Читать книгу Endodontic Materials in Clinical Practice - Группа авторов - Страница 13

It is clear that substances released unaltered from the dentine matrix must retain their biological function and activity, although whether the balance that originally obtained during development in the many complex interacting pathways is effectively and usefully maintained remains a matter for investigation. Nevertheless, it is proper to argue that this is indeed biological activity – bioactivity, to use the current jargon – because these are natural substances involved in entirely normal biological processes. Unfortunately, the field of dentistry is heavily trampled and muddied by the indiscriminate use of the term in any context where a biological response is elicited. That is, in the absence of those natural biological substances, any action, process, or material that provokes a response of any kind is automatically labelled ‘bioactive’. Such responses fall for now into just two classes: simple chemical and challenge defence.

Simple chemical responses typically involve the provision of a species that perturbs a chemical equilibrium, such as by changing the local pH. To take an ordinary example, adding sufficient calcium ions to a tissue fluid (by dissolution of a component of a material, say) must locally drive the precipitation of a calcium phosphate, assuming nucleation can occur. Because this is inevitable simple chemistry, with no sign of the involvement of a biological process, there is no logic or sense in labelling the source material ‘bioactive’, yet this is commonplace. We may note in passing that a frequently‐used test of ‘bioactivity’ involves immersing the test material in a metastable supersaturated solution of calcium and phosphate, the criterion being the appearance in due course of an apatitic precipitate on that material. The fact is that almost everything produces that effect, due to the ease with which apatitic material nucleates under those circumstances – there are many papers reporting such an outcome. It is worth remembering that tissue fluids are not, in general, supersaturated with respect to apatites. Simplistic calculations based on analytical values without taking into account speciation (and, especially, binding by many specialized protein systems) fail to give sensible results. Whilst hypercalcification (heterotopic ossification) is a real and distressing disease, we do not as a matter of course calcify promptly and locally in response to cuts and bruises, which effect would otherwise be expected. To make this point more clearly, highly supersaturated calcium phosphate solutions can be prepared that can stand for days without doing anything. Yet, merely shaking the flask can result in the prompt and massive precipitation of the excess: any seed is enough. There is no discernible chemical difference between such a system and the ‘bioactivity’ test. There is simply no biology involved.

Challenge defence responses are elicited by anything that represents a foreign body, toxicity, osmotic imbalance, boundary layer disturbance (via zeta potentials or surface chemistry), pH change, or merely an unusual ion – that is, a chemical challenge, an insult to the tissue. The body's natural reaction is to mount a defensive response such as encapsulation and immune reactions, if outright apoptosis and necrosis does not occur. When calcification (e.g. dentine formation) is involved, it is greeted with pleasure. But then, such an effect occurs with low‐level challenges such as caries anyway. It does not seem to be sensible to label materials that provoke a defensive response, however natural or normal, as ‘bioactive’. On that basis, formaldehyde is bioactive, zinc oxide‐eugenol is bioactive, and calcium hydroxide is bioactive.

By extension, then, it is a puzzle how materials that cause disruption or degradation of the dentine matrix can be labelled ‘bioactive’ simply because in the course of that damage some truly biologically active substances happen to be released, and quite regardless of the fact that such substances may have local beneficial effects. What we see is a creeping inflation of titular importance that bears no relation to underlying processes. It is one of the worst examples of the hijacking of a term to make the products it is attached to seem more valuable and useful. There are many such in dentistry. The problem is that, in the absence of understanding by the general user of the products' actual chemistry, their use and effects are misunderstood. We do not serve patients' best interests by such exaggeration and misinformation.

All that said, there is a conceptual class of material that can truly be described as bioactive, and although there is nothing at present on the market, it has been demonstrated in principle. That is, the incorporation of a naturally occurring biological substance or substances that may stimulate or trigger a natural process that leads to a suitable outcome, such as bone growth or dentine deposition. By definition, this is a substance that is normally involved, but whose artificial provision enables, facilitates, or amplifies the pathway. One would expect that the vehicle for such a delivery would be otherwise benign, not representing a challenge in itself – for example, a resorbable, noninflammatory material.

We must be careful, though, not to stray into the realm of pharmaceutical products (which incidentally has all kinds of implications for marketing and promotion, never mind supply and use). That is, pharmaceuticals are intended to be biologically active in that they may, for example, modulate or trigger natural processes. The question is whether a material that is the vehicle for a substance not normally involved in the usual biochemistry of repair can be considered ‘bioactive’. Imagine a material carrying, say, aspirin: it would be wrong to say this is bioactive. Thus, salicylate‐based cements and liners are not. Whether the provision of a normal, human, biological substance in such a fashion is pharmaceutical is for others to debate and decide. Ponder the taking of vitamin D, or melatonin, for example. Antibiotics clearly cross the line.

Overall, then, the key is that we must inspect the chemistry to ascertain what is going on. If it is a simple chemical effect that does not involve any biology as such, or if it is a chemical challenge that results in a defensive (albeit normal) response, it is quite improper to apply the term ‘bioactive’: it is an advertising malfeasance. If – or, perhaps, when – materials are available that are the vehicles for any of the many biologically active substances that offer the possibility of true reparative or regenerative responses, the label will be fully justified and accurate. Until then, it is suggested that much more careful thought is required, which goes beyond the allure of advertising hype and wishful thinking. Mere repetition does not make it so. Believing one's own propaganda is not scientific.

A similar abuse occurs in the term ‘bioceramic’. A ceramic material is, in simple chemical terms, anything that is not metallic or organic polymeric. The prefix ‘bio’ only seems to refer to the context in which it is used: in a medical or dental application. This is pretentiously misleading. It does not automatically confer special properties on the material in question, which has in any case been chosen (one hopes) on grounds of its general inertness and suitable mechanical properties. There are no classes of materials that in any sense earn the label, except possibly those of bone, dentine, and enamel – natural hard tissues – and even then, it serves no real purpose. Can it be applied to mollusc shells? Quite possibly. But how does that help us understand the value of marketing hype? Its extension to setting cements and sealers is incomprehensible [2].

Chemistry is frequently a weak point in other areas. Take ‘MTA’ as perhaps the most egregious example: this is the trade‐name abbreviation for what is described as ‘mineral trioxide aggregate’. Try as one might, this phrase makes no sense whatsoever: it does not inform in any way at all – it does not even describe the material itself – yet it is bandied about as if it were a meaningful label. It is inorganic, admittedly, but as the Oxford English Dictionary has it: ‘Mineral: A naturally occurring substance of neither animal nor vegetable origin; an inorganic substance. (Not now in technical use.)’. MTA plainly does not qualify.¹ The only ‘mineral’ present as such is gypsum, possibly – but not originally. Then again, ‘mineral aggregate’ is a term for ‘rock’ that has fallen out of fashion. This kind of product is not a rock, nor derived as such from one. Otherwise, ‘aggregate’ ordinarily means the rough granular material used in concrete, for example, such as pebbles, crushed rock, slag, and so on – the first thing that springs to mind – but that is clearly not what is meant (where it is in fact the core or filler in that composite material).

The first publication to refer to ‘MTA’ claims that one of the ‘principle [sic] compounds present’ is ‘tricalcium oxide silicate oxide’ [3]. This is not an identifiable substance; indeed, it is chemical nonsense. There are no details given whatsoever of provenance, processing, or analysis. The next paper says, ‘The principle compounds present . . . tricalcium oxide, and silicate oxide’, which speaks of a lack of understanding and an earlier failure to proof‐read (and of very poor reviewing on both occasions), but quite simply neither compound exists, nor can the labels be parsed in a chemically meaningful fashion [4]. Later, we find: ‘All MTA was divided into calcium oxide and calcium phosphate’ – this was for the set material [5]. Calcium oxide cannot survive contact with water, and no calcium phosphate has been seen since. There is not a trioxide anywhere claimed, not does one exist in either the initial or the reacted powder. The word ‘aggregate’ seems merely to have been used as a synonym for ‘mixture’. Can it be that ‘MTA’ simply stands for ‘mixture of three solid oxides’? Even that is quite untrue. (The later‐incorporated so‐called ‘bismuth trioxide’ does not exist as such – the Bi(III) oxide actually used would better be called ‘sesquioxide’, which would be accurate if not currently the standard term). The point of all this is to say that accuracy and precision are required for science and proper communication – to understand what is being done and what might be expected to happen.

It is, of course, necessary to identify products fully and accurately in recording and reporting work, whether clinical or experimental. However – and especially given the number of products subsequently sold – it is clear that the continual use of the trade name as a generic is both wrong and misleading. Genericization, or ‘trademark erosion’, is commonly viewed as detrimental to (and by) the owners of trademarks, but in the contexts of teaching, research, insurance, and standardization, too, it plainly has severe drawbacks. It is proper then to use a label that conveys the essential information succinctly, for a class of materials. It was on the basis of this argument that the term ‘hydraulic silicate cement’ (HSC) was proposed [6]. The qualifying ‘hydraulic’ is necessary and sufficient to distinguish such materials from the now‐obsolete silicate cements which relied on reaction with phosphoric acid (i.e. a type of acid–base system): water is the reactant for the setting of an HSC. The persistence of ‘MTA’ might reflect chemical ignorance, again, but certainly it represents an unthinking adherence to habit.

The term ‘hydraulic’ is also applied in another context: so‐called ‘hydraulic condensation’, or the technique of forcing a fluid material to fill the space of a root canal by means of, say, a gutta‐percha cone pushed into it. The relationship of the term to hydraulic machinery is obvious: transmission of pressure using a liquid. In that physical sense, it is legitimate [7] (but then a syringe is also ‘hydraulic’). The difficulty seems to be in prevention of extrusion (v.s.) – simple hydrostatics says that this is likely, and promotional material seems to imply that it is expected. It is for others to decide whether the use of such techniques is appropriate.