-ceramic scaffolds for hard tissue engineering: From the parent phosphate glass to its bone-like macroporous derivatives. J Biomat Appl 2014; 28: 1287–1303.

12.

Franchini

Lusvardi

Malavasi

. Gallium-containing phospho-silicate glasses: Synthesis and in vitro bioactivity. Mater Sci Eng C Mater Biol Appl 2012; 32: 1401–1406.

13.

Lusvardi

Malavasi

Menabue

. Gallium-containing phosphosilicate glasses: functionalization and in-vitro bioactivity. Mater Sci Eng C Mater Biol Appl 2013; 33: 3190–3196.

14.

Valappil

Ready

Abou Neel

. Controlled delivery of antimicrobial gallium ions from phosphate-based glasses. Acta Biomater 2009; 5: 1198–1210.

15.

Ahmed

Lewis

Olsen

. Phosphate glasses for tissue engineering: Part 1. Processing and characterisation of a ternary-based P₂O₅–CaO–Na₂O glass system. Bimaterials 2004; 25: 491–499.

16.

Knowles

. Phosphate based glasses for biomedical applications. J Mater Chem 2003; 13: 2395–2401.

17.

Abou Neel

Pickup

Valappil

. Bioactive functional materials: a perspective on phosphate-based glasses. J Mater Chem 2009; 19: 690–701.

18.

Valappil

Owens

Miles

. Effect of gallium on growth of Streptococcus mutans NCTC10449 and dental tissues. Caries Res 2014; 48: 137–146.

19.

Makela

Salo

Uitto

. Matrix metalloproteinases (MMP-2 and MMP-9) of the oral cavity: cellular origin and relationship to periodontal status. J Dent Res 1994; 73: 1397–1406.

20.

Steele J and O'Sullivan I. Adult dental health survey 2009 – Summary report. The health and social care information centre, dental and eye care team. The NHS information centre for health and social care part of the Government statistical service 2011.

21.

Garcia

Henshaw

Krall

. Relationship between periodontal disease and systemic health. Periodontol 2000 2001; 25: 21–36.

22.

Fujimoto

Mouri

Iwata

. A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 2 (72-kDa gelatinase/type IV collagenase) using monoclonal antibodies. Clinica Chimica Acta 1993; 221: 91–103.

23.

Boskey

Ziecheck

Guidon

. Gallium nitrate inhibits alkaline phosphatase activity in a differentiating mesenchymal cell culture. Bone Miner 1993; 20: 179–192.

24.

Kiili

Cox

Chen

. Collagenase-2 (MMP-8) and collagenase-3 (MMP-13) in adult periodontitis: molecular forms and levels in gingival crevicular fluid and immunolocalisation in gingival tissue. J Clin Periodontol 2002; 29: 224–232.

25.

Eley

Manson

. Periodontics, London: Elsevier Ltd, 2004.

26.

Donnelly

Bockman

Doty

. Bone particles from gallium-treated rats are resistant to resorption in vivo. Bone Mineral 1991; 12: 167–179.

27.

Guidon

Jr Salvatori

Bockman

. Gallium nitrate regulates rat osteoblast expression of osteocalcin protein and mRNA levels. J Bone Miner Res 1993; 8: 103–112.

28.

Panagakos

Kumar

Venescar

. The effect of gallium nitrate on synoviocyte MMP activity. Biochimie 2000; 82: 147–151.

29.

Valappil

Coombes

Wright

. Role of gallium and silver from phosphate-based glasses on in vitro dual species oral biofilm models of Porphyromonas gingivalis and Streptococcus gordonii. Acta Biomater 2012; 8: 1957–1965.

30.

Scharfman

Kroczynski

Carnoy

. Adhesion of Pseudomonas aeruginosa to respiratory mucins and expression of mucin-binding proteins are increased by limiting iron during growth. Infect Immun 1996; 64: 5417–5420.

31.

Olakanmi

Britigan

Schlesinger

. Gallium disrupts iron metabolism of Mycobacteria residing within human macrophages. Infect Immun 2000; 68: 5619–5627.

32.

Yoneda

Yoshikane

Motooka

. Stimulation of growth of Porphyromonas gingivalis by cell extracts from Tannerella forsythia. J Periodon Res 2005; 40: 105–109.

33.

Moon

Park

Lee

. Antibacterial action of polyphosphate on Porphyromonas gingivalis. Antimicrob Agents Chemother 2011; 55: 806–812.

34.

Bullen

Rogers

Spalding

. Iron and infection: the heart of the matter. FEMS Immunol Med Microbiol 2005; 43: 325–330.

35.

Yukitake

Naito

Sato

. Effects of non-iron metalloporphyrins on growth and gene expression of Porphyromonas gingivalis. Microbiol Immunol 2011; 55: 141–153.

36.

Bitar

Salih

Mudera

. Soluble phosphate glasses: in vitro studies using human cells of hard and soft tissue origin. Biomaterials 2004; 25: 2283–2292.