Local Drug Delivery Systems for Vital Pulp Therapy: A New Hope

Parhizkar, Ardavan; Asgary, Saeed

doi:https://doi.org/10.1155/2021/5584268

International Journal of Biomaterials

On this page

Abstract Introduction Conclusions Conflicts of Interest Authors’ Contributions References Copyright Related Articles

Review Article | Open Access

Volume 2021 | Article ID 5584268 | https://doi.org/10.1155/2021/5584268

Local Drug Delivery Systems for Vital Pulp Therapy: A New Hope

Ardavan Parhizkar¹and Saeed Asgary¹

Academic Editor: Carlo Galli

Received18 Feb 2021

Revised18 Aug 2021

Accepted09 Sept 2021

Published15 Sept 2021

Abstract

Vital pulp therapy (VPT) is deliberated as an ultraconservative/minimally invasive approach for the conservation of vital pulpal tissues, preservation of dental structure, and maintenance of tooth function in the oral cavity. In VPT, following the exposure of the dental pulp, the environment is prepared for the possible healing and probable refunctionalisation of pulpal connective tissue. However, to succeed in VPT, specific biomaterials are used to cover and/or dress the exposed pulp, lower the inflammation, heal the dental pulp, provoke the remaining odontoblastic cells, and induce the formation of a hard tissue, i.e., the dentinal bridge. It can be assumed that if the employed biomaterial is transferred to the target site using a specially designed micro-/nanosized local drug delivery system (LDDS), the biomaterial would be placed in closer proximity to the connective tissue, may be released in a controlled and sustained pattern, could properly conserve the remaining dental pulp and might appropriately enhance hard-tissue formation. Furthermore, the loaded LDDS could help VPT modalities to be more ultraconservative and may minimise the manipulation of the tooth structure as well as pulpal tissue, which could, in turn, result in better VPT outcomes.

1. Introduction

Nowadays, vital pulp therapy (VPT) modalities are regarded as increasingly common ministrations and/or minimally invasive procedures [1] implemented to conserve/preserve the vitality of the dental pulp and maintain its function when the vital connective pulpal tissue has been compromised but not fully impaired by various stimuli [2, 3]. Currently, VPT is considered an important alternative ultraconservative approach to conventional root canal therapy techniques, since it seems to (i) promote regenerative endodontics [4], (ii) preserve dental structure and function in the oral cavity [5], (iii) cause more tooth resistance against masticatory forces compared to traditionally endodontically treated teeth [6], and (iv) maintain the physiological process in the exfoliation of primary teeth [7]. VPT modalities differ from minimally or semi-invasive (i.e., stepwise excavation, indirect pulp capping, and direct pulp capping) to relatively invasive (i.e. miniature, partial pulpotomy, and full pulpotomy) forms.

In brief, VPT is initiated with an access of the healthy layers of dental pulpal tissue following the removal of the inflamed pulp in different scales, from 1 mm in miniature pulpotomy to the entire tissue of the coronal chamber in full pulpotomy and haemorrhage control of the remaining vital pulp. After gaining haemostasis, the selected endodontic biomaterial is applied as close as possible to the surviving connective pulpal tissue and undifferentiated mesenchymal cells to conceivably induce cell differentiation and, subsequently, form of a hard tissue barrier [8, 9]. If the biomaterial is well adapted to the remaining vital tissue/surrounding dentinal walls in the absence of any blood clot and creates an impermeable seal, the healing process is expected to occur more rapidly with the most desirable outcomes [1]. In fact, VPT owes its success to the dental pulp, which is deliberated as a capable connective tissue with high potential for healing and regeneration [10, 11]. Existence of human dental pulp stem cells (DPSCs), grounds for cellular differentiation to odontoblasts, matrices for development of new tissues, and similar phenomena make the dental pulp a unique environment for regenerative processes [12]. Therefore, if the vital/surviving pulp is well protected from irritating agents and properly supported, it could maintain its vitality and resume its functions after injuries and inflammation. Consequently, specific endodontic biomaterials have been introduced for use in VPT to (i) dress and protect the pulpal tissue from its surroundings, (ii) assist the dental pulp in the preparation of a proper matrix for hard-tissue formation, and (iii) help the dental pulp regain its normal condition [13], which sequentially could result in less complicated or aggressive treatment procedures.

2. Local Drug Delivery Systems

Today, due to problems associated with systemic drug delivery methods, local drug delivery systems (LDDSs) have acquired great attention [14, 15]. Various studies have shown that LDDSs seem to be able to (i) transfer the loaded agent(s) to the target site and act as targeted drug delivery vehicles [16, 17], (ii) release the loaded agent(s), e.g., drugs/antibiotics/growth factors, in a designated, controlled, and sustained pattern [18], (iii) provide the anticipated therapeutic dose of agent(s) on the desired site [19], and (iv) lower the possible adverse effects of the systemic dose of the agent(s) [20]. LDDSs have long been used in medicine with acceptable degrees of success, and owing to the recent accomplishments in bio/nanotechnology, various types of LDDSs have started to be applied in different fields of dentistry from research to clinical applications and from operative dentistry to periodontology/periodontics [21, 22] and endodontology/endodontics [23].

Micro-/nanoparticles have been vastly studied for use in endodontic treatments [24]. A recent experimental/in vitro investigation has introduced an innovative local delivery system of bioceramic microparticles, made from hydroxyapatite and β-tricalcium phosphate, coated with a biopolymer, i.e., polylactic coglycolic acid (PLGA), so as to transfer loaded antibiotics to the root canal system (target drug delivery) and remove dominant intracanal microorganisms, exhibiting successful outcomes [25]. Comparably, Virlan et al. have presented PLGA microparticles with added zein loaded with an antibiotic (i.e., amoxicillin) and PLGA microparticles in a PLGA/calcium phosphate cement loaded with growth factors to be used in root canal treatments and endodontic regeneration, respectively [26]. Seemingly, PLGA microparticles have been/are immensely regarded as appropriate microcarriers for sustained drug release by different investigations [27–29]. Similarly, Álvarez et al. have suggested microencapsulation techniques as well as the application of microparticles in vitro/in vivo for the delivery of different agents (i.e., antibiotics, drugs, and growth factors) to the root canal cavity [30]. Moreover, analogous in vitro/in vivo studies have shown successful results when loaded/seeded LDDS are employed in endodontic ministrations, e.g., the addition of amoxicillin-loaded microspheres to mineral trioxide aggregate and the delivery of antibiotic-loaded microcarriers via the calcium silicate-based cement to the anticipated site [31] as well as the application of alginate/laponite hydrogel biopolymer-based microspheres transferring DPSCs and vascular endothelial growth factor (VEGF) as a signalling protein for regenerative endodontics to the target space [32]. A recent study claims that microspheres, hydrogels, and fibers are the most common vehicles for the transfer and sustained release of agents in endodontics [33].

Furthermore, “Gels” have been enormously used in dentistry as a local drug delivery system, especially in periodontics [34–36], and due to their promising potentials and capabilities, they have been investigated in endodontics [24, 37]. Hydrogels with their cross-linked hydrophilic network have shown comparable properties to the dental pulpal tissue [38] as well as the ability to carry, transfer, and release agents/drugs to the intended site. Consequently, they are being regarded as suitable vehicles for the regeneration of the dentine-pulp complex and corresponding protocols [39]. Moreover, it has been demonstrated that hydrogels can be a very useful structure for controlling the porosity and viscosity of endodontic intracanal scaffolds [40]. Besides, injectable hydrogels merged with stem/progenitor cells seem to be considered a favourable technique/method for possible regeneration of the dentine-pulp complex and could play an important part in endodontic regeneration protocols [41]. Natural polymer-based hydrogels have shown bioactivity, high biocompatibility, and biodegradability by hydrolysis/enzymes [42] whereas synthetic polymer-based hydrogels have presented acceptable mechanical properties, reliable durability, and appropriate thermostability compared to natural hydrogels [43]. Therefore, the hybrid form of hydrogels could be identified for use in endodontic regeneration and engineering of pulpal tissue, exhibiting both characteristics and properties of their components [44]. In addition, Ribeiro et al. have recently introduced an injectable matrix metalloproteinase- (MMP-) responsive nanotube-modified gelatine hydrogel for possible sustained intracanal application to be used against endodontic infections owing to its credible affinity of cell tissue and degradability [45]. Nevertheless, hydrogels and their application in endodontic treatments should be further investigated.

Films, strips, and fibers have been widely studied for oral drug delivery, particularly in the management of periodontal diseases and endodontic problems [30, 46]. Chitosan/PLGA and degradable PLGA films have been introduced to the periodontal pocket as local drug delivery systems to transfer and/or release loaded agent(s)/drug(s), e.g., ipriflavone, and act against periodontal pathogens [47, 48]. In addition to films, biodegradable or nonbiodegradable polymer strips have been reported to be an efficient method of administering antibacterials for periodontal treatments [49]. Drug-loaded strips, specifically with tetracycline hydrochloride and metronidazole, have been successfully used in patients with advanced periodontal pathosis, with tetracycline being more successful than metronidazole in the conducted investigations [50]. Moreover, strips have been used as mucoadhesive local delivery systems for fluoride-incorporated layered double hydroxides in periodontal treatments with reasonable safety and efficient release of fluoride ions to prevent caries through an ion-exchange mechanism with the surrounding environment [51]. Similarly, fibers have shown significant potential for the transfer of agents/bioactive materials/drugs, e.g., tetracycline [52], to their designated target sites (e.g., periodontal pocket) and releasing them in a controlled pattern [53]. Moioli et al. claim that nanofibers, along with microparticles and hydrogels, can be considered for use in the regeneration of tooth and periodontal tissues [54], with a notable focus on the PLGA micro-/nanofiber system, a biopolymer approved for numerous applications and production of scaffolds/matrices in tissue engineering [55]. Due to the reported biocompatibility and biodegradability, polymer-based nanofiber systems made from natural or synthetic biomaterials seem to be effective means for local delivery [21]. Sequentially, fibers have been deliberated for use in endodontic treatments/investigations. Haugen et al. claim that nanofibers can be considered for pulp tissue engineering and regenerative endodontics due to their potential use for dental tissues [56]. Related studies have reported that fibers can act biomimetically to create microenvironments and behave as an appropriate scaffold for the pulp-dentine complex, mimicking the native pulp and function [57]. Fibers and nanofibrous constructs can be regarded as an alternative approach for intracanal disinfection [58], since they appear to operate/serve as a drug delivery vehicle for a number of antibiotics, revealing analogous antibacterial effects to antibiotic pastes, however, with minimum concentration of the drugs used [59]. It has been shown that chitosan/gelatine nanofiber membranes are able to carry cinnamon extract and sustained release the loaded substance to prevent infection on the implanted site [60]. Polymeric fibers incorporated with curcumin have shown antibacterial properties and possible use for the disinfection of root canal cavity [61]. Moreover, clindamycin-modified triple antibiotic polydioxanone-polymer-based nanofibers have shown to act effectively against intracanal microbiota and different root canal microorganisms [62].

Additionally, LDDSs have shown to be able to transfer a variety of agents to their target sites, including calcium hydroxide (CH) [63] as the first “Gold Standard” biomaterial for VPT [64] and triple antibiotic paste (TAP) and/or modified TAP (mTAP), to combat microorganisms and bacterial biofilm [65]. A recent study has shown that calcium hydroxide-loaded PLGA nanoparticles as LDDSs can show a prolonged profile of agent/drug release and excellent penetration in the dentinal tubules compared to CH alone [66]. Furthermore, LDDSs could show other characteristics beside their ability to carry/transfer agents owing to the types of (bio)materials used in their synthesis. Bioceramics, e.g., silica, calcium phosphates, and calcium silicates, have been widely used in bone healing [67]. Moreover, ceramic microparticles/scaffolds made from hydroxyapatite and bi/tricalcium phosphates have shown biocompatibility, bioactivity, and ability to form hard-tissue barriers [68]. Since the existence of a dentinal construct is of utmost importance in VPT [69], bioceramic LDDSs could be a noted candidate for use in VPT modalities, specifically calcium silicate-based cements. Besides, polymer-based LDDSs have revealed an ability to control/sustain-release therapeutic agents as well as carry hydrophobic and hydrophilic drugs [70]; e.g., biocompatible and biodegradable hydrogels have shown to be able to release Ca²⁺ from the loaded calcium hydroxide [63]. Inorganic materials and synthetic/natural polymers have been advocated to devise LDDSs for dentin-pulp tissue engineering [71], since (i) bioactive molecules (BMs) needed for regeneration could be encapsulated and transferred by the mentioned LDDSs, (ii) BMs could be released in the concentrations needed for tissue engineering, and (iii) LDDSs can function as fundamental scaffolds and provide support for the ingrowth of the tissue during regeneration [67].

3. Biomaterials

It is believed that dental biomaterials have revolutionised/caused present-day approaches and treatments in dentistry, specifically in periodontics and endodontics [72]. Vital pulp therapy, as a modern concept and accepted modality [73], is grounded on the removal of causative factors which results in the reduction/elimination of inflammation and pathosis of the dental pulp, stimulation of the connective tissue to rebuild itself, and proper haemodynamics in the pulpal tissue [73, 74]. Studies have reported that an effective VPT needs alleviation of further injury to the remaining odontoblasts and encouragement of new odontoblasts to differentiate [75]. Consequently, the applied biomaterials considered for VPT should help to achieve sealing of the exposure site, reduction of inflammation, formation of a dentinal bridge, and differentiation of potent cells [76]. Furthermore, they should be ideally biocompatible, bioactive, bioinductive, and bioconductive and be able to adhere to the tooth structure, preserve sealability, display insolubility, demonstrate dimensional stability, and show nontoxicity [69]. Studies and investigations have focused on different biomaterials for VPT; however, the most important/common ones are based on calcium hydroxide (e.g., Dycal) and calcium silicate (e.g., mineral trioxide aggregate “MTA,” calcium enriched mixture “CEM” cement, and Biodentine). The biomaterials are applied after VPT initial clinical stages and following the necessary primary preparation of the exposure site and pulpal tissue.

3.1. Calcium Hydroxide (CH)

Calcium hydroxide is considered the traditional biomaterial for pulp capping and was introduced to dentistry by Hermann et al. in the 1930s [77]. Once the “gold standard” for VPT [11], CH is able to release/dissociate calcium and hydroxyl bioactive ions to its surrounding environment [78], trigger wound healing, and promote regeneration in pulp capping procedures [12]. It seems that the velocity of ionic dissociation of calcium hydroxide greatly depends on/is defined by its vehicle [77].

Calcium hydroxide has been compared with adhesives and bonding systems for use in VPT. It is expected that adhesives are able to effectively seal the exposed pulp and stop the leakage of microorganisms into the connective tissue. However, it has been shown that the exudation and moisture from the exposure site can affect the seal caused by adhesives/bonding systems and bacteria may leak into the pulp [79]. In addition, the potential cytotoxicity of adhesives and the needed techniques for their application have questioned their solicitation in VPT [80, 81], and as a result, using a bonding system next to CH is not currently recommended [5]. In comparison with resin modified glass ionomer (RMGI) materials, CH has shown to be the material for VPT, since RMGI can cause moderate to severe pulp inflammation and possible tissue necrosis with lack of dentinal bridge formation [82].

Although calcium hydroxide has exhibited basic pH values [83] and could be theoretically regarded as an antibacterial agent, application of CH has resulted in poor antibacterial activity as well as lack of trusted seal, no adherence to dentinal walls [11], and a porous dentinal bridge [84]. Therefore, CH is no longer elaborated as the material of choice for VPT. Several calcium silicate-based cements/biomaterials have been proposed for use as replacements for CH, since they have revealed higher rates of success amongst different biomaterials used for VPT. Calcium silicate-based materials have shown to release high amounts of calcium and, thus, should be able to induce hard-tissue (i.e., dentinal bridge) formation [85]. In a recent systematic review, it has been claimed that MTA, CEM cement, and Biodentine are the common calcium silicate-based cements of choice to be used in VPT modalities for different conditions of the pulp [86].

3.2. Mineral Trioxide Aggregate (MTA)

Various studies state that MTA is a more successful calcium silicate-based endodontic cement/biomaterial in comparison to CH, and thus, MTA has claimed the place of CH in VPT [87, 88]. Mineral trioxide aggregate is a fast setting bioactive calcium-silicate based cement [89], which means it can release calcium ions and form an interfacial layer between the biomaterial and dentine. Consequently, MTA has shown to cause biomineralisation beneath the pulp exposure site and has been advocated to maintain the vitality of pulpal tissue [90]. The release of calcium ions from MTA and their reaction with phosphates in tissue fluids cause the cement to be capable of developing the formation of hydroxyapatite in contact with tissue body fluids [91] as well as the induction of the regenerative process through forming nanocrystals [92]. A histological study has indicated that MTA is effective on the regeneration potential of the dental pulp tissue and can cause adequate metabolic activity and favourable cellular response, resulting in less tunnel effect and higher clinical success rate [93, 94]. Therefore, there have been a number of expanding applications for MTA, e.g., direct [95]/indirect pulp capping next to the repair of root/furcation perforations [96] and apexification [97], making MTA superior calcium silicate-based cement over CH [98]. Although MTA has shown excellent properties and acceptable biocompatibility, there are drawbacks to MTA, including high price, long setting time, triggering discolouration [99], and difficult manipulation/handling [100, 101]. Nonetheless, MTA is currently regarded as the “Gold Standard” calcium silicate-based cement/biomaterial for VPT modalities [102].

3.3. Biodentine™ (BD)

Biodentine™ is a tricalcium silicate-based biomaterial with properties appropriate for endodontic treatments, particularly VPT. Biodentine™ has revealed acceptable marginal seal due to its mechanical retention in dentinal tubules and adequate bond strength to dentine comparable to that of MTA [103]. In addition, when BD is used as calcium silicate-based cement for direct pulp capping and/or pulpotomy in mature permanent teeth with carious exposure, it has shown similar success rates to MTA [90]. Furthermore, studies have demonstrated that once BD is directly applied onto the dental pulp, it can (i) induce reparative dentine comparable to primary dentine [104], (ii) reliably form a dental bridge [105], and (iii) cause possible decrease/absence of inflammatory response in the pulp as well as probable increase in cell differentiation [106]. Moreover, Biodentine has exhibited improvements in properties in comparison to other calcium silicate-based cement, i.e., high compressive strength, short setting time [107], and favourable bond strength. These features have resulted in a wider scope of use in endodontic therapy, especially VPT modalities, e.g., in full pulpotomy for the management of irreversible pulpitis with/without apical periodontitis [108, 109]. Additionally, Biodentine has revealed less solubility, tighter seal, and higher mechanical strength when compared to CH [110]. Despite excellent properties, BD has shown to lose its radiopacity with time which makes it difficult to be radiographically observed in long term [90].

3.4. Calcium-Enriched Mixture (CEM) Cement

Calcium-enriched mixture cement, as a calcium silicate-based biomaterial, has shown to have favourable physical properties, i.e., flow, film thickness, primary setting time [111], and comparable clinical applications to MTA, e.g., in the repair of root resorption/furcation perforation and use in VPT modalities [112]. Various studies have shown that CEM cement exhibits acceptable biological properties, has proved to be biocompatible, and is able to release calcium ions during its setting reaction showing bioactive properties. It seems that the reaction between calcium ions and phosphorus results in the formation of hydroxyapatite; which, in turn, could cause enzyme activity in cells, preparing a matrix for healing and possible hard-tissue formation [113]. Besides, the antibacterial activity of the cement is similar to that of CH and appears to be superior to that of MTA [112, 114]. Other studies have claimed that CEM cement has acceptable sealability comparable to that of MTA after root resection and in apical sealing [115]. In addition, there seems to be no statistical difference in the sealing ability between CEM cement and MTA in the apical area, which can be related to the chemical properties and handling characteristics of CEM cement [116]. CEM cement is claimed to be suitable calcium silicate-based cement for use in a variety of clinical applications, e.g., VPT modalities, root-end filling, perforation, resorption, and regenerative endodontics [112].

3.5. Bioactive Glass (BG)

Bioactive glass is a bioceramic material consisting of silica, calcium oxide, sodium oxide, and phosphorus pentoxide and has been regarded as an active biomaterial for use in hard-tissue formation through the development of the hydroxyapatite layer [117, 118]. Therefore, it can be hypothesised that BG can be considered for use in dental treatments when formation of hydroxyapatite and biocompatibility without cytotoxic effects are necessary for the achievement of a successful outcome [119]. Subsequently, a bioactive glass-based endodontic sealer has been introduced and further efforts are on the way to enhance glass-based bioactive cement [69]. Consequently, BG seems to be a promising/potential biomaterial for use in VPT modalities, so as to cause and/or induce hard-tissue formation, i.e., a dentinal bridge, on the pulp exposure site if applied as a pulp capping biomaterial directly over the pulp [120]. Further investigations are, nevertheless, necessary for the application of BG as a dressing in VPT.

It has been shown that LDDSs can have efficient impacts on the outcomes of VPT, since they are likely to be able to (i) transfer/deliver antimicrobials directly to the exposure site, (ii) remove the pathogenic microbiota, (iii) regulate/reduce the inflammation, and (iv) decrease the destruction in the pulpal tissue, as were reported by Kalyan et al. using chlorhexidine polymer scaffold as LDDSs for VPT [121]. In addition, the local regeneration of the dentine-pulp complex has been suggested/investigated using a local delivery system loaded with perfect combination of growth factors, e.g., fibroblast growth factors and bone morphogenetic proteins, with a scaffold for DPSCs [69, 122, 123]. Moreover, use of a biostimulation membrane in the dentine-pulp complex has shown success in the maintenance of dental pulp tissue as well as the physiological process of exfoliation in primary teeth [2]. It has been suggested that, with the application of local biodegradable/biocompatible carrier vehicles to transfer signalling/bioactive molecules to the capping site in VPT, induction of odontoblastic-like cell differentiation, formation of reparative dentine, and stimulation of fibrodentine may be anticipated, the phenomena which, in turn, could result in the reconstitution of normal tissue architecture in the dentine-pulp interface [124]. A comparable experimental study has shown that chitosan/β-glycerophosphate hydrogel has been able to sustain-release VEGF and may trigger the odontogenic differentiation of DPSCs, promoting/contributing to the idea of using LDDSs in VPT modalities [125].

Currently, local delivery systems are used to transferring drugs/agents to their target sites so that they could be released in their desired/therapeutic concentration and optimum time, resulting in their needed effect. In VPT, vitality of the remaining tissue and maintenance of its capacity for healing is of great importance. Consequently, direct transfer of drugs/agents, i.e., biomaterials in VPT, to the area of pulp exposure, individually or as a combination, on a specially designed vehicle may prepare the environment for healing of the exposed site as well as the pulpal tissue. The direct transfer and subsequent release of the loaded biomaterials on the pulpal wound in the required dose and controlled manner next to further cell differentiation and less inflammation of the remaining pulp are anticipated to be observed in the mentioned strategy/method. Furthermore, the local delivery of biomaterials could compensate more for the extension of the exposure site and manipulation of the remaining pulp, making the technique more ultraconservative. Hence, with the proper choice of biomaterials selected for the local delivery, the promoted induction/formation of hard tissue, i.e., a dentinal bridge, is anticipated.

4. Conclusions

The agents/biomaterials needed for VPT could be locally transferred to the target site, i.e., pulp exposure, using small-sized local delivery systems. This allows specific controlled release of loaded biomaterials/molecules/substances/drugs to the desired location while enhancing the effect(s) of the agents. In the local delivery, the transferred agents will be in close proximity to the pulpal connective tissue and could further push the differentiation of DPSCs to odontoblasts. In addition, the preparation of pulp exposure site shall be reduced to its minimum/smallest possible size, which is of great significance in ultraconservative VPT approaches. Moreover, and although local dentine regeneration seems a difficult task, due to the type of biomaterials used for the synthesis of the delivery system and the kind of vehicle employed for agent/drug transfer, the formation of dentinal bridge could be more encouraged and induced.

Despite the low level of evidence on the application of LLDSs in VPT, next to local transfer of biomaterials to the pulpal exposure site via microcarriers/vehicles, it seems that LDDSs should be practised in VPT in experimental/in vitro and in vivo investigations next to animal models as well as related randomised controlled trials after being properly produced, perfectly experimented, vigilantly tested, and carefully evaluated. Patients’ signs and symptoms should be recorded, clinical examinations should be wisely performed, and radiographic evaluations ought to be attentively considered. In addition, the formation of a dentinal bridge and the healing of pulpal tissue should be evaluated, analysed, and valued.

Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

Authors’ Contributions

“Ardavan Parhizkar” and “Saeed Asgary” both contributed equally as the first authors in the manuscript.

References

N. Meschi, B. Patel, and N. B. Ruparel, “Material pulp cells and tissue interactions,” Journal of Endodontics, vol. 46, no. 9s, pp. S150–S160, 2020.
View at: Publisher Site | Google Scholar
M. A. A. M. Machado, T. C. Stafuzza, L. L. R. Vitor et al., “Pulp repair response after the use of a dentin-pulp biostimulation membrane (BBio) in primary teeth: study protocol for a randomized clinical trial,” Trials, vol. 21, no. 1, p. 874, 2020.
View at: Publisher Site | Google Scholar
J. Ghoddusi, M. Forghani, and I. Parisai, “New approaches in vital pulp therapy in permanent teeth,” Iranian Endodontic Journal, vol. 9, no. 1, pp. 15–22, 2013.
View at: Google Scholar
W. L. O. da Rosa, E. Piva, and A. F. da Silva, “Disclosing the physiology of pulp tissue for vital pulp therapy,” International Endodontic Journal, vol. 51, no. 8, pp. 829–846, 2018.
View at: Publisher Site | Google Scholar
A. Khademi and N. Akhlaghi, “Outcomes of vital pulp therapy in permanent teeth with different medicaments based on review of the literature,” Dental Research Journal, vol. 12, no. 5, p. 406, 2015.
View at: Publisher Site | Google Scholar
T. Dammaschke, J. Leidinger, and E. Schäfer, “Long-term evaluation of direct pulp capping-treatment outcomes over an average period of 6.1 years,” Clinical Oral Investigations, vol. 14, no. 5, pp. 559–567, 2010.
View at: Publisher Site | Google Scholar
S. Asgary, G. Ansari, S. Tavassoli-Hojjati, A. Sarraf Shirazi, and A. Parhizkar, “Clinical applications of hydraulic calcium silicate-based biomaterials in paediatric endodontics,” Endodontic Practice Today, vol. 14, no. 3, pp. 229–241, 2020.
View at: Google Scholar
A. B. Fuks, “Vital pulp therapy with new materials for primary teeth: new directions and treatment perspectives,” Pediatric Dentistry, vol. 30, no. 3, pp. 211–219, 2008.
View at: Publisher Site | Google Scholar
S. Asgary, M. Fazlyab, S. Sabbagh, and M. J. Eghbal, “Outcomes of different vital pulp therapy techniques on symptomatic permanent teeth: a case series,” Iranian Endodontic Journal, vol. 9, no. 4, pp. 295–300, 2014.
View at: Google Scholar
S. Asgary and M. Ahmadyar, “Can miniature pulpotomy procedure improve treatment outcomes of direct pulp capping?” Medical Hypotheses, vol. 78, pp. 283–285, 2011.
View at: Google Scholar
S. Simon, A. J. Smith, P. J. Lumley, P. R. Cooper, and A. Berdal, “The pulp healing process: from generation to regeneration,” Endodontic Topics, vol. 26, no. 1, pp. 41–56, 2012.
View at: Publisher Site | Google Scholar
G. Schmalz and A. J. Smith, “Pulp development, repair, and regeneration: challenges of the transition from traditional dentistry to biologically based therapies,” Journal of Endodontics, vol. 40, no. 4 Suppl, pp. S2–S5, 2014.
View at: Publisher Site | Google Scholar
M. Goldberg, A. Njeh, and E. Uzunoglu, “Is pulp inflammation a prerequisite for pulp healing and regeneration?” Mediators of Inflammation, vol. 2015, Article ID 347649, 2015.
View at: Publisher Site | Google Scholar
L. Serwer, R. Hashizume, T. Ozawa, and C. D. James, “Systemic and local drug delivery for treating diseases of the central nervous system in rodent models,” Journal of Visualized Experiments, vol. 42, no. 42, Article ID 1992, 2010.
View at: Publisher Site | Google Scholar
H. Wen, H. Jung, and X. Li, “Drug delivery approaches in addressing clinical pharmacology-related issues: opportunities and challenges,” The AAPS Journal, vol. 17, no. 6, pp. 1327–1340, 2015.
View at: Publisher Site | Google Scholar
Y. H. Bae and K. Park, “Targeted drug delivery to tumors: myths, reality and possibility,” Journal of Controlled Release, vol. 153, no. 3, pp. 198–205, 2011.
View at: Publisher Site | Google Scholar
K. Öztürk-Atar, H. Eroğlu, and S. Çalış, “Novel advances in targeted drug delivery,” Journal of Drug Targeting, vol. 26, no. 8, pp. 633–642, 2018.
View at: Publisher Site | Google Scholar
S. B. Adams, M. F. Shamji, D. L. Nettles, P. Hwang, and L. A. Setton, “Sustained release of antibiotics from injectable and thermally responsive polypeptide depots,” Journal of Biomedical Materials Research. Part B, Applied Biomaterials, vol. 90, no. 1, pp. 67–74, 2009.
View at: Publisher Site | Google Scholar
G. Tiwari, R. Tiwari, L. Bhati, S. Pandey, P. Pandey, and B. Sriwastawa, “Drug delivery systems: an updated review,” International Journal of Pharmaceutical Investigation, vol. 2, no. 1, pp. 2–11, 2012.
View at: Publisher Site | Google Scholar
J. Liang, X. Peng, X. Zhou, J. Zou, and L. Cheng, “Emerging applications of drug delivery systems in oral infectious diseases prevention and treatment,” Molecules, vol. 25, no. 3, 2020.
View at: Publisher Site | Google Scholar
D. Joshi, T. Garg, A. K. Goyal, and G. Rath, “Advanced drug delivery approaches against periodontitis,” Drug Delivery, vol. 23, no. 2, pp. 363–377, 2016.
View at: Publisher Site | Google Scholar
Y. Wei, Y. Deng, S. Ma et al., “Local drug delivery systems as therapeutic strategies against periodontitis: a systematic review,” Journal of Controlled Release, vol. 333, no. 4, 2021.
View at: Publisher Site | Google Scholar
P. Dahake and S. Baliga, “Local drug delivery systems for pain management during and after endodontic therapy,” Acta Scientific Dental Sciences, vol. 4, pp. 01–07, 2020.
View at: Google Scholar
F. Shahri and A. Parhizkar, “Pivotal local drug delivery systems in endodontics; a review of literature,” Iranian Endodontic Journal, vol. 15, no. 2, pp. 65–78, 2020.
View at: Google Scholar
A. Parhizkar, H. Nojehdehian, F. Tabatabaei, and S. Asgary, “An innovative drug delivery system loaded with a modified combination of triple antibiotics for use in endodontic applications,” International Journal of Dentistry, vol. 2020, 2020.
View at: Publisher Site | Google Scholar
M. J. R. Virlan, D. Miricescu, A. Totan et al., “Current uses of poly(lactic-co-glycolic acid) in the dental field: a comprehensive review,” Journal of Chemistry, vol. 2015, pp. 1–12, 2015.
View at: Publisher Site | Google Scholar
M. Torshabi, H. Nojehdehian, and F. S. Tabatabaei, “In vitro behavior of poly-lactic-co-glycolic acid microspheres containing minocycline, metronidazole, and ciprofloxacin,” Journal of Investigative and Clinical Dentistry, vol. 8, no. 2, Article ID e12201, 2017.
View at: Publisher Site | Google Scholar
R. Soflou, H. Nojehdehyan, M. Torshabi, and F. Tabatabaei, PLGA Microspheres Containing Minocycline as Drug Delivery System, Iranian Division Meeting, Tehran, Iran, 2013.
F. F. O. Sousa, A. Luzardo-Álvarez, A. Pérez-Estévéz, R. Seoane-Prado, and J. Blanco-Méndez, “Development of a novel AMX-loaded PLGA/zein microsphere for root canal disinfection,” Biomedical Materials, vol. 5, no. 5, Article ID 055008, 2010.
View at: Publisher Site | Google Scholar
A. L. Álvarez, F. O. Espinar, and J. B. Méndez, “The application of microencapsulation techniques in the treatment of endodontic and periodontal diseases,” Pharmaceutics, vol. 3, no. 3, pp. 538–571, 2011.
View at: Publisher Site | Google Scholar
F. R. Bohns, V. C. B. Leitune, I. M. Garcia et al., “Incorporation of amoxicillin-loaded microspheres in mineral trioxide aggregate cement: an in vitro study,” Restorative dentistry and endodontics, vol. 45, no. 4, p. e50, 2020.
View at: Publisher Site | Google Scholar
R. Zhang, L. Xie, H. Wu et al., “Alginate/laponite hydrogel microspheres co-encapsulating dental pulp stem cells and VEGF for endodontic regeneration,” Acta Biomaterialia, vol. 113, pp. 305–316, 2020.
View at: Publisher Site | Google Scholar
D. Aubeux, O. A. Peters, S. Hosseinpour et al., “Specialized pro-resolving lipid mediators in endodontics: a narrative review,” BMC Oral Health, vol. 21, no. 1, pp. 1–13, 2021.
View at: Publisher Site | Google Scholar
A. Abraham, R. Raghavan, A. Joseph, M. P. S Devi, M Varghese, and P. V Sreedevi, “Evaluation of different local drug delivery systems in the management of chronic periodontitis: a comparative study,” The Journal of Contemporary Dental Practice, vol. 21, no. 3, pp. 280–284, 2020.
View at: Google Scholar
R. Yadav, I. L. Kanwar, T. Haider, V. Pandey, V. Gour, and V. Soni, “In situ gel drug delivery system for periodontitis: an insight review,” Future Journal of Pharmaceutical Sciences, vol. 6, no. 1, p. 33, 2020.
View at: Publisher Site | Google Scholar
L. Nastri, A. De Rosa, V. De Gregorio, V. Grassia, and G. Donnarumma, “A new controlled-release material containing metronidazole and doxycycline for the treatment of periodontal and peri-implant diseases: formulation and in vitro testing,” International Journal of Dentistry, vol. 2019, Article ID 9374607, 2019.
View at: Publisher Site | Google Scholar
K. Puri and N. Puri, “Local drug delivery agents as adjuncts to endodontic and periodontal therapy,” Journal of medicine and life, vol. 6, no. 4, pp. 414–419, 2013.
View at: Google Scholar
C. R. Silva, P. S. Babo, M. Gulino et al., “Injectable and tunable hyaluronic acid hydrogels releasing chemotactic and angiogenic growth factors for endodontic regeneration,” Acta Biomaterialia, vol. 77, pp. 155–171, 2018.
View at: Publisher Site | Google Scholar
P. Amrollahi, B. Shah, A. Seifi, and L. Tayebi, “Recent advancements in regenerative dentistry: a review,” Materials Science and Engineering: C, vol. 69, pp. 1383–1390, 2016.
View at: Publisher Site | Google Scholar
N. Zein, E. Harmouch, J. C. Lutz et al., “Polymer-based instructive scaffolds for endodontic regeneration,” Materials, vol. 12, no. 15, 2019.
View at: Publisher Site | Google Scholar
M. M. S. Abbass, A. A. El-Rashidy, K. M. Sadek et al., “Hydrogels and dentin-pulp complex regeneration: from the benchtop to clinical translation,” Polymers (Baseline), vol. 12, no. 12, 2020.
View at: Publisher Site | Google Scholar
A. M. Ferreira, P. Gentile, V. Chiono, and G. Ciardelli, “Collagen for bone tissue regeneration,” Acta Biomaterialia, vol. 8, no. 9, pp. 3191–3200, 2012.
View at: Publisher Site | Google Scholar
K. Varaprasad, G. M. Raghavendra, T. Jayaramudu, M. M. Yallapu, and R. Sadiku, “A mini review on hydrogels classification and recent developments in miscellaneous applications,” Materials Science and Engineering: C, vol. 79, pp. 958–971, 2017.
View at: Publisher Site | Google Scholar
X. Jia and K. L. Kiick, “Hybrid multicomponent hydrogels for tissue engineering,” Macromolecular Bioscience, vol. 9, no. 2, pp. 140–156, 2009.
View at: Publisher Site | Google Scholar
J. S. Ribeiro, E. A. F. Bordini, J. A. Ferreira et al., “Injectable MMP-responsive nanotube-modified gelatin hydrogel for dental infection ablation,” ACS Applied Materials and Interfaces, vol. 12, no. 14, pp. 16006–16017, 2020.
View at: Publisher Site | Google Scholar
S. Nguyen and M. Hiorth, “Advanced drug delivery systems for local treatment of the oral cavity,” Therapeutic Delivery, vol. 6, no. 5, pp. 595–608, 2015.
View at: Publisher Site | Google Scholar
P. Perugini, I. Genta, B. Conti, T. Modena, and F. Pavanetto, “Periodontal delivery of ipriflavone: new chitosan/PLGA film delivery system for a lipophilic drug,” International Journal of Pharmaceutics, vol. 252, no. 1-2, pp. 1–9, 2003.
View at: Publisher Site | Google Scholar
P. Makvandi, U. Josic, M. Delfi et al., “Drug delivery (nano) platforms for oral and dental applications: tissue regeneration, infection control, and cancer management,” Advanced Science, vol. 8, no. 8, Article ID 2004014, 2021.
View at: Publisher Site | Google Scholar
A. Lacević, E. Vranić, and I. Zulić, “Endodontic-periodontal locally delivered antibiotics,” Bosnian Journal of Basic Medical Sciences, vol. 4, no. 1, pp. 73–78, 2004.
View at: Publisher Site | Google Scholar
S. Şenel, A. I. Özdoğan, and G. Akca, “Current status and future of delivery systems for prevention and treatment of infections in the oral cavity,” Drug Delivery and Translational Research, vol. 11, no. 4, pp. 1703–1734, 2021.
View at: Publisher Site | Google Scholar
A. Hoxha, D. G. Gillam, A. J. Bushby, A. Agha, and M. P. Patel, “Layered double hydroxide fluoride release in dental applications: a systematic review,” Dentistry Journal, vol. 7, no. 3, p. 87, 2019.
View at: Publisher Site | Google Scholar
D. Steinberg and M. Friedman, “Development of sustained-release devices for modulation of dental plaque biofilm and treatment of oral infectious diseases,” Drug Development Research, vol. 50, no. 3-4, pp. 555–565, 2000.
View at: Publisher Site | Google Scholar
S. K. Yadav, G. Khan, M. Bansal et al., “Multiparticulate based thermosensitive intra-pocket forming implants for better treatment of bacterial infections in periodontitis,” International Journal of Biological Macromolecules, vol. 116, pp. 394–408, 2018.
View at: Publisher Site | Google Scholar
E. K. Moioli, P. A. Clark, X. Xin, S. Lal, and J. J. Mao, “Matrices and scaffolds for drug delivery in dental, oral and craniofacial tissue engineering,” Advanced Drug Delivery Reviews, vol. 59, no. 4-5, pp. 308–324, 2007.
View at: Publisher Site | Google Scholar
C. M. Agrawal and R. B. Ray, “Biodegradable polymeric scaffolds for musculoskeletal tissue engineering,” Journal of Biomedical Materials Research, vol. 55, no. 2, pp. 141–150, 2001.
View at: Publisher Site | Google Scholar
H. J. Haugen, P. Basu, M. Sukul, J. F. Mano, and J. E. Reseland, “Injectable biomaterials for dental tissue regeneration,” International Journal of Molecular Sciences, vol. 21, no. 10, p. 3442, 2020.
View at: Publisher Site | Google Scholar
S. N. Kaushik, B. Kim, A. M. C. Walma et al., “Biomimetic microenvironments for regenerative endodontics,” Biomaterials Research, vol. 20, no. 1, p. 14, 2016.
View at: Publisher Site | Google Scholar
M. G. C. Sousa, M. R. Maximiano, R. A. Costa, T. M. B. Rezende, and O. L. Franco, “Nanofibers as drug-delivery systems for infection control in dentistry,” Expert Opinion on Drug Delivery, vol. 17, no. 7, pp. 919–930, 2020.
View at: Publisher Site | Google Scholar
E. A. Münchow and M. C. Bottino, Current and Future Views on Biomaterial Use in Regenerative Endodontics, Springer, Berlin, Germany, 2019.
S. Ahmadi, A. Hivechi, S. H. Bahrami, P. B. Milan, and S. S. Ashraf, “Cinnamon extract loaded electrospun chitosan/gelatin membrane with antibacterial activity,” International Journal of Biological Macromolecules, vol. 173, pp. 580–590, 2021.
View at: Publisher Site | Google Scholar
J. M. Sotomil, E. A. Münchow, D. Pankajakshan et al., “Curcumin-A natural medicament for root canal disinfection: effects of irrigation, drug release, and photoactivation,” Journal of Endodontics, vol. 45, no. 11, pp. 1371–1377, 2019.
View at: Publisher Site | Google Scholar
P. Montero-Miralles, J. Martín-González, O. Alonso-Ezpeleta, M. C. Jiménez-Sánchez, E. Velasco-Ortega, and J. J. Segura-Egea, “Effectiveness and clinical implications of the use of topical antibiotics in regenerative endodontic procedures: a review,” International Endodontic Journal, vol. 51, no. 9, pp. 981–988, 2018.
View at: Publisher Site | Google Scholar
S. H. Chung and Y.-S. Park, “Local drug delivery in endodontics: a literature review,” Journal of Drug Delivery Science and Technology, vol. 39, pp. 334–340, 2017.
View at: Publisher Site | Google Scholar
Z. Li, L. Cao, M. Fan, and Q. Xu, “Direct pulp capping with calcium hydroxide or mineral trioxide aggregate: a meta-analysis,” Journal of Endodontics, vol. 41, no. 9, pp. 1412–1417, 2015.
View at: Publisher Site | Google Scholar
A. Parhizkar, H. Nojehdehian, and S. Asgary, “Triple antibiotic paste: momentous roles and applications in endodontics: a review,” Restorative dentistry and endodontics, vol. 43, p. e28, 2018.
View at: Publisher Site | Google Scholar
F. Elmsmari, J. A. González Sánchez, F. Duran-Sindreu et al., “Calcium hydroxide loaded PLGA biodegradable nanoparticles as an intracanal medicament,” International Endodontic Journal, 2021.
View at: Google Scholar
S. Shrestha and A. Kishen, “Bioactive molecule delivery systems for dentin-pulp tissue engineering,” Journal of Endodontics, vol. 43, no. 5, pp. 733–744, 2017.
View at: Publisher Site | Google Scholar
J. Park, Bioceramics: Properties, Characterizations, and Applications, Springer, Manhattan, NY, USA, 2009.
T. Morotomi, A. Washio, and C. Kitamura, “Current and future options for dental pulp therapy,” Japanese Dental Science Review, vol. 55, no. 1, pp. 5–11, 2019.
View at: Publisher Site | Google Scholar
W. B. Liechty, D. R. Kryscio, B. V. Slaughter, and N. A. Peppas, “Polymers for drug delivery systems,” Annual Review of Chemical and Biomolecular Engineering, vol. 1, no. 1, pp. 149–173, 2010.
View at: Publisher Site | Google Scholar
Z. Yuan, H. Nie, S. Wang et al., “Biomaterial selection for tooth regeneration,” Tissue Engineering Part B Reviews, vol. 17, no. 5, pp. 373–388, 2011.
View at: Publisher Site | Google Scholar
E. Patel, P. Pradeep, P. Kumar, Y. E. Choonara, and V. Pillay, “Oroactive dental biomaterials and their use in endodontic therapy,” Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 108, no. 1, pp. 201–212, 2020.
View at: Publisher Site | Google Scholar
American Association of Endodontists, “AAE position statement on vital pulp therapy,” Journal of Endodontics, vol. 47, no. 9, pp. 1340–1344, 2021.
View at: Publisher Site | Google Scholar
S. N. Hanna, R. Perez Alfayate, and J. Prichard, “Vital pulp therapy an insight over the available literature and future expectations,” European Endodontic Journal, vol. 5, no. 1, pp. 46–53, 2020.
View at: Google Scholar
R. Vij, J. Coll, P. Shelton, and N. Farooq, “Caries control and other variables associated with success of primary molar vital pulp therapy,” Pediatric Dentistry, vol. 26, pp. 214–220, 2003.
View at: Google Scholar
M. S. Pedano, X. Li, K. Yoshihara, K. V. Landuyt, and B. Van Meerbeek, “Cytotoxicity and bioactivity of dental pulp-capping agents towards human tooth-pulp cells: a systematic review of in-vitro studies and meta-analysis of randomized and controlled clinical trials,” Materials, vol. 13, no. 12, Article ID 2670, 2020.
View at: Publisher Site | Google Scholar
S. Navit, N. Jaiswal, S. A. Khan et al., “Antimicrobial efficacy of contemporary obturating materials used in primary teeth- an in-vitro study,” Journal of Clinical and Diagnostic Research : Journal of Clinical and Diagnostic Research, vol. 10, no. 9, pp. ZC09–ZC12, 2016.
View at: Publisher Site | Google Scholar
C. Estrela and R. Holland, “Calcium hydroxide: study based on scientific evidences,” Journal of Applied Oral Science, vol. 11, no. 4, pp. 269–282, 2003.
View at: Publisher Site | Google Scholar
M. L. R. Accorinte, A. D. Loguercio, A. Reis, and C. A. S. Costa, “Response of human pulps capped with different self-etch adhesive systems,” Clinical Oral Investigations, vol. 12, no. 2, pp. 119–127, 2008.
View at: Publisher Site | Google Scholar
A. Paranjpe, L. C. F. Bordador, M.-y. Wang, W. R. Hume, and A. Jewett, “Resin monomer 2-hydroxyethyl methacrylate (HEMA) is a potent inducer of apoptotic cell death in human and mouse cells,” Journal of Dental Research, vol. 84, no. 2, pp. 172–177, 2005.
View at: Publisher Site | Google Scholar
C. Cui, X. Zhou, X. Chen, M. Fan, Z. Bian, and Z. Chen, “The adverse effect of self-etching adhesive systems on dental pulp after direct pulp capping,” Quintessence International, vol. 40, pp. e26–34, 2009.
View at: Google Scholar
A. B. do Nascimento, U. F. Fontana, H. M. Teixeira, and C. A. Costa, “Biocompatibility of a resin-modified glass-ionomer cement applied as pulp capping in human teeth,” American Journal of Dentistry, vol. 13, no. 1, pp. 28–34, 2000.
View at: Google Scholar
I. M. Faraco and R. Holland, “Response of the pulp of dogs to capping with mineral trioxide aggregate or a calcium hydroxide cement,” Dental Traumatology, vol. 17, no. 4, pp. 163–166, 2001.
View at: Publisher Site | Google Scholar
C. F. Cox, R. K. Sübay, E. Ostro, S. Suzuki, and S. H. Suzuki, “Tunnel defects in dentin bridges: their formation following direct pulp capping,” Operative Dentistry, vol. 21, no. 1, pp. 4–11, 1996.
View at: Google Scholar
M. G. Gandolfi, F. Siboni, T. Botero, M. Bossù, F. Riccitiello, and C. Prati, “Calcium silicate and calcium hydroxide materials for pulp capping: biointeractivity, porosity, solubility and bioactivity of current formulations,” Journal of Applied Biomaterials and Functional Materials, vol. 13, no. 1, pp. 43–60, 2015.
View at: Publisher Site | Google Scholar
M. Zanini, M. Hennequin, and P. Cousson, “Which procedures and materials could be applied for full pulpotomy in permanent mature teeth? a systematic review,” Acta Odontologica Scandinavica, vol. 77, no. 7, pp. 541–551, 2019.
View at: Publisher Site | Google Scholar
J. A. Coll, N. S. Seale, K. Vargas, A. A. Marghalani, S. Al Shamali, and L. Graham, “Primary tooth vital pulp therapy: a systematic review and meta-analysis,” Pediatric Dentistry, vol. 39, no. 1, pp. 16–123, 2017.
View at: Google Scholar
E. Stringhini Junior, M. G. C. Dos Santos, L. B. Oliveira, and M. Mercadé, “MTA and biodentine for primary teeth pulpotomy: a systematic review and meta-analysis of clinical trials,” Clinical Oral Investigations, vol. 23, no. 4, pp. 1967–1976, 2019.
View at: Publisher Site | Google Scholar
O. Fakheran, R. Birang, P. R. Schmidlin, S. M. Razavi, and P. Behfarnia, “Retro MTA and tricalcium phosphate/retro MTA for guided tissue regeneration of periodontal dehiscence defects in a dog model: a pilot study,” Biomaterials Research, vol. 23, no. 1, p. 14, 2019.
View at: Publisher Site | Google Scholar
M. Kunert and M. Lukomska-Szymanska, “Bio-inductive materials in direct and indirect pulp capping-a review article,” Materials, vol. 13, no. 5, 2020.
View at: Publisher Site | Google Scholar
N. Sarkar, R. Caicedo, P. Ritwik, R. Moiseyeva, and I. Kawashima, “Physicochemical basis of the biologic properties of mineral trioxide aggregate,” Journal of Endodontics, vol. 31, no. 2, pp. 97–100, 2005.
View at: Publisher Site | Google Scholar
S. Jitaru, I. Hodisan, L. Timis, A. Lucian, and M. Bud, “The use of bioceramics in endodontics - literature review,” Clujul Medical (1957), vol. 89, no. 4, pp. 470–473, 2016.
View at: Google Scholar
A. Paula, M. Laranjo, C. M. Marto et al., “Biodentine(™) boosts, WhiteProRoot(®)MTA increases and Life(®) suppresses odontoblast activity,” Materials, vol. 12, no. 7, 2019.
View at: Publisher Site | Google Scholar
P. Laurent, J. Camps, and I. About, “Biodentine™ induces TGF-β1 release from human pulp cells and early dental pulp mineralization,” International Endodontic Journal, vol. 45, no. 5, pp. 439–448, 2012.
View at: Publisher Site | Google Scholar
C. Zhu, B. Ju, and R. Ni, “Clinical outcome of direct pulp capping with MTA or calcium hydroxide: a systematic review and meta-analysis,” International Journal of Clinical and Experimental Medicine, vol. 8, no. 10, pp. 17055–17060, 2015.
View at: Google Scholar
K. Baroudi and S. Samir, “Sealing ability of MTA used in perforation repair of permanent teeth; literature review,” The Open Dentistry Journal, vol. 10, no. 1, pp. 278–286, 2016.
View at: Publisher Site | Google Scholar
M. Vijayran, S. Chaudhary, N. Manuja, and A. U. Kulkarni, “Mineral trioxide aggregate (MTA) apexification: a novel approach for traumatised young immature permanent teeth,” BMJ Case Reports, vol. 2013, Article ID bcr2012008094, 2013.
View at: Google Scholar
T. J. Hilton, J. L. Ferracane, and L. Mancl, “Comparison of CaOH with MTA for direct pulp capping: a PBRN randomized clinical trial,” Journal of Dental Research, vol. 92, no. 7 Suppl, pp. 16s–22s, 2013.
View at: Publisher Site | Google Scholar
E. A. Bortoluzzi, G. S. Araújo, J. M. Guerreiro Tanomaru, and M. Tanomaru-Filho, “Marginal gingiva discoloration by gray MTA: a case report,” Journal of Endodontics, vol. 33, no. 3, pp. 325–327, 2007.
View at: Publisher Site | Google Scholar
M. Parirokh and M. Torabinejad, “Mineral trioxide aggregate: a comprehensive literature review-part III: clinical applications, drawbacks, and mechanism of action,” Journal of Endodontics, vol. 36, no. 3, pp. 400–413, 2010.
View at: Publisher Site | Google Scholar
M. Parirokh, M. Torabinejad, and P. M. H. Dummer, “Mineral trioxide aggregate and other bioactive endodontic cements: an updated overview—part I: vital pulp therapy,” International Endodontic Journal, vol. 51, no. 2, pp. 177–205, 2018.
View at: Publisher Site | Google Scholar
M. Bossù, F. Iaculli, G. Di Giorgio, A. Salucci, and A. PolimeniS. D. Carlo, “Different pulp dressing materials for the pulpotomy of primary teeth: a systematic review of the literature,” Journal of Clinical Medicine, vol. 9, no. 3, 2020.
View at: Google Scholar
M. Kaup, C. H. Dammann, E. Schäfer, and T. Dammaschke, “Shear bond strength of Biodentine, ProRoot MTA, glass ionomer cement and composite resin on human dentine ex vivo,” Head and Face Medicine, vol. 11, no. 14, 2015.
View at: Publisher Site | Google Scholar
X. Tran, H. Salehi, M. Truong et al., “Reparative mineralized tissue characterization after direct pulp capping with calcium-silicate-based cements,” Materials, vol. 12, no. 13, Article ID 2102, 2019.
View at: Publisher Site | Google Scholar
A. H. Bui and K. V. Pham, “Evaluation of reparative dentine bridge formation after direct pulp capping with biodentine,” Journal of International Society of Preventive and Community Dentistry, vol. 11, no. 1, pp. 77–82, 2021.
View at: Google Scholar
A. Nowicka, M. Lipski, M. Parafiniuk et al., “Response of human dental pulp capped with biodentine and mineral trioxide aggregate,” Journal of Endodontics, vol. 39, no. 6, pp. 743–747, 2013.
View at: Publisher Site | Google Scholar
L. Grech, B. Mallia, and J. Camilleri, “Investigation of the physical properties of tricalcium silicate cement-based root-end filling materials,” Dental Materials, vol. 29, no. 2, pp. e20–e28, 2013.
View at: Publisher Site | Google Scholar
Ö Malkondu, M. Karapinar Kazandağ, and E. Kazazoğlu, “A review on biodentine, a contemporary dentine replacement and repair material,” BioMed Research International, vol. 2014, Article ID 160951, 2014.
View at: Publisher Site | Google Scholar
X. V. Tran, L. T. Q. Ngo, and T. Boukpessi, “BiodentineTM full pulpotomy in mature permanent teeth with irreversible pulpitis and apical periodontitis,” Healthcare, vol. 9, no. 6, p. 720, 2021.
View at: Publisher Site | Google Scholar
I. About, “Biodentine: from biochemical and bioactive properties to clinical applications,” Giornale Italiano di Endodonzia, vol. 30, no. 2, pp. 81–88, 2016.
View at: Publisher Site | Google Scholar
S. Asgary, S. Shahabi, T. Jafarzadeh, S. Amini, and S. Kheirieh, “The properties of a new endodontic material,” Journal of Endodontics, vol. 34, no. 8, pp. 990–993, 2008.
View at: Publisher Site | Google Scholar
S. Utneja, R. R. Nawal, S. Talwar, and M. Verma, “Current perspectives of bio-ceramic technology in endodontics: calcium enriched mixture cement - review of its composition, properties and applications,” Restorative Dentistry and Endodontics, vol. 40, no. 1, pp. 1–13, 2015.
View at: Publisher Site | Google Scholar
S. Asgary, M. J. Eghbal, M. Parirokh, J. Ghoddusi, S. Kheirieh, and F. Brink, “Comparison of mineral trioxide aggregate’s composition with portland cements and a new endodontic cement,” Journal of Endodontics, vol. 35, no. 2, pp. 243–250, 2009.
View at: Publisher Site | Google Scholar
M. Hasan Zarrabi, M. Javidi, M. Naderinasab, and M. Gharechahi, “Comparative evaluation of antimicrobial activity of three cements: new endodontic cement (NEC), mineral trioxide aggregate (MTA) and Portland,” Journal of Oral Science, vol. 51, no. 3, pp. 437–442, 2009.
View at: Publisher Site | Google Scholar
M. Hasheminia, S. Loriaei Nejad, and S. Asgary, “Sealing ability of MTA and CEM cement as root-End fillings of human teeth in dry, saliva or blood-contaminated conditions,” Iranian Endodontic Journal, vol. 5, pp. 151–156, 2010.
View at: Google Scholar
S. Asgary, M. J. Eghbal, and M. Parirokh, “Sealing ability of a novel endodontic cement as a root-end filling material,” Journal of Biomedical Materials Research Part A, vol. 87A, no. 3, pp. 706–709, 2008.
View at: Publisher Site | Google Scholar
L. L. Hench, “The story of Bioglass,” Journal of Materials Science: Materials in Medicine, vol. 17, no. 11, pp. 967–978, 2006.
View at: Publisher Site | Google Scholar
T. Kokubo and H. Takadama, “How useful is SBF in predicting in vivo bone bioactivity?” Biomaterials, vol. 27, no. 15, pp. 2907–2915, 2006.
View at: Publisher Site | Google Scholar
A. Washio, A. Nakagawa, T. Nishihara, H. Maeda, and C. Kitamura, “Physicochemical properties of newly developed bioactive glass cement and its effects on various cells,” Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 103, no. 2, pp. 373–380, 2015.
View at: Publisher Site | Google Scholar
K. Hanada, T. Morotomi, A. Washio et al., “In vitro and in vivo effects of a novel bioactive glass‐based cement used as a direct pulp capping agent,” Journal of Biomedical Materials Research Part B: Applied Biomaterials, vol. 107, no. 1, pp. 161–168, 2019.
View at: Publisher Site | Google Scholar
K. S. D. R. Kalyan, C. Vinay, K. Arunbhupathi, K. S. Uloopi, R. Chandrasekhar, and K. S. RojaRamya, “Preclinical evaluation and clinical trial of chlorhexidine polymer scaffold for vital pulp therapy,” Journal of Clinical Pediatric Dentistry, vol. 43, no. 2, pp. 109–115, 2019.
View at: Publisher Site | Google Scholar
T. Morotomi, Y. Tabata, and C. Kitamura, “Dentin-pulp complex regeneration therapy following pulp amputation,” Advanced Techniques in Biology and Medicine, vol. 3, no. 3, pp. 1–5, 2015.
View at: Publisher Site | Google Scholar
C. Kitamura, T. Nishihara, M. Terashita, Y. Tabata, and A. Washio, “Local regeneration of dentin-pulp complex using controlled release of FGF-2 and naturally derived sponge-like scaffolds,” International Journal of Dentistry, vol. 2012, Article ID 190561, 2012.
View at: Publisher Site | Google Scholar
D. Tziafas, G. Belibasakis, A. Veis, and S. Papadimitriou, “Dentin regeneration in vital pulp therapy: design principales,” Advances in Dental Research, vol. 15, no. 1, pp. 96–100, 2001.
View at: Publisher Site | Google Scholar
S. Wu, Y. Zhou, Y. Yu et al., “Evaluation of chitosan hydrogel for sustained delivery of VEGF for odontogenic differentiation of dental pulp stem cells,” Stem Cells International, vol. 2019, Article ID 1515040, 2019.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2021 Ardavan Parhizkar and Saeed Asgary. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

1436

Downloads

1509

Citations