WG1: Plasma Therapeutics.
The Action will study plasma treatment of wounds (to promote
healing) and plasma suppression of tumours. In both cases, there is evidence
that plasma treatment can be efficacious, but the mechanisms involved are
uncertain. Animal experiments show that wound infection is reduced and
healing accelerated by a course of plasma treatment. It is thought that
plasma treatment eliminates infectious agents from the wound, but it has also
been suggested that the patient's own immune system may be stimulated by the
plasma. There are also indications that the direct action of electric fields
may be important in both cancer treatment and wound healing. There are,
naturally, concerns about safety, and the nature of any adverse effects of
the plasma needs to be better understood. In particular, the effect of the
plasma on cell death by aptosis and necrosis, and on cell proliferation needs to be studied in
more detail.
The Action aims to develop a programme of plasma measurement and
modelling combined with process characterisation that will shed light on the
dominant mechanisms and facilitate process optimisation. This is the most
challenging and consequently the riskiest of the work areas, but also the one
with the greatest potential for innovation and the growth of entirely new
ideas.
Issues of particular concern are:
- Selectivity is of
crucial importance. The plasma must destroy pathogens or malignant cells
in preference to healthy tissue. The origin of this selectivity needs to
be understood.
- There almost certainly
are adverse side-effects, such as DNA damage, for example, because of UV
radiation. The Action will attempt to establish the nature of any
adverse effects, and determine safe limits for plasma exposure.
- Characterisation and
quantification of the effects of plasma exposure must be carried out in
a manner that facilitates comparison between experiments carried out by
different partners. The Action must agree upon some common techniques,
and the methodology for applying them. (This will be essential to the effective
operation of the Action, but also valuable for the global scientific
community.)
- Critical evaluation
and comparison of experiments conducted using different plasma sources
may allow identification of the reagents responsible for the principle
therapeutic effects and for side effects. If this is so, then the Action
may lead to insight into the nature of an optimal plasma source.
- Some modelling studies
have appeared with relevance to plasma-cell interactions, especially
concerning the influence of electric fields. The partners in the Action
will consider whether to initiate modelling studies addressing these
questions.
WG2: Functional Coatings for
Biomaterials.
Prostheses and biomedical devices generally are of increasing
importance. These are sometimes temporary (such as catheters) but may be
permanent or semi-permanent (such as stents or replacement joints). These
devices interact directly with living tissue. Their surfaces mediate this
interaction and are of critical importance. However, the relationship between
surface characteristics and performance in vivo
is not well understood. The aim of this project is to understand the
relationship between measurable surface characteristics and in vivo behaviour, using in vitro studies as an
intermediate step, and hence to understand how to produce high performance
biocompatible coatings using plasma processes. Particular areas of concern
are:
- It is not certain what
chemical functionality and physical morphology leads to an optimally
biocompatible surface, and indeed there may be no universal solution. In
vitro
studies of cell growth on plasma processed surfaces with
well-characterised properties can shed light on this question. Combined
studies involving biologists, materials scientists and plasma experts will
be a focus for the Action, again coordinating nationally funded
programmes to achieve synergistic outcomes.
- If the nature of the
surface to be produced is understood, then the development of a plasma
source or sources optimised for this can be pursued. It is not
immediately clear what properties of the plasma source are of primary
importance, and this is an issue that the Action must address.
- In some cases, the
ability to incorporate therapeutic agents into films may be important,
for example to enhance initial integration of an implant or reduce the
risk of inducing a thombosis. A carefully
designed plasma process may be able to incorporate such agents without
otherwise compromising the coating.
WG3: Bio-Plasma Interactions.
Plasmas are effective sterilisation agents, often with the advantage
that a surprising degree of selectivity can be exhibited, which may even make
plasma sterilisation of skin a practical possibility. However, the mechanisms
are not well known, and process development is difficult. In particular, biofilms can be found in many contamination scenarios (e.g., oral, wound, food), and
present a physical barrier to impinging plasmas. Current evidence shows
plasma efficacy against immature biofilm but less
so against mature biofilm. A key question is how
plasma chemistry and plasma delivery could be manipulated to enable effective
destruction of biofilm.
The following issues are of particular interest:
- A variety of plasma
sources have shown some effectiveness against biofilms.
However, different plasma sources have been employed against different biofilms, which makes it difficult to draw any
general conclusions. The Action will address this issue either by
defining procedures for producing biofilm
samples, or by exchanging samples between partners.
- Such a programme could
reveal that different biofilms are destroyed
by different reagents, or that destruction of biofilm
requires different plasma conditions to those required for
destruction of bacteria. If this is so, then a fully effective procedure
might involve either multiple plasma sources or a single plasma source
with time modulated characteristics. The Action will attempt to address
this question by systematically treating similar biofilm
samples with different plasma sources, by combining the capabilities of
several partners.
WG4: Plasma Sources for
Biomedical Applications.
A key aim of the action is to develop plasma sources optimised for
particular biomedical applications. This entails a programme of plasma diagnostic
development and application, and close dialogue with clinicians and
application experts, directed at understanding the role of specific agents
produced by the plasma. Examples of the issues to be addressed are listed
under the headings above.
With the exception of applying biocompatible coatings, the
applications of interest involve operation of the plasma in a regulated
environment where the use of potentially toxic gases is not permissible.
Consequently, most of these applications must function with a mixture of
atmospheric gases, possibly with non-toxic additives such as rare gases.
Humid air chemistry, although extensively studied, is complex and there are
many radical species that might prove important. At present, it is not known
whether different plasma sources produce systematically different kinds or
proportions of reactive species, nor is it known how to manipulate the
chemical composition of the effluent from a plasma source.
- The Action will review
the diagnostic techniques that are available for atmospheric pressure
plasma. Many traditional plasma diagnostics (Langmuir probes, certain
spectroscopic techniques) are unsuitable for use in atmospheric pressure
plasmas, so that plasma characterisation is difficult and sometimes
controversial. This situation is an impediment to systematic studies of
atmospheric pressure plasma applications. The Action will establish best
practice across the partners, and facilitate widespread adoption of that
best practice.
- The Action will design
a collective programme that will lead to a systematic characterisation
of the atmospheric pressure plasma sources in use by the partners, with
the aim of revealing whether the sources differ in ways that affect
their suitability for applications. (For example, the character of the
plasma produced by low-pressure sources does not essentially depend on
the excitation mechanism. It is not known if this is true of atmospheric
pressure sources.)
- The Action will
investigate how the radical composition varies with the gas composition
(for example, by varying the ratio of oxygen and nitrogen), and attempt
to correlate the varying radical species densities with the results of
application experiments. This procedure might not be economically
attractive in practice, but it may be a scientifically fruitful approach
to understanding the basic mechanisms in applications. The most
important results will come from a coordinated approach between the
partners, leveraging the resources of national programmes.
- In addition to physico-chemical characteristics, other properties
of the plasma sources may be important. For example, in many relevant
applications, the ability to process the surface of an irregularly
shaped object with a large area in a reasonable time is desirable. Techniques
for achieving this end will be an important focus of the Action.
- The Action will also
coordinate modelling activities across the partners. Particularly
because of the difficulties with experimental characterisation,
modelling may give powerful insights into the physics and chemistry of
discharges. But different groups are adopting different approaches,
which likely have complementary strengths. Critical comparison of these
models, together with validation of models by pooling experimental data
from the partners will be important, and will be facilitated by a
widespread adoption of best practice in diagnostics, as discussed above.
The Action will establish Working Groups in each of these areas. The
membership of these groups will be cross-disciplinary and consist of both academic, clinical and industrial partners. Other
Working Groups may be established by the Management Committee. The Working
Groups will identify and coordinate activities that support the scientific
development of the research area and highlight areas of innovation.
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