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Chemical Retraction Agents - in vivo and in vitro Studies into their Physico-
Chemical Properties, Biocompatibility with Gingival Margin Tissues and
Compatibility with Elastomer Imp...

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DOI: 10.2174/1389557516666160418122701

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 Mini-Reviews in Medicinal Chemistry, 2017, 17, 000-000 1

REVIEW ARTICLE

Chemical Retraction Agents – in vivo and in vitro Studies into their

Physico-Chemical Properties, Biocompatibility with Gingival Margin
Tissues and Compatibility with Elastomer Impression Materials

Danuta Nowakowska1*, Jolanta Saczko2, Julita Kulbacka2 and Włodzimierz Więckiewicz3

1
Department of Dental Materials, Wroclaw Medical University, Poland; 2Department of Medical Biochemistry,
Wroclaw Medical University, Poland; 3Department of Prosthodontics, Wroclaw Medical University, Poland

Abstract: Gingival margin retraction/displacement (GMR/D) is a commonly accepted procedure in

ARTICLE HISTORY
Received: June 08, 2016
Revised: August 10, 2016
Accepted: September 14, 2016
DOI:
10.2174/18715273156661609271103
05
restorative dentistry. Of the various retraction methods, the chemo-mechanical approach with retraction
media and chemical retraction agents (ChRAs) is mostly used. Different local and/or systemic side
effects were observed after “chemical attacks” from these retraction agents. Moreover, no consensus
exists as to the compatibility of chemical agents with different impression materials. This paper reports
the findings of in vivo and in vitro studies and we discuss the physico-chemical properties of chemical
retraction agents, their undesirable clinical side effects, biological activity and compatibility with
selected groups of elastomer impression materials.

Keywords: Gingival margin retraction, chemical retraction agents, cytotoxicity, compatibility

INTRODUCTION negative esthetic results, tissue necrosis, damage of the deep

Predictable gingival tissue management, such as gingival
margin retraction/displacement (GMR/D), in restorative
dentistry is a generally accepted procedure to provide temporary
access, visibility and dryness in the gingival sulcus space for
diagnostic, preventive and therapeutic purposes. Via control
of gingival bleeding, sulcular fluid flow and saliva
contamination, it is possible to achieve a moisture effect, and
create optimal conditions in the operating field to perform
direct and indirect tooth reconstructions. Safe GMR/D is a
key element ensuring long-term clinical success from the
point of view of cosmetic effect, and marginal and
periodontal adaptation.
Various alternative strategies of gingival margin soft
tissue management have been developed: surgical,
mechanical, chemical and combinations thereof [1-5]. The
methods of gingival tissue displacement can be broadly
classified as surgical and non-surgical techniques, with non-
surgical being the more commonly practiced method [6].
Retraction surgery (rotary curettage, electro- and laser
surgery) is recommended in selected clinical situations to
reduce hyperplastic gingival tissues, because of reported
damage in the dental-gingival complex. Usually, complete
tissue healing is obtained after 10-14 days [7]. However,
gingival recession has been observed, which could produce
*Address correspondence to this author at the Department of Dental
Materials, Wroclaw Medical University, Poland; Tel: +48 7840290; Fax: 48
784 02 92; E-mail: danuta.nowakowska@umed.wroc.pl
tissue layers, and retarded healing [8]. Another study has
reported that retraction surgery cannot constitute a potential
health risk for the patient. This clinical study, using diode
lasers, showed that gingival sulcus were evenly spread in
mesio-, mid- and distal buccal regions (±400 µm) when as
limit of minimum retraction is taken to be 200 µm [9]. Al-
Ani et al. identified that a relatively high number of New
Zealand dentists applied surgery for gingival retraction
around natural teeth, and 18% of dentists used gingival
retraction around implants, while 31% preferred plain cord,
25% cord with chemicals, and 23% gingival surgery [10].
In mechanical GMR/D techniques different retraction
media have been applied. Initially, cooper bands and dry
retraction cords were used [11]. Recently, alternative
retraction materials have been developed, such as impression
matrices from self-cured resins, light-cured composites and
elastomers [12, 13], polyvinyl acetate strips [14], self-
expanding polyvinyl siloxane foam [15] and plastic collars
[16].
The classification of retraction materials is based on their
clinical forms and can be divided into three classes of
standard materials: open (cords, strips), closed (rings, caps)
and injection forms (gels, pasts). One class of materials
processed individually for patients was proposed by
Nowakowska et al. [17]. Different cord types, cord
techniques and new cordless systems have been described
[18]. The retraction cords were placed using either single
cord or double cord techniques, whereby the double cord

1389-5575/17 $58.00+.00 © 2017 Bentham Science Publishers

2 Mini-Reviews in Medicinal Chemistry, 2017, Vol. 17, No. 0
was found to be more effective [19]. Dry cords have been
proved to induce a disruption of the sulcular and junctional
epithelium with intracellular degeneration, stripping, and
desquamation of epithelium [20–23]. Pure cotton retraction
cords also lead to a significant increase in crevicular fluid
flow and should be avoided [24]. In the study by Beier et al.
cordless retraction with expanding polyvinyl siloxane foam
appeared to be less traumatic and provided an alternative
method of gingival retraction [15].
Chemo-mechanical methods are widely applied and are
still being developed. They are based on the mechanical
action of retraction media supported by various medicaments.
Chemical retraction agents (ChRAs) in fluids form have
been used for pre-impregnation of retraction cords by
manufacturers or for ex tempore soaking of cords by dentists.
Later, the chemicals were incorporated into retraction gels,
and then into compule-based and/or syringe-based kaolin
pasts, recently in silicone elastomers [25, 26]. Xu et al. have
proposed a novel water-swelling retraction polymer [27]. In
clinical practice, all retraction agents can be applied as
injection and non-injection type systems [5].
Comparative clinical and histological studies of
mechanical and chemo-mechanical methods with conventional
cords and new cordless systems have been presented in
many various studies [28-36]. Gupta et al. compared vertical
and horizontal retraction after copper wires reinforced by
retraction cords, PVS foam (without chemicals), and
kaolin/aluminum chloride retraction paste, and concluded
that PVS foam was clinically more effective [28]. Another
study indicated that polyvinyl acetate strips are more
efficient in gingival displacement than plain retraction cord
[29]. Also, the majority of authors indicate that the chemo-
mechanical retraction systems as the most effective. Phatale
et al. achieved better results with kaolin/aluminum chloride
paste than with self-expanding PVS foam and with 5%
aluminum chloride impregnated cords. Moreover, these
authors observed a significant association between retraction
materials and the relative degree of injury to the sulcular
epithelium. Kaolin/aluminum injection-type materials were
also found to be better than cord, as assessed by the
histological method, with respect to the periodontium [30].
Prasanna et al. showed better response of the kaolin/
astringent paste in achieving horizontal displacement of the
gingival sulcus than gingival retraction cord [31]. Acar et al.
reported that, except for non-impregnated cords, displacement
paste with/or without a retraction cap was comparable due to
the ease of clinical application, time spent, bleeding,
remnants and sulcus dilatation as well to perfect or
acceptable impression qualities [32]. Al Hamad et al.
described that all techniques (expanding PVS foam, paste-
like material and conventional retraction cord) caused a
temporary gingival inflammation, the most harmful occurred
with paste, which also induced a slower recovery [33]. In
two comparative studies, Bennani et al. concluded that the
pressure generated by a retraction cord was significantly
higher than the pressure generated by cordless gingival
displacement materials (Expasyl, Expasyl New, 3M ESPE
Astringent Retraction Paste and Magic Foam Cord). All
cordless retraction systems produced atraumatic pressures,
with Expasyl and Expasyl New pressure were considered as
Nowakowska et al.
the most effective [34, 35]. Chaudhari et al. showed
displacement cords with aluminum chloride and
tetrahydozoline to be comparable to clinical maximum
displacement systems; however, Expasyl was able to achieve
the least amount of displacement [36].
The GMR/D procedures in restorative dentistry are
recommended before direct and not direct tooth reconstruction.
Imaging for prosthetic and implant treatment requires
finished lines of the tooth preparations and implant structure
designs. These data need to be transported to the dental
laboratory. The visualization of the local “status quo” can be
realized via a traditional impression made with the use of
elastomer impression materials or new techniques, such as
an optical impression in the patient’s mouth or external
scanning of the models in Computer Aiding Design/
Computer Aiding Manufacturing (CAD/CAM) technologies
[5, 37]. Gingival retraction should ensure optimal horizontal
and vertical space between an epithelial attachment and the
epithelium of gingival sulcus and prosthetic abutment, so
that the impression material or scanner could map the
prepared and/or non-prepared hard tissue of the tooth, with a
location 0.3–0.4 mm below finish line and/or the emergence
profile of the implant structure [38–40]. Dimensionally
accurate impressions are possible in sulcus of 0.15 mm and
larger. Hence, clinicians must choose the proper retraction
methods to obtain a width greater than 0.35 mm [41].
Gingival displacement is also helpful before luting
procedures to fixed prostheses, especially with an adhesive
method, and for prospective control of their adherence to
natural or artificial abutments.
The GMR/D strategies prevent accidental damage to the
periodontium, protect the biological space and minimize the
risk of iatrogenic gingival recession [21–23, 42, 43]. On the
other hand, in clinical studies and in research on animal
models local and/or systemic “chemical attacks” of retraction
agents are observed. Oxidative and inflammatory damage is
not yet completely understood. The accuracy of impressions
made by impression elastomers after chemo-mechanical
displacement has been questioned [44]. In this study, we
review the findings of in vivo and in vitro studies and discuss
the physico-chemical properties of chemical retraction
agents, their local and/or systemic side effects, biological
activity, and compatibility with selected types of elastomeric
impression materials.
1. Physico-Chemical Properties And Undesirable Clinical
Side-Effects of Chemical Retraction Agents
According to the data from survey studies from the past
six decades, the chemo-mechanical GMR/D strategy has
been identified as the most popular in dental practices in
various countries [45–50]. However, the chemical retraction
agents preferred by dentists have changed over this period.
In the US epinephrine-impregnated cords were preferred in
1977 by 77% [45], in 1985 by 79% [46], in 1986 by 55%
[47], in 1999 by 39% [48], and in 2015 by 29% of
respondents [49], and in Poland in 2004 by 21% [50].
Recently, a higher number of dentists use astringents. In the
study by Hansen et al., buffered aluminum chloride (55%)
and ferric sulfate (23%) were most frequently used [48].
Chemical Retraction Agents – in vivo and in vitro Studies
Nowakowska et al. reported that 80.9% of Polish dentists
applied retraction procedures, 94.3% preferred the chemo-
mechanical method using retraction cords impregnated or
soaked with astringents (78.9%) such as aluminum chloride
(56.6%) and ferric sulfate (18.6%) [50]. Ahmed and
Donovan stated that 60% of dentists used displacement cords
impregnated with a medicament: including 13% with
aluminum chloride, and 18% with aluminum potassium
sulfate [49].
Progress and difficulty in the use of chemo-mechanical
GMR/D strategies can be observed. The two categories of
ChRAs with different pharmacological activity are:
Conventional Retraction Agents (CRAs) – astringents
(coagulants, hemostatics) and Experimental Retraction
Agents (ERAs) – adrenergics (vasoconstrictors) [51–53]. We
could also distinguish chemical properties, and indicate the
following categories: astringents based on inorganic metal
salts, such as aluminum chloride, aluminum sulfate and
ferric sulfate; and adrenergics based on organic salts of
hydrochloride acid; the α- and ß-adrenergic (HCl-
epinephrine); and α-adrenergics (HCl-tetrahydrozoline, -
oxymetazoline and -phenylephrine).
The chemical action of astringents reduces the volume of
the free gingival tissue via the mechanism of hemostasis,
precipitates blood proteins which physically inhibit bleeding
from microvessels and decreases the exudation of gingival
fluid [52]. These astringents do not penetrate cells, but only
affect the superficial layer of mucosa [54]. However, their
effects on the gingival tissues are not clearly understood.
Numerous clinical studies report adverse local effects
provoked by astringents contained in pre-impregnated or
soaked retraction cords and built-in cordless systems on
gingival tissues, such as gingival inflammation connected
with bleeding, red marks, swelling, ulceration and pain.
Differences have been observed in the assessment of clinical
effects. Most authors report that inflammation is temporary
and disappears within a period ranging from 1 to 14 days
[22, 55-60]. Other authors observe tissue necrosis and
irreversible damage of the gingival sulcus and epithelial
attachment caused by styptic agents not currently used in
dental practice [61, 62]. In addition, the removal of cords
impregnated with astringents increases gingival hyperemia in
operative procedures [63]. The clinical studies of Sarmento
et al. compared conventional (gingival cord plus 25%
aluminum chloride gel) and cordless systems (15%
aluminum chloride/kaolin paste). Both before 10 days after
treatment, these two treatment procedures significantly
increased mean concentrations of periodontal inflammatory
factors such as interleukin 1ß, interleukin 6 and tumor
necrosis factor α in gingival crevicular fluid. The
conventional technique produced the highest level of the
three cytokines [64]. Probably all retraction procedures may
lead to acute injury on the periodontium. Feng et al. reported
an elevation of proinflammatory cytokines, such as TNF-α,
in gingival fluids after retraction with no-medicament
retraction cords [65].
For a long time the most popular adrenergic agent has
been epinephrine, which has been used in various
concentrations (from 4% to 32%) to achieve retraction goals.
This has been effected via the temporary constriction of
Mini-Reviews in Medicinal Chemistry, 2017, Vol. 17, No. 0 3
blood vessels, and the reduction of blood flow, volume of
gingival tissues, and the production and seepage of gingival
fluid. Several clinical and animal model studies have
reported that after application of 4% or 8% epinephrine
impregnated cords, the “Syndrome of epinephrine” has
manifested itself via increased heart rate and blood pressure,
anxiety, pallor of the skin and mucosa, heavy sweating,
shortness of breath, discomfort and even fainting and fatality
[62, 66-71]. Some authors have reported that epinephrine
also causes local gingival tissue inflammation [22, 55, 61],
while other authors have not observed any impact in situ,
when the gingiva is non-lacerated [72]. Injury and other side-
effects induced by epinephrine increased when the gingival
margin tissue is damaged during main teeth preparation, and
in the case of patients with hypersensitivity [73, 74].
Moreover, an adverse interaction of retraction vasoconstrictors
has been reported with selected drugs, involving tricyclic
antidepressants, non-selective beta-adrenergic blocking
drugs and in cases of cocaine intoxication [75, 76].
A new suggestion has been made for a lower
concentration of epinephrine, 0.1% by Fazekas et al. and
0.01% by Csillag et al. These studies focused on
vasoconstrictor response in gingival tissue without systemic
side-effects [63, 77]. The 0.01% epinephrine did not lead to
prolonged local hypoxia and local congestion, even in cases
of increased production of gingival fluid, which could also
lead to inaccurate impressions [77, 78]. The quantity of
gingival crevicular fluid and the active level of aspartate
amino-transferase (AST) on the first and third day after
retraction with 0.1% HCl-epi were lower than with 15.5%
ferric sulfate [79].
Bowles et al. proposed α-adrenergic sympathomimetic
amines as potential alternative retraction agents [51]. This
agent is commercially available as a nasal and ophthalmic
decongestive that constricts gingival blood vessels and
provokes minimal systemic effects and is characterized by
respectively higher levels of pH. Comparative histological
evaluations of biological responses of the astringents (10%
and 25% aluminum chloride, 20% aluminum sulfate) and
0.05% HCl-tet in the gingival tissue of Beagle dogs have
demonstrated a low damaging potential for this α-
sympathomimetic amine [56, 57]. Also, Kostić et al.
performed experiments on rabbit gingival tissue and reported
that 0.05% HCl-tet resulted in significantly lower intensity
of inflammatory response in comparison to other chemicals
(10% and 25% aluminum chloride and 8% epinephrine) let
to acute inflammatory infiltration of gingival tissues in
rabbits. The inflammatory response to 0.05% HCl-tet was
significantly lower, with observed complete regeneration of
the gingival tissue [60]. The retractive capabilities of HCl-tet
and HCl-oxy with HCl-epi and the astringents group were
evaluated and both α-adrenergic agents had greater gingival
retraction effects compared to other agents [80].
Probably, the differences in oxidative and inflammation
damage intensity caused by clinical application of retraction
agents from both groups depend on their pH level. Several
studies have shown a very low pH (pH < 3) for CRAs and a
higher one (pH > 3) for ERAs [81-86]. A list of commonly
used ChRAs with their pH level is presented in Table 1.
Those astringents with low pH level can provoke a
4 Mini-Reviews in Medicinal Chemistry, 2017, Vol. 17, No. 0 Nowakowska et al.

Table 1. The pH-level of commonly used conventional and experimental chemical retraction agents in different studies.

Chemical retraction pH level

Manufacturer Active ingredient
agents W L K A-Y N&R

Astringedent® Ultradent 15.5 % Fe2 (SO 4)3 1.6 0.8 − 1.3 0.0

Stasis Gingi-Pak 21 % Fe2 (SO 4)3 1.1 0.8 − − −

Rastringent Pascal 25% Al2(SO4) 3 3.0 − − − −

Rastringent Two Pascal 20% Al2(SO4) 3 − − 2.6 − −

Orbat sensitive Lege artis 25% Al2(SO4) 3 − − − − 0.7

Hemogin-L Van R 25% AlCl3 0.9 0.9 − − −

™
Hemodent Premier D 21.3 % AlCl3 1.7 1.3 − 1.5 −

Gingi-Aid 25% Gingi-Pak 25 % AlCl3 − 1.9 − − −

Racestypine Septodont 25% AlCl3 − − 0.8 − 0.0

®
Ultradent Ultradent 25% AlCl3 (buffered) − − − 1.7 −

Stypin Van R 20% AlCl3 2.0 1.3 − − −

Alustin Chema 20% AlCl3 − − − − 0.1

Gingiva Liquid Roeko 10% AlCl3 − − 1.8 − 1.4

Orostat 8% Gingi-Pak 8% HCl-epinephrine − 2.0 − − −

Inj. Adrenalini 0.1%* Polfa 0.1% HCl-epinephrine − − − − 2.8

Inj. Adrenalini 0.01%* Self-made 0.01%HCl-epinephrine − − − − 3.4

®
Visine * Pfizer 0.05% HCl-tetrahydrozoline 6.2 6.8 5.6 − 6.8

Afrin®* Schering 0.05% HCl-oxymetazoline 6.3 − − − 4.8

Ocu Clear* Health Care 0.05% HCl-oxymetazoline − 6.5 − − −

®
Neosynephrin-POS * Ursapharm 10 % HCl- phenylephrine − − − − 3.6
*Experimental Retraction Agents (ERAs).
0.0 – pH non-appointed with potential-metric method;
W = Woody et al. [81]; L = Land et al. [82]; K = Kopač et al. [84]; A = Ayo-Yusuf et al. [85]; N&R = Nowakowska & Raszewski [86].

“chemical attack” both on gingival soft tissue and on the
hard tissue of the tooth.
In recent years, other undesirable effects of astringents
resulting from their highly acidic properties have been
observed. The exposure of prepared dentine surfaces to
astringent retraction fluids (21.3% aluminum chloride
hexahydrate, 15.5% ferric sulfate and 25% buffered
aluminum chloride) alters their morphology and reduce
dentine susceptibility to acid-etching [85]. Some studies
have demonstrated that the use of astringents as hemostatic
agents removes the smear layer, and is a potential cause of
postoperative sensitivity [82, 83]. An adverse effect on the
bonding mechanism of adhesive cements systems and resin
cements has also been observed [87, 88]. O’Keffe et al.’s
study showed that rinsing ferric sulfate and aluminum
chloride hemostatic agents with water before using self-etch
adhesives caused higher bond strength than non-rinsing ones
[89]. On the other hand, Kimmes et al. described that rinsing
contaminated dentine surfaces with ferric sulfate gels after
blood contamination did not alter the shear bond strength of
the bonding agent to the dentin [90]. Also, Ebrahimi et al.
showed that 20% ferric sulfate gel contamination had no
significant effect on the shear bond strength of two adhesives
to the dentin [91]. Kumar et al. reported minimum micro-
leakage after saliva contamination versus maximum by
hemostatic agent, 20% aluminum chloride, for two bonding
systems. Clinically, in order to achieve successful bonding in
Class V cavities, contamination should be avoided by
thorough isolation and tissue retraction prior to bonding [92].
Also, the cordless gingival retraction system Expasyl with
15% aluminum chloride in laboratory studies on human
molars significantly reduced the shear bond strength of the
self-etch and total-etch adhesive systems. The total-etch
technique achieved better compatibility to the Expasyl paste
than the self-etch [93].
Additionally, ferric sulfate-based agents cause a brown-
to-black staining of gingival tissues and prepared dentin
under porcelain crowns. One hypothesis explains that the
high acidity ferric sulfate results in interaction with bacterial
byproducts and precipitation of insoluble ferric sulfide on the
Chemical Retraction Agents – in vivo and in vitro Studies
porous demineralized dentin [94]. Recently, studies have
reported that the aluminum/kaolin paste cordless technique
can affect implant structures. Cooper et al. in vitro identified
the effect of surface chemistry alteration after exposure of a
sterile titanium surface to gingival retraction paste [95].
2. Biological Activity of Chemical Retraction Agents
In recent years, several in vitro studies into the exposure
of conventional and experimental ChRAs to different cell
lines have been performed [84, 96–105]. Kopač et al.
demonstrated that 10% and 25% aluminum chloride, and
25% aluminum sulfate in 1:10 dilution are significantly more
cytotoxic than 0.05% HCl-tet on diploid fibroblasts from
lungs of Chinese hamsters, line V-379 A only after 1 min
treatment. Using the colony forming ability test, these
retraction agents diluted to 1:10 the greatest number of
colonies emerged with samples treated with 0.05% HCl-tet
[84]. The same authors also reported fewer cytotoxic effects
from 0.05% HCl-tet than 25% aluminum chloride on
cultured rat keratinocytes from gingiva after 10 min
incubation [96]. Lodetti et al. stated that a commonly used
astringent, 15.5% ferric sulfate, was most cytotoxic to
human keratinocytes [97]. Liu C-M et al. evaluated the
cytocompatibility to HGFs of three extracts from gingival
retraction cords impregnated with different medicaments
after 10 min and 24 h. The cytotoxicity decreased in the
following order: DL-epinephrine HCl-impregnated cord >
aluminum sulfate-impregnated cord > non-drug impregnated
cord [98]. Yalçin et al. concluded that two commercial
hemostatic solutions, 25% and 24.8% aluminum chloride,
have a significant cytotoxic effect on HGFs [99]. A
comparison of cytotoxicity between different chemical
agents toward human gingival fibroblasts by Liu J et al.
showed that all the evaluated agents caused cell damage and
inhibited proliferation. The ability of a cytotoxic effect
increased in the following order: 0.01% HCl-epi < 0.1%
HCl-epi < 5% aluminum sulfate < 20% aluminum sulfate <
15.5% ferric sulfate [100]. Also, a new form of the plant
extract Ankafared Blood Stopper (ABS) was tested. The
results showed that ABS in lower concentrations was not
cytotoxic to human pulp fibroblasts, as evaluated with the
MTT assay [101]. ABS caused a significant increase in
hemolytic activity in human erythrocytes, with a
simultaneous increase in ABS concentration. In addition,
ABS had a proliferative effect on human leukocytes. Based
on these results, ABS can be considered an alternative and
safe blood stopping agent [102].
In previous in vitro studies Nowakowska et al. performed
the monitoring of dynamic HGF response after exposure to
conventional and experimental ChRAs [103, 104]. In both
experiments, fibroblasts taken from healthy gingival tissues
of patients were isolated with a method described and
patented by Saczko et al. (Patent No.: P 3,812,045) [105,
106]. Incubation times with the retraction agents were 3, 5
and 10 minutes, according to the preferences of retraction
time of Polish dentists [107], and a standard time of 24
hours. In the first study, five astringent solutions (10%, 20%
and 25% aluminum chloride, 25% aluminum sulfate, 15.5%
ferric sulfate) and five astringent-containing gels (two 20%
aluminum chloride from different manufacturers, 25%
Mini-Reviews in Medicinal Chemistry, 2017, Vol. 17, No. 0 5
aluminum chloride, 25% aluminum sulfate, 20% ferric
sulfate) were evaluated in 1:10 and 1:20 dilutions.
Surprisingly, it was observed that mitochondria of HGFs
after 10 minutes of exposure to all evaluated agents
exhibited a higher activity, which suggested an increase in
their antioxidative defense capabilities. A low cytotoxic
potential was revealed for aluminum chloride and an
increased cytotoxic effect was induced by aluminum sulfate.
The most cytotoxic agent was ferric sulfate; however, this
was proved to be less damaging in gel form than as a
solution [103]. In a subsequent study these authors compared
the cytotoxic effect of an experimental group of 10
vasoconstrictor agents, including 3 α- and ß-adrenergic
agents (HCl-epi), 4 commercial preparations containing α-
adrenergics in the form of solutions, and 3 self-made
retraction gels. The cytotoxicity of these compounds
decreased in the following order: 0.1% > 0.05% and 0.01%
HCl-epi > 0.05% HCl-oxy > 10% HCl-phe > 0.05% HCl-tet
solutions/gels. The high survival rate of HGFs showed that
all experimental gels may provide a basis for the selection of
the most biocompatible agent with human gingival tissues
[104].
The evaluation of the biological activity of the same
agents from the ERA group via an assessment of selected
oxidative stress markers and cytoskeleton reorganization was
performed in primary cultures of HGFs. Lipid peroxidation
indicated an increase in malondialdehyde (MDA) levels for
all the samples incubated with adrenergic retraction agents at
a dilution of 1:10. At all concentrations, HCL-epi caused the
most significant protein damage. A statistically significant
increase in -SH group levels was observed after incubation
with 0.05% HCl-tet and experimental gels at a dilution of
1:20. However, at all concentrations epinephrine caused the
greatest protein damage. The clonogenic assay after
incubation with 0.1% HCl-epi, 0.05% HCl-oxy and 10%
HCl-phe did not demonstrate survival of any fraction. The
highest percentage of cell survival was noted with
experimental gels. The findings for expression of manganese
superoxide dismutase (MnSOD) showed that all agents led to
an increase in its level and caused significant HGFs
abnormal morphology. 24 and 72 hour incubation with the
three experimental gels revealed the expression of the
enzyme at the control level. Cellular cytoskeleton proteins
(alpha actin and beta tubulin) visualized with the CLSM
method after 24 hour incubation with 0.01% and 0.05% HCl-
epi revealed normal cellular morphology, including
cytoplasm and nucleus. Incubation with 0.1% HCl-epi
affected the defragmentation of nuclei and numerous cell
divisions and increased the amount of actin. Among
commercial drugs based on α-adrenergic, only 0.05% HCl-
oxy did not cause changes, 10% HCl-phe reduced the
number of cells and initiated changes in the cytoskeleton
(abnormal structure of actin proteins). The results indicate
that all the evaluated commercial retraction vasoconstrictors
caused statistically significant changes in the biological
activity in HGFs. Less disruption to the vital functions of
HGFs was caused by the new experimental retraction gels
which appeared to be more biocompatible. The cytoskeleton
cellular changes suggested that only the group of
experimental retraction gels did not lead to their degradation
[108].
6 Mini-Reviews in Medicinal Chemistry, 2017, Vol. 17, No. 0
These data provide a tentative understanding of cytotoxic
effect and of the mechanism of biological activity of
commonly used and experimental CRAs. However, further
experiments are needed to explain the biochemical impact of
retraction devices on the human periodontium before the
introduction to dental practices of most biocompatible
chemical retraction agents.
3. Compatibility of Chemical Retraction Agents With
Different Types of Impression Elastomers
The penetration capacity of the gingival sulcus, setting
time and permanent deformation depend on the chemical
characteristics of elastomeric impression materials [38, 109,
110]. Problems have been reported with the perfect surface
detail reproduction of elastomer impression materials after
chemo-mechanical GMR/D strategy. Earlier study has
clarified that sulfur originating from latex gloves, dental dam
sheets and retraction cords impregnated with aluminum
sulfate and ferric sulfate contaminated the platinum catalyst
and prolonged the polymerization time of PVS.
Contamination from dental gloves has been eliminated by
static and dynamic mixing systems and alternative glove
materials [111-115].
The compatibility of ChRAs with CRA and ERA groups
with different elastomer impression materials was not
satisfactory. The chemical retraction agents can come into
contact during the primary phase of the 2-step putty/wash
impression technique where thin soaked or impregnated
cords are placed into gingival sulcus, and after the cord is
removed, and if the gingival sulcus space has not been
carefully rinsed of residues of retraction chemicals.
In previous studies commonly used elastomeric
impression materials, such as polysulfide (PS), condensation
silicones (CS), polyvinyl siloxanes (PVS), polyethers (PE)
and vinylsiloxanether (VSXE), were evaluated after contact
with retraction agents from both groups (Table 2). Changes
were observed in different properties of impression
elastomers. The polymerization time of PS was not inhibited
by conventional and experimental agents, where the tensile
strength decreased after contact with retraction astringents
such as aluminum chloride and experimental agent 0.05%
HCl-oxy [116]. Nowakowska et al. showed CS to be non-
reactive with three astringent solutions: 10% and 25%
aluminum chloride and 15.5% ferric sulfate [117]. Also,
Sabio et al. confirmed that CS were compatible with
aluminum chloride and experimental retraction agents, such
as 0.05% HCl-tet and 0.05% HCl-oxy [116].
Numerous conflicting findings concerning the compatibility
of PVS with both groups of retraction agents have been
presented. O’Mahony et al. reported the deterioration of
surface reproduction by retraction astringents such as
aluminum chloride, ferric sulfate, and ferric subsulfate/ferric
sulfate, would be unacceptable as a clinical impression
material [44]. Sabio et al. documented that after
polymerization PVS in contact with aluminum chloride
showed significantly lower tensile strength [116]. Singh
et al. proved that at 32ºC the surface detail reproduction
of the PVS was adversely affected by two astringents –– 5%
aluminum chloride and 13.3% ferric sulfate –– and
Nowakowska et al.
experimental agent 0.1% epi [118]. In contrast, the same
studies reported that retraction agents had no inhibitory
potential on PVS impression materials [117, 119-122].
Camargo et al. found that aluminum sulfate and ferric sulfate
did not effect on PVS polymerization [119]. Machado and
Guedes considered that astringent hemostatic solutions, such
as aluminum sulfate, ferric sulfate and aluminum chloride,
did not show any inhibitory effect on polymerization of the
addition silicone, and they observed no changes in PVS
polymerization as a result of interaction with retraction cords
handled with latex gloves [120]. Nowakowska et al.
observed no changes after visual inspection at 3×
magnification of the surface samples of PVS after contact
with three astringents, such as 10% and 25% aluminum
chloride and 15.5% ferric sulfate [117]. Also, Cylwik et al.
proved that 20% aluminum chloride has no effect on
different parameters of PVS elastomers [121]. Kumbulogu
et al. showed that no medicaments (astringents and
vasoconstrictors) have an influence on the surface
characterization of the PVS [122].
The available studies have reported that PE impression
materials are not compatible with selected conventional and
experimental retraction agents. According to Sabio et al.
polyether presented decreased tensile strength after contact
with aluminum chloride and experimental solutions, e.g.
0.05% HCl-oxy and 0.05% HCl-tet. However, the
polymerization process was inhibited only by aluminum
chloride [116]. Nowakowska et al. noticed the inhibition of
polymerization processes of three PEs after contact with
10% and 25% aluminum chloride, and 15.5% ferric sulfate
[117]. The surface texture disruption of two PEs as a
depolymerization effect was provoked by 25% aluminum
chloride solution and 20% ferric sulfate gel, as observed by
Piotrowski et al. [123].
The studies were performed only at laboratory
temperature. However, according to Berg et al. and
Takahashi et al., the kinetics of setting and rheological
properties of PVS and PE depend on temperature [124, 125].
To analyze the effect of retraction agents from conventional
and experimental groups on the polymerization time of most
PVS and VSXE impression elastomers used in clinical
practice, Nowakowska et al. conducted series experiments at
laboratory (23°C) and intraoral (37°C) temperature [126,
127]. The Polymerization Time Compatibility Index (PTCI)
was used as the main factor for comparison of the setting
time of evaluated elastomers before and after contact with 10
retraction agents: 5 astringents (10%, 20% and 25%
aluminum chloride, 25% aluminum sulfate, 15.5% ferric
sulfate) and 5 adrenergics (0.1% and 0.01% HCl-epi, 0.05%
HCI-tet, 0.05% HCl-oxy, 10% HCl-phe). The obtained
results showed that the ERAs achieved higher average PTCI-
values than CRAs, with 2 evaluated types of impression
elastomers in oral cavity and laboratory environments. The
PTCI-values indicated that the experimental agents 0.01%
HCl-epi and 0.05% HCl-tet and conventional 15.5% ferric
sulfate minimal affected VSXE and PVS setting time at both
temperature studies [126, 127]. Aluminum chloride based
agents at higher concentrations in both temperature studies
significantly prolonged or inhibited the setting time of all
evaluated impression elastomer materials, so direct contact
Chemical Retraction Agents – in vivo and in vitro Studies Mini-Reviews in Medicinal Chemistry, 2017, Vol. 17, No. 0 7

Table 2. The compatibility of chemical retraction agents with conventional and experimental retraction agents.

Condensation Polyvinyl Vinylsilo-

Authors Chemical Retraction Agents Polysulfides Polyethers
Silicones Silicones xanether

O’Mahony CRA: No compatible

X X X X
et al./ 2000 [44] Astringedent Astringedent

CRAs:
No compatible
Nowakowska Gingiva Liquid,
X Compatible Compatible Racestyptine, X
et al./2005 [117] Racestyptine,
Astringedent
Astringedent
Cylwik et al./ CRA:
X X Compatible X X
2006 [121] Alustin

CRAs: Racestyptine, No compatible

Piotrowski et al./
Visco Stat, Gel cord X X Compatible Racestyptine, X
2007 [123]
ERAs: Visine, Afrin Visco Stat

No compatible
Sabio et al./ CRA: Hemostop No compatible No compatible
Hemostop, Compatible X
2008 [116] ERAs: Vislin, Afrin Hemostop Vislin, Afrin
Afrin
Machado &
CRAs: Hemostop,
Guedes/2011 X X Compatible X X
Astringedent
[120]
No compatible
Singh et al./ CRA: Astringedent
X X Astringedent, X X
2013 [118] ERA: 0.1% HCl-epi
0.1% HCl-epi

CRAs: Gingiva Liquid, Alustin,

Racestyptine, Orbat sensitive,
Nowakowska &
Astringedent No compatible
Raszewski/ X X X X
ERAs: 0.1% and 0.01% HCl- Alustin
2011 [126]
epi, Visine classic, Afrin,
Neosynephrin

CRAs: Gingiva Liquid, Alustin,

Racestyptine, Orbat sensitive,
Nowakowska Astringedent No compatible
X X X X
et al./ 2014 [127] ERAs: 0.1% and 0.01% HCl- Alustin
epi, Visine classic, Afrin,
Neosynephrin
X – non-evaluated.

with them should be avoided. These findings supported the
hypothesis that temperature may affect the polymerization
time of all evaluated impression elastomers after contact
with conventional and experimental ChRAs.
CONCLUSION
In this review, we summarized the physico-chemical
properties, local and/or systemic side-effects, and biological
activity of conventional and experimental chemical
retraction agents based on in vivo and in vitro experiments.
Retraction astringents from the conventional group are
characterized by a high cytotoxicity probably related to their
very low pH, and therefore their use in clinical conditions
should be limited. An alternative and attractive GMR/D
strategy was to identify as α-sympathomimetic amines as
experimental agents and these proved to be the least
cytotoxic effects. The results of biological activity monitored
in human fibroblasts primary cultures (HGFs) indicated that
experimental gels based on 0.05% HCl-tet were the most
biocompatible.
The compatibility of retraction agents from both groups
with elastomer impression materials was also analyzed.
These findings proved that all evaluated agents may affect
the polymerization time of VSXE, PVS and PE; however,
the experimental agents reached higher and statistically
significant PTCI-values.
The ideal retraction agents should also have the capacity
for effective moisture control, be free of cytotoxic effects
and compatible with elastomer impression materials. Further
research into ChRAs, including biochemical and behavioral
studies, is needed to identify the best minimally invasive
agents for GMR/D strategies in restorative dental
procedures.
LIST OF ABBREVIATIONS
GMR/D = Gingival Margin Retraction/Displacement
ChRAs = Chemical Retraction Agents
CRAs = Conventional Retraction Agents
ERAs = Experimental Retraction Agents
8 Mini-Reviews in Medicinal Chemistry, 2017, Vol. 17, No. 0 Nowakowska et al.

HCl-epi = HCl-epinephrine [15] Beier, U.S.; Kranweiter, R.; Dumpfart, H. Quality of impressions
after use of the Magic Foam Cord gingival retraction system - a
HCl-tet = HCl-tetrahydrozoline clinical study of 269 abutment teeth. Int J Prosthodont, 2009,
22(2), 143-147.
HCl-oxy = HCl-oxymetazoline [16] Deogade, S.C.; Mantri, S.S.; Dube, G; Shivasastava, R.; Noorani,
S. A new trend in recording subgingival tissue around an implant
HCl-phe = HCl-phenyleprine while making a direct abutment impression. Case Rep Dent, 2014,
doi: 10.1155/2014/847408.
HGFs = Human Gingival Fibroblasts [17] Nowakowska D., Panek H.: Classification of Retraction Materials
in the Aspect of Biocompatibility with Gingival Sulcus
PTCI = Polymerization Time Compatibility Index Environment. Polish J of Environ Stud, 2007, 16(2C): 204-208.
[18] Jokstad, A. Clinical trial of gingival retraction cords. J Prosthet
PS = Polysulfide Dent, 1999, 81(3): 258-261.
CS = Condensation silicone [19] Cloyd, S.; Puri, S. Using the double-cord packing technique of
tissue retraction for making crown impressions. Dent Today, 1999,
PVS = Polyvinyl siloxane 18(1), 54-59.
[20] Ruel, J.; Schuessler, P.J.; Malament, K.; Mori, D. Effect of
PE = Polyether retraction procedures on the parodontium in humans. J Prosthet
Dent. 1980, 44(5): 508-515.
VSXE = Vinylsiloxanether [21] Löe, H.; Reactions of marginal periodontal tissues to restorative
procedures. Int Dental J, 1968, 18: 759-778.
[22] Löe, H.& Silness, J. Tissue reaction to string packs used in fixed
CONFLICT OF INTEREST restorations. J Prosthet Dent, 1963, 13:318-323.
[23] Goldberg, P.V.; Higginbottom, F.L; Wilson, T.G. jr. Periodontal
The author(s) confirm that this article content has no considerations in restorative and implant therapy. Periodontology
conflict of interest. 2000, 2001, 25, 100-109.
[24] Wöstmann, B.; Rehman, P.; Balkenhol, M. Influence of different
ACKNOWLEDGEMENTS retraction techniques on crevicular fluid flow. Int J Prosthodont,
2008, 21(3): 215-216.
Declared none. [25] Poss S., An innovative tissue-retraction material, Compend Contin
Educ Dent, 2002, 23(1): 13-17.
[26] Burke, F.J.; Crisp, R.J. Evaluation of novel compule-based gingival
REFERENCES retraction system in UK general dental practices. Dent Update,
[1] La Forgia, A.; Mechanical-chemical and electrosurgical tissue 2014, 41(5); 437-438.
[27] Xu, X.; Zhu, X.; Ning, T.; Liu, W.; Li, Q. Synthesis and evaluation
retraction for fixed prosthesis. J Prosthet Dent. 1964, 1107-1114.
[2] Nemetz, H. Tissue management in fixed prosthodontics. J Prosthet of a novel injectable and water swelling gingival displacement
materials. Chin Dent J, 2012, 30(2): 139-142.
Dent, 1974, 31(6): 628-636.
[3] Nemetz H, Donovan T, Landesman H. Exposing the gingival [28] Gupta, A.; Prithviraj, D.R.; Gupta, D.; Shruti, D.P. Clinical
evaluation of three new gingival systems: a research report. J
margin: A systematic approach for the control of hemorrhage. J
Prosthet Dent. 1984, 51: 647-651. Indian Prosthodont Soc, 2013, 13(1), 36-42.
[29] Shivasakthy, M.; Asharaf, S. Comparative study on the efficacy of
[4] Benson, B.W.; Bomberg, T.J.; Hatch, R.A.; Hoffman, W. Jr. Tissue
displacement methods in fixed prosthodontics. J Prosthet Dent, gingival retraction using polyvinyl acetate strips and conventional
retraction cord - an in vivo study. J Clin Diagn Res, 2013, 7(10):
1986, 55(2): 175-181.
[5] Bennani, V.; Schwass, D.; Chandler, N. Gingival retraction 2368-2371.
[30] Phatale, S.; Marawar, P.P.; Byakod, G.; Lagdive, S.B.; Kalburge,
techniques for implants versus teeth. JADA, 2008, 139(10), 1354-
1363. J.V. Effect of retraction materials on gingival health: A
histopathological study. J Indian Soc Periodontol, 2010, 14(1): 35-
[6] Thomas, M.S.; Joseph, R.M.; Parolia, A. Nonsurgical gingival
displacement in restorative dentistry. Compend Contin Educ Dent, 39.
[31] Prasanna, G.S.; Reddy K.; Kumar R.K.; Shivaprakash, S.
2011, 32(5), 26-34.
[7] Azzi, R.; Tsao, T.F.; Carranza, F.A.; Kenney, E.B. Comparative Evaluation of efficacy of different gingival displacement materials
on gingival sulcus with. J Contemp Dent Pract, 2013, 14(2): 217-
study of gingival retraction methods. J Prosthet Dent, 1983, 50(4):
561-565. 221.
[32] Acar, O.; Ercut, S.; Ozçelik, T.B,; Ozdemir, E.; Akçil, M. A
[8] Coelho, D.H.; Cavallaro, J.; Rotshild, E.A. Gingival recession with
electrosurgery for impression making. J Prosth Dent, 1975, 33(0): clinical comparison of cordless and conventional displacement
systems regarding clinical performance and impression quality. J
422-426.
[9] Kriszna, Ch.V.; Gupta, N.; Reddy, K.M.; Sekhar, N.C.; Aditya, V.; Prosthet Dent, 2014, 111(5), 389-394.
[33] Al Hamad, K.Q.; Azar, W.Z.; Alwaeli, H.A.; Said, K.N. A clinical
Reddy, G.V. Laser gingival retraction: a quantitive asseement. J
Clini Diagn Res, 2013, 7(8), 1787-1788. study on the effects of cordless and conventional retraction
techniques on the gingival and periodontal health. J Clin
[10] Al-Ani, A.; Bennani, V.; Chandler, N.P.; Lyons, K.M.; Thomson,
W.M. New Zealand dentists’use of gingival retraction techniques Periodontol, 2008, 35(12), 1053-1058.
[34] Bennani, V.; Aarts, J.M.; He, L.H. A comparison of pressure
for fixed prosthodontics and implants. N Z Dent, 2010, 106(3), 92-
96. generated by cordless gingival displacement techniques. J Prosth
Dent, 2012, 107(6), 388-392.
[11] Porzier, J.; Benner-Jordan, L. ; Bourdeau, B. ; Losfeld, R. Accès
aux limites intra-créviculaires des préparations en prothèse fixée. [35] Bennani, V.; Inger, M.; Aarts, J.M. Comparison of pressure
generated by cordless gingival displacement materials. J Prosth
Cah. Prothès, 1991, 73(3): 7-20.
[12] Jones JD, Kaiser DA. A new gingival retraction impression system Dent, 2015, 112(2), 163-167.
[36] Chaudhari, P.; Prajapati P.; Patel J.; Setharaman R.; Naveeen Y.G.
for a one stage root-form implant. J Prosthet Dent, 1998, 80(3):
371-373. Comparatove evaluation of the amount of gingival displacement
produced by three different gingival retreaction systems: An in vivo
[13] Livaditis, G.J.; The matrix impression system for fixed
prosthodontics. J Prosthet Dent, 1998, 79(2): 208-216. study. Contemp Clin Dent., 2015, 6(2):189-195.
[37] Kurbad A. Impression-free production techniques. Int J Comput
[14] Ferrari, M.; Cagidiaco, M.C.; Ercoli C. Tissue management with a
new gingival retraction material: A preliminary clinical report. J Dent. 2011, 14(1): 59-66.
[38] Aimjiarkul, P.; Masuda, T.; Takahashi, H.; Miura, H. Gingival
Prosthet Dent, 1996, 75(3), 242-247.
sulcus simulation model for evaluating the penetration
Chemical Retraction Agents – in vivo and in vitro Studies
characteristics of elastomeric impression materials. Int J
Prosthodont, 2003, 16(4): 385-389.
[39] Baharav, H.; Laufer, B.Z.; Langer, Y.; Cardash, H. The effect of
Displacement Time on Gingival Crevice Width. Int J Prosthodont,
1997, 10(3), 248-253.
[40] Laufer BZ, Bahrav H, Langer Y, Cardash HS. The closure of the
gingival crevice following gingival retraction for impression
making. J Oral Rehabil,1997, 24(9):629-635.
[41] Naveen, Y.G.; Patil, R. Effect of the impression margin thickness
on the linear accuracy of impression and stone dies: an in vitro
study. J Indian Prosthodont Soc. 2013,13(1): 13-18.
[42] Ahmad, I. Anterior dental aesthetics: gingival perspective. Br Dent
J, 2005, 199(4), 195-202.
[43] Dominiak, M.; Konopka, T.; Szajkowski, K. Gingival recession in
relation to potential aetiological factors. Stomat Współczesna, 2002,
9(2), 22-28.
[44] O’Mahony, A.; Spencer, P.; Wiliams, K.; Corcoran, J. Effect of 3
medicaments on the dimensional accuracy and surface detail
reproduction of polivinylsiloxane impressions. Quintessence Int,
2000, 31(3): 201-206.
[45] Shillingburg, H.T.; Hatch, R.A.; Keenan, M.P.; Hemphill M.W.
Impression materials used for cast restoration in eight states. J Am
Dent Assoc, 1980, 100, 696-699.
[46] Donovan, T.E.; Gandara, B.K.; Nemetz, H. Review and survey of
medicaments used with gingival retraction cords. J Prosthet Dent,
1985, 53(4), 525-531.
[47] Shaw, DH.; Krejci, R.F.; Gingival retraction preference of dentists
in general practice, Quintessenz Int, 1986, 17(5), 277-280
[48] Hansen, P.A.; Tira, D.A.; Barlow, J. Current methods of finish-line
exposure by practicing prosthodontists. J Prosthodont, 1999, 8(3),
163-170.
[49] Ahmed, S.N.; Donovan, T.E.: Gingival displacement: Survey
results of dentists’ practice procedures. J. Prosth Dent, 2015,
114(1), 81-82.
[50] Nowakowska. D.; Panek, H.; Nowakowska, M.; Nowakowska A.
Gingival retraction - survey results of Polish dentists. Part 1.
Methods, materials and chemical retraction agents preferences.
Protet. Stomatol, 2006, 56(5): 352-360.
[51] Bowles, W.H.; Tardy, S.J.; Vahadi, A. Evaluation of new gingival
retraction agents. J Dent Res, 1991, 70(11):1447-1449.
[52] Felpel, L.P. A review pharmacotherapeutics for prosthetic
dentistry: part I. J Prosthet Dent, 1997, 3, 285-292.
[53] Nowakowska, D. Classification of chemical retraction agents.
Protet. Stomatol, 2008, 58(3): 202-208.
[54] Mohan, M.; Gupta, A.; Shenoy, V.; Parolia A. Pharmacological
Agents in dentistry: A review. Br J Pharm Res, 2011, 1(3): 66-87.
[55] De Gennaro, G.G.; Landesman, H.M.; Calhoun, J.E.; Martinoff,
J.T. A comparison of gingival inflammation related to retraction
cords. J Prosthet Dent, 1982, 47(4), 384-386.
[56] Kopač, I.; Cvetko, E.; Marion, L. Gingival inflammatory response
induced by chemical retraction agents in Beagle dogs. Int J Prosth,
2002, 15(1):14-19.
[57] Kopač, I.; Cvetko, E.; Pavlica, Z.; Marion, L. Gingival tissue
inflammatory response following treatment with chemical
retraction agents in Beagle dogs. Pflugers Arch Eur J Physiol.
2001, 442, (suppl 1), R 145-R 146.
[58] Akca, E.A.; Yldirim, E.; Dalkiz, M.; Yavuzyilmaz, H.; Beydemir,
B. Effects of different retraction medicaments on gingival tissue.
Quintessence Int, 2006, 37(1), 53-59.
[59] Ahmadzadeh, A.; Majd, N.E,.; Chasteen, J.; Kaviani, A,; Kavoosi,
M.A. Inflammatory response of canine gingiva to a chemical
retraction agent placed at different time intervals. Dent Res, 2014,
11(1): 81-86.
[60] Kostić, I.; Mihailović, D.; Najman, S.; Stojanović, S.; Kostić, M.
The rabbit gingival tissue response to retraction liquids and
tetahydrozoline. Vojnosanit Pregl. 2014, 71(1): 46-51.
[61] Harrison, J.D. Effect of retraction materials on the gingival sulcus
epithelium. J Prosthet Dent, 1961, 11:514-521.
[62] Woycheshin, F.F. An evaluation of the drugs used for gingival
retraction. J Prosthet Dent, 1964,14 (4), 769-776.
[63] Fazekas, A.; Csempesz, F.; Csabai, Z.; Vag, J. Effects of pre-
soaked retraction cords on the microcirculation of the human
gingival margin. Oper Dent, 2002, 27(4), 343-348.
[64] Sarmento, H.R.; Leite, F.R.; Dantas, R.V.; Ogliari, F.A.; Demarco,
F.F; Faot, F. A double-blind randomized clinical trial of two
Mini-Reviews in Medicinal Chemistry, 2017, Vol. 17, No. 0 9
techniques for gingival displacement. J Oral Rehabil, 2014, 41(4):
306-313.
[65] Feng, J.; Aboyoussef, H.; Weiner, S.; Singh, S.; Jandinski, J. The
effect of gingival retraction procedures on periodontal indices and
crevicular fluid cytokine levels: A pilot study. J Prosthodont, 2006,
15(2): 108-112.
[66] Gogerty, J.H.; Strand, H.A.; Ogilve, A.L.; Dille, J.M.; Seattle,
M.D. Vasopressor effects of topical epinephrine in certain dental
procedures. Oral Surg Oral Med Oral Pathol, 1957, 10(6), 614-
622.
[67] Phatak, N.M.; Lang, R.L. Systemic hemodynamic effects of R-
epinephrine gingival retraction cord in clinic patients. J Oral Ther
Pharmacol, 1966, 2(6), 393-398.
[68] Forsyth, R.P.; Stark, M.M.; Nicholson, R.J.; Peng, CT. Blood
pressure responses to epinephrine treated gingival retraction strings
in the rhesus monkey. J Am Dent Ass, 1969, 78: 1315-1319.
[69] Houston, J.B.; Mettler, L.; Shapiro, N. Epinephrine absorption
from retraction cord: a study in dogs. Pharmacol Ther Dent, 1978,
3(1): 17-23.
[70] Pelzner, R.B.; Kepler, D.; Stark, M.M.; Lum, L.B.; Nicholson, R.J.;
Soelberg, K.B. Human blood pressure and pulse rate response to
racemic epinephrine retraction cord. J Prosthet Dent, 1978, 39(3):
287-292.
[71] Hilley, M.D.; Milam, S.B.; Giescke, A.H. Jr.; Giovannitti, J.A.
Fatality associated with combined use of halothane and gingival
retraction cord. Anesthesiology, 1984, 60(6), 587-588.
[72] Hatch, C.L.; Chernow, B.; Terezhalmy, G.T.; Van Ness, M.; Hall-
Boyer, K.; Lake, C.R. Plasma catecholamine and hemodynamic
responses to the placement of epinephrine-impregnated gingival
retraction cord. 0ral Surg Oral Med. Oral Pathol, 1984, 58(5), 540-
544.
[73] Kellam, S.A.; Smith, J.R.; Scheffel, S.J. Epinephrine absorption
from commercial gingival retraction cords in clinical patients. J
Prosthet Dent, 1992, 68(5): 761-765.
[74] Pogue, W.L.; Harrison, J.D. Absorption of epinephrine during
tissue retraction. J Prosthet Dent, 1967, 18(3): 242-247.
[75] Yagiela, J.A. Adverse drug interactions in dental practice:
interactions associated with vasoconstrictors. Part V of a series.
JADA, 1999, 130(5), 701-709.
[76] Moore, P.A.; Gage, T.W.; Hersh, E.V.; Yagiela, J.A.; Haas, D.A.
Adverse drug interactions in dental practice. Professional and
educational implications. JADA, 1999, 130(1):47-54.
[77] Csillag, M.; Nyiri, G.; Vag, J.; Fazekas, A. Dose-related effects of
epinephrine on human gingival blood flow and crevicular fluid
production used as a soaking solution for chemo-mechanical tissue
retraction. J Prosthet Dent, 2007, 97(1): 6-11.
[78] Polat, N.T.; Őzdemir, A.K.; Turgut, M. Effects of gingival
retraction materials on gingival blood flow. Int J Prosthodont,
2007, 20(1): 57-62.
[79] Sun, X.W.; Sun, G.L.; Ciao,L.J. Evaluation of gingival
inflammation related to different retraction agents. Chin Dent J,
2008, 26(1): 53-55.
[80] Feng, Y.Z.; Zeng, X.H. The retractive effects of different gingival
retraction agents. Chin Dent J, 2011, 29(1): 53-56.
[81] Woody, R.D.; Miller, A.; Staffanou, R.S. Review of the pH of
hemostatic agents used in tissue displacement. J Prosthet Dent,
1993, 70(2): 191-192.
[82] Land, M.F.; Rosenstiel, S.F.; Sandrik, J.L. Disturbance of the
dentinal smear layer by acidic hemostatic agents. J Prosthet Dent,
1994, 72(1): 4-7.
[83] Land, M.F.; Couri, C.C.; Johnston, W.M. Smear layer instability
caused by hemostatic agents. J. Prosthet. Dent, 1996, 76 (5): 477-
482.
[84] Kopač, I.; Batista, U.; Cvetko, E.; Marion, L. Viability of
fibroblasts in cell culture after treatment with different chemical
retraction agents. J Oral Rehab, 2002, 29(1): 98-104.
[85] Ayo-Yusuf, O.A.; Driessen, C.H.; Botha, A.J. SEM-EDX Study of
prepared human dentine surfaces exposed to gingival retraction
fluids. J Dent, 2005, 33(9), 731-739.
[86] Nowakowska D., Raszewski Z.: The pH value of conventional and
experimental gingival margin retraction medicaments. Dent Med
Probl, 2010, 47(1): 76-80.
[87] Kuphasuk, W.; Harnirattisai, C.; Senawongse, P.; Tagami, J. Bond
strenghts of two adhesive systems to dentin contaminated with a
hemostatic agent. Oper Dent, 2007, 32(4), 399-405.
 10 Mini-Reviews in Medicinal Chemistry, 2017, Vol. 17, No. 0
[88] Harnirattisai, C,; Kuphasuk, W.; Senawongse, P.; Tagami, J. Bond
strengths of resin cements to astringent-contaminated dentin. Oper
Dent, 2009, 34(4): 415-422.
[89] O’Keffe, K.L.; Pinzon, L.M.; River, B.; Powers, J.M. Bond strengh
of composite to astringent-contamination dentin using self-etching
adhesives. Am J Dent, 2005, 18: 168-172
[90] Kimmes, N.S.; Olson, T.L.; Shaddy, R.S.; Latta, M.A. Effect of
ViscoStat and Viscostat Plus on composite shear bond strenght in
the presence and absence of blood. J Adhes Dent, 2006, 8: 363-366.
[91] Ebrahimi, S.F.; Shadman, N.; Abrishami, A. Effect on ferric sulfate
contamination on the bonding effectiveness of etch-and-rinse and
self-etch adhesives to superficial dentin. J Conserv Dent, 2013,
16(2): 126-130.
[92] Kumar, P.; Shenoy, A.; Joshi, S. The effect of various surface
contamination on the microleakage of two different generation
bonding agents: A stereomicroscopic study. J Conserv Dent, 2012,
15, 265-269.
[93] Baker, AM.; Araby, AE.; Amri, MD.; Anil, S The impact of
Expasyl® Gingival retraction paste on the Bond strenght of self-
etch and total-etch systems. J Contemp Dent Pract, 2015,
16(5):335-339.
[94] Conrad, H.J.; Holtan J.R. Internalized discoloration of dentin under
porcelan crowns: a clinical report. J Prosth Dent, 2009, 101(3):
153-157.
[95] Cooper, K.; Bennani, V.; Tawse-Smith, A.; Reid, M.; Stirling, C.;
Dias, G. Effect of a cordless retraction paste on titanium surface: a
topographic, chemical and biocompatibility evaluation. Braz Oral
Res, 2013, 27(3): 211-217.
[96] Kopač, I.; Sterle, M.; Marion, L. Electron microscopic analysis of
the effects of chemical retraction agents on cultured rat
keratinocytes. J Prosthet Dent, 2002, 87(1): 51-56.
[97] Lodetti, G.; D’Abrosca, F.; Fontana, P. Set up of in vitro methods
able to detect the safety of astringent liquids. Minerva Stomatol,
2004, 53(6): 361-367.
[98] Liu, C-M.; Huang, F-M.; Yang, L-C.; Chou, S-S.; Chou, M-Y.;
Chang,Y-C. Cytotoxic effects of gingival retraction cords on
human gingival fibroblasts in vitro. J Oral Rehab, 2004, 31: 368-
372.
[99] Yalçin, M.; Barutcigil Ç.; Umar I.; Bozkurt, B.S.; Hakki, S.S.
Cytotoxicity of hemostatic agents on the human gingival
fibroblasts. Eur Rev Med. Pharmacol Sci, 2013, 17(7): 984-988.
[100] Liu, J.; Hang, X.M.; Hao, P.J.; Hui, M.; Yu, H.Y Comparison of
cytotoxicity between chemical retraction agents on human gingival
fibroblasts in vitro. Chin Dent J, 2009, 27(2): 202-205.
[101] Odabas, M.E.; Ertürk, M.; Çinar Ç.; Tüzüner,T.; Tulunoğlu, Ö.
Cytotoxicity of a new hemostatic agent on human pulp fibroblasts
in vitro. Med. Oral Patol Oral Cir Bucal, 2011, 16(4): e584-587
[102] Mihmanli, A.; Ulker, Z.; Alpsoy, L.; Eziganli, S. Evaluation of
cytotoxicity og a new hemostatic agent Ankafered Blood Stopper®
using different assays. Hum Exp Toxicol .2012, 31(8); 780-787.
[103] Nowakowska, D.; Saczko, J.; Kulbacka, J.; Choromanska, A.
Dynamic oxidoreductive potential of astringent retraction agents.
Folia Biol, (Praha), 2010, 56(6): 263-268.
[104] Nowakowska, D.; Saczko, J.; Kulbacka, J.; Choromanska, A.;
Raszewski Z. Cytotoxic Potential of Vasoconstrictor Experimental
Gingival Retraction Agents - in Vitro Study on Primary Human
Gingival Fibroblasts. Folia Biol (Praha), 2012, 58(1): 37-43.
[105] Saczko, J.; Dominiak, M.; Kulbacka, J.; Chwiłkowska, A.;
Krawczykowska, H. A simple and established method of tissue
culture of human gingival fibroblasts for gingival augmentation.
Folia Histochem Cytobiol 2008, 46(1): 117-119.
[106] Saczko, J. (2008) Patent No: P3812045
[107] Nowakowska D.; Panek H.; Nowakowska M.; Nowakowska A..
Gingival retraction - survey results of Polish dentists. Part 2.
Clinical habits related to retraction procedures. Protet. Stomatol,
2006, 56(5): 361-366.
[108] Nowakowska, D.; Saczko, J.; Bieżuńska-Kusiak, K.; Choromańska,
A; Dubińska-Magiera, M.; Ziętek M.; Kulbacka, J. The influence
of retraction agents on cytoskeleton reorganization and oxidative
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stress in primary human gingival fibroblasts (HGFs). Arch Oral
Biol, 2014, 59(3): 341-348.
[109] Balkenhol, M.; Haunschild, S; Erbe, C; Wöstmann, B. Influence of
prolonged setting time on permanent deformation of elastomeric
impression materials. J Prosth Dent, 2010; 103: 288-293.
[110] German, M.J.; Carrick, T.E.; McCabe, J.F.; Surface detail
reproduction of elastomeric impression materials related to
rheological properties. Dent Mater, 2008; 24:951-956.
[111] Reitz, C.D.; Clark, N.P. The setting of vinyl polysiloxane and
condensation silicone putties when mixed with gloved hands. J Am
Dent Assoc, 1988, 116(3): 371-375.
[112] Kahn, R.L.; Donovan, T.E.; Chee, W.W.L. A pilot study of
polymerization inhibition of poly (vinyl siloxane) materials by
latex gloves. Int Prosthodont, 1989, 2, 128-130.
[113] Chee, W.W.L.; Donovan, T.E.; Kahn, R.L. Indirect inhibition of
polimeryzation of a polyvinyl siloxane impression material: a case
report. Quintessence Int, 1991, 22(2): 133-135.
[114] Baumann, M.A. The influence of dental gloves on the setting of
impression materials. Br Dent J, 1995, 19, 179(8): 130-135.
[115] Kimoto, K.; Tanaka, K.; Toyota, M.; Ochiai, K.T. Indirect latex
glove contamination and its inhibitory effect on vinyl polysiloxane
polymerization. J Prosthet Dent, 2005, 93(5): 433-438.
[116] Sabio, S.; Franciscone, P.A.; Mondelli, J. Effect of conventional
and experimental gingival retraction solution on the tensile strenght
and inhibition of polymerization of four types of impression
materials. J Appl Oral Sci. 2008, 16(4):280-285.
[117] Nowakowska, D.; Małecka, K.; Sobolewska, A. In vitro evaluation
of the compatibility of selected chemical retraction agents with
elastomeric impression materials used for fixed prosthodontics.
Part I - retraction cord medicaments Prot. Stom, 2005, 55(3): 207-
213.
[118] Singh, R.; Singh, J.; Gambhir, R.S.; Singh, R.; Nanda, S.
Comparison of the effect of different medicaments on surface
reproduction of two commercially available polyvinyl siloxane
impression materials - an in vitro study. J Clin Exp Dent, 2013,
5(3): 138-143.
[119] De Camargo, L.M.; Chee, W.W.; Donovan, T.E. Inhibition of
polymerization of polyvinyl siloxanes by medicaments used on
gingival retraction cords. J Prosthet Dent, 1993, 70(2), 114-117.
[120] Machado, C.E.; Guedes, C.G. Effects of sulfur-based hemostatic
agents and gingival retraction cords handled with latex gloves on
the polymerization of polyvinyl siloxane impression materials. J
Appl Oral Sci, 2011, 19(6): 628-633.
[121] Cylwik, D.; Taraszkiewicz-Sulik, K.; Jamiołkowski, J.; Romaniuk,
J.; Gołębiewska, M. Influence of aluminum chloride on selected
parameters of vinyl polysiloxane impression materials -
preliminary report. Prot Stom, 2006, 56(1), 59-64.
[122] Kumbuloglu O., User A., Toksavul S., Boyacioglu H.: Clinical
evaluation of different gingival cords. Quintessence Int, 2007;
38(2):91e92-98
[123] Piotrowski, P. ; Marcinkowska. A.; Rzątowski, S. The influence of
medicaments in retraction cords on reproduction of preparation
line. Protet Stomatol, 2007, 57(5): 371-376.
[124] Berg, J.C.; Johnson, G.H.; Lepe, X.; Adan-Plaza, S. Temperature
effects on the rheological properties of current polyether and
polysiloxane impression materials during setting. J Prosthet Dent,
2003, 90(2):150-161
[125] Takahashi, H; Finger, W.J.; Kurokawa, R.; H.; Komatsu, M. Sulcus
depth reproduction with polyvinyl siloxane impression material:
effects of hydrophilicity and impression temperature. Quintessence
Int,, 2010, 41(3), 43-45
[126] Nowakowska, D.; Raszewski, Z. Effect of gingival margin
retraction agents on the polymerization time of the
vinylsiloxanether impression elastomer in rheometer study. J
Stoma, 2011, 64(11): 887-894.
[127] Nowakowska, D.; Raszewski, Z.; Saczko, J.; Kulbacka, J.;
Więckiewicz, W. Polymerization time compatibility index of
polyvinyl siloxane impression materials with conventional and
experimental gingival margin displacement agents, J Prosth Dent,
2014, 112(2): 168-175.