Dental pulp capping nanocomposites

Dental pulp capping nanocomposites

4

Priyanka Rani⁎, Dilipkumar Pal†, Mohammad Niyaz Hoda‡, Tahseen Jahan Ara§, Sarwar Beg¶, M. Saquib Hasnain‖, Amit Kumar Nayak# ⁎ Department of Chemistry, IFTM University, Moradabad, India, †Department of Pharmaceutical Sciences, Guru Ghasidas Vishwavidyalaya, Bilashpur, India, ‡Department of Pharmacy, Hamdard University, New Delhi, India, §Department of Chemistry, L.N.M. University, Darbhanga, India, ¶Jubilant Generics Limited (Formerly Jubilant Life Sciences Division), Noida, India, ‖Department of Pharmacy, Shri Venkateshwara University, Gajraula, India, #Department of Pharmaceutics, Seemanta Institute of Pharmaceutical Sciences, Mayurbhanj, India

4.1 Introduction With the progress of nanotechnology, extensive research has been done on designing and developing newer nanobiomaterials, such as nanoparticles, nanocapsules, nanovesicles, nanoceramics, nanocomposites, nanofibers, nanocoatings, nanotubes, nanorods, and so forth, for various biomedical applications [1–8]. Among these newer nanobiomaterials, nanocomposites are comprised of multiple nanoscale materials, or a nanoscale material incorporated into a bulk material [9, 10]. Numerous composites and nanocomposites of diverse types have already been synthesized and evaluated for applications in diverse biomedical sectors such as orthopedics, dentistry, drug delivery, tissue engineering, cardiac prosthesis, biosensors, and so forth [7, 11–20]. With the steady expansion of nanodentistry, a variety of dental nanocomposites are being developed and investigated for dentin-pulp regeneration, dental restoration, enamel substitution, periodontal ligament regeneration, periodontal drug delivery, and so forth [21–24]. The purpose of direct and/or indirect pulp capping is the care and treatment of exposed crucial pulp by the use of capping material for ease of reparative dentin formation and to maintain the exposed pulp [25]. Calcium hydroxide [Ca(OH)2]-based cements such as Dycal and mineral trioxide aggregate (MTA) are frequently-used pulp-capping materials in clinics [26]. Additionally, adhesive resin-based composites have been reviewed as an efficient pulp capping substance [27]. While formerly there were no sufficient treatments for uncovered pulp, these new solutions offer the possibility of recovery and hope. The development of diverse pulp capping composites has significantly improved the epoch of vital-pulp treatment. In recent years, a variety of pulp capping nanocomposites for fortification of multifaceted vital dentin pulp has been investigated [28]. Further, caries, mechanical sources, and trauma are the three core causes of vital pulp exposure. Pulp disclosure prior to entirely removed caries is termed “caries exposure,” while disclosure during the generation of a cavity lacking Applications of Nanocomposite Materials in Dentistry. https://doi.org/10.1016/B978-0-12-813742-0.00004-3 © 2019 Elsevier Inc. All rights reserved.

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Applications of Nanocomposite Materials in Dentistry

caries is known as “mechanical exposure.” Mechanical exposure is typically due to problems occurring during tooth preparation. For example, a sports injury that causes a chipped coronal part of the tooth could result in traumatic pulp disclosure. There is a broad spectrum of treatment choices for disclosed vital pulp, for example, direct and/ or indirect pulp-capping, pulpectomy, or pulpotomy [25, 29]. The patient’s physical condition and symptoms should be evaluated before dressing of any direct pulp capping material. The most significant test is pulp vitality for evaluation of clinical pulp conditions. A negative result from the pulp vitality test indicates pulp necrosis, and a positive pulp vitality test indicates vital pulp [25]. This chapter presents a comprehensive review on the use of nanocomposites in dental pulp capping.

4.2 Dental pulp capping Usually, vital pulp can easily be categorized into three different types on the basis of the clinical manifestation: normal or standard pulp, reversible pulpitis, and steady or irreversible pulpitis [30]. Normal pulp has no clinical symptoms [31]. Reversible pulpitis generally has a short-termed thermal sensitivity, which potentially will vanish instantly after the elimination of thermal stimulation. Irreversible pulpitis causes pain [32]. A pulp-capping treatment can be applied on a tooth with reversible pulpitis or normal pulp [30, 33]. It is used in dental restorations for preventing necrosis after exposure during cavity generation. The removal of dental caries from a tooth leads to removal of all, or the largest part, of the softened/contaminated enamel and dentin are detached, which may leave the tooth pulp either nearly, or completely, uncovered, which results in pulpitis (secondary development of caries). Pulpitis, sequentially, can become permanent, which leads chiefly to toothache and pulp necrosis, which requires either a root canal technique or extraction for treatment [25]. The final target of stepwise caries elimination, or pulp capping, is to avoid the requirement of a root canal treatment, and fortification of a healthy dental pulp. The dentist can set a small quantity of a sedative covering, such as, Ca(OH)2, its cement, or MTA in order to arrest the decline of pulp, along with starting a dental revamp close to the pulp. These substances shield the pulp from destructive agents such as heat, cold, trauma, and microbes, and trigger the cellrich pulp zone to lay down a viaduct for renovation of dentin. Usually, it takes approximately a minimum of 30 days to initiate dentin formation, starting from pulp capping (there is also a possibility of delay in the outset of dentin genesis in the case of injured pulp odontoblast, a type of cell), and a maximum of 130 days to terminate [34].

4.3 Types of pulp cap 4.3.1 Direct pulp cap A single-stage technique of direct pulp cap includes placement of protective dressing directly over an uncovered pulp. The technique is used for disclosed vital pulp, including the dressing of a pulp capping composite over the bare vicinity to smooth out the

Dental pulp capping nanocomposites67

progress of both the enrichment of protective barrier [35–37], and the continuance of imperative pulp [38, 39]. This technique is used in the case of slightly unclad pulp, either through unintentional caries removal, or by caries extending to the pulp pocket. It is only probable whenever pulpal exposure takes place throughout uninfected dentin and there is a lack of topical history of impulsive pain and/or lasting pulpitis, and an antibacterial seal can be executed. The exposure of paramount pulp is followed by the isolation of the tooth from saliva to intercept contamination by using a dental dam in case if it was not previously placed. Now, the tooth is washed, dried, and followed finally by the placement of a preventive matter for dental revamp, which provides a compact seal to hinder bacterial infection. Although pulp capping is mostly successful to maintain the vivacity of the pulp, dental surgeons will typically maintain the condition of the tooth under regular examination for about 6 months after the treatment.

4.3.2 Indirect pulp cap Indirect pulp cap, or, in other words, gradual caries removal, is a 2-stage method over about 6 months including placement of protective dressing on the apex in a fine film of softened dentin that can replace the pulp. The utilization of this technique takes place in the case of removal of the majority of a tooth because of decay from a profound cavity. However, some decay and softened dentin ruins the pulp cavity, which, if removed, can result in permanent pulpitis. Usually, dental surgeons prefer to leave the softened dentin decay in position and use a deposit of temporary shielding material in order to promote repeated mineralization of the pulpy dentin throughout the tooth. This temporary shielding establishes the material in place. After a period of half a year, the cavity is reopened, and usually there is enough dentin bridge or sound dentin throughout the pulp that any surplus of softened dentin can be detached, and a durable filling can be established. The pulp capping materials necessarily contain some basic properties, which are represented in Fig. 4.1.

Sterile Release fluoride Radiopaque

Maintain pulpal vitality Properties of capping materials

Adhere to dentin

Adhere to restorative material Provide bacterial seal Bactericidal or bacteriostatic Resist forces during restoration placement

Fig. 4.1  Basic properties of pulp capping materials.

Stimulate reparative dentin formation

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Functional, biologically active substances are accessible as possible scaffolds and self-possessed natural or artificial polymers, and can be categorized in three groups: (1) naturally occurring organic material such as collagen, (2) synthetic organic matter such as polylactic acid (PLA), alginate, or polyglycolic acid (PGA), along with their copolymers, and (3) inorganic matter, such as different compositions of hydroxyapatite (HA), calcium phosphate, and tricalcium phosphate (TCP), along with compositions of silicate, bioglasses, and phosphate (PO4) glasses.

4.4 Composites: An insight A composite material, also known as composition material, is a material synthesized by the treatment of two or more constituent materials having particularly diverse chemical and physical characteristics that, after combination, result in the formation of a material with properties different from the discrete components [9, 40]. Direct composite restorations for posterior teeth have achieved more recognition during the past few years, and are presently thought of as the foremost choice of treatment [21]. Now, indirect restorations can also use composite materials in accordance with their ability to persevere teeth in the face of occlusal loads, and for use in adhesive cementations. The composite materials for pulp capping are comprised of three constituents [21, 41]: a resin matrix (organic part), fillers (inorganic constituent), and various coupling materials. The classification of various composites used in dentistry on the basis of matrix components is presented in Table 4.1. Strong chemical bonding with the tooth structure, and their esthetic properties, are the two major reasons that the resin-based composite materials are well-known dental restorative materials [41]. These self-possessed resin matrices often contain bis-GMA (bisphenol A glycol dimethacrylate), inorganic glass fillers, and silane as coupling agents. The resin phase of composite materials is made of organic monomers, such as triethylene glycol dimethacrylate (TEGDMA), pyromellitic glycerol dimethacrylate (PMGDMA), urethane dimethacrylate (UDMA), bisphenol A-glycidyl ­methacrylate

Table 4.1  Classification of various composites used in dentistry on the basis of matrix components Matrix

Chemical system

Group

Examples

Conventional matrix

Pure methacrylate

Inorganic matrix

Inorganic polycondensate Polar groups

Hybrid composite Nanocomposite Ormocers Compomers

Tetric EvoCeram Filtek supreme XT Admira Definite Dyract eXtra

Siloranes

Filtek Silorane

Acid modified methacrylate Ring opening epoxide

Cationic polymerization

Dental pulp capping nanocomposites69

(Bis-GMA), its ethoxylated version (BisEMA), and 2-hydroxyethyl methacrylate (HEMA) [41]. Moreover, these materials can be classified into four different groups on the basis of the matrix nature: (1) methacrylates, (2) ormocers, (3) compomers, and (4) silorane-based.

4.4.1 Methacrylates The most well-known materials in the dental composite material group are the methacrylates hybrid composites [42]. The composition of methacrylates (MA) and different varieties of fillers, coupled with silane (SinH2n + 2), are used in dentistry. The fillers are composed of quartz, silica, ceramics, and other oxides. The enhanced filler content results in polymerization shrinkage and water absorption, while the linear expansion coefficient is minimized [43]. These composition materials contain dissimilar filler particles, for example, agglomerated nanoclusters (prepolymerized and finely milled); glass or silica particles (larger, submicron-sized), and individual nanoranged particles. Examples of these materials include Filtek supreme XTE and Filtek Z250 XT (3 M ESPE; St. Paul, Minnesota) IPS Empress Direct and Tetric Evo Ceram (Ivoclar Vivadent; Amherst, New York) Enamel Plus HRi (Micerium; Avegno (GE), Italy Miris 2 and Synergy D6 (Coltene/Whaledent; Cuyahoga Falls, Ohio) Herculite Ultra and Premise (Kerr; Orange, California)

4.4.2 Ormocers Basically there are three constituents of ormocers: organic and inorganic fragments, and the polysiloxanes. A change in a fraction of these components may alter the optical, mechanical, and thermal attributes of the matter. (i) The organic polymers are responsible for polarity, the capacity to cross link, hardness, and optical attributes. (ii) The glass and ceramic constituents (inorganic components) influence chemical stabilities and thermal expansion. (iii) The polysiloxanes direct the interface characteristics, elasticity, and processing.

4.4.3 Compomers The compomers category includes the chemical composition of composites and glass ionomers. This material is an amended composite of polyacrylic-/polycarboxylic acid. The point of compomers is to combine the beneficial properties of glass ionomers by using composite technology. However, this objective has been only moderately achieved, owing to low fluoride release. Compomers are widely acceptable for revamp in the ephemeral dentition because of their opposition to moderate abrasion [44, 45]. In cervical restorations, compomer restorations behave more positively, as compared with resin-modified glass ionomers, but slightly more negatively than hybrid composites [46].

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4.4.4 Silorane Silorane-based composites originate from siloxanes and oxirans. A spectrum of properties, such as less marginal discoloration, lower shrinkage, and longer resistance to fading is the main attraction of this product category. There is a sharp difference between silorane monomer rings and chain-monomers of hybrid and fused composites. The siloxanes are accountable for increased hydrophobicity of the material, such as reduced water absorption and exogenous discoloration. The oxirane nucleus influences the physical properties, along with low polymerization shrinkage (<1% shrinkage), as compared with other composites (>1.5% shrinkage), which offer low microleakage and better marginal integrity. Siloranes are polymerized by a critical mass of cations, followed by the cationic reaction, which is responsible for the highest ambient light stability, in contrast to methaycrylates and crosslink via radicals. The photo initiating system is placed on three constituents: a light absorbing camphor nucleus (camphorquinone), an electron donor group (such as, amine), and an iodonium salt. The camphor component is activated, and proceeds with the electron rich fragment, which decomposes the iodonium salt, and hence an acidic cation is formed during the mechanism. Now, the process of oxirane ring opening initiates in the course of the polymerization process, and this opening compensates for the polymerization progression of contraction. The fillers present in Filtek Silorane, the only example of silorane accessible at the moment, consist of radiopaque yttrium fluoride and 0.1–2.0 μm ranged quartz (silica) particles [47]. The siloranes’ low shrinkage promotes a reduced contraction stress [48–50]. The silorane-based filling material was found to possess properties of minimum water absorption and reduced water solubility [51]. The reduced adhesion of streptococci was distinguished on the facet of silorane makeover, possibly due to its hydrophobic properties, the distinguished tendency of nonpolar substances to cluster in aqueous solution and eliminate water molecules [52].

4.5 An overview on the spectrum of composites 4.5.1 Calcium hyroxide [Ca(OH)2] At first, in 1921, Hermann and coworkers introduced Ca(OH)2 in the field of dentistry, which was the “gold standard” for composites of direct pulp capping techniques for many decades [53–55]. It is thought that chemical injury or abrasion provoked by the hydroxyl ions is responsible for the beneficial outcome of Ca(OH)2. The dressing of Ca(OH)2 to revealed pulp is immediately followed by the initial effect of evolution of a peripheral necrosis. Superficial firm necrosis causes gentle irritation; gives momentum to pulp for defense, maintenance, and renewal of a reparative dentin bridge via a series of cellular differentiations; releases an extracellular matrix; and initiates successive remineralization. On the other hand, the generation of a heterogenous dentin bridge has been thought of as the optimal solution for the positive clinical outcome of direct pulp capping. On the grounds of a report, around 89%–90% of human dentin bridges established by Ca(OH)2 cement contained tunnel defects in monkeys [55].

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These tunnel defects formed heterogeneously, and a rough dentin bridge could not succeed in generating a stable barrier and providing a long-lasting, tight biological clasp to arrest bacterial infection. Additional drawbacks of Ca(OH)2-like dissolution and microleakage may cause the generation of a dead zone [54, 56]. Calcium cations and hydroxyl anions are formed by the dissociation of Ca(OH)2. These calcium ions minimize capillary permeability, which diminishes the serum flow, and consequently reduces the secretion of obstructing pyrophosphates that initiate mineralization. The hydroxyl anions neutralize and maintain the optimum pH, 7.0 of acid formed by osteoclasts for pyrophospahatase action resulting in elevated extent of calcium based pyrophosphatase, which diminish the extent of inhibitory pyrophosphate causing remineralization.

4.5.2 Ca(OH)2-based cement Due to the downside of the aqueous solution of Ca(OH)2 mentioned herein, Ca(OH)2based cement with more setting properties was prepared, and has been vastly used by dentists in clinical applications. The well accepted illustration of this cement is Dycal, which is equal parts catalyst and base material. The catalyst fragment is composed of Ca(OH)2, zinc oxide (ZnO), N-ethyl-o/p-toluene sulfonamide, zinc stearate, and titanium dioxide (TiO2), while the base portion contains 1,3-butylene glycol disalicylate, ZnO, calcium phosphate, and calcium tungstate. Another example is Life (Kerr, Orange, California, United States), which is similar on the basis of the reaction mechanism between salicylic acid ester (methyl salicylate) and ZnO to that of Dycal, but differs only in its constituents. The catalysts of Life are barium sulfate (BaSO4), TiO2, and methyl salicylate, while the base part is made of Ca(OH)2, ZnO, and butyl benzene sulfonamide.

4.5.3 Zinc oxide eugenol (ZOE) cement In 1974, Tronstad reported that a therapy of ZOE cement works more positively against inflamed and revealed pulp [57]. Conversely, literature has proved that enhanced chronic inflammation, deficiency of a calcific barrier, and finally necrosis is a result of direct interaction of ZOE cement with the vital pulp tissue [58]. The chemical composition of ZOE is: zinc oxide, white rosin, zinc acetate, zinc stearate, eugenol, and olive oil as 69.0%, 29.3%, 1.0%, 0.7%, 85%, and 15%, respectively.

4.5.4 Corticosteroids and antibiotics Glucocorticoid scaffolds containing a cortisol nucleus in combination with numerous antibiotics have been documented in the literature for direct pulp capping. Corticosteroids such as hydrocortisone, cortisone, cleocin, Ledermix (a composition of Ca(OH)2 and prednisolone), neomycin, penicillin, and Keflin (cefalotin sodium, a first generation cephalosporin antibiotic) in composition with Ca(OH)2 cement were considered for vital pulp capping with the possibility of diminished or hindered pulp inflammation. It was reviewed that vancomycin, an antibiotic used to treat a number

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of bacterial infections, in composition with Ca(OH)2, to a limited degree, was more potent than the use of Ca(OH)2 alone, and accelerated a more continuous reparative homogenous dentin bridge. In 1981, Watts and Paterson strongly recommended that any antiinflammatory agent should not be used by dental patients because of the risk of bacteremia [59, 60].

4.5.5 Zinc polycarboxylate cement Zinc polycarboxylate cement is accessible as a liquid, and in powdered form. The solid powder form contains oxides of zinc, magnesium, bismuth, aluminum, and stannous; while the liquid contains an aqueous solution of polyacrylic acid (30%–40%), its copolymers having a molecular weight ranging from 3000 to 50,000, and unsaturated carboxylic acids such as itaconic acid, tricarboxylic acid, and maleic acid. The powder and liquid are mixed in the proper proportions. Attack of acid on the powdered cement results in the immediate release of zinc, magnesium, and stannous ions. The reaction of ions with carboxylic groups of polyacid chains leads to the formation of a cross-linked salt. Zinc polycarboxylate cement is employed in the fixation of dental crowns and inlays, along with cavity linings [61].

4.5.6 Inert materials A composite of 2-methylpropyl 2-cyanoprop-2-enoate and TCP ceramic was investigated as a direct pulp capping material. Typical cyanoacrylate products contain ethyl cyanoacrylate, isobutyl cyanoacrylate, or N-butyl-cyanoacrylate. Pulpal hemorrhage, a major crisis during pulpotomy, did not occur in these tests of butyl cyanoacrylate adhesive on miniature swine. However, the pulpal response appears as unpredictable dentin bridging, and diminished inflammation was documented in the literature. However, because of the association of some cases of contact allergy, onychodystrophy, and eczema with ethyl-2-cyanoacrylatenone, these compounds have been accepted as a practicable technique [62].

4.5.7 Collagen scaffolds Collagen, the natural polymer and a predominant component of dentin matrix, is a necessary protein present inside the human body. This is a self-possessed insoluble fiber material and supports the initiation of calcification. According to a report, collagen fibers were found less irritating in comparison with Ca(OH)2, and gave momentum to mineralization, but did not support thick dentin bridge formation [62].

4.5.8 Calcium phosphate Calcium phosphate cement, a biodegradable and bioactive grafting material available both in the powder and liquid forms, upon mixing, sets as primarily HA. Calcium phosphates lie at the cluster of biologically energetic synthetic scaffolds. The most often used calcium phosphate material in hard tissue engineering is TCP, which is

Dental pulp capping nanocomposites73

considered resorbable. However, HA is considered a nonresorbable material. The calcium phosphate cement group is often used, owing to its crystallographic structures, osteoconductivity, and chemical formulation comparable to the pulp tissue. Its predominant compressive strength, good biocompatibility, and relatively quick conversion into hydroxyapatite make the cement a feasible substitute. It was demonstrated that a composite of Ca(OH)2 cement and tetracalcium phosphate created a reparative dentin bridge, and significantly reduced pulp inflammation with no peripheral tissue necrosis [63]. FI-CP cement was found to be well settled into a micro-porous matter of hydroxyapatite, the only mineral portion of natural human dentin. It is considered nonhazardous, antiallergic, antipyrogenic, and soft-tissue compatible [63].

4.5.9 Laser Lasers offer attractive properties in terms of hemostasis, neutralization, or removal of dangerous substances, radioactivity, or germs from the pulpal area for field preparation through direct pulp cap sealing; although the treatment revealed vital pulp with the dental dressing matters such as Ca(OH)2, calcium phosphate, HA, MTA, or bonded composite resin materials. Initially, carbon dioxide (CO2) laser irradiation of 1 W was clinically used in patients for direct pulp capping during the years 1985–87 [64, 65]. According to literature, the outcome of the CO2 laser beam has been evaluated for the mineralization process of dental pulp cells and tissues in rats. It was illustrated that CO2 laser irradiation accelerated remineralization in vital pulp cells [66]. Emission of an infrared beam (a wavelength of 1064 nm) by a neodymium-doped yttrium‑aluminum-garnet laser is a therapeutically promising agent for pulpotomy and direct pulp capping techniques in clinical trials [67]. When laser types such as diodes, gallium aluminum arsenide (GaAlAs) indium gallium arsenide (InGaAs), neodymium:YAG (Nd:YAG), erbium, chromium:YSGG (Er,Cr:YSGG), erbium:YAG (Er:YAG), and CO2 were used with the emitted wavelengths of 670–830, 980, 1064, 2780, 2936, and 10,600 nm, respectively, the results exhibited decontamination and photo-biomodulation by all the laser types, but strong hemostasis was exhibited by only CO2, Nd:YAG, and the diode [68].

4.5.10 Glass ionomer/resin modified glass ionomer Glass ionomers were found to provide good biocompatibility and magnificent bacterial resistance; but when used in close composition with other materials, no direct contact was found with the pulp. However, there were a few negative outcomes. Resinmodified glass ionomer (RMGI) composites employed as direct pulp capping materials manifested slight chronic inflammation and insufficiency of a reparative dentin bridge; though the Ca(OH)2 composites unveiled significantly preferable pulpal relief [69]. When Ca(OH)2 (CH, first group) and RMGI, vitrebond (VIT, second group) were evaluated as pulp capping materials for human pulp response, it was found that only CH enables pulp restoration and entire dentin bridging throughout the exposed pulp site. VIT ingredients placed into the hard pulp tissue triggered a steady inflammatory reaction, which seems to be correlated with a lack of homogenous bridge development [70].

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4.5.11 Mineral trioxide aggregate (MTA) MTA materials are the combination of refined Portland cement and bismuth oxide, along with trace amounts of CaO, SiO2, MgO, Na2SO4, and K2SO4. Various authors reported that MTA induced acceleration to conventional hard tissue barrier generation and reduced pulpal inflammation in comparison with hard-setting CH [71]. Now two forms of MTA have been recognized: WMTA (white MTA), considered as ProRootMTA, and GMTA (gray MTA). It is a bioactive substance that chiefly consists of calcium and silicate. ProRoot MTA Gray (Dentsply Tulsa Dental Specialties, Johnson City, Tennessee, United States), was available in the market in 1998, and included Portland cement (type I), bismuth oxide, and calcium sulfate dehydrate as 75%, 20%, and 5%, respectively. Further, Portland cement consists of tricalcium silicate (3CaO·SiO2) and dicalcium silicate (2CaO·SiO2), near about 55 and 19 wt% as major constituents, while tricalcium aluminate (3CaO·Al2O3), tetracalcium aluminoferrite (4CaO·Al2O3·Fe2O3), magnesium oxide, and magnesium sulfate are nearly 10, 7, 2.9, and 2.8 wt%, respectively. The minor constituent of the cement is free calcium oxide, as 1.0 wt% only. Calcium sulfate and bismuth oxide are the setting modifier and radiopacifier, respectively. The materials containing calcium silicate have a familiar property of apatite generation. This material is a priority for dental pulp treatment, apexogenesis, apexification, correcting procedural errors, and moreover, as a root-end filling substance for the apicoectomy process. The gray type of MTA, incorporated with tetracalcium aluminoferrite alone and as a composite with similar composition of the WMTA, is less favored due to esthetic reasons, but various products are accessible, including: ProRoot MTA Gray, Gray MTA Plus (Avalon Biomed, Bradenton, FL, USA), MTA Angelus (Angelus, Londrina, Brazil), Ortho MTA (BioMTA, Daejeon, Korea), and EndoCem MTA (Maruchi, Gangwon-do, Korea). Sealing ability, bioactivity, biocompatibility, and ability to accelerate mineralized tissue formation have been the points of interest of MTA. Additionally, MTA is proposed to be excellent as compared with calcium hydroxide because of its more homogenous and thicker reparative dentin bridge generation, minimized inflammatory effect, and reduced necrosis of pulp hard tissue [72–74].

4.5.12 MTYA1-Ca MTYA1-Ca is the resinous direct pulp capping composite material composed of Ca(OH)2 and is available in both powder and liquid forms. The MTYA1-Ca powder consists of microfillers, Ca(OH)2, and benzoyl peroxide as 89.0%, 10.0%, and 1.0%, respectively, mixed with liquid containing triethyleneglycol dimethacrylate (TEGDMA), glyceryl methacrylate (GMA), dimethyl aminoethyl methacrylate (DMAEMA), o-methacryloyl tyrosine amide, and camphorquinone as 67.5%, 30.0%, 1.0%, 1.0%, and 0.5%, respectively. MTYA1-Ca leads to thick dentine bridge formation in the absence of a necrotic layer evolution, has positive physical characteristics, and was significantly better than Dycal histopathologically. Consequently, it was recommended that the newly synthesized material, MTYA1-Ca, has the potential to act as a better direct pulp capping composite [75].

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4.5.13 Monomers It was found that a composite of only the resins, viz. HEMA, BisGMA, UDMA, and TEGDMA with an antimicrobial agent such as quaternary ammonium salt monomer (e.g., 2-methacryloxylethyl dodecyl methyl ammonium bromide) was a successful pulp dressing composite for crucial pulp protection and healing of deep caries [76].

4.5.14 Growth factors Growth factors control the development of hard tissue, and initiate quick healing and reformation. Growth factors are also called “cytokines” or “metabologens.” A list of growth factors used in the biomedical area is presented in Table 4.2. TGF-β1, BMP, and IGF-1 are the constituents of the extracellular milieu of vital pulp, and were found to regulate the differentiation course of odontoblasts during generation of dentin and predentin in mature teeth. The spectrum of BMPs have been concerned in the tooth progression and related to the separation of ameloblasts and odontoblasts, which is responsible for enamel and dentin. Members of the FGF group have attracted attention for the contribution of calcification and mineralization of the dental matrix secretion. Bone morphogenic protein (BMP): BMP is a member of a super class of a transforming growth factor β (TGF-β) of proteins. TGF β is used as an influential modulator of tissue healing in divergent conditions. Various BMPs such as BMP2, BMP4, and BMP7 play a key role during differentiation of mature pulpal cells into odontoblasts during pulp healing. Lianjia et  al. have reported that when BMPs were used as direct protectors, they were responsible for dentinogenesis, introducing undifferentiated mesenchymal cells from dental pulp to generate odontoblast-like cells, resulting osteo and tubular dentin deposition [77]. Recombinant insulin-like growth factor-I: Lovschall et al. used rat molars for evaluation of the recombinant insulin-like growth factor-I (RIGF-I) and came to the conclusion that the extent of dentin bridge formation was not less than Dycal after a continuous supervision of 28 days [78]. Other growth factors: According to a report, numerous growth factors such as TGF-β1, insulin-like growth factor II (IGF II), epidermal growth factor (EGF), basic fibroblast growth factors (FGFs), and platelet-derived growth factor (PDGF) were Table 4.2 

Growth factors used in biomedical area

Abbreviations

Growth factors

References

BMPs

Bone morphogenetic protein Transforming growth factor-β Basic fibroblast growth factor Insulin growth factor-I

[76a]

TGF-β1 BFGF-2 IGF-I

[76b] [76c] [76d]

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e­ valuated in rat molar teeth and researchers came to the conclusion that only transforming growth factor beta 1, or in short, TGF-β1, a polypeptide representative of TGF-β1 super class of cytokines, augments reparative dentin formation [79]. TGF-β1 performs various cellular tasks such as influence of cell growth, proliferation, differentiation, and apoptosis, and therefore, is responsible for excellent dentin bridge formation.

4.5.15 Bone sialoprotein According to the literature, bone sialoprotein (BSP) was the most capable bioactive nucleus, a component of mineralized tissues such as bone, dentin, and cementum. BSP has the capability to induce remineralized and homogenous reparative dentin. Both BSP and BMP-7 were found to surpass Ca(OH)2 for their features to induce mineralization [80].

4.5.16 Biodentin Biodentine, a material relying on calcium silicate, is used for repairing of perforations and resorption, apexification, and root-end fillings. Biodentine is available in powder and liquid forms. The biodentine powder form includes tricalcium silicate, dicalcium silicate with calcium carbonate, and a filler of zirconium oxide (as radiopacifier). The liquid form contains calcium chloride in an aqueous solution, and an admixture of polycarboxylate. Tricalcium silicate and dicalcium silicate are the primary and secondary core components, respectively. It is novel bioactive cement with lower porosity leading to dentin-like higher mechanical strength that can be used as a dentin alternative. It has a positive outcome on vital pulp cells, and accelerates tertiary dentin bridge generation due to its positive properties such as microhardness, compressive strength, radiopacity, and bond strength [81].

4.5.17 Enzymes 4.5.17.1 Heme oxygenase-1 Heme oxygenase-1 (HMOX1) is the essential rate-limiting enzyme that catalyzes the degradation of heme. Oxidatively distressed pulp cells and odontoblasts illustrate HMOX-1, indicating that the dental pulp cells definitely respond to oxidative pressure at the molecular scale. Manifestation of HMOX-1 is sheltered against hypoxic distress, and cytotoxicity mediated by nitric oxide. It has been determined that carbon monoxide released from HMOX-1 reactions accomplished cytoprotective functions against proinflammatory cytokines and influenced the function of nitric oxide synthase in human dental pulp cells. Moreover, bismuth oxide containing Portland cement (BPC) induced HMOX-1 illustration in pulp cells, which played a preventative role in becoming resistant to cytotoxic effects of BPC [82].

4.5.17.2 Simvastatin Simvastatin (3-hydroxy-3-methylglutaryl coenzyme A, HMG Co A reductase), a rate-limiting enzyme for cholesterol biosynthesis that is available under the trade name

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Zocor is a first-line drug responsible for endogenous production of cholesterol, and is used to treat dyslipidemia and reductase inhibitors. Statin enhances the osteoblast activity, via BMP-2 route and arrest osteoclast function, which leads to enhanced bone genesis and development. Hence, statin may raise the working of odontoblasts, consequently leading to accelerated dentin formation. Statin is well-known for the induction of angiogenesis, and the increment of neuronal cells, reflecting the plausible virtue of statin in pulp and dentin reformation. It has also found antiinflammatory applications in different tissues, and accordingly, it is now expected as a standard stimulant component in pulp capping to create momentum for reparative dentin generation [83].

4.5.18 Propolis (Russian penicillin) The proprietary composition of Propolis (Russian penicillin) includes various aromatic compounds, including caffeic acid phenethyl ester, flavonoids, phenolics, and elements such as iron and zinc. According to a histological comparison among materials such as MTA, Dycal, and propolis in human vital pulp, the authors concluded that Propolis and MTA illustrated comparable dentin bridge formation in comparison with Dycal [84].

4.5.19 Novel endodontic cement (NEC) NEC is a composite matter of phosphate, oxide, silicate, carbonate, chloride, and sulfate of calcium. When a comparison was made between MTA and NEC for capping of vital human dental pulp, it was concluded that both MTA and NEC manifested comparable biocompatibility and positive reaction in pulp capping therapy and inducing the property of dentinal bridge formation, but the dentin bridge formed by NEC was thicker, with reduced dental pulp inflammation [85].

4.5.20 Emdogain (EMD) EMD, an enamel matrix derivative extracted during porcine fetal tooth maturity, is laid down by secretion of Hertwig’s epithelial root sheath. It is a key controller of enamel biomineralization, and acts as an important player parallel to periodontal hard and soft tissue formation. It triggers the revival of periodontal ligaments, a cellular cementum, and alveolar bone. EMD includes a BMP-like nucleus and BMP-expressing cells. The role of BMP and such scaffolds in EMD is to accelerate odontoblast differentiation and homogenous reparative dentin bridge formation. Recently it was concluded that EMD defeats inflammatory cytokine secretion by immunocytes and comprises TGFβ-like scaffolds. It might create a positive milieu for enhancing wound healing in the damaged pulp cells and tissues [86]. According to a published report, the extent of hard tissue generated in EMD-treated pulp was found to be greater than double that of the Ca(OH)2 treated control pulp [87]. When Ca(OH)2, white Portland cement, and ProRoot White MTA were evaluated after EMD treatment on the revealed pulp, MTA manifested better facets of reparative hard tissue reaction with the combined use of EMD as compared with Ca(OH)2 [88].

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4.5.21 Odontogenic ameloblast-associated protein (ODAM) ODAM is demonstrated in odontoblasts, dental pulp cells, and ameloblasts. ODAM directs ameloblast growth and tooth enamel calcification. It was found that ODAM, a major player in hypermineralization of enamel, enhances formation of reactionary calcified tissue surrounding the pulp cavity of a tooth in the vicinity of the pulp disclosure zone, hence conserving traditional odontoblasts in the persistent pulp [89].

4.5.22 Endo sequence root repair material Endo sequence root repair material is comprised of silicates and calcium phosphate, oxide of zirconium and tantalum, and dominant fillers, along with thickening materials [90]. When a comparison was made for cytotoxicity among MTA-Angelus, Brasseler Endo-sequence root repair putty (ERRP), Dycal and a composite of Ultrablend plus (UBP)/light curable Ca(OH)2, it was concluded that ERRP and UBP have reduced cytotoxicity [91].

4.5.23 Tetracalcium phosphate (TTCP) A melt compounding technique was used for synthesis of a novel biologically resorbable composite of polylactide and calcium phosphate with enhanced mechanical strengths using a more general filler, TTCP. Interfacial interaction between TTCP and polylactide (PLA) was enhanced by using the pyromellitic dianhydride (PMDA) and N-(2-aminoethyl)-3-aminoproplytrimethoxysilane (AEAPS). On the other hand, the focus of AEAPS is to improve the diffusion of TTCP in the matrix, while PMDA reacts with the terminal OH group of polylactide and the NH2 group on the surface of AEAPS modifies TTCP, enabling it to improve the interfacial strength. Further, the tensile strength of PLA/TTCP composite containing 20 wt% of TTCP was found as 51.5 MPa, while an improvement in that of PLA/TTCP-AEAPS composite was as 68.4 MPa. Dynamic mechanical results suggested that there was nearly 51% more perfection in the storage modulus than in PLA alone. Hence, the incorporation of PMDA into a PLA/TTCP-AEAPS composite having 0.2 wt% of PMDA and 5 wt% of TTCP revealed better results. By the use of novel bioresorbable PLA composites fused with general filler for clinical biomedical practice, the allergic effect and inflammation caused by degraded acidic product were predicted to be diminished. TTCP composed of bioresorbable polylactide composite can be consolidated with any fundamental filler for biomedical purposes. It has been found to diminish inflammation and allergic outcomes caused by acidic matter [92].

4.5.24 Castor oil bean (COB) cement The COB or Ricinus communis polyurethane (RCP) consists of 80%–95% triglycerol of ricinoleic acid, and is deemed as a natural polyol having three hydroxyl radicals. Oleate and linoleates are the minor constituents. COB was initially used as a biocomposite for repairing and regeneration of bone due to local bone injury.

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Later on, because of these positive characteristics, it was considered a higher priority material for use in direct pulp capping [93].

4.5.25 Castor oil bean (COB) polymer Polyol and prepolymer are the two main constituents of castor oil polyurethane resin. The polyol was prepared from castor oil and multipurpose polyester with a hydroxyl degree of 330 mg KOH/g. The intermediate was prepared from diphenylmethane diisocyanate as a starting material, and prepolymerized with a polyol synthesized from castor oil. Castor oil polymer mortars were found to possess higher mechanical properties as compared with polyester polymer mortars, even only for 12% castor oil resin composites. When a comparison was made between equal percentages of castor oil polymer mortars and epoxy polymer mortars (12% of both), approximately equal compressive strength was revealed. Castor oil polymer mortars revealed 2.2% less compressive strength and reduced fracture toughness, which is near to 1.5%. Even though a slight reduction in fracture toughness and compressive strength drastically enhanced the flexural strength by around 39.0%.

4.5.26 MMA-TBB composite Tronstad and Spångberg reported an in vivo collation of methyl methacrylate (MMA)based composites with various composite resins [57]. A comparison was made for pulp reaction in deep cavities of class V in monkeys between two composite resins, bis-GMA-based (Concise, 3 M, St. Paul, Minnesota, United States) and MMA-based initiated either by tributylborane (TBB) (Polycap, Ivoclar Vivadent) or by sulfinic acid (Sevriton, de Trey, Zürich, Switzerland). After 8 days of treatment, the degrees and percentages of reactions were observed to be mild, moderate, and drastic in the following order: 30%, 50%, and 20% for concise; 75%, 25%, and 0% for Polycap; and, 30%, 20%, and 50% for sevriton. No critical response was observed after using polycaps. In other words, the severity of the pulp reaction was observed to be a minimum for polycaps in comparison with that of sevriton, and more concise. The noteworthy difference in the reaction of pulp for sevriton and polycap is important because of the MMA monomer as a fundamental component of both the resins, but only the polymerization initiator (catalyst) is different. This manifests in that the pulp reaction to composites or resins is drastically influenced by two factors; first, the nature of the resin monomer, and second, the polymerization-initiating nucleus. During 1968, a report successfully completed a clinical trial of a composite of MMA-TBB resin cement, by filling F1 (MMA-TBB resin) reflecting a diminished pulp damage histologically after a period of 9–12 months of filling in uncovered cavities of crucial teeth [94, 95]. A comparable clinical trial with positive results was published during 1976, indicating the complete absence of pulp necrosis, but a minor pulpitis could be found after 30–32 months of treatment of filling composite MMA-TBB resin (Polycap) in uncovered cavities of vital human teeth [96]. Hence, the MMA-TBB composite was considered to be beneficial as a pulp capping material. A report has paid attention to 4 META-MMA-TBB, a composite of MMA-TBB

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resin and 4-[2-(methacryloyloxy)-ethoxycarbonyl] phthalic anhydride, as a practically propertied bonding material for treatment of pulp capping [31]. Hybridizing dentin bonding agents and 4-META-MMA-TBB adhesives simultaneously provides predominant adhesion to marginal hard tissues, and potent seal resistance to microleakage. Nevertheless, the agents exhibited a very mild outcome caused by its cytotoxic upshot and complete lack of calcific bridge generation [97].

4.5.27 TheraCal TheraCal is a light colored, resin-modified calcium silicate and a pulp protectant/liner specially designed and synthesized for treatment of direct and/or indirect pulp capping, as a shielding base material under various cements, amalgams, composites, and other basics. TheraCal LC came to light as a protectant, insulator, and basic barrier for treating dental pulp complexes. TheraCal LC, a combination of tri- and dicalcium silicate particles as a proprietary hydrophilic monomer, executes consequential calcium release, which makes it a persistent and exclusively steady substance as a base or liner. Chemical composition of TheraCal includes oxide and silicate particles of calcium, fussed silica, strontium glass, sulfate and zirconate of barium, and resin incorporating Bis-GMA and PEGDMA. Calcium release gives momentum to HA, leading to a thick secondary dentin bridge formation. The direct placement of TheraCal LC on pulpal exposures after hemostasis makes it better than other materials. It is utilized for any kind of pulpal exposures; for example, carious exposures, mechanical exposures, and exposures because of trauma. It was found that 4.4 MPa shear bond strength, 2.6 mm Al radiopacity, and 213 g/cm2 calcium release (24 h) were the strong physical properties responsible for key features and benefits of TheraCal LC [98]. When chemical and physical characteristics of various capping composites, such as TheraCal, ProRoot MTA, and Dycal were compared, it was concluded that the TheraCal exhibited superior calcium releasing ability, with diminished solubility, compared with either ProRoot MTA or Dycal. The potential of TheraCal was 1.7 mm, ruling out the probability of untimely dissolution. These characteristics offer extensive negative points in direct pulp capping treatments [99].

4.5.28 Doxadent Doxadent is a composite of calcium aluminate, accessible as both liquid and powder forms. It can be used as a persistent therapeutic material. The proprietary formulation of doxadent consists of alumina, water, calcium oxide, zirconium dioxide, and variant alkali oxides. First, powder and liquid forms are mixed, and calcium aluminate powder is dissolved in water, and progressively, aluminum, calcium, and hydroxyl ions are formed, and finally, formation of katoite and gibbsite takes place [100].

4.5.29 Hydroxyapatite (HA) HA is the emerging bioceramic that is dynamically stable, and a superior form of synthetic CPC (calcium phosphate based ceramics) [101]. It is widely used in various biomedical applications, mainly in dental and orthopedic applications, because of its

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close resemblance with inorganic mineral constituents of teeth and bone [102–104]. Its chemical formula is Ca10(PO4)6(OH)2. Actually, OH groups of it can be replaced by F−, Cl−, CO2−, and other ions in the collagen fiber matrix of the teeth and bone tissues [101, 105]. HA possesses exceptional biocompatibility and unique bioactivity [106]. It can be used as an ideal scaffold for the newly synthesized mineralized tissue [107]. HA has been employed in the development of a variety of dental devices for prostheses, implantations, drug deliveries, and so forth [102–106].

4.5.30 Hydroxyapatite (HA) composites Numerous HA nanocomposites made of nanoHA and synthetic polymers or inorganic metallic substances have been reviewed and evolved as a backbone to boost the mechanical positive points of microporous hydroxyapatite and vice versa, and to upgrade excellent connections to dentin walls, after fillings in tooth perforations [108, 109]. Investigation and synthesis of nanoHA/polymer composite scaffolds with a high degree of porosity and well-captured microporous architectures revealed the mechanical and morphological properties, along with protein adsorption potential of the composite materials. Fusions of nanoHA and PLA scaffolds upgrade fibrous morphological properties, which sequentially showed threefold improvement in protein adsorption over a nonfibrous nucleus. Table 4.3 presents a list of HA composites. Table 4.3 

Some examples of HA composites

HA composites

Outcome

References

Titanium oxide and HA composites Nanocrystalline hydroxyapatite/polylactide composite Nanocrystalline HA/poly (hexamethylene adipamide) composite

Biocompatible and excellent at promoting cell activity Steady increase in tensile modulus

[109a]

Small sized crystals of nanocrystalline HA enhanced the surface area and therefore, more surface energy and activity and consequently strong bonding between polymer and HA Young’s modulus improved near about 3–15 GPa, since HA content increased 0%–40% while tensile strength reduced from 80 to 44 MPa parallel with the similar increment in HA volume fraction Fewer stress concentrations through the whole matrix with a boost in HA content Mechanical properties were improved Improved sinterability, mechanical properties, and biological properties Favorable cellular responses

[109b]

HA/polyetheretherketone

Polylactide/collagen/HA composite Zirconia/HA composite P-glass/HA composite HA/CaO·P2O5 composite

[92]

[109c]

[109d]

[109] [109e] [108]

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4.5.31 Dentin phosphophoryn (DPP)/collagen composite DPP, the main noncollagenous multianionic protein found in dentin has been dressed over vital pulp in composition with atelo collagen fibrils [110]. The DPP/collagen composite induced reparative dentin formation more swiftly than calcium hydroxide. In the morphometrical analysis, it was found that the reparative dentin formation rate by DPP/collagen composition was similar to that evaluated from calcium hydroxide nearly 3 weeks later. Nonetheless, the compactness and thickness of reparative dentin that resulted from DPP/collagen composition was superior to that of Ca(OH)2. Additionally, DPP/collagen composition exhibited a high awning ability of exposed pulp. Also, DPP/collagen composite hinders mild pulp inflammation only at the initial stage, while the necrotic layer formed by Ca(OH)2 adjacent to the material arrested drastic inflammation in hard tissues of pulp after a week. The latest studies support the prospective role of composite DPP/collagen as a fast biocompatible stimulator during the course of formation of reparative dentin having excellent quality [110].

4.5.32 Bioceramic/poly (glycolic)-poly (lactic acid) (PLGA) composite A composite of β TCP-HA bioceramic or Ca(OH)2 or and/or PLGA stuff was used to observe the histopathological dental pulp reaction followed by direct pulp dressing of mechanically disclosed pulp in rats. In the meantime, a composite bioceramic/PLGA group exhibited moderate to good inflammatory reduction, and initiated a complete dense and homogenous dental bridge. It was concluded that composite bioceramic/ PLGA manifested an enlarged zone of tertiary dentin, and successfully restored the dental pulp complex [111].

4.6 Nanomaterials Nanomaterials, either alone or in combination with drugs, stem cells, and growth factors form nanocomposites, and can be used for dental pulp capping [21, 41]. The synthesis of biosubstances at the nanoscale is an unavoidable requirement for dental pulp regeneration. It permits the concentration of various materials in a small zone, and exhibits the property enhancement by delivering the energetic scaffolds at a low cost. Nanomolecules focusing on the initial stage of dental pulp capping have been synthesized with two polymers such as poly-l-lysine Dendrigraft and poly-glutamic acid (PGA), along with an antiinflammatory hormone such as Alpha Melanocyte Stimulating Hormone (α-MSH) [41]. A composite of PGA/alpha-MSH activates the reduced inflammation of pulp connective tissue, and works on fibroblasts and monocytes.

4.6.1 Crosslinked collagen composite Crosslinked collagen composites were prepared to design a vital support scaffold by a composition of a crosslinked collagen nucleus within a root canal zone to induced

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blood clots, and exposure of dentin enamel. This emerged as a competent point of focus to generate a vital supporting scaffold for treating imperfect teeth with acute periodontitis [112].

4.6.2 PGA-MSH nanoassemblies Various PGA-MSH nanocomposites accelerate the starting of pulp connective tissue regeneration, resulting in adhesion and development of pulp fibroblasts. A report was published in 2010 to manifest the consequences of composite PGA-α-MSH on pulp fibroblasts. Lipopolysaccharide (LPS) provoked fibroblasts (incubated with composite PGA-α-MSH) demonstrated a late occasion of IL-10, an early time dependent arrest of TNF-alpha, and no effect was found on IL-8 excretion [113]. Nonetheless, composite PGA-α-MSH initiates IL-8 discharge and proliferation of dental pulp fibroblasts in the absence of LPS. On the other hand, only α-MSH alone arrests this proliferation. Hence, PGA-α-MSH has been proved as a potential scaffold to induce adhesion of pulp fibroblasts, along with cell proliferation. This composite can also diminish the inflammatory condition of LPS restorative dental pulp fibroblasts seen during gram negative bacterial infections. This outcome revealed that novel PGAα-MSH may be proved as an antiinflammatory agent for the therapy of endodontic injury and lesions [113].

4.6.3 Electrospun matrices of poly (ε-caprolactone) (PCL) Composites made of electrospun matrices of PCL exhibited positive results for connective tissue regeneration. PCL, a biomimetic 3 dimensionally thick nanofibrous composite scaffold, was provided by electrospinning of the biodegradable, bioresorbable, and FDA-approved polymer. The designed nanocomposite material was capable of stimulating in vivo calcific bone initiation [114].

4.6.4 BMP-2/chitosan nanoassemblies The technique of functioning of nanofibers by nanoreservoirs of BMP-2 illustrated effectiveness for bone origination and boosted the differentiation and development of mesenchymal stem cells (MSCs), increasing the tissue production in vivo. A layer-­ after-layer immobilization of the BMP-2 growth factor in combination with poly-l-­ lysine or chitosan throughout the nanofibers was expressed. It suggested a way toward effective recondition of bone imperfections with minimized threats [115, 116].

4.6.5 Electrospun PCL/gelatin/nanoHA scaffold According to a report, in  vivo and in  vitro performance of dental pulp stem cells (DPSCs) evolved on a composite, and electro-spun PCL/gelatin with the supplement of nanoHA was investigated, and it was concluded that inclusion of nanoHA in nanofibers certainly increased differentiation of DPSCs toward a phenotype similar to an odontoblast in vitro and in vivo [117].

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4.6.6 Nanofibrous poly (l-lactic acid) (PLLA)/BMP-7 and dexamethasone (DXM) scaffolds According to a report, odontogenic differentiation of DPSCs was acquired on NFPLLA nucleuses both in vitro and in vivo. The assembly of BMP-7 and DXM initiated odontogenic differentiation with high efficiency as compared with DXM alone. The NF-PLLA nucleus and fused odontogenic inducive facets offer an excellent milieu for DPSCs for regeneration of dentin and dental pulp [118].

4.7 Conclusion Coherence on the comprehension of technological fostering, biology of caries, and persuasion about boosted restorative materials has established a preserved pulp, fortunately for the patient and the clinician. The invention and relevance of nanocomposites synthesized from synthetic biologically resorbable and active polymers and bioceramics/inorganic materials such as HA, TTCP, or favored bioactive glasses became progressively more considerable, offering the convenience of bioactive and resorbable uniqueness to direct tissue generation procedures. In this manner, the design is focusing on minimum disadvantages and the exploitation of the advantageous properties of the single constituent to expand an optimistic tissue engineering scaffold with well-defined properties, plus a degradation rate in vivo balanced with the generation of fresh tissue. An additional benefit of the composites is the elevated hardness of the scaffold. In contrast, resorbable polymers are better for fabrication, but very feeble in meeting the necessities of dental tissue regeneration. Moreover, cell adhesion, cell spreading, and cells’ viability development onto polymer-bioglass composites could be enhanced, and assert the high biocompatibility and bioactivity for hard tissue renovation. Nanotechnological research has revamped the distribution of potent scaffolds and the extracellular mimetic structure of nucleuses. Hence, these come into sight as essential techniques to orchestrate pulp cell differentiation and colonization, and to arrest and/or control inflammation and infection. These multitasking nanocomposites are equipped to face the challenge of complicated dental pulp renewal.

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