Vật liệu hoạt tính sinh học, hoặc vật liệu sinh học, có khả năng tương tác sinh học với mô mà nó được đưa vào và kích thích sự lắng đọng của mô khoáng hóa. Gốm làm từ canxi photphat là vật liệu đầu tiên được biết đến trong nha khoa có hoạt tính sinh học, và hiện tại, những vật liệu này được sử dụng nhiều nhất cho các mục đích y sinh, với các đặc điểm hình thái khác nhau. Trong nha khoa, những vật liệu này đã đạt được tầm quan trọng to lớn bằng cách kích thích sự lắng đọng của mô xốp trong xương bị thương, và bằng cách có khả năng tái khoáng hóa các mô cứng của răng (men răng và ngà răng). Hơn nữa, vật liệu sửa chữa dựa trên khoáng chất trioxit tổng hợp hoặc canxi hydroxit là vật liệu sinh học cổ điển và được sử dụng rộng rãi trong nha khoa, chủ yếu tiếp xúc với mô tủy răng hoặc dây chằng nha chu, cho các quá trình sửa chữa. Tuy nhiên, các công thức khác nhau của những vật liệu này xuất hiện mọi lúc để tìm kiếm vật liệu lý tưởng. Nhìn chung, các vật liệu hoạt tính sinh học đã được chứng minh là thúc đẩy việc giải phóng các ion canxi, natri, silic và photphat, được cơ thể chuyển hóa, có tác dụng như hình thành mạch và hành động kháng khuẩn, có thể được cải thiện tùy thuộc vào thành phần của vật liệu. Mô bột giấy là một mô nha khoa chuyên biệt cao và là chủ đề của các nghiên cứu gay gắt về phản ứng với vật liệu sinh học. Người ta cũng hiểu rằng một số thay đổi toàn thân ở cá nhân có ảnh hưởng đến hoạt động của các chất hoạt tính sinh học trong quá trình sửa chữa mô. Do đó, cuốn sách này sẽ đề cập đến việc sử dụng các vật liệu hoạt tính sinh học khác nhau trong nha khoa, xem xét hiệu suất của các vật liệu sinh học này trong các mô cứng của răng, và phản ứng của tủy răng, cũng như ảnh hưởng của thành phần của các vật liệu này và của những thay đổi mang tính hệ thống của cá nhân về hoạt tính sinh học và hoạt động kháng khuẩn. Một số thử nghiệm in vivo và in vitro để đánh giá hoạt tính sinh học của vật liệu sinh học cũng sẽ được giải quyết.
Trang 2B IOACTIVE M ATERIALS
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Library of Congress Cataloging-in-Publication Data
Names: Benetti, Francine, 1990- editor
Title: Bioactive materials in dentistry: remineralization and biomineralization / editor, Francine Benetti, PhD (Department of Restorative Dentistry, Sao Paulo State University (UNESP), School of Dentistry, Aracatuba, Sao Paulo, Brazil)
Description: Hauppauge, New York: Nova Science Publishers, Inc., 2019 |
Series: Dentistry and oral sciences | Includes bibliographical references and
index | Description based on print version record and CIP data provided by publisher; resource not viewed Identifiers: LCCN 2019015271 (print) | LCCN 2019017491 (ebook) | ISBN 9781536153255 () | ISBN 9781536153248 (softcover)
Subjects: LCSH: Fillings (Dentistry) | Bioactive compounds | Dental materials | Dental technology | Biomineralization
Classification: LCC RK517 (ebook) | LCC RK517 B56 2019 (print) | DDC 617.6/75 dc23
LC record available at https://lccn.loc.gov/2019015271
Published by Nova Science Publishers, Inc † New York
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Trang 6C ONTENTS
Chapter 1 Remineralizing Performance of
Different Materials on Teeth Hard Tissues 1
Marjorie de Oliveira Gallinari, Luciano Tavares Angelo Cintra, Carlos Roberto Emerenciano Bueno, André Luiz Fraga Briso,
Gustavo Sivieri de Araújo, Vanessa Abreu Sanches Marques and Francine Benetti
Chapter 2 Current Methodologies for Evaluating
Remineralization and Biomineralization
Leticia Citelli Conti, Vanessa Abreu Sanches Marques, Luciano Tavares Angelo Cintra, Rogério de Castilho Jacinto, Marjorie de Oliveira Gallinari, Marina Trevelin Souza and Francine Benetti
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Trang 7Chapter 3 Bioceramic Materials 45
Carlos Roberto Emerenciano Bueno, Luciano Tavares Angelo Cintra, Francine Benetti, Renan Dal Fabbro, Rogério de Castilho Jacinto
and Elói Dezan-Júnior
Chapter 4 Antimicrobial Activity of Bioactive Materials 93
Carlos Roberto Emerenciano Bueno, Leopoldo Cosme-Silva, Francine Benetti, Elói Dezan-Júnior,
Luciano Tavares Angelo Cintra, Paulo Carvalho Tobias Duarte and Rogério de Castilho Jacinto
Chapter 5 Bioactive Materials and Dental Pulp 115
Paulo Carvalho Tobias Duarte, Luciano Tavares Angelo Cintra, Carlos Roberto Emerenciano Bueno, Leopoldo Cosme-Silva,
João Eduardo Gomes-Filho, Elói Dezan-Júnior and Francine Benetti
Chapter 6 Systemic Alterations and Different Tissue
Renan Dal Fabbro, Leopoldo Cosme-Silva, Francine Benetti, Gustavo Sivieri de Araújo Letícia Citelli Conti, João Eduardo Gomes-Filho and Luciano Tavares Angelo Cintra
Chapter 7 Bioactive Glasses Composition and the Influence
on Remineralization and Biomineralization 165
Marina Trevelin Souza, Francine Benetti, Luciano Tavares Angelo Cintra
and Edgar Dutra Zanotto
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Trang 8Editor Contact Information 195
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Trang 10P REFACE
Bioactive materials, or biomaterials, have the ability to interact biologically with the tissue to which it is inserted, and to stimulate the deposition of mineralized tissue The calcium phosphate-based ceramics were the first known materials in dentistry to have bioactivity, and currently, these materials are the most used for biomedical purposes, with different morphological characteristics In dentistry, these materials have achieved immense importance by stimulating the deposition of osseous tissue in injured bone, and by having the ability to remineralize hard tooth tissues (enamel and dentin)
Furthermore, repair materials based on aggregated trioxides mineral or
on calcium hydroxide are classic biomaterials and widely used in dentistry, mainly in contact with the pulp tissue or periodontal ligament, for repair processes However, various formulations of these materials appear all the time, in search of the ideal material In general, bioactive materials have been shown to promote the release of calcium, sodium, silicon and phosphate ions, which are metabolized by the body, having effects such as angiogenesis and antimicrobial action, which can be improved depending
on the composition of the material Pulp tissue is a highly specialized dental tissue and is the subject of intense studies about the response to biomaterials It is also understood that some systemic alterations in
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Trang 11individuals have an influence on the action of bioactive materials during tissue repair processes
Thus, this book will address the use of different bioactive materials in dentistry, considering the performance of these biomaterials in the hard tissues of the tooth, and the response of the dental pulp, as well as the influence of the composition of these materials and of the individual’s systemic alterations in bioactivity and in antimicrobial activity The several
in vivo and in vitro tests to evaluate the bioactivity of a biomaterial will also be addressed
Chapter 1 - The teeth hard tissues are mineralized structures constituted by enamel and dentin, mainly formed by inorganic components, such as hydroxyapatite The mineralized structures cover and protect the pulp tissue, responsible for dentin formation, beside sensibility and immune response to injury The interaction between hard (dentin) and soft (pulp) tissues is known as dentin-pulp complex and when damaged, is the key to induce the formation of a dentin barrier (tertiary dentin) to protect the pulp However, this mineralized tissue may be affected by different demineralization processes, observed during cariogenic activity, intrinsic/extrinsic dental erosion or dental bleaching, leading to loss of mineral compounds and consequent cavitation The demineralization of dental hard tissue is counterbalanced by the constant physiological remineralization process induced by the saliva Nowadays, it’s common to enhance this dental remineralization with the aid of proper remineralizating materials, such as calcium/sodium fluoride-based (gels, varnishes and dentifrices) or bioactive materials (peptides, nano-hydroxyapatite, bioactive-glass and glass-ceramic) Although caries prevalence has been decreasing, is still present in all age groups worldwide, as the most common disease and main responsible for dental cavitation or dental loss Thus, this chapter discusses the main mechanism of the constant demineralization-remineralization balance, along with remineralizer agents and future perspectives of in dentistry
Chapter 2 - The dental scientific production aims to solve the needs and problems found in the clinical routine With the research and its results
it is possible to produce knowledge that directs the professional to the
Trang 12improvement and change of the quality of life of the individual Among the various challenges is the difficulty in forming and regenerating lost mineralized tissues that is present in the various areas of dentistry Therefore, it is necessary to carry out an extensive investigation regarding these tissues, since when they lose structures, they usually present physiological or functional deficiency It is known that biomineralization is
a complex, dynamic and permanent process that involves the precipitation
of inorganic substances in organic matrices to give rise to biological tissues, such as enamel, dentin, cement and bone The remineralization occurs when there is an increase in the mineral volume of the dental tissues, through the deposit, mainly, of crystals of calcium and phosphate, after a process of demineralization In the attempt to find solutions to these mineralizing deficiencies, the development and execution of different methodologies are essential in the search to unravel the metabolic process
of the tissues and, from this information, to create bioactive materials and clinical procedures that are capable of contributing to neoformation or mineralization of the tissue In this chapter the authors discussed different
laboratory methodologies developed in vivo, in vitro and/or in situ with the
purpose of directing the development of the research on the mineralization process
Chapter 3 - Biomaterials are conceptualized as natural or synthetic materials used in contact with biological systems with the purpose of repairing or replacing lost hard or soft tissue Ceramics are inorganic materials made by the heating of raw materials Thus, the term
“bioceramics” refers to biocompatible ceramic materials, preferential not only bio-inert, but with bioactive characteristics and the ability to stimulate repair on soft and hard tissues Bioinert ceramics, as alumina and zirconia, are used for prosthetic reasons, due to its elevated resistance Bioactive ceramics have a larger indication, classified according to its main component into calcium silicate cements (mineral trioxide aggregate), bioactive glass, calcium phosphates (hydroxyapatite, ß-tricalcium phosphates, biphasic phosphates) and silicate based sealers In dentistry, bioceramics are mainly used in periodontology and in implantodontology
as bone filling material, because its osteoinductivity ability More recently,
Trang 13bioceramics are being added to implant surfaces to enhance osteointegration Since bioceramic materials applications were introduced
in the endodontics field, its hydraulic characteristics allows a wide variety
of use, making this a choice material for bone defects, pulpotomy, retrograde filling, apexificaton, revascularization, root perforations and, more recently, as an obturating endodontic sealer This chapter discuss the main bioceramics used in dentistry, encompassing composition, properties, mechanism of action, applications and advantages, along with future perspectives
Chapter 4 - Bacteria are observed in the entire human body When colonizing or forming biofilm in the oral cavity, may lead to primary, persistent or recurrent infections, resulting in destruction of dental hard and soft tissues Since in health sciences, decreasing or eliminating bacterial levels is directly related to success, there has been a continuous effort to increase antimicrobial properties of biomaterials used for different purposes Antimicrobial activity refers to the process of killing or
inhibiting bacterial growth Thus, an antibacterial bioactive material has
the ability to kill bacteria or suppress growth or their ability to proliferate,
by stimulating the host living tissues to produce an unfavorable environment For over 100 years, antimicrobial properties referred to the ability to kill bacteria in a planktonic phase However, almost all bacteria live in biofilm, which is an orientated aggregation of microorganism enclosed in extracellular polymeric substance, increasing resistance 1,000
to 1,500 times in comparison to their resistance in planktonic phase This paradigm change led researches to improve bacteriology tests, incorporating the antibiofilm concept to the antimicrobial activity Since the understanding of the biofilm functioning, the improvement of bacterial tests has become paramount In dentistry, a wide range of dental materials used in cariology, endodontics, restorative dentistry and periodontology shows improved antibacterial ability, compared to earlier generations According to the literature, the key of antimicrobial effects of bioceramic dental materials is directly related to the biomineralization ability, induced
by calcium silicates/phosphates components Up to this date, literature shows that bioactive materials, such as MTA-based cements, have
Trang 14antibacterial and antifungal effect, due to their basic components However, despite the large number of reported satisfactory antimicrobial results, constant research is needed to continue improving the performance
of those materials in dental practice, and to assess the newly introduced materials, regarding their different compositions and consistencies This chapter discusses bacteria and biofilm characteristics along with the main antimicrobial activity mechanism of bioactive ceramics used in dental research
Chapter 5 - Conservative pulp therapies are therapeutic maneuvers that allow the conservation of tooth vitality, such as indirect pulp-capping, direct pulp-capping, and pulpotomy All these therapies aim essentially at maintaining pulp vitality and inducing formation of tertiary dentin However, preservation of the dental pulp depends on its condition, such if this is healthy, inflamed or necrotic Conservative therapies can be performed on tooth with reversible or irreversible pulpitis, but not in pulp with necrosis process These characteristics are clinically evaluated The bioactive materials for will be used in direct contact with dental pulp are basically calcium hydroxide and bioceramic materials, such as calcium silicate-base materials This chapter discusses the response of pulp tissue caused by these materials and shows a series of studies that evaluated this response, with the aim of guiding the clinician in the choice of materials for conservative treatments of vital tooth pulp
Chapter 6 - Bioactive materials are constantly indicated in several areas of dentistry in order to induce favorable responses and consequently
to modulate/restore the health of tissues that are altered by some pathology These materials come in direct contact with pulp tissue, bone tissue, cementum, and periodontal ligament However, the chemical composition
of bioactive materials can affect the tissue response and the repair process,
as well as compromise systemic health In this chapter, bioactive material types/indications, systemic changes in the two pathways, and different tissue responses to bioactive materials will be addressed
Chapter 7 - In the range of procedures preconized by the minimal intervention dentistry (MID) practice, enamel and dentine remineralization has been consolidated as an effective strategy to prevent caries and dental
Trang 15erosion A variety of remineralizing agents have been proposed and tested along the years, but one particular type is drawing significant attention, not
only in academia but also commercially, bioactive glasses (BGs) A vast
literature has shown that the use of BGs for remineralization, regardless of their formulation or application technique, can be more effective in enamel remineralization than other classical topical agents, such as fluoride and casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) Bioactive glasses are capable of continuously releasing calcium and phosphate ions into the local environment, leading to the precipitation of a hydroxyl carbonate apatite (HCA) layer, which provides long-term protection for the enamel and dentinal tubules These features make this biomaterial a very interesting alternative for treating dentine hypersensitivity (DH), and also for remineralization of white spot lesions
or after bleaching procedures Tailoring bioactive glass compositions by incorporating different ions to the original formula has been effective on granting positive outcomes regarding biomineralization This Chapter presents a concise update on bioactive glasses used for enamel remineralization and the influence of composition changes on their
biomineralization potential
Trang 16Chapter 1
R EMINERALIZING P ERFORMANCE
OF D IFFERENT M ATERIALS
ON T EETH H ARD T ISSUES
Marjorie de Oliveira Gallinari1, Luciano Tavares Angelo Cintra2, Carlos Roberto Emerenciano Bueno2,
André Luiz Fraga Briso1, Gustavo Sivieri de Araújo2,
Vanessa Abreu Sanches Marques2 and Francine Benetti2,*
1Department of Restorative Dentistry, São Paulo State University (Unesp), School of Dentistry,
Araçatuba, São Paulo, Brazil 2
Department of Endodontics, São Paulo State University (Unesp), School of Dentistry, Araçatuba, São Paulo, Brazil
Trang 17
ABSTRACT
The teeth hard tissues are mineralized structures constituted by enamel and dentin, mainly formed by inorganic components, such as hydroxyapatite The mineralized structures cover and protect the pulp tissue, responsible for dentin formation, beside sensibility and immune response to injury The interaction between hard (dentin) and soft (pulp) tissues is known as dentin-pulp complex and when damaged, is the key to induce the formation of a dentin barrier (tertiary dentin) to protect the pulp However, this mineralized tissue may be affected by different demineralization processes, observed during cariogenic activity, intrinsic/extrinsic dental erosion or dental bleaching, leading to loss of mineral compounds and consequent cavitation The demineralization of dental hard tissue is counterbalanced by the constant physiological remineralization process induced by the saliva Nowadays, it’s common
to enhance this dental remineralization with the aid of proper remineralizating materials, such as calcium/sodium fluoride-based (gels, varnishes and dentifrices) or bioactive materials (peptides, nano- hydroxyapatite, bioactive-glass and glass-ceramic) Although caries prevalence has been decreasing, is still present in all age groups worldwide, as the most common disease and main responsible for dental cavitation or dental loss Thus, this chapter discusses the main mechanism of the constant demineralization-remineralization balance, along with remineralizer agents and future perspectives of in dentistry
Keywords: bioactive materials, dentin, enamel, remineralization, teeth
hard tissues
1 MINERAL CONTENT OF DENTAL HARD TISSUE
Dental caries, also known as tooth decay, is one of the most prevalent chronic diseases, since windows of susceptibility are throughout a lifetime,
if oral hygiene or dentist appointments are not respected It has been associated as a main cause of oral pain and tooth loss (Fejerskov et al 2015) During caries process, cariogenic bacteria produce several organic acids, mainly lactate and acetate among others (Hojo et al 1991) which has the ability to dissolve dentin inorganic components, demineralizing and facilitating bacterial penetration deeper in dentin, to perpetuate the process
Trang 18(Michelich et al 1980) Caries disease starts from molecular changes in the dental apatite crystals, extending to a white-spot lesion (demineralized dentin) and leading to dentin cavitation On the other hand, saliva has been considered a major biological allied against dental cavitation by cariogenic acids, due to: its neutralizing and buffering ability on acids; formation of protective membrane on tooth surface (acquired pellicle) and; provide calcium, phosphate and fluoride to enamel and dentin surface, as a constant remineralization process (Hara & Zero 2014, Tung & Eichmiller 2004) Therefore, the cavitation progression requires a continuous imbalance between pathological (caries acid) and protective factors (saliva), resulting
in the dissolution of apatite crystals and loss of calcium, phosphate from the tooth, in a phenomenon known as demineralization It’s important to emphasize that this demineralization progression can be reversed in its early stages, but is often not self-limiting and without proper attention, its progress may lead to destruction of the dental element
The process of remineralization is characterized by the replacement of minerals that have been subtracted from the dental structure for some reason The dental hard tissues are composed by minerals, mainly by calcium and fluorine, and it is very common to undergo constant demineralization and remineralization When dental structure is dehydrated
by cariogenic acids, the teeth hard tissue absorbs liquids from the medium;
if fluoride is applied to a dehydrated tooth, a significant remineralization starts, returning the majority of the lost minerals during the demineralization phase
In this chapter, the composition of the dental hard tissues (enamel and dentin), the main demineralization causes and the different used materials
to re-mineralize dental elements is discussed
1.1 Dental Enamel
Dental enamel is considered the base of the entire dental structure, composed of 96% of inorganic material and only 4% of organic material, besides water (Alkattan et al 2018) More precisely, it shows 92-94% of
Trang 19hydroxyapatite, 2-3% of water, 2% of carbonate, traces of various elements (1% in total) such as sodium, magnesium, potassium, chlorine, zinc, less than 1% of lipids and also 0.01-0.05% of fluorine (Hicks et al 2003, 2004a, 2004b, Featherstone 2004) When fluoride (F) is present, these ions may substitute hydroxyl groups and decrease the apatite solubility, forming
a new mineral called fluoridated apatite (fluorapatite) (Dowker 2018) It differs from calcified tissues because it has epithelial origin (ectoderma) and also considered the only fully acellular after formation
The mechanism of enamel formation may be elucidated by combining
in vitro crystal growth research with the biological process, when analyzed
in vivo (Simmer et al 2012) To ensure in vitro formation of
hydroxyapatite crystals, it is necessary to achieve the supersaturation condition of a product ionic activity - calcium phosphate in one of its phases (Moreno & Margolis 1988) These crystals turn into a stable form
of hydroxyapatite (Colfen & Mann 2003, Margolis et al 2014)
Previous studies results regarding those crystals formation allowed researchers to create materials capable of reproducing these formation steps, which leads to the ability to form a structure similar to tooth enamel
or other mineralized tissues
1.2 Dentin
The dentin tissue is considered the largest tissue of the tooth, and its formation resembles in several aspects with the formation of bone tissue (Panseri et al 2016) The composition of dentin is slightly different from tooth enamel, consisting of a complex mixture of proteins and other molecules linked to the mineralized tissue (Butler & Ritchie 1995) In percentages, the dentin is composed by approximately 70% of hydroxyapatite crystals (inorganic compounds), 18% by organic tissue and water
Trang 20In addition, dentin is also considered a specialized, avascular, mineralized connective tissue that forms the major part of the tooth, supporting and balancing the vulnerability that dental enamel shows The dentin has two types of portions: one consistes as the coronary portion, and the other in the root portion The dentin limits the pulp cavity (pulp chamber and root canal), where the dental pulp is located The dental pulp
is a living tissue, formed by outer layer of specialized cells named odontoblasts, just below the dentin tissue The odontoblasts has cellular extensions that remain inside the dentin tubules, responsible for most of the environment sensibility, as temperature, differences in pH and damage to the tooth surface The intimate relationship between dentin and the dental pulp, along with its biological interactions, forms an association known as dentin-pulp complex
The dentin-pulp complex is dynamic functional structure, indispensable for immune defense of pulp, tissue repair and regeneration response to trauma or infection, by depositing hard tissue to act as a barrier between the pulp and the etiological agent This protective barrier is deposited by odontoblasts cells, by synthesizing organic dentin matrix as the dentinogenesis process advance (Pashley 1996, Kim 2017)
2 DEMINERALIZING PHENOMENON IN DENTISTRY
2.1 Dental Caries
Dental caries are considered a multifactorial disease, encompassing factors such as: host susceptibility (Alkattan et al 2018); acid production
by cariogenic bacteria that metabolizes sugars and carbohydrates ingested
by the host (Featherstone 2004); sugar-rich diet favoring bacterial activity (Hicks et al 2003) exposure time (Hicks et al 2004a), among others factors (Cummins 2013, Oliveira et al 2014)
Trang 21These bacterial organic acids resulted from the fermentation of carbohydrates, might induce changes in the biofilm, capable of forming the cariogenic bacterial dental plaque As previously mentioned, exposure time is also a determinant factor in the severity of the disease Besides, it’s important to considerate behavioral factors, as educational, cultural and socioeconomic status of the population with caries disease (Fejerskov
2004, Costa et al 2012, Cummins 2013, Al-Meedani & Al-Dlaigan 2016), since it shows high prevalence, considered as a public health problem (Cochrane et al 2010)
A recent global epidemiology review of caries prevalence in different ages groups showed that dental caries is the most common disease worldwide and although the prevalence has decreased, the disease is still observed in all age groups (Frencken et al 2017) The elevated rate of patients with chronic caries disease is due in part to the incorporation of sugars into the daily diet, commonly observed in industrialized countries, associated with poor/infrequent oral hygiene Dental caries may progress to advanced stages, causing pain and reducing the quality of life, with consequent malnutrition due to the impossibility of eat properly This disease can also impair the facial aesthetic, compromising the smile and causing emotional disturbance by affecting the patient’s self-confidence and self-esteem (Cummins 2013)
Caries lesion is observed in early stages as sub-superficially demineralized zones, in the tooth enamel, known as “white spot” (Arends
& Christoffersen 1986 Cummins 2013) Initially, this demineralization is reversible When the bacterial acid is removed from the dental surface, the saliva begins the remineralization process, due to its saturation with calcium and phosphate ions, promoting an ion exchange for the demineralized area and repairing the damaged dental structure, mainly composed by hydroxyapatite (Cummins 2013)
Evidences of a cariogenic process ranges from microscopic molecular change in apatite crystals to a visible white spot lesion and eventual deeper cavitation involving dentin Thus, this progression results from a process of disequilibrium between pathological and protective factors, leading to the
Trang 22dissolution of the hydroxyapatite crystals by loss of calcium, phosphate and other ions observed in the dental structure (Cochrane et al 2010)
2.2 Dental Erosion
In addition to caries disease, which is daily observed in clinical practice, it is possible to notice that the diet of the population has also contributed significantly to the dental erosion This clinical condition is characterized by an enamel exposure to acidic substances, specifically on the outer layer of the teeth This erosion process is characterized by chemical action that does not involve bacteria, and is as result of extrinsic
or intrinsic source of acid exposure Extrinsic erosion is induced by diet (Salas et al 2015) decreasing oral pH to critical levels, with the ingestion
of citric or acid food Intrinsic erosion is associated with eating disorders (nervous bulimia), or stomach acids due to gastroesophageal reflux (Ali et
al 2002) The constant presence of acids and critical pH in oral cavity cause progressive and irreversible loss of dental mineral structure (Lazarchik & Frazier 2009 de Souza 2018)
The difference between the two conditions mentioned so far is that, in the caries scenario, exposure to organic acids triggers the formation of a subsurface lesion by loss of 50% of mineral, but the outer layer of the enamel is still intact, which allows its remineralization Dental erosion occurs due to exposure to acids of pH lower than resulting in the destruction of enamel in layers, explaining the fact that in erosion, no remineralization is expected (Mangueira et al 2011)
Lazarchik & Filler (1997) stated that chronic exposure to gastric acid has several causes and can result in lesions on hard and soft tissues of the oral cavity, without, however, presenting pathognomonic lesions They also stated that dental erosion may be considered the main oral manifestation of gastroesophageal reflux However, its diagnosis is difficult, since non-carious lesions have a multifactorial etiology and factors such as saliva quality may interfere with the process
Trang 232.3 Dental Bleaching
Dental bleaching is achieved with the use of oxidative products (Benetti et al 2018a, 2018b), often with acidic pH (Benetti et al 2018c) Studies have shown that these bleaching materials can cause loss of calcium and phosphorus in different degrees (Borges et al 2012, Heshmat
et al 2014) The amount of mineral loss may be related to the concentration and acidity of bleaching agents This acidity can be associated with two components of bleaching gels: carbopol, which is a polyacrylic acid that confers viscosity to the product, enhancing manipulation and citric/phosphoric acids (Schwarz & Levy 1958)
The active component of the bleaching gel is hydrogen peroxide, which acts by releasing reactive oxygen species (ROS) (Cintra et al 2013, 2016a, 2016b) When enamel is touched by ROS and acidic components, hydrogen ions rapidly dissolve the mineral portion of the dental structures, resulting in the loss of calcium and phosphorus ions, culminating in a reduction hydroxyapatite crystals proportion (Gomes et al 2018) Another compound that may be lost during the dissolution process is the carbonate, promoting the formation of spaces (voids) that bind and destroy the delicate protein structure that surround the crystals (Featherstone et al 1979)
In addition, changes similar to erosion have been observed in the enamel after bleaching (Pinheiro & Cardoso 2011), especially when low
pH and highly concentrated peroxides are used (Borges et al 2010) The reduction in microhardness may be associated with a greater susceptibility
to erosive loss, since loss of surface hardness is the first step of erosion Thus, it can be assumed that bleaching agents could contribute to the further development of erosion, particularly in high-risk individuals, since after each daily bleaching procedure, teeth will almost certainly be exposed
to demineralizing factors, as the ingestion of acidic food (Ren et al 2009) Although the at-home dental bleaching involves the use of low-concentration gels, it is performed for longer periods and may represent an additional risk factor for the development and progression of enamel erosion Potentially additive deleterious effects of bleaching and acid
Trang 24exposure to enamel have been reported, with different results observed according to the concentration of hydrogen peroxide, study protocol (Abouassi et al 2011, Benetti et al 2018d), as well as the acid exposure regime (Ren et al 2009)
3 REMINERALIZING AGENTS
3.1 Calcium/Sodium Fluoride-Based Remineralizing Agents
There are several fluoride-based products that help in the remineralization of tooth structure, such as gels, varnishes and dentifrices The fluoride gel was developed with the aim of maintaining fluoride in intimate contact with tooth reactive surface for a prolonged time It’s commercially available for use in a proper tray or brush and should remain
in contact with the dental surfaces for at least 1 minute Then, the patient is normally recommended to remain for at least 30 minutes without food, liquid or mouthwash
The acidulated phosphate fluoride (APF) developed by Brudevold et
al (1963) contains 1.23% of sodium fluoride (NaF) added to 0.1 M buffered phosphoric acid at a pH between 3 and 4, based on the observation that the enamel has increased acquisition of calcium fluoride (CaF2) by the use of acidified solutions, than neutral solutions (Brudevold
et al 1963) The 2% sodium fluoride (neutral), initially proposed by Bibby (1945) and Knutson & Amstrong (1946), is effective as any other method
of topic fluoride application, showing advantages such as chemical stability, acceptable taste, low cost, simplicity in technique, without causing staining on teeth and restorations
Fluoride varnish was developed by Schmidt in 1966 with the purpose
of prolonging the contact between enamel and fluoride ions, by increasing fluorapatite formation on the adamantine surface (Schmidt 1966) This was later marketed under the name Duraphat®, containing 5% sodium fluoride (equivalent to 2.26% fluorine) in a natural colony base, presented as a viscous yellowish material which, upon taking prey, becomes a yellow-
Trang 25brown covering over the tooth Fluorniz® and Duraflur® are broadly used
as Duraphat®-like varnishes with similar clinical efficacy
3.2 Bioactive Materials
Bioactive materials (see chapter 3) enable interactions with surrounding tissues, stimulating the host response, triggering a series of physiological event that culminate in an enhanced tissue response (Best et
al 2008) Since the introduction of bioactive materials in dentistry, the scientific community has focused in the development of bioactive materials to be used as remineralizing agents and consequently desensitizers, such as the Amorphous Calcium Phosphate (ACP) (Schiavoni et al 2006), Casein-Phosphopeptite and Amorphous-Calcium-Phosphate (CPP-ACP) (Jiang et al 2007), nano-hydroxyapatite (Haghgoo
et al 2016), bioglasses and glass-ceramics (Bakhsh et al 2017, Chinelatti
et al 2017)
The bioactive materials aim to promote the remineralization of dental structure, based on the formation of a layer of ACP on the surface where the product is applied and subsequent incorporation of hydroxyl, carbonate and fluoride ions from the oral medium, initiating the crystallization of this superficial layer in the form of apatite (Schiavoni et al 2006)
3.2.1 Peptides
Most of the specific peptides currently investigated have been developed based on results regarding the protective action of salivary proteins, including peptides derived from statin
Based on this assumption, the study of ACP shows a production of a thin layer of hydroxyapatite when applied topically This is a surface phenomenon, fundamentally different from the remineralization of subsurface lesions and enamel, which require the actual penetration of ions into the enamel (Walsh 2009) The casein-phosphopeptide (CPP) present in milk stabilizes the calcium and phosphate ions by forming complexes that are more easily absorbed by the intestine The same concept was applied to
Trang 26the CPP-ACP complex The bioavailable complexes of calcium and phosphate are created in the form suitable for optimal remineralization of subsurface lesions in the enamel, not restricted to the surface CPP also locates the ACP in the dental plaque biofilm (Cross et al 2007) The high gradient resulting from the concentration of calcium and phosphate ions leads the ions to the lesions below the surface and reaches high rates of remineralization (Reynolds 1997)
The concept of CPP-ACP as a remineralizing agent was first postulated in 1998 They are nanocomplex compounds derived from bovine milk protein, casein, calcium and phosphate Subsequent laboratory studies have demonstrated that CPP-ACP has anticariogenic activity in animal and human experiments Modern studies on progression require the measurement of small changes in the mineral content of the enamel, especially in isolated carious lesion (Zhou et al 2014)
The study conducted by Beerens et al (2010) compared in vivo the
effects of CPP-ACP denture versus control dentifrice on the remineralization of bleached enamel blemishes lesions and plaque composition and did not observe advantages in the use of CPP-ACP dentifrice to supplement normal oral hygiene during 12 weeks In this context, others studies have shown that the application of CPP-ACP-containing pastes, such as Minimal Invasive (MI) Paste Plus, after bleaching procedure was able to increase the enamel hardness of bleached teeth (Bayrak et al 2009)
3.2.2 Nano-Hydroxyapatite
Nano-hydroxyapatite (nanoHAp) is considered one of the most biocompatible bioactive materials The hydroxyapatite nanoparticles are similar to the HA crystals present in the dental enamel in both morphological and crystal structure When this nanoHAp is used for remineralization and treatment of fluoride-associated dentin hypersensitivity, it penetrates more easily into enamel micro titration, providing a high quality seal, restoring the microstructure and surface composition of the tooth (Huang et al 2009)
Trang 27Browning et al (2011) in a randomized clinical trial evaluated a nanoHAp-based paste to determine its efficacy in reducing sensitivity after bleaching treatment Forty-two patients were randomly divided into two groups, in which a paste containing nano-HAp was used and the other was
a placebo paste For bleaching, 7% hydrogen peroxide bleaching gel was used twice daily for 14 days After the use of the bleaching gel, patients were instructed to apply the paste assigned to them for 5 minutes By the end of the experiment, authors found that 51% of participants in the placebo group reported sensitivity, while only 29% of the experimental group had the same complain The authors concluded that the nanohydroxyapatite paste decreased sensitivity when compared to the placebo
3.2.3 Bioactive Glass and Glass-Ceramics
The mechanism of bioceramics occurs through the stabilization of the lost ions calcium (Ca2+) and phosphate (PO43-) Considered remineralizing agents, those ceramics strengthen the mineralized structures of the tooth, minimizing the damages caused by several clinical conditions that cause loss of minerals of the dental structure
Recent studies have shown that the remineralizing function of these materials is due to their remarkable osteoconductivity and osteoinductivity (Andersson & Kangasniemi 1991) It has been proven that this product has the ability to restore the amount of calcium and phosphate on the surface of enamel and dentin through the precipitation of apatite, enabling the remineralization lost during the bleaching treatment (Gjorgievska & Nicholson 2011) In addition, it has been reported that the product may contribute to the obliteration of exposed dentinal tubules (Vollenweider et
al 2007, Curtis et al 2010), which may influence the movement of the dentin fluid and, consequently, the tooth sensitivity
Based in recent advances on bioceramics showing optimum mineralization potential, a multidisciplinary research group from the Federal University of São Carlos (UFSCar, São Carlos, São Paulo, Brazil)
in the Laboratory of Vitreous Materials, developed a bioactive ceramic, named Biosilicate® (Tirapelli et al 2010, 2011) This novel
Trang 28glass-material has shown satisfactory a promising results, as an option for dentin hypersensitivity treatment, capable to minimize the dental sensitivity observed after bleaching procedure, which is one of the dental procedures that leads to loss of minerals (Tirapelli et al 2010, 2011, Pintado-Palomino
et al 2015)
Currently, there are several formulations of bioactive glass, but in dentistry, the Bioglass 45S5 formulation is preferred The formulation name refers to its composition, which means that, this bioactive glass is formed by 45% SiO2 and 5 Ca/P ratio per molar (approximately 24.5% CaO and 6% P2O5) (Tirapelli et al 2010, 2011, Deng et al 2013) Normally, the composition of the glass is 70% SiO2 (silicon dioxide), 15%
Na2O (sodium oxide), 10% CaO (calcium oxide) and 5% MgO (magnesium oxide) (Clark 1986) Therefore, bioactive glass shows reduced amount of SiO2, increasing the glass solubility and providing a larger number of active ions Moreover, the concentration of CaO was increased and P2O5 (phosphorus pentoxide) was added as a new element for the development of the apatite layer on the glass surface (Hench & Paschall
1973, Clark 1986)
CONCLUSION
The dentistry community has increasingly sought to meet patients’ expectations and also, professionals who seek to offer the best treatment Due to this, the researches have worked ceaselessly in the creation of products that could decrease the demineralization process, observed in the daily life of patients The goal is to develop a biologically acceptable product capable of restoring teeth that for some reason have lost their ions This decrease in ions alters the chemical structure of the tooth, which can often cause side effects like sensitivity
The evolution of these materials is already being invested, creating ever more effective and biologically accepted materials that have the ability to reset lost ions, as well as their chemical structure
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Trang 36Chapter 2
C URRENT M ETHODOLOGIES
FOR E VALUATING R EMINERALIZATION AND B IOMINERALIZATION IN D ENTISTRY
Leticia Citelli Conti1, Vanessa Abreu Sanches Marques1,
Luciano Tavares Angelo Cintra1, Rogério de Castilho Jacinto1, Marjorie de Oliveira Gallinari2, Marina Trevelin Souza3
and Francine Benetti1,*
Trang 37is a complex, dynamic and permanent process that involves the precipitation of inorganic substances in organic matrices to give rise to biological tissues, such as enamel, dentin, cement and bone The remineralization occurs when there is an increase in the mineral volume
of the dental tissues, through the deposit, mainly, of crystals of calcium and phosphate, after a process of demineralization In the attempt to find solutions to these mineralizing deficiencies, the development and execution of different methodologies are essential in the search to unravel the metabolic process of the tissues and, from this information, to create bioactive materials and clinical procedures that are capable of contributing to neoformation or mineralization of the tissue In this
chapter we discussed different laboratory methodologies developed in vivo, in vitro and/or in situ with the purpose of directing the development
of the research on the mineralization process
Keywords: biomineralization, dentistry, methodology, tooth remineralization
1 INTRODUCTION
The biomineralization process is complex, dynamic and permanent in which living beings control the precipitation of inorganic substances in organic matrices to give rise to biological tissues, such as enamel, dentin, cement and bone Knowledge of the mineral deposition process is important for treatments of diseases involving mineralization to be discovered and also for the innovation and development of materials that
Trang 38aid in this physiological mineralizing dynamics (Abou Neel et al 2016) In addition, these hard tissues have different regenerative capacity
Enamel, dentin, cement and bone are mineralized tissues of the oral cavity that have different proportions of organic and inorganic compounds (Gelse et al 2003) This difference in constitution results in specific properties for each tissue type, for example, the high amount of inorganic components found in the enamel provides the greatest strength resistance when compared to any other hard tissue present in the human body Unlike dentine because it contains a high rate of organic content, it is more resilient when compared to cementum and dental enamel (Abou Neel et al 2016)
The demineralization process occurs due to an imbalance between this phenomenon and remineralization, which leads to the dissolution of the mineral content of dental tissues Thus, remineralization occurs when there
is an increase in mineral volume, mainly deposition of calcium and phosphate crystals (Heilman et al 1997), either daily, by salivary flow, or
by the application of remineralizing agents and products that capable of inducing this process Saliva is considered one of the most important biological factors in the determination of intraoral neutralizing effects In addition to its antibacterial and cleansing action, it acts as a constant source
of calcium and phosphate that helps maintain supersaturation relative to tooth minerals, inhibits dental demineralization during periods of low pH and promotes remineralization when pH returns to the state neutral (Abou Neel et al 2016) On the other hand, remineralizing agents are available in various forms, such as restorative materials, fissure sealants, mouthwashes and dentifrices, endodontic cements, in addition to fluoride which is considered the main remineralizing agent for caries lesions, for example (Malekafzal et al 2015, Vyavhare et al 2015) However, frequently in dental specialties, several alternative materials are proposed to act in the biomineralization of tissues, either for enamel and dentin remineralization, apical sealing through a hard tissue barrier, bone neoformation or replacement of a previously lost tissue, or all, with the aim of restoring the patient’s function, aesthetics and oral health (Benetti & Cintra 2016)
Trang 39In this sense, the scientific research is carried out with the intention of investigating possible dental procedures and dental materials that are capable of inducing biomineralization or remineralization Such physiological events are aimed at recovering damaged dental structures, mineralizing a tissue, or even replacing a non-mineralized tissue with a mineralized one In addition, the studies are necessary to guarantee the reliability of these products, since later, they will have clinical application
The objective of this chapter is to describe in vivo and in vitro
laboratory methods currently used to investigate the mineralization process and, based on reliable scientific results, to enable the development of biomineralization and remineralization of hard tissues Knowledge of the methods will provide a broad overview of the scientific methodologies currently carried out on this subject so that researchers are able to develop and contribute to science according to their research needs
2. IN VIVO METHODOLOGIES
The use of methodologies in scientific experiments on animals is extremely important, as they enable results that are increasingly similar to the reality found in humans (Estrela 2018)
The use of different species, such as rats, mice, dogs and rabbits, are used to evaluate the biological response of dental materials, such as root canal sealer (Cintra et al 2017a), repair materials (Cintra et al 2017, Benetti et al 2018a), bone grafts (Zhang et al 2017), membranes collagen (Yang et al 2015) and fluoride compounds (Queiroz et al 2008) Depending on the objective of the biological investigation, the materials can be tested in defects created in dental alveoli (Rodrigues et al 2016), subcutaneous connective tissue (Cintra et al 2017, 2017a, Benetti et al 2018a), long bones (Bernabé et al 2011) and skull caps (Nagata et al 2010)
Polyethylene tubes filled with materials and implanted in rat subcutaneous tissue is a method widely used in preclinical studies to biologically test the reactions of connective tissue to materials and their
Trang 40biomineralizing capacity This methodology allows removal of the tissue adjacent to the tube, which after laboratory processing, provides histological sections that can be evaluated by means of histological analysis techniques (Cintra et al 2017, Benetti et al 2018a, Bueno et al 2018) Bueno et al (2018) demonstrate in their study a representative scheme of tissue analysis using polyethylene tubes in rat subcutaneous tissue
Staining techniques can be used in the histological sections for different evaluations according to the purpose of the study, since they allow observing the reactions generated in the tissue by the experimental material which was directly in contact at the opening of the tube The most commonly used staining for histological sections is hematoxylin and eosin, which allows the evaluation of inflammatory infiltrate, presence or absence
of fibrous capsule and necrosis (Cintra et al 2017) On the other hand, the sections stained according to the von Kossa technique allow the observation of mineralized tissue structures, which are visualized in black
on histological images (Holland et al 1999a) The non-staining of the histological section allows analyzing under polarized light the presente of birefringent structures related to calcium carbonate crystals resulting from the interaction of the material with the tissue (Gomes-Filho et al 2016) Masson’s trichome is widely used to evaluate collagen and deposition of bone and dentin matrix (Estrela 2018)
Specific staining such as immunofluorescence and histochemistry allow cellular components to be evaluated according to the selection of specific markers to detect cellular components present in the tissue under evaluation; Real Time Polymerase Chain Reaction (PCR) methods can also be used for this purpose, but its mechanism is to multiply nucleic acids and quantify the DNA obtained, where the initial genetic material is RNA, which is transcribed into its DNA complement by reverse transcriptase Taking into account the interest in evaluating the biomineralization or neoformation of bone tissues, analysis of mineralization markers are indicated, such as the constituents proteins of the organic matrix of mineralized tissues or those present during