REVIEWS

Dent. Med. Probl. 2015, 52, 4, 485–490 © Copyright by Wroclaw Medical University and Polish Dental Society
DOI: 10.17219/dmp/58819 ISSN 1644-387X

Dagmara Piesiak-PańczyszynA–D, Alina Wrzyszcz-KowalczykA, D, F,

Joanna Kobierska-BrzozaB, D, E

A Comparison of Selected Regenerative Materials

Used in the Management of Pulp Diseases
– Review of the Literature
Porównanie wybranych materiałów regeneracyjnych
stosowanych w leczeniu chorób miazgi zębów – przegląd piśmiennictwa
Department of Conservative and Pediatric Dentistry, Wroclaw Medical University, Wrocław, Poland

A – research concept and design; B – collection and/or assembly of data; C – data analysis and interpretation;
D – writing the article; E – critical revision of the article; F – final approval of article

Abstract
The authors present a group of regenerative materials recommended for the treatment of deep caries, pulp expo-
sure, endodontic treatment of immature teeth involving apexogenesis and apexification, and management of inter-
nal resorption and chronic periapical inflammations. Biomaterials which demonstrate biocompatibility, expressed
by direct integration with dentine on a molecular level, also stimulate the formation of secondary and reparative
dentine by odontoblasts. Calcium hydroxide is the oldest and has been the most widely used biomaterial since
the 19th century. However, due to some inconveniences experienced during treatment with this material, modern
odontotropic materials like Mineral Trioxide Aggregate (MTA) or Biodentine are more frequently and more pref-
erably used. New materials like MTA and Biodentine make it possible to develop new protocols of treatment and
create opportunities for their successful results. Biodentine, in comparison with MTA, seems to be easier to prepare
and apply, with a much shorter setting time.
However it should be emphasized that observations of the performance of these new regenerative materials are
relatively limited, so further research is required to confirm their long term performance and usefulness and to
formulate reliable conclusions (Dent. Med. Probl. 2015, 52, 4, 485–490).
Key words: dental materials, MTA, Biodentine.
Słowa kluczowe: materiały stomatologiczne, MTA, Biodentyna.

Bioactive materials constitute the group of since that time it has been commonly used in var-
products which both in vitro and in vivo do not ious indications, especially due to its strong alka-
harm vital cells and minimally affect the immune lizing, antibacterial, antinflammatory potential as
system. In dental therapies these materials, pre- well as its capacity to stimulate pulpal regenera-
senting biocompatibility expressed by direct inte- tive processes [5–10]. The mechanism of action of
gration with dentine on a molecular level, are tol- calcium hydroxide products is based on its abili-
erated by pulpal cells and demonstrate the capa- ty to dissociate in aqueous solutions into free Ca2+
bility to stimulate the formation of secondary and ions and hydroxyl ions which activate many chem-
reparative dentine (odontotropic action) [1–4]. ical reactions in contact with vital tissue as well
For many years calcium hydroxide Ca(OH)2 as provide a highly alkaline environment with pH
has been one of the most recognizable and most of approximately 12.5 [5–10]. Free hydroxyl ions
widely used of odontotropic materials. It was in- show enormous reactivity with many various bio-
troduced into dentistry in the 19th century and molecules. They have an influence on the activity
486 D. Piesiak-Pańczyszyn, A. Wrzyszcz-Kowalczyk, J. Kobierska-Brzoza

of alkaline phosphatase and ATP-ases which are treatment [6, 11, 12, 14]. Numerous studies [5, 9,
the catalysts of odontotropic processes and which 12, 13] have revealed that dentinal bridges formed
are able to neutralize some mediators of the in- as a result of odontotropic processes are irregular
flammatory reactions such as hydrolases or lac- and quite thin. They frequently include so-called
tic acid. They also initiate differentiations of mes- tunnels (gaps), which may predispose the patient
enchymal cells into fibroblasts, cementoblasts and to infection of the pulp. Materials based on calci-
osteoblasts. The extremely high pH provides an um hydroxide are not indicated for the treatment
alkaline environment triggering bacteriocidic and of immature permanent teeth if there are rem-
bacteriostatic properties of the preparations. The nants of vital pulp within the canal, due to the risk
intracellular action leads to irreversible damage of formation of a layer of highly mineralized tissue
of DNA, proteins, enzymes and lipids within bac- which obstructs the root canal leading to the inhi-
terial cells and hydrolysis of the lipopolysaccha- bition of regenerative processes [8, 9, 12]. Calcium
rides in their cytoplasmatic membranes [6, 8–11]. hydroxide may also harm Hertwig sheat cells re-
Absorption of carbon dioxide from the environ- sulting in the loss of their capability to stimulate
ment potentiates the bactericidal effects of this the transformation of undifferentiated cells into
material, additionally exerting its negative im- odontoblasts [15, 16].
pact on anaerobe microorganisms [9, 12]. Calci- Keeping in mind the potential complications
um hydroxide is also capable of denaturing pro- and some inconveniences related to treatment
teins, eliminating the remnants of necrotic pulp. with the use of calcium hydroxide products, prac-
It also demonstrates long term anti-inflammatory titioners nowadays increasingly prefer modern
properties through inhibition of enzyme phospho- odontotropic materials which present the proper-
lipase, activation of Ca canals and hygroscopic ac- ties outperforming those of previously used ma-
tion [6, 9, 10, 12]. Other significant advantages of terials. They include primarily Mineral Trioxide
this material are low toxicity and allergenic poten- Aggregate (MTA) and Biodentine.
tial and resorbability of the material inadvertent- Mineral Trioxide Aggregate (MTA) was intro-
ly deposited behind the apex during endodontic duced into dentistry in early 1990 for prompt ob-
treatment [6, 8, 11]. The relatively low costs, flex- turation of the apical part of root canals and seal
ible consistency and availability of various formu- closure of perforations in the canal walls which
lations are not without significance. Depending on occurred during endodontic treatment. This is
the manner of setting, these materials are divided a mixture of aluminum, calcium, magnesium,
into two main groups: non-setting solutions which sodium and potassium oxides with bismuth ox-
release ions immediately and constantly and set- ide and calcium phosphate. The composition is
ting pastes with delayed and periodic release of similar to Portland cement enhanced with about
ions. The above-mentioned advantages contribute 20% of bismuth oxide, added for the effect of ra-
to the wide range of its use in dentistry, among diographic contrast (comparable to gutta-percha)
others in the treatment of deep caries, pulp expo- and with a diminished content of heavy metals
sures, endodontic treatment of immature teeth re- and gypsum at the same time, which delay its set-
quiring apexogenesis and apexification, different ting time [6, 17–20]. The material is manufactured
types of internal resorption and chronic apical le- in the form of hydrophilic powder which hard-
sions [6–9, 12, 13]. Unfortunately, the coinciding ens in the presence of water, forming a colloidal
drawbacks of calcium hydroxide preparations oc- consistency compared to wet sand. Two types of
casionally exclude their use or increase the risk of MTA are available: esthetic and non discoloring
unfavorable outcomes. This includes a high sen- white MTA – White Mineral Trioxide Aggregate
sitivity to moisture, causing its dissolution and (WMTA) and gray MTA – Gray Mineral Trioxide
washing out, lack of adhesion to the dentine or to Aggregate (GMTA) with the addition of ferric ox-
bonding systems which is responsible for microle- ide which may cause discoloration of treated teeth
akage and post treatment sensitivity [6, 7, 10]. The and periapical tissue, but it presents greater me-
relatively low diffusion coefficient of calcium hy- chanical strength [6, 20–22]. Preparation of this
droxide, impeding the achievement of high con- material for use involves mixing the powder with
centrations of the ions in tissues, and the signifi- liquid (distilled water) for approximately 30 sec-
cant decrease of pH from 12.5 to 8.0 in 2–3 weeks onds to obtain a homogenous material for imme-
cause prolongation of the treatment of contam- diate application. Then the treated tooth should
inated root canals which in turn may weaken be closed with adequately sealed temporary obtu-
the tooth and increase the risk of fracture of the ration (glassionomer or IRM enhanced with res-
crown. The loss of restoration in the coronal part ins). The deposited material should be covered by
of the tooth, discolorations of hard tissues and re- a wet cotton ball for at least 6 hours. MTA hardens
infections were also observed after endodontic in about 3–4 hours from the time the components
Regenerative Materials Used in Pulp Diseases 487

were mixed and then, after a hard barrier in the ar- of 70 MPa and insolubility in fluids [18, 19, 27, 32].
ea of application has been obtained, further treat- Additionally, the study by Wilkoński et al. [17]
ment may follow [6, 22, 23]. The hydrophilic na- and Camilleri et al. [32] reveal deposition of Ca-P
ture of the metal oxide particles makes it possible complexes on the surface of MTA and formation of
to set the material in the presence of organic fluids early forms of apatites in their presence. This has
such as blood or saliva [19, 22–25]. The mechanism a favorable impact either on the processes of apexi-
of action of MTA is probably based on providing fication or obtaining an adequate marginal seal.
very high pH in a short time (10.5 increasing to According to the research conducted by Yildir-
12.5 in 3 hours) and alkalizing the local environ- im et al. [24], the smear layer does not affect the
ment. This inhibits microorganisms and inflam- seal of MTA, hence there is no need for its remov-
matory reactions in vital pulp as well as stimu- al before application of Mineral Trioxide Aggre-
lates remineralizing processes [18, 19, 22]. Accord- gate. Among the disadvantages of MTA, one can
ing to Reyes-Carmona et al. [26], MTA promotes list the long setting time which lasts minimum 4 to
the formation of regenerative dentine through 6 hours, complicated mode of storage, preparation
its alkalizing potential and precipitation of apa- and application and high cost [6, 19, 22, 23, 31].
tites in the acute phase of the inflammation pro- Manufacturers pay special attention to the man-
cess. Additionally, during the reaction of setting, ner of storage because the material absorbs ambi-
calcium oxide is released, which subsequently re- ent moisture, as well as to the strict adherence to
acts with tissue fluids and forms calcium hydrox- the instructions in the matter of powder to liquid
ide [20]. This activates odontotropic processes by ratios. Practitioners complain of difficulties with
stimulation of osteoblasts, providing biologically the application of MTA due to its hard-to-man-
active substrates and the production of cytokines age consistency of wet sand, which forces them to
responsible for bone metabolism, improving the use additional instruments: plastic or metal car-
bone cells’ adherence to the material, enhancing riers (Endodontic Carrier, p–MTA Pistolet-Kit),
the proliferation of fibroblasts and the production potential discoloration of the teeth (with the use
of alkalic phosphatase [11, 17, 20, 27, 28]. Mineral of Grey MTA) and necessity to postpone the fi-
Trioxide Aggregate presents antibacterial proper- nal procedures until the subsequent visit. MTA is
ties (also against anaerobes and Enterococcus fae- successfully used in various aspects of pulpal pa-
calis) as well as antifungal. Ferk et al. [29] proved thology. Several studies have confirmed its effec-
the strongest action against colonies of Streptococ- tiveness in direct pulp capping, closure of perfora-
cus mutans, Streptococcus mitis and Lactobacillus tions, obturation of root canals with wide apical
acidophilus. Al-Kahtani et al. [30] analyzed the re- foramina, apexogenesis and apexification as well
lationship between the thickness of a layer of Min- as in the treatment of internal and external resorp-
eral Trioxide Aggregate and microbial microleak- tion [6, 18, 19, 22, 25, 28].
age. They revealed that only a layer of 5 mm or Another increasingly popular alternative for
more is adequately sealed and provides sufficient calcium hydroxide and also MTA is the biocom-
protection against an infection of Actinomyces vis- patible material Biodentine. This is the first bioac-
cosus and Staphylococcus. Several studies [17, 20, tive cement which can entirely substitute dentine
25, 31] have confirmed the biocompatibility of within the crown and the root [4, 33]. The mate-
MTA excluding its potential cytotoxic, genotoxic rial is prepared ex tempore from precise amounts
or mutagenic effect on vital cells, especially pulp- of powder deposited in a capsule and liquid in the
al cells. MTA does not cause any disturbances in pipette. The composition of the powder resembles
their differentiation or functioning. For these rea- Portland cement and its main components are tri-
sons, post treatment sensitivity is not observed calcium silicate (3CaO SiO2) and dicalcium silicate
and inflammatory reactions within the pulp occur (2CaO SiO2), responsible for setting. Calcium car-
quite rarely. Łuczaj-Cepowicz et al. [19] showed bonate plays the role of a filler whereas zirconi-
100% effectiveness of MTA in direct pulp capping um dioxide provides radiographic contrast. The
obtained by the formation of a hard barrier with liquid is an aqueous solution of calcium chloride
a simultaneous lack of pulp inflammation. It has (CaCl2 2H2O), which acts as a catalyst, accelerat-
been observed that dentinal bridges stimulated by ing the setting reaction [27, 34, 35]. The applica-
MTA are formed more quickly and are thick, com- tion powder is mixed with the liquid for 30 sec-
pact, homogenous, more regular in their structure onds in a mixing machine. The result of this pro-
and free of so-called tunnel effects which are typ- cess is a ready-to-use hydrated calcium silicate gel
ical with the use of calcium hydroxide [13, 15, 20, – CSH and calcium hydroxide. The working time
28]. MTA is characterized by very good marginal is about 6 minutes, and the setting time lasts an-
seal due to its excellent adaptation to the hard tis- other 6 minutes. After this time, the material be-
sues, high compressive strength within the range comes hard and the next step of the procedure may
488 D. Piesiak-Pańczyszyn, A. Wrzyszcz-Kowalczyk, J. Kobierska-Brzoza

be executed [34–36]. According to the manufac- are: direct and indirect pulp capping, closure of
turer, the final hardness occurs about 30 days af- perforations, obturation of the root canals with
ter application. The mechanism of action is based wide apical foramina, apexogenesis and apexifi-
on the release of calcium hydroxide, either during cation, and treatment of internal and external re-
the setting reaction or a long time after hardening sorption [25, 33, 36]. The high biocompatibility,
and the immediate local provision of very high pH low risk of inflammatory reaction of vital tissues,
(pH = 12.5) [36]. This stimulates the vital pulp to regenerative capacity, short setting time and con-
form a secondary and reparative dentine, and ini- sistency allowing easy application make this ma-
tiates differentiation of the cells within the pulp terial a valuable alternative to conventional calci-
and periapical tissues [4, 34, 35]. Dentinal bridg- um hydroxide materials or MTA. However it has
es stimulated by Biodentine, similarly to the use been observed that temporary restorations made
of MTA, are characterized by increased thickness, with Biodentine demonstrated partial loss of mar-
mechanical strength and reduced permeabili- ginal integrity after 3 to 6 months, which could
ty [4, 16, 35, 36]. Studies have revealed that Bioden- lead to a defective marginal seal and microleak-
tine, like MTA, does not demonstrate significant age [34, 37, 38]. The reason might be the low qual-
cytotoxic, genotoxic or mutagenic effects [4, 34– ity of the entire restoration or its finishing. Man-
36]. The cytotoxicity of Biodentine ranges from ufacturers recommend shaping of the material in
10% (in the first day) to 7% (after 7 days) and is the cavity after at least 6 minutes since mixing.
similar to that of MTA [35]. Comparably to other Excessive condensation, shaping and modeling
agents used in pulp therapy, Biodentine very rare- may damage the crystalline microstructure and
ly induces adverse reactions in the form inflam- disturb the setting reaction or even make it im-
mation of the pulp or periapical tissues [26, 36]. possible. The material should be applied with the
High alkaline pH (pH = 12.5) facilitates binding use of carriers and the exertion of slight pressure.
with the dentine without the necessity of use of ac- The rotational instruments are not recommended
ids and bonding systems which may provoke post- as well as the polishing of the restoration. The pa-
treatment sensitivity [37, 38]. This action is called tient should be asked not to overload the restored
surface conditioning of the enamel and dentine tooth during the first few hours and to avoid hot,
and relies on the dissolution of organic matter in very cold and sour food. Koubi et al. [34] report-
peritubular spaces and exposure of tubular orific- ed abrasive features marked in 25% of the restora-
es. This leads to the formation of mineralized tags tion after 6 months and 30% in the period of 6 to
within the dentinal tubules resulting in a dynamic 12 months. Some authors [35, 38] recommend the
and biomimetic bonding of the material with den- use of two visit procedures with the removal of the
tal hard tissues [38]. upper layer of Biodentine after 1 week to 6 months
Observations obtained in several studies [17, and replacing it with glass ionomer or composite.
27, 31] suggest a conclusion that Biodentine demon- While planning the use of Biodentine, its unsatis-
strates physical properties similar to or even better fying white opaque shade should be kept in mind
than MTA and definitely superior to calcium hy- as well as its high cost, exceeding that of conven-
droxide. They include an excellent and long-last- tional material like calcium hydroxide. In con-
ing marginal seal, high dimensional stability and trast to MTA, which sets in the presence of phys-
optimal mechanical performance approximate to iological fluids, Biodentine is highly sensitive to
those of dentine (compressive strength – 220 MPa, moisture during the initial phases of setting [32].
microhardness – 60 VHN, modulus of elasticity The studies of Lipski et al. [27] and Wilkoński
– 22 GPa) [35, 38]. The crush strength is 34 MPa et al. [17], which compared the ability of MTA and
after two hours and is comparable to the param- Biodentine to seal the root canals, revealed that
eters of glass ionomer cements [37]. Research has they both lead to a similar effect. The availabil-
shown [32] a high resistance of Biodentine against ity of odontotropic materials makes it possible to
acids in comparison to the other cements. The lack perform various procedures allowing there to re-
of free monomers minimizes the potential for al- main vital and healthy pulp. This kind of treat-
lergic reactions while the ease of application and ment is always related to a high risk and the final
short setting time allow efficient performance of outcome depends on many additional factors. The
the procedure. This is especially significant in bi- oldest and best-known material, calcium hydrox-
ological treatments, when the possibility of closure ide, apart from its undeniable advantages, also
of the cavity during one visit diminishes the risk of presents many drawbacks, lowering its value and
complications and increases the chances of a suc- contributing to uncertain outcomes. New materi-
cessful outcome. The advantageous properties of als like MTA and Biodentine make it possible to
Biodentine have led to its wide use in restorative develop the new protocols of treatment and give
dentistry and endodontics. The indications for use chances for their successful results. Biodentine in
Regenerative Materials Used in Pulp Diseases 489

comparison with MTA seems to be easier for pre- generative materials are relatively limited, so fur-
paring and application with a much shorter set- ther research is required to confirm their long
ting time. However it should be emphasized that term performance and usefulness and to formu-
observations of the performance of these new re- late reliable conclusions.

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Address for correspondence:

Dagmara Piesiak-Pańczyszyn
Department of Conservative and Pediatric Dentistry
Wroclaw Medical University
Krakowska 26
50-425 Wrocław
Poland
E-mail: dagmara piesiak-panczyszyn@umed.wroc.pl

Conflict of Interest: None declared

Received: 7.05.2015
Revised: 13.06.2015
Accepted: 15.07.2015