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Bioactive glass S53P4

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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

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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.[7]

Applications

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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

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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.

  • Na, Si, Ca, and P ions are released.
  • A silica gel layer forms on the bioactive glass surface.
  • CaP crystallizes, forming a layer of hydroxyapatite on the surface of the bioactive glass.

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.

  • Bioactive glass bonds to bone – facilitating new bone formation.
  • Osteostimulation begins by stimulating osteogenic cells to increase the remodeling rate of bone.
  • Radio-dense quality of bioactive glass allows for post-operative evaluation.

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.

  • Bone consolidation occurs.
  • S53P4 bioactive glass continues to remodel into bone over a period of years.[19]

Inhibition of bacterial growth

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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]


References

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  1. ^ Cunha MT, Murça MA, Nigro S, Klautau GB, Salles MJ (April 2018). "In vitro antibacterial activity of bioactive glass S53P4 on multiresistant pathogens causing osteomyelitis and prosthetic joint infection". BMC Infectious Diseases. 18 (1). BioMed Central: 157. doi:10.1186/s12879-018-3069-x. PMC 5883601. PMID 29614973.
  2. ^ Virolainen P, Heikkilä J, Yli-Urpo A, Vuorio E, Aro HT (April 1997). "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. doi:10.1002/(SICI)1097-4636(199704)35:1<9::AID-JBM2>3.0.CO;2-S. PMID 9104694.
  3. ^ Zhang D, Leppäranta O, Munukka E, Ylänen H, Viljanen MK, Eerola E, et al. (May 2010). "Antibacterial effects and dissolution behavior of six bioactive glasses". Journal of Biomedical Materials Research. Part A. 93 (2): 475–83. doi:10.1002/jbm.a.32564. PMID 19582832.
  4. ^ Leppäranta O, Vaahtio M, Peltola T, Zhang D, Hupa L, Hupa M, et al. (February 2008). "Antibacterial effect of bioactive glasses on clinically important anaerobic bacteria in vitro". Journal of Materials Science: Materials in Medicine. 19 (2): 547–51. doi:10.1007/s10856-007-3018-5. PMID 17619981. S2CID 21444777.
  5. ^ Drago L, De Vecchi E, Bortolin M, Toscano M, Mattina R, Romanò CL (2015). "Antimicrobial activity and resistance selection of different bioglass S53P4 formulations against multidrug resistant strains". Future Microbiology. 10 (8): 1293–9. doi:10.2217/FMB.15.57. PMID 26228640.
  6. ^ Drago L, Vassena C, Fenu S, De Vecchi E, Signori V, De Francesco R, Romanò CL (2014). "In vitro antibiofilm activity of bioactive glass S53P4". Future Microbiology. 9 (5): 593–601. doi:10.2217/fmb.14.20. PMID 24957087.
  7. ^ a b "Our story, Glass into bone". Bonalive Biomaterials. Bonalive Biomaterials Ltd. Retrieved May 11, 2020.
  8. ^ de Veij Mestdagh PD, Colnot DR, Borggreven PA, Orelio CC, Quak JJ (July 2017). "Mastoid obliteration with S53P4 bioactive glass in cholesteatoma surgery". Acta Oto-Laryngologica. 137 (7): 690–694. doi:10.1080/00016489.2017.1279346. PMID 28125327. S2CID 4520396.
  9. ^ Bernardeschi D, Pyatigorskaya N, Russo FY, De Seta D, Corallo G, Ferrary E, et al. (April 2017). "Anatomical, functional and quality-of-life results for mastoid and epitympanic obliteration with bioactive glass s53p4: a prospective clinical study" (PDF). Clinical Otolaryngology. 42 (2): 387–396. doi:10.1111/coa.12748. PMID 27608143. S2CID 1060470.
  10. ^ Vos J, de Vey Mestdagh P, Colnot D, Borggreven P, Orelio C, Quak J (December 2017). "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. doi:10.1007/s00405-017-4757-7. PMID 28956143. S2CID 20851852.
  11. ^ Bigoni M, Turati M, Zanchi N, Lombardo AS, Graci J, Omeljaniuk RJ, et al. (April 2019). "Clinical applications of Bioactive glass S53P4 in bone infections: a systematic review". European Review for Medical and Pharmacological Sciences. 23 (2 Suppl): 240–251. doi:10.26355/eurrev_201904_17498. PMID 30977891. S2CID 109940029.
  12. ^ Godoy-Santos AL, Rosemberg LA, de Cesar-Netto C, Armstrong DG (January 2019). "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. doi:10.12968/jowc.2019.28.Sup1.S14. PMID 30724119. S2CID 73428010.
  13. ^ Malat TA, Glombitza M, Dahmen J, Hax PM, Steinhausen E (April 2018). "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. doi:10.1055/s-0043-124377. PMID 29665602. S2CID 263428196.
  14. ^ Lindfors N, Geurts J, Drago L, Arts JJ, Juutilainen V, Hyvönen P, et al. (2017). "Antibacterial Bioactive Glass, S53P4, for Chronic Bone Infections – A Multinational Study". A Modern Approach to Biofilm-Related Orthopaedic Implant Infections. Advances in Experimental Medicine and Biology. Vol. 971. pp. 81–92. doi:10.1007/5584_2016_156. hdl:10138/252437. ISBN 978-3-319-52273-9. PMID 28050878. S2CID 22072415.
  15. ^ Frantzén J, Rantakokko J, Aro HT, Heinänen J, Kajander S, Gullichsen E, et al. (October 2011). "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. doi:10.1097/BSD.0b013e31822a20c6. PMID 21909036. S2CID 28088570.
  16. ^ Rantakokko J, Frantzén JP, Heinänen J, Kajander S, Kotilainen E, Gullichsen E, Lindfors NC (2012). "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. doi:10.1177/145749691210100113. PMID 22414472. S2CID 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. doi:10.21182/jmisst.2018.00332.
  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. doi:10.1002/jbm.b.31636. PMID 20524190.
  19. ^ Bonalive Smart Healing (EN), version 91308d/3. Bonalive Biomaterials Ltd. Retrieved May 11, 2020.
  20. ^ "Bacterial growth inhibition of Bonalive® granules", version 91310f/1" (PDF). Bonalive Biomaterials Ltd. Retrieved June 12, 2020.
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