Bioactive glass S53P4 explained

Bioactive glass S53P4 (BAG-S53P4) is a biomaterial consisting of sodium, silicate, calcium and phosphate.[1] S53P4 is osteoconductive and also osteoproductive in the promotion, migration, replication and differentiation of osteogenic cells and their matrix production.[2] In other words, it facilitates bone formation and regeneration (osteostimulation). S53P4 has been proven to naturally inhibit the bacterial growth of up to 50 clinically relevant bacteria strains.[3] [4] [5] [6]

History

The S53P4 bioactive glass has its roots in the bioglass 45S5 developed by Larry Hench in the late 1960s in New York.[7] A couple of decades later, in the 1980s, the compound S53P4 bioactive glass was developed in Turku, Finland. S53P4 was found to be osteostimulative (non-osteoinductive), but it also had one new additional property: the composition of 53% silica and smaller weights of sodium, calcium and phosphorus gave rise to surface reactions in vitro that appeared to inhibit bacterial growth – a material that could not be infected by bacteria was discovered.

Applications

Areas of use include a wide range of indications that require the filling of bone cavities, voids, and gaps as well as the reconstruction or regeneration of bone defects. Several long-term studies have shown that mastoid cavities in both cholesteatoma, old radical cavities, and chronic otitis media can be successfully obliterated with S53P4 bioactive glass.[8] [9] [10]

Clinical application has been gained from several extensive studies where patients with bone infections have been treated. S53P4 has shown promising results in chronic osteomyelitis surgery, septic non-union surgery, segmental defect reconstructions and other infectious complications, such as sternum infections, diabetic foot osteomyelitis and spine infections.[11] [12] [13] [14]

S53P4 has gained clinical experience within spine surgery in spine fusions and spinal deformity surgery.[15] [16] [17]

S53P4 has also been used successfully in the filling of benign bone tumor cavities in both adults and children, sustaining the bone cavity volume long term. Clinical experience has been gained from aneurysmal bone cysts (ABC), simple bone cysts (UBC), enchondroma and nonossifying fibroma (NOF).[18]

Mechanism of action

When S53P4 bioactive glass is implanted into a bone cavity, the glass is activated through a reaction with body fluids. During this activation period, the bioactive glass goes through a series of chemical reactions, creating the ideal conditions for bone to rebuild through osteoconduction.

Once the hydroxyapatite layer is formed, the bioactive glass interacts with biological entities, i.e. blood proteins, growth factors and collagen. Following this interactive, osteoconductive and osteostimulative process, new bone grows onto and between the bioactive glass structures.

In the final transformative phase, the process of bone regeneration and remodeling continues. Over time, the glass is fully remodeled into bone, restoring the patient's natural anatomy.

Inhibition of bacterial growth

The bacterial growth inhibiting properties of S53P4 derive from two simultaneous chemical and physical processes, occurring once the bioactive glass reacts with body fluids. Sodium (Na) is released from the surface of the bioactive glass and induces an increase in pH (alkaline environment), which is not favorable for the bacteria, thus inhibiting their growth. The released Na, Ca, Si and P ions give rise to an increase in osmotic pressure due to an elevation in salt concentration, i.e. an environment where bacteria cannot grow.[20]

Notes and References

  1. Cunha MT, Murça MA, Nigro S, Klautau GB, Salles MJ . In vitro antibacterial activity of bioactive glass S53P4 on multiresistant pathogens causing osteomyelitis and prosthetic joint infection . BMC Infectious Diseases . 18 . 1 . 157 . April 2018 . 29614973 . 5883601 . 10.1186/s12879-018-3069-x . . free .
  2. Virolainen P, Heikkilä J, Yli-Urpo A, Vuorio E, Aro HT . Histomorphometric and molecular biologic comparison of bioactive glass granules and autogenous bone grafts in augmentation of bone defect healing . Journal of Biomedical Materials Research . 35 . 1 . 9–17 . April 1997 . 9104694 . 10.1002/(SICI)1097-4636(199704)35:1<9::AID-JBM2>3.0.CO;2-S .
  3. Zhang D, Leppäranta O, Munukka E, Ylänen H, Viljanen MK, Eerola E, Hupa M, Hupa L . 6 . Antibacterial effects and dissolution behavior of six bioactive glasses . Journal of Biomedical Materials Research. Part A . 93 . 2 . 475–83 . May 2010 . 19582832 . 10.1002/jbm.a.32564 .
  4. Leppäranta O, Vaahtio M, Peltola T, Zhang D, Hupa L, Hupa M, Ylänen H, Salonen JI, Viljanen MK, Eerola E . 6 . Antibacterial effect of bioactive glasses on clinically important anaerobic bacteria in vitro . Journal of Materials Science: Materials in Medicine . 19 . 2 . 547–51 . February 2008 . 17619981 . 10.1007/s10856-007-3018-5 . 21444777 .
  5. Drago L, De Vecchi E, Bortolin M, Toscano M, Mattina R, Romanò CL . Antimicrobial activity and resistance selection of different bioglass S53P4 formulations against multidrug resistant strains . Future Microbiology . 10 . 8 . 1293–9 . 2015 . 26228640 . 10.2217/FMB.15.57 .
  6. Drago L, Vassena C, Fenu S, De Vecchi E, Signori V, De Francesco R, Romanò CL . In vitro antibiofilm activity of bioactive glass S53P4 . Future Microbiology . 9 . 5 . 593–601 . 2014 . 24957087 . 10.2217/fmb.14.20 .
  7. Web site: Our story, Glass into bone. May 11, 2020. Bonalive Biomaterials. Bonalive Biomaterials Ltd.
  8. de Veij Mestdagh PD, Colnot DR, Borggreven PA, Orelio CC, Quak JJ . Mastoid obliteration with S53P4 bioactive glass in cholesteatoma surgery . Acta Oto-Laryngologica . 137 . 7 . 690–694 . July 2017 . 28125327 . 10.1080/00016489.2017.1279346 . 4520396 .
  9. Bernardeschi D, Pyatigorskaya N, Russo FY, De Seta D, Corallo G, Ferrary E, Nguyen Y, Sterkers O . 6 . Anatomical, functional and quality-of-life results for mastoid and epitympanic obliteration with bioactive glass s53p4: a prospective clinical study . Clinical Otolaryngology . 42 . 2 . 387–396 . April 2017 . 27608143 . 10.1111/coa.12748 . 1060470 .
  10. Vos J, de Vey Mestdagh P, Colnot D, Borggreven P, Orelio C, Quak J . Bioactive glass obliteration of the mastoid significantly improves surgical outcome in non-cholesteatomatous chronic otitis media patients . European Archives of Oto-Rhino-Laryngology . 274 . 12 . 4121–4126 . December 2017 . 28956143 . 10.1007/s00405-017-4757-7 . 20851852 .
  11. Bigoni M, Turati M, Zanchi N, Lombardo AS, Graci J, Omeljaniuk RJ, Zatti G, Gaddi D . 6 . Clinical applications of Bioactive glass S53P4 in bone infections: a systematic review . European Review for Medical and Pharmacological Sciences . 23 . 2 Suppl . 240–251 . April 2019 . 30977891 . 10.26355/eurrev_201904_17498 . 109940029 .
  12. Godoy-Santos AL, Rosemberg LA, de Cesar-Netto C, Armstrong DG . The use of bioactive glass S53P4 in the treatment of an infected Charcot foot: a case report . Journal of Wound Care . 28 . Sup1 . S14–S17 . January 2019 . 30724119 . 10.12968/jowc.2019.28.Sup1.S14 . 73428010 .
  13. Malat TA, Glombitza M, Dahmen J, Hax PM, Steinhausen E . The Use of Bioactive Glass S53P4 as Bone Graft Substitute in the Treatment of Chronic Osteomyelitis and Infected Non-Unions – a Retrospective Study of 50 Patients . Zeitschrift für Orthopädie und Unfallchirurgie . 156 . 2 . 152–159 . April 2018 . 29665602 . 10.1055/s-0043-124377 . 263428196 .
  14. Book: Lindfors N, Geurts J, Drago L, Arts JJ, Juutilainen V, Hyvönen P, Suda AJ, Domenico A, Artiaco S, Alizadeh C, Brychcy A, Bialecki J, Romanò CL . Antibacterial Bioactive Glass, S53P4, for Chronic Bone Infections – A Multinational Study . 6 . A Modern Approach to Biofilm-Related Orthopaedic Implant Infections . 971 . 81–92 . 2017 . 28050878 . 10.1007/5584_2016_156 . 978-3-319-52273-9 . Advances in Experimental Medicine and Biology . 10138/252437 . 22072415 . free .
  15. Frantzén J, Rantakokko J, Aro HT, Heinänen J, Kajander S, Gullichsen E, Kotilainen E, Lindfors NC . 6 . Instrumented spondylodesis in degenerative spondylolisthesis with bioactive glass and autologous bone: a prospective 11-year follow-up . Journal of Spinal Disorders & Techniques . 24 . 7 . 455–61 . October 2011 . 21909036 . 10.1097/BSD.0b013e31822a20c6 . 28088570 .
  16. Rantakokko J, Frantzén JP, Heinänen J, Kajander S, Kotilainen E, Gullichsen E, Lindfors NC . Posterolateral spondylodesis using bioactive glass S53P4 and autogenous bone in instrumented unstable lumbar spine burst fractures. A prospective 10-year follow-up study . Scandinavian Journal of Surgery . 101 . 1 . 66–71 . 2012 . 22414472 . 10.1177/145749691210100113 . 38296163 .
  17. Saarenpää I, Hirvonen J, Rinne J, Frantzén J. 2018. Novel bioactive glass putty (S53P4) as bone graft expander in minimally invasive lumbosacral interbody fusion. J Minim Invasive Spine Surg Tech. 3. 2. 52–8. 10.21182/jmisst.2018.00332. free.
  18. Lindfors NC et al. . 2010. A prospective randomized 14-year follow- up study of bioactive glass and autogenous bone as bone graft substitutes in benign bone tumours. J Biomed Mater Res. 94B. 1. 57–64. 10.1002/jbm.b.31636 . 20524190 .
  19. Book: Bonalive Smart Healing (EN), version 91308d/3 . . May 11, 2020.
  20. Web site: Bacterial growth inhibition of Bonalive® granules", version 91310f/1 . . June 12, 2020.

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