Biomaterial sciences are major fields of research in the current era of tissue engineering
and regenerative medicine strategies, and these new developments define the new Frontier
in many medical disciplines [1]. Biomaterials play a significant role in the expansion
of regenerative treatments of the maxilla, to allow more sophisticated oral rehabilitation
of edentulous patients [2, 3]. Periodontology, oral surgery, esthetic and implant
Dentistry (the POSEID disciplines) are significant beneficiaries of these recent promising
developments and these interconnected clinical domains are themselves major sources
of research in implantable materials, particularly dental implants (new implant design,
surfaces) [4], bone materials [2], or surgical adjuvants [3].
In the previous special issue focused on new biomaterials and regenerative medicine
strategies in periodontology, oral surgery, esthetic and implant dentistry [1], we
highlighted how these fields of research are deeply interconnected and represent major
topics of transversal (multidisciplinary) and translational (from basic sciences to
clinical applications) research, in order to develop new concepts and therapeutic
strategies. In this 2016 edition of this issue, it is important to recall some ethical
and legal issues related to this field.
In general, when referring to ethical issues, authors mostly limit their considerations
to animal experiments, human trials, and their associated regulatory issues and need
for Ethical Committee approval. However, regulatory issues are also very significant
nowadays and should be considered with a lot of care as they have significant scientific
consequences.
In the last years, the growth of the market of implantable materials in oral and maxillofacial
applications (mostly the POSEID disciplines) has led to a dramatic and uncontrolled
increase of the industrial producers and related stakeholders [5]. If we limit the
discussion to dental implants and bone materials, the market evolved from a few major
manufacturers to more than 500 manufacturers worldwide. On these official producers,
one must count the numerous (at least the double) “pirate” producers, particularly
active in some countries such as Brazil, Italy, or South Korea, that is, small manufacturers
or retailers of small productions often operating without (or with limited) legal
licenses (no CE marking, no FDA approval, etc.). Actually, many manufacturers, not
only the pirates, are not legally up to date with their products, and serious controls
by national health agencies would lead to a massive withdrawal of products (even in
some major manufacturers in some cases) [6].
This situation appears as a strange paradox: drugs are very thoroughly investigated
and controlled in most countries, but the control of biomedical devices and implantable
materials appears very much neglected, particularly on oral and maxillofacial applications
[6].
In front of this chaotic market, scientific and academic stakeholders have to be particularly
careful with whom they collaborate and what they accept to publish in the international
database. Many scientific articles available on Pubmed are in fact now investigating
products that have no legal existence or remain at the borderline. Presented and appearing
like “normally available products” in some scientific articles, some devices and materials
that should not be on the market use the credibility of the journals to gain existence
in the eyes of the readers.
Two interesting examples can be cited in 2016.
The first example is the permanent disorder on the dental implant market [5]: when
investigating the evolution of the surfaces of the dental implants of a manufacturer
year after year [7, 8], we can easily observe many significant variations of the production
between years, sometimes even between batches produced in the same period [9]! The
same observation can be raised when considering bone substitutes [2]. Many manufacturers
are not following strict quality rules to standardize their production, which can
lead to very poor quality products with batches contaminated with severe pollutions
[9]; but many other manufacturers are in fact changing voluntarily the characteristics
of their products during time, based on the feedback of clinicians, without informing
the regulatory authorities of these changes; such changes revealing the weakness of
the preclinical research normally needed to validate a product before being sold on
the market [10]. For example, in the recent years, by tracking some products year
by year, we could detect almost 12 significantly different versions of the implant
surface from a major manufacturer, while these changes have never been disclosed or
investigated.
The second example, particularly important in 2016, is related to the production of
platelet concentrates for surgical use from the PRF (Platelet-Rich Fibrin) family
[11]. Among those products, the most frequent material is classified as L-PRF (Leukocyte-
and Platelet-Rich Fibrin) and is widely used in oral and maxillofacial applications
[3, 12]. To use this method, there is only one system available on the market officially
as a CE-marked and FDA-cleared device, based on the method that was developed 15 years
ago and widely spread (Intra-Spin System, Intra-Lock, Boca-Raton, FL, USA) [11]. For
a few years, many custom-made devices and protocols, using inadequate centrifuges,
tubes, and devices, were used and sometimes marketed in many countries and different
forms to produce this blood derivative, creating confusion and chaos in the mind of
users. Some other variations of the original materials and techniques appeared also
recently in the literature (e.g., the A-PRF system, so-called “Advanced Platelet-Rich
Fibrin” as a trademark, low-cost and poor quality devices and tubes that are sold
without any CE marking, FDA approval, or any forms of regulatory clearance) [13, 14],
creating even more confusions for the readership. In fact, each change of the materials
and protocols generates a new version of the PRF with different characteristics from
the original L-PRF biomaterial, leading to nonreproducible results, mixed clinical
outcomes in comparison to the original method, and finally major bias in the literature.
Facing this new threat for the credibility of the scientific literature and for their
reputation, dental and biomaterial journals should make their standards of selection
evolve and apply drastically the ethical standards used in high impact factor journals
in the medical field, particularly to clarify systematically if the material of a
research in an article is duly authorized, regulatory cleared, and standardized. Investigations
on products, which have no legal existence in major markets, must be marked and clearly
stated as experimental. In most major journals, to avoid this kind of disorder and
confusions, authors have to fill a disclosure during the submission which is enforcing
the regulatory issues related to tested products. For example, such texts are in use:
“If your manuscript discusses an unlabeled use of a commercial product or device or
an investigational use of a product or device not yet approved by the FDA for any
purpose, you must specifically disclose in the manuscript that the product is not
labeled for the use under discussion or that the product is still investigational.”
When observing the chaos growing with L-PRF technologies (and it is just starting)
and their dramatic scientific and sanitary consequences, editors should force authors
for such disclosure. It would be very beneficial for everyone.
These regulatory issues are not small administrative issues. The fact that tested
products have no legal existence is a method of hijacking the scientific database
for commercial purposes and is extremely damaging for the journal's credibility. But
more important, the absence of regulatory controls also allows the development of
unclear, undefined materials, with an absence of standardization of devices leading
finally to unclear and biased scientific results. If the characteristics of biomaterials
are not standardized, not declared in a legally binding way, and changing frequently
without disclosure, what is the value of scientific results obtained with such materials
[8, 11]?
As a conclusion, this 2016 special issue of new biomaterials and regenerative medicine
strategies in periodontology, oral surgery, esthetic and implant dentistry continues
its task to gather a meaningful corpus of relevant articles. But more than before,
a better control of biomaterials placed on the market and of what is published in
the specialized literature is needed.