27pC01
プラズマ医療研究の最前線
Frontiers of Plasma Medicine Research
浜口智志
Satoshi Hamaguchi
大阪大学工学研究科
Graduate School of Engineering, Osaka University

Low temperature plasmas have been applied toa wide range of industrial processes such as
fabrication of micro and nano-scale structures on
the surfaces of semiconductor chips and thin film
deposition for surface coating of various materials.
Recently, as one of such applications, use of
low-temperature plasmas for medical treatment andmaterial processing for medical applications has
attracted much attention in the plasma researchcommunity. In this presentation, the recent trend
and progresses in this field, known collectively as“plasma medicine,” will be reviewed.
In general, research in plasma medicine may be
categorized into three subfields. One of them issurface modification/treatment of biomedical
materials [1-3]. For example, surfaces of petri
dishes (made of polystyrene) are typically
pretreated by oxygen plasmas. Surface coating of
metal artificial joints by hydroxyapatite is often
done with plasma spraying with the use of thermal
plasmas. Surface polymerization by plasma CVD(chemical vapor deposition) is also widely studied
for the formation of biocompatible films.
Another subfield that is also widely studied is
plasma sterilization [4-6]. Including commercial
products such as plasma-based air purifiers, thissubfield
has
seen
much
technologicaldevelopment in recent years in areas beyond
medical equipment although the fundamental
mechanisms of bactericidal effects by plasmas have
yet to be understood better. Furthermore, there areother sources for infectious diseases that are still
difficult to remove by plasmas, such as spore
forming bacteria, viruses, and prions, andinactivation of them is still a topic of active
research in this subfield. Usually difficulty oftreating such infection sources by plasmas lies in
the fact that, in reality, removal of them needs to bedone without damaging the environments (such as
human bodies or medical equipment) where they
exist, and often in a cost effective manner.
The third but not least subfield of the three isstudy on therapeutic or clinical use of plasmas. Thissubfield is often considered as plasma medicine in
narrow sense. Probably the best known plasma
device that is already in use for surgical operationsis argon plasma coagulator (APC) [7-9]. For thisdevice, heat generated by Ar plasma is used forcauterization or thermal ablation of tissues. In thissense, the APC is similar to an electrical scalpel.
The essential difference between them is that the tipof an APC device is contactless with tissues.
In current research of the above subfield,
however, low-temperature, non-cauterizing plasma
devices have been much of the focus for scientificand technological development. Recent studies
have shown that application of low-temperatureplasmas directly to living cells and tissues has sometherapeutic effects such as blood coagulation,angiogenesis, prevention of organ adhesion, andwound healing [10]. The origin of such effects is
considered to be reactive species (RS) generated byplasmas. Under typical discharge conditions in air,plasma efficiently generates reactive oxygenspecies (ROS) /reactive nitrogen species (RNS)
such as atomic oxygen O, hydroxyl radical OH,
hydroperoxyl (or perhydroxyl) radical HOO, singlet
oxygen 1O2, and nitric oxide (or nitrogen monoxide)
NO. Such chemically reactive species are often
generated from endogenous sources in living bodies
and play crucial roles in controlling cell signaling
pathways and maintaining homeostasis. In this sense,
perhaps it is not surprising that externally generated
ROS/RNS by plasmas can have some significant
effects on living cells and tissues under certainconditions.
In this presentation, first addressing non-expertsof plasma medicine, the author will review generalgoals and motivations of research as well as various
plasma generating systems used in this field.
Second, addressing those who already work or havestrong interest in this field, the author will briefly
review some of the latest discoveries and hot topics
in plasma medicine. Then, as an example of a

specific research topic, some latest results that theauthor and his collaborators have obtained in theirstudy on plasma application for orthopedics will bediscussed at length [11].
It has been known that chemically reactive
species generated by atmospheric-pressure plasmas(APPs) can enhance cell proliferation. As an
example of orthopedic application of plasma effects,
effects of APP application on growth ofmesenchymal stem cells and other cells that are ofinterest in orthopedics will be discussed first. In theexperiments, three conditions were tested. In thefirst condition, low-temperature APPs were directly
injected into a culture medium [Dulbecco's
Modified Eagle Medium (DMEM) with fetal
bovine serum (FBS)] containing cells and the cells
were cultures in the same medium for a few days.
In the second condition, immediately after themedium containing cells was exposed to plasmas,
the plasma-exposed medium was discarded andreplaced with a fresh medium of the same kind andthe cells were cultured for a few days in the newmedium. In the third conditions, plasma jets wereinjected into the same medium without cells, andthen the cells were cultured in the plasma treatedmedium for a few days. In each case, cellproliferation (or cell death in the case ofoverexposure of the plasmas) was observed, whichindicates that the presence of either chemicallyreactive species dissolved in the medium or solutes
modified by such chemically reactive species
affects cell viability. The level of free radical
generation in the medium was examined by dROMs
tests [12] and correlation between cell proliferationand oxidative stress were observed.
As a second example, plasma treatment ofartificial bones made of interconnected porous
calcium hydroxyapatite (IP-CHA) will be discussed.
It has been found that dielectric barrier discharge(DBD) plasma treatment at a relatively low pressure
with an admixture of He and O2 gases significantly
improves hydrophilicity of the surfaces of IP-CHA,
particularly that of wall surfaces of the internalpores. IP-CHA has been clinically used as amaterial for bone substitutes in bone tissueregeneration. Various in-vitro and in-vivo
experiments have shown that plasma-treated
IP-CHA
exhibits
higherosteoconductivity.
Especially Alkaline Phosphatase (ALP) Assays ofAdipose Derived Stem Cells (ADSC) cultured
inside plasma-treated IP-CHA have indicatedplasma treatment enhances differentiation of suchcells. Figure 1 shows photographs of IP-CHA
implant into calvarial defects of rats [13].
The experimental studies by the author and hiscolleagues discussed above were performed incollaboration with Prof. H. Yoshikawa and his
group members at the School of Medicine, OsakaUniversity.
References[1] B. D. Ratner, et al. “Biomedical Engineering
Desk Reference” by (Academic Press, 2009).
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[3] P. K. Chu, J. Y. Chen, L. P. Wang, and N. Huang,Mat. Sci. Eng. R36 (2002) 143.
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[7] A. Postgate1, B. Saunders1, J. Tjandra, J. Vargo,Endoscopy 39 (2007) 361.
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[11] D.-S. Lee, Y. Moriguchi, A. Myoui, H.
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[13] Y. Moriguchi, D.-S. Lee, K. Masuda, A. Myoui,
H. Yoshikawa, and S. Hamaguchi, ICPM-4(Orléans, France, 2012).

Figure 1 : Critical calvarial defects in rats
were filled with a untreated IP-CHA discin left and a plasma-treated IP-CHA discin right. It is seen that increasedhydrophilicity by plasma treatment
allows rapid penetration of blood into
IP-CHA [13].