Bioactivity—Symphony or Cacophony? A Personal View of a Tangled Field
That is to say, they are passive until triggered externally. This is a point that seems to have escaped general attention in the present context: they do not do anything on their own.“… smart materials are also known as responsive materials. These are usually translated as “active” materials although it would be more accurate to say “reactive” materials.”
2. What Is Bioactivity?
“3.3. Bioactivityproperty that elicits a specific biological response at the interface of the material, which results in the formation of a bond between tissue and material”
This is a plain admission of the absence of biology, a purely passive, simple chemical outcome of the reactivity of the glass and the composition of the medium. Thus, there is—by definition!—no biology involved, merely SBF, or occasionally other media such as distilled water. In fact, that such reactions occur in water alone underlines the point so strongly that it is difficult to see how the label can then be applied without embarrassment. Reactive is the best that can be said.“For the purposes of this review, a [bioactive glass] is defined as a glass capable of forming an apatite layer when immersed in physiological solutions.”
One would expect that the vehicle for such a delivery would be otherwise benign, not representing a challenge in itself, for example, a resorbable, non-inflammatory material (as with the demonstrated gelatine ). However, it is clear that the modulating or signalling effects envisaged cannot apply automatically to the “ionic dissolution products” mentioned where these are covered by either the simple chemical or challenge–defence categories already discussed. These kinds of response must be explicitly excluded, by properly controlled experimentation, for the claim to hold. This has not been done. Hench goes on to posit that:“Bioactive materials release chemicals in the form of ionic dissolution products, or growth factors such as bone morphogenic protein (BMP), at controlled rates, by diffusion or network breakdown, that activate the cells in contact with the stimuli.”
where it is not clear that silicates (which it is presumed were meant, silica not being soluble or ionizable) are other than toxic enough to elicit a challenge defence, or that the calcium (calcia ions do not exist) falls under the ‘simple chemical’ process heading, especially when he also says“The key phenomenon [sic] is controlled rates of release of ionic dissolution products, especially critical concentrations of soluble silica [sic] and calcia [sic] ions.”
is involved with Bioglass, which statement unwittingly makes both of my points for me. “Rapid release” is not controlled, and “critical concentrations” do not appear to have been demonstrated. The progression from proposition to supposition is worrying.“… rapid release of soluble ionic species and formation of a high surface area hydrated silica and polycrystalline hydroxy carbonate apatite (HCA) bi-layer on the glass surface”
but there is no indication anywhere that BMP is used. In fact, quite the opposite for NovaBone . NovaMin does not appear to have worked as planned , while NovaThera is in fact a company name —the product is TheraGlass; neither product has claimed to have BMP.“NovaBone, NovaMin and NovaThera products are all third generation bioactive glass products”
The hierarchical sequence used here would appear to be reasonable, but it is not so often followed, which suggests a certain lack. Be that as it may, to take osteo-induction first, the authors expand on that:“The terms osteoinduction, osteoconduction and osseointegration are frequently, but not always correctly, used terms in many orthopaedic papers.”
This process seems to presuppose the non-existence of any bone-forming cells at the site, whereas in the contexts relevant now an implant is placed in contact with or very close proximity to bone. It also seems to require that stem cells are everywhere available. It would appear, however, that some kind of appositional growth of that pre-existing bone is then involved, as opposed to the creation of entirely new bone, an entirely distinct proposition: the seeming contradiction is not resolved. Indeed, it is difficult to conceive of any current practical circumstances where completely new, isolated bone needs to be conjured from other tissues, although of clear theoretical interest, taking a long view. Equally clearly, for such growth to occur a trigger is required, a signal to induce that cellular transformation. I shall return to this aspect. However, highly-localized appositional growth could be in itself a useful outcome, assuming, that is, that it is constrained physically or biologically; uncontrolled, it would be pathological.“This term means that primitive, undifferentiated and pluripotent cells are somehow stimulated to develop into the bone-forming cell lineage.”
which is a syntactic and logical mess. They go on to say:“Bone conduction, or osteoconduction, is a bone matrix that provides bones with the materials they need to remain strong.”
whereby only a physical presence is necessary, but there is more than an overtone of active direction (but for which there is no evidence of necessity). Elsewhere we find:“Osteoconduction provides the guidance, …”
and although it is not clear where the ‘drive’ might come from, a certain Murphy (in turn citing a Turner) was said to have remarked:“… osteoconduction as an important driving force during bone regeneration … ”
which is contradictory. Note that now certain cells are “osteogenetic”. Weber  then deduces that Murphy“[The] graft is not osteogenetic, but simply osteoconductive. Provided it be in contact at one or both extremities with other living bone, the graft acts simply as a scaffolding for the growth of the capillaries with their osteogenetic cells as they advance from the living contact extremities into the graft.”
again without any indication from where this drive might arise. However, the elaboration has:“certainly realized that osteo-conduction was an important driving force for bone regeneration”
but bad though this is as a definition, the process aspect is explicit (if again contradictory), and seems to be based simply on the ability of the bone to grow (which presumably could apply to the case where there is an absence of scaffold), despite the alternative view:“Osteoconduction is defined as a three-dimensional (3D) process of ingrowth … ”
and“Osteo-conduction means that bone grows on a surface.”
This appears to be clear enough, and in accord with Murphy’s remark, and at the right level. Overall, the concept seems to be that a surface or scaffold is to be perceived as benign by the growing tissue, in other words completely ignored as of no consequence in itself, only the space matters (cf. the bread scaffold discussed above ). Properly inert and uninterfering, such a scaffold is essentially invisible except for the physical contact providing a niche. This is not bioactivity.“… [the] material acts as a structural framework for bone growth”
Indeed, “rigid fixation” is stressed as the criterion. This can be interpreted in a purely mechanical sense: the interface between the bone and the implant can be no less strong than either material, or at least not appreciably so. It must be a functionally load-bearing union. Quite clearly this could be a pure materials science question: does the newly-formed biological apatite (BAp) adhere chemically to the substrate? Plainly, soft tissue can do no more than wet the surface. The work of adhesion, properly defined, may well be relatively high, but this is not enough: soft tissue is weak, and the van der Waals-mediated interfacial interaction weaker. Further, no matter how robust a fibrous capsule may be, this is never considered a useful outcome. This concept then has no biology involved except that the BAp is deposited in an uncompromised fashion and forms a bond with the underlying oxide on titanium or similar alloys. This is a smooth surface statement.“Osseointegration is the stable anchorage of an implant achieved by direct bone-to-implant contact.”
It seems obvious from even this small survey, from seemingly authoritative sources (certainly, relied on by many), that all definitions need to be revisited. Plainly, there is more than enough confusion in the literature, with intention and desire prejudicing the interpretation of terms to suit local purposes. Vague, ad hoc, local and inconsistent definitions raise several red flags. It is essential to stand back and take a broad view, then dissect and reconstruct the terminology. To be so widely contradictory is simply extraordinary, and really quite unscientific. Bearing in mind that unless communicated it is not science—i.e., objective systematized knowledge , it follows that accuracy and precision are essential. Writing definitions is hard to do well (a fray I hesitate to enter here now), but we may not play Humpty Dumpty .“Ingrowth of bone in a porous-coated prosthesis may or may not represent osseointegration.”
where, quite generally, these are prosthetic devices of one kind of another, just as for fillings: alien, with not a cell or physiological process in sight. It is not clear quite what purpose is served by such labels but it is evident that, as with ‘biomaterials’ (Introduction, ) there is a kind of terminological creep to validate or justify: the prefix that overrides logic and science has an apparent cachet. Whether for journals or grant bodies, the bandwagon is joined, juggernaut  rolls on. Sadly, this diminishes the advances made in tissue engineering, whereby artificial (i.e., created by artifice) truly biological materials are created, even if through the use of an intermediary foreign body.“Broadly speaking all materials used in dental reconstructions are biomaterials”
However, there is no evidence that structure has been recreated, merely that the space has been filled. Whether or not this is beneficial, biomimesis is not demonstrated by such a simple precipitation process, and the implication of remineralization prejudicial. Drop the prefix and the wishful thinking, and plain ‘mineralization’ would make sense.“Biomimetic remineralization represents a different approach to this problem by attempting to backfill the demineralized dentin collagen with liquid-like amorphous calcium phosphate nanoprecursor particles that are stabilized by biomimetic analogs of noncollagenous proteins.”
where in fact there is no evidence for a rebuilt structure, as implied, other properties notwithstanding. Indeed, it was also said that there was:“The PILP process provided significant recovery of both structure and mechanical properties”“the volume and structure, including some peritubular dentin, could be recovered after PILP remineralization”
which very clearly indicates what is happening: simple precipitation. This state of affairs has been acknowledged:“over growth of mineral at the treated surface and tubule’s wall”
and a rational motivation explained:“morphologies that were distinct from normal dentin with a clear line of demarcation between the outer and sloped portions of the lesion”
Plainly, there is no intent here to recreate the dentine structure, just the mechanical and chemical properties—which makes sense in a functional or operational sense, as stated.“Few studies have attempted to define the essential metrics for load bearing integrity of calcified tissues. One such metric is based on a fundamental mechanical property, namely indentation elastic modulus as measured in hydrated tissues, and in this work recovery of this property was determined after applying the PILP process to artificial carious lesions. Thus functional remineralization is the result of a process that yields recovery of physical and chemical properties otherwise lost due to disease.”
but the footnote says:“the first oral care system … able to regenerate tooth enamel mineral 1, reversing the early enamel erosion process”
which rather gives the game away. The headline claim is patently and admittedly false. In other words, it is only the functional aspect of mechanical integrity that is being obtained: not enamel, or even enamel mineral in the strict sense, just a precipitated coating, albeit apatitic, as the image clearly demonstrates [30,31].“Acts on early invisible stages of enamel erosion by restoring its mineral content and micro hardness”
Conflicts of Interest
- Woodforde, J. The Strange Story of False Teeth; Routledge & Kegan Paul: London, UK, 1968. [Google Scholar]
- Howard, P. Weasel Words; Corgi: London, UK, 1983. [Google Scholar]
- Darvell, B.W. Materials Science for Dentistry; Woodhead: Cambridge, UK, 2018. [Google Scholar]
- Available online: www.iberdrola.com/innovation/smart-materials-applications-examples (accessed on 25 January 2021).
- Vallittu, P.; Boccaccini, A.; Hupa, L.; Watts, D. Bioactive dental materials—Do they exist and what does bioactivity mean? Dent. Mater. 2018, 34, 693–694. [Google Scholar] [CrossRef] [PubMed]
- Pan, H.B.; Zhao, X.L.; Darvell, B.W.; Lu, W.W. Apatite-formation ability—Predictor of “bioactivity”. Acta Biomater. 2010, 6, 4181–4188. [Google Scholar] [CrossRef] [PubMed]
- Kokubo, T. Apatite formation on surfaces of ceramics, metals and polymers in body environment. Acta Mater. 1998, 46, 2519–2527. [Google Scholar] [CrossRef]
- Hench, L.L.; Splinter, R.J.; Allen, W.C.; Greenlee, T.K. Bonding mechanisms at the interface of ceramic prosthetic materials. J. Biomed. Mater. Res. 1971, 5, 117–141. [Google Scholar] [CrossRef]
- ISO 23317. Implants for Surgery—In Vitro Evaluation for Apatite-Forming Ability of Implant Materials; International Standards Organization: Geneva, Switzerland, 2014. [Google Scholar]
- Tiskaya, M.; Shahid, S.; Gillam, D.; Hill, R. The use of bioactive glass (BAG) in dental composites: A critical review. Dent. Mater. 2020, in press. [Google Scholar] [CrossRef] [PubMed]
- Holmes, J.T.; Jaberansari, Z.; Collins, W.; Leblanc Latour, M.; Modulevsky, D.J.; Pelling, A.E. Homemade bread: Repurposing an ancient technology for low cost in vitro tissue engineering. bioRxiv 2020. [Google Scholar] [CrossRef]
- Fiume, E.; Serino, G.; Bignardi, C.; Verné, E.; Baino, F. Bread-derived bioactive porous scaffolds: An innovative and sustainable approach to bone tissue engineering. Molecules 2019, 24, 2954. [Google Scholar] [CrossRef][Green Version]
- Okamoto, M.; Takahashi, Y.; Komichi, S.; Cooper, P.R.; Hayashi, M. Dentinogenic effects of extracted dentin matrix components digested with matrix metalloproteinases. Sci. Rep. 2018, 8, 10690. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Hench, L. The story of Bioglass. J. Mater. Sci. Mater. Med. 2006, 17, 967–978. [Google Scholar] [CrossRef] [PubMed]
- Available online: www.meddeviceonline.com/doc/independent-clinical-study-suggests-novabone-0001 (accessed on 25 January 2021).
- Khijmatgar, S.; Reddy, U.; John, S.; Badavannavar, A.N.; Souzab, T.D. Is there evidence for Novamin application in remineralization? A Systematic review. J. Oral Biol. Craniofac. Res. 2020, 10, 87–92. [Google Scholar] [PubMed]
- Available online: www.biospace.com/article/releases/novathera-ltd-b-bristol-b-and-b-cranfield-universities-b-to-pioneer-new-applications-for-theraglass-based-nanomaterials-/ (accessed on 25 January 2021).
- Hoppe, A.; Güldal, N.S.; Boccaccini, A.R. A review of the biological response to ionic dissolution products from bioactive glasses and glass–ceramics. Biomaterials 2011, 32, 2757–2774. [Google Scholar] [CrossRef]
- Albrektsson, T.; Johansson, C. Osteoinduction, osteoconduction and osseointegration. Eur. Spine J. 2001, 10 (Suppl. 2), S96–S101. [Google Scholar]
- Available online: www.icoi.org/glossary/bone-conduction-osteoconduction/ (accessed on 25 January 2021).
- Weber, F.E. Reconsidering osteoconduction in the era of additive manufacturing. Tissue Eng. Part B 2019, 25, 375–386. [Google Scholar] [CrossRef] [PubMed]
- Available online: www.orthobullets.com/basic-science/9011/bone-grafting (accessed on 25 January 2021).
- Darvell, B.W. A Glossary of Terms for Dental Materials Science. 2020. Available online: www.academia.edu/25576805/A_Glossary_of_Terms_for_Dental_Materials_Science_12th_ed_revised_ (accessed on 25 January 2021).
- Darvell, B.W. Terminological Inexactitudes. Dent. Asia 2006, 2, 54–57. [Google Scholar]
- Available online: en.wikipedia.org/wiki/Juggernaut (accessed on 25 January 2021).
- Niu, L.N.; Zhang, W.; Pashley, D.H.; Breschi, L.; Mao, J.; Chen, J.H.; Tay, F.R. Biomimetic remineralization of dentin. Dent. Mater. 2014, 30, 77–96. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Saeki, K.; Chien, Y.C.; Nonomura, G.; Chin, A.F.; Habelitz, S.; Gower, L.B.; Marshall, S.J. Recovery after PILP remineralization of dentin lesions created with two cariogenic acids. Arch. Oral Biol. 2017, 82, 194–202. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Burwell, A.K.; Thula-Mata, T.; Gower, L.B.; Habeliz, S.; Kurylo, M.; Ho, S.P.; Chien, Y.C.; Cheng, J.; Cheng, N.F.; Gansky, S.A.; et al. Functional femineralization of dentin lesions using polymer-Induced liquid-precursor process. PLoS ONE 2012, 7, e38852. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Regenerate Enamel Science Advanced Toothpaste. Available online: www.regeneratenr5.co.uk/products/advanced-toothpaste (accessed on 23 February 2021).
- Regenerate Enamel Science Advanced Toothpaste. Available online: cdn.shopify.com/s/files/1/0129/2068/4608/files/enamel-changes-with-advanced-toothpaste_1104x.png?v=1555595838 (accessed on 23 February 2021).
- Sun, Y.K.; Li, X.K.; Deng, Y.; Suna, J.N.N.; Tao, D.Y.; Chen, H.; Hu, Q.H.; Liu, R.J.; Liu, W.N.; Feng, X.P.; et al. Mode of action studies on the formation of enamel minerals from a novel toothpaste containing calcium silicate and sodium phosphate salts. J. Dent. 2014, 42, S30–S38. [Google Scholar] [CrossRef]
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Darvell, B.W. Bioactivity—Symphony or Cacophony? A Personal View of a Tangled Field. Prosthesis 2021, 3, 75-84. https://doi.org/10.3390/prosthesis3010008
Darvell BW. Bioactivity—Symphony or Cacophony? A Personal View of a Tangled Field. Prosthesis. 2021; 3(1):75-84. https://doi.org/10.3390/prosthesis3010008Chicago/Turabian Style
Darvell, Brian W. 2021. "Bioactivity—Symphony or Cacophony? A Personal View of a Tangled Field" Prosthesis 3, no. 1: 75-84. https://doi.org/10.3390/prosthesis3010008