Biomaterials for Regeneration of the Dentin-Pulp Complex

Abstract

Biomaterials or bioactive materials interact with the surrounding environment, stimulating growth and promoting the regeneration of damaged or lost dental tissues. They can be natural, derived from animal or plant tissues, synthetic like bioceramics, or a combination of both. Natural biomaterials include substances from animal or plant tissues like dentin, bone, and collagen, while synthetic ones include materials like bioceramics, bioactive glass, and polymers. These materials are used in various dental treatments such as direct pulp capping, indirect pulp capping, partial and total pulpotomy, and pulp regeneration. This method aims to promote pulp healing and the formation of a mineralized tissue barrier, avoiding more invasive and extensive treatments. The formation of mineralized tissue is considered a favorable response of the exposed pulp tissue, showing its ability to recover. Different biomaterials, their mechanisms of action, clinical indications, applications, and future perspectives will be described in this chapter.

1. Introduction

Regenerative dentistry represents a paradigm as it aims to reconstruct dental tissues using the potential of stem cells and bioactive materials [1]. Stem cells possess the ability to differentiate, repair, and regulate inflammation. Bei Li et al. have demonstrated that stem cells also exhibit clonogenic capacity and the ability to differentiate into various stromal lineages [2]. Bioactive materials like calcium phosphate (CaP) and silicate-based materials interact with the surrounding environment, stimulating biocompatibility and the capacity to induce cell migration, proliferation, and differentiation. Among the biomaterials available are collagen hydrogels that promote cell adhesion and differentiation [1]. Ceramic biomaterials such as hydroxyapatite and tricalcium phosphate have been shown to stimulate dentin formation and support tissue repair [3]. Synthetic and natural biomaterials, including autologous, allogeneic, and xenogeneic materials, as well as nanostructured or microporous biomaterials composed of hydroxyapatite nanoparticles in three dimensions [4, 5].

In this context, the selection and evaluation of biomaterials play a crucial role in the success of these procedures. This chapter aims to thoroughly explore the range of biomaterials, their mechanisms of action in dentin-pulp regeneration analyzing their long-term efficacy, interaction with surrounding tissues, and applicability in clinical settings. Existing clinical studies will be critically examined to provide a comprehensive overview of current advancements and suggest potential directions for future research to enhance treatment personalization and address ethical and safety challenges.

2. Biomaterials used in regeneration of the dentin-pulp complex

Biomaterials play an integral role in the dentin-pulp regeneration process by providing both physical and biological support. They are classified based on various criteria (e.g., Table 1).

Composition	Natural biomaterials:	Derived from natural sources such as dentin, enamel, collagen, or stem cells.
	Synthetic biomaterials:	Manufactured using synthetic materials like cements, resins, or polymers.
	Hybrid biomaterials:	Combine natural and synthetic materials [4].
Mechanism of action	Bioactive biomaterials:	These biomaterials interact with pulp tissue to stimulate the formation of new tissue.
	Biomimetic biomaterials:	These biomaterials imitate the structure and function of natural tissues.
	Combined biomaterials:	These biomaterials combine two or more types to achieve a synergistic effect [4].
Function	Coating biomaterials:	These biomaterials are used to protect dental pulp from infection and irritation.	Biodentine [6].; MTA [7].; Bioactive Glass [8].
	Matrix biomaterials for new tissue formation:	These biomaterials provide physical support for the formation of new tissue.	Collagen Biomaterials [3].; Hydroxyapatite Biomaterials [9].; Polymer Biomaterials [10].
	Growth factor-releasing biomaterials:	These biomaterials release growth factors that stimulate the formation of new tissue [4].	Biomaterials with cell adhesion proteins [10, 11].; Biomaterials with isolated growth factors [10, 11].; Biomaterials with complex growth factors [10, 11].

Table 1.

Classification of biomaterials for dentin-pulp regeneration according different criteria.

To achieve the safest tissue response and optimize outcomes in therapies, new complex biomaterials have emerged to preserve pulp vitality during conservative operations and restorative dental procedures [9, 12]. However, the wide range of biomaterials available for dentin-pulp coating (DPC) should possess several characteristics, including ease of manipulation during operative procedures, adhesion to dental substrate, antibacterial properties, excellent sealing ability, insolubility in tissue fluids, biocompatibility, bioactivity, radiopacity, absence of tooth discoloration, and promotion of mineralized tissue barrier formation. Unfortunately, no current DPC biomaterial possesses all these characteristics [13].

2.1 Calcium hydroxide (CH)

Calcium hydroxide is a chemical compound with the formula Ca(OH)2 and a basic pH of 12.5–13.5 due to the release of hydroxyl ions, which helps protect the pulp tissue by stimulating fibroblasts [14]. For decades, it has been considered a standard material for DPC, possessing antimicrobial activity and the ability to remineralizer carious dentin [15, 16, 17].

Disadvantage: Its main drawback is inadequate adhesion to hard tissues, failing to provide optimal sealing.

Another disadvantage of calcium hydroxide is its capacity to dissolve. However, the specific mechanism responsible for dissolution in the tissue remains largely unexplored in the existing literature and requires further research [18, 19].

Mechanism of action:

It leads to a tunnel-like phenomenon in the dentin bridge, although this imperfection decreases as the dentin bridge thickness increases [15, 20].

When placed over exposed pulp, it shows satisfactory clinical outcomes as a material for DPC in superficial necrosis [14], stimulating the formation of a reparative dentin bridge through cellular differentiation, extracellular matrix secretion, and potential mineralization, creating a microenvironment oversaturated with calcium ions in close proximity to the pulp. The effectiveness of calcium hydroxide depends on the application type and the severity of the pulp injury; it is effective in protecting the pulp from infection and inflammation but is not always effective in regenerating it. Long-term clinical research on DPC follow-up using calcium hydroxide has yielded success rates ranging from 37% to 81.8%. This observation remains consistent despite multiple studies demonstrating the effectiveness of calcium hydroxide in promoting pulp healing [14, 21]. Findings from studies with follow-up durations exceeding 5 years have shown a broad success rate: 77.6% between 2 and 6 years, 58.7% up to 9 years, and over 10 years, 72.7% [22].

Clinical applications:

• Direct Pulp Capping: Calcium hydroxide is applied directly to the exposed dental pulp to create a physical barrier that protects the pulp tissue.

• Regenerative Pulp Therapy involves the use of CH as a base as it has the ability to restore dental pulp through the process of differentiation, leading to the formation of odontoblasts, dentin, and blood vessels [9, 20].

• Deep Caries: Remineralizes carious dentin and prevents pulp exposure.

• Irreversible Pulp Lesions: It can be used to relieve pain and inflammation in cases [9, 20].

Contraindications:

• Should not be used in cases of active pulpal infection.

• Apical root fracture.

Side effects:

• Common and transient side effects of calcium hydroxide include: burning sensation, sensitivity to touch, slight inflammation in the treated area for a few days [9, 20].

2.2 Bioceramic cements

2.2.1 Mineral trioxide aggregate (MTA)

It is a biomaterial derived from Portland cement, its main components consist of tricalcium silicate, dicalcium silicate, and tricalcium aluminate, supplemented with bismuth oxide to improve radiopacity [23]. Initially developed for apical perforation repair procedures, it is currently a versatile material with bioactive properties that have expanded its use to regenerative dentistry due to its ability to form a dentin barrier, stimulate the formation of hard tissues, and exhibit low cellular toxicity [24, 25, 26]. This material presents the following beneficial properties for pulp repair:

• Exceptional biocompatibility when applied to the pulp wound

• Sealing capacity that facilitates excellent cell/material adhesion

• Low solubility

• Prevents bacterial infiltration

• Stimulation of mineralized matrix formation [24].

Mechanism of action:

It exhibits physicochemical properties due to the release of calcium ions and the alkalinity of the material, inducing the formation of reparative dentin by attracting and activating cells responsible for the formation of hard tissues, thus contributing to the development of a matrix and the mineralization process [27, 28].

It triggers the migration of progenitor cells (specifically fibroblasts) from the central pulp to the site of exposure. This process helps improve their replication and specialization into odontoblast-like cells while avoiding the induction of apoptosis in pulp cells [27].

MTA initiates a time-dependent pro-inflammatory environment that facilitates wound regeneration through positive regulation of cytokines. Positive regulation of cytokines is responsible for stimulating biomineralization, achieved by the production of collagen fibrils or apatite-like groups at the interface between dentin and MTA. The release of calcium ions by MTA induces antibacterial effects and promotes mineralization in the area beneath the exposed pulp, potentially preserving pulp vitality. When used in conjunction with a sealed restoration, MTA prevents bacterial leakage and may help preserve pulp tissue, facilitate healing, and maintain pulp vitality [29, 30]. The primary calcium ion released by MTA participates in a reaction with phosphates present in tissue fluid, resulting in hydroxyapatite formation. This process makes the material biocompatible and capable of ensuring sufficient sealing [31, 32].

Advantages:

The inflammatory response triggered by MTA is transient and less severe compared to that induced by CH [33].

It has the ability to decrease levels of inflammation, hyperemia, and pulpal necrosis, while also being able to dissolve the bioactive proteins involved in the tooth repair process [28].

Disadvantages:

Extended setting time, which can be several hours.

Difficult material manipulation.

Discoloration, currently countered with new presentations (MTA WHITE).

High cost [17, 26, 34].

Clinical application of MTA in pulp-dentin regeneration:

Pulpotomy and partial pulpotomy

Apexification and periapical Surgery: Used to promote apical formation and closure in cases of open apices or periapical lesions.

Retroapical filling and endodontic surgery: Preferred material for retrograde filling in endodontic surgery [35].

Direct pulp capping in situations of pulp exposure, for its ability to promote reactive dentin formation [36].

Efficiency

Efficiency in apexification, with positive results in root apex regeneration [37]. Recent research studies have presented findings indicating that MTA demonstrates a higher rate of clinical success, induces a lower degree of pulpal inflammatory response, and facilitates the formation of mineralized tissue barriers compared to CH in DPC [38, 39, 40]. A comprehensive study involving 49 teeth with carious pulp exposure in 37 patients, where MTA was used, revealed an overall success rate of 97.96% after a span of 9 years [31]. The authors of this study claimed that MTA, when used in a two-visit treatment protocol, shows potential as a pulp capping material for direct exposures in permanent teeth [31]. In another study covering 122 teeth with caries and mechanical exposure in 108 patients, both MTA and CH were used for capping. The overall success rate of MTA for carious and mechanical exposure was 80% and 70%, respectively, while for CH it was 62% and 50%, respectively, after a duration of 1 to 6.6 years. The study concluded that after DPC, MTA appears to be more effective than CH in maintaining long-term pulpal vitality [41].

A recent study conducted on 229 teeth with mechanical and carious exposure in 205 patients, using MTA and CH, revealed an overall success rate of 80% and 84% for MTA in cases of mechanical and carious exposure, respectively, while for CH, it was 57% and 70%, respectively, after a duration of 2 to 10 and 25 year. The findings of this study suggested that when used as a DPC agent, MTA provides better long-term results compared to CH, and immediate placement of a permanent restoration after DPC was recommended. Within the parameters of these studies, MTA appears to be a suitable substitute for CH in DPC [11]. Therefore, it can be stated that MTA has been established as a suitable protective agent and a reliable treatment option for exposed pulp, with a certain degree of predictability in DPC [5].

2.2.2 Biodentine – dentin substitute

Biodentine, a biomaterial developed by Septodont in Saint-Maur-des-Fossés, France [26], has emerged as a prominent choice for dentin-pulp complex regeneration. It is a mixture of powder and liquid components containing tricalcium silicate, tricalcium aluminate, calcium carbonate, and water, demonstrating notable bioactive characteristics by releasing calcium and silicate ions [41]. Unlike other materials, it does not contain inorganic compounds such as calcium aluminate, calcium sulfate, or bismuth oxide [26, 42].

The documented efficacy of Biodentine in the dentin-pulp complex for mechanically exposed pulps is comparable to that of MTA [32].

Advantages:

• It has better mechanical properties.

• Improved color stability.

• Simpler application process.

• Faster initial setting time compared to MTA [4, 39, 43, 44, 45].

Disadvantages:

• It has limitations in terms of radiopacity and achieving the desired or optimized consistency.

• Controlled release and regeneration of ions with Biodentine may not meet all clinical needs.

Despite its limitations, Biodentine remains a valuable option in dentistry for a variety of procedures, thanks to its bioactive properties and its ability to promote dentin-pulp tissue regeneration.

Controlled release of ions by Biodentine promotes mineralization and hard tissue formation, favoring dentin-pulp regeneration, emphasizing Biodentine’s ability to induce reparative dentin formation and its excellent biocompatibility. Biodentine has been found to release significantly higher amounts of calcium compared to CH cement and MTA [46, 47, 48, 49]. An increase in the amount of released calcium indicates a simultaneous increase in hydroxyl ions. The antibacterial properties of Biodentine are attributed to its high pH, achieved through the action of hydroxyl ions on the surrounding tissue [19]. Due to the elevated pH, a thin layer of coagulative necrosis forms between the vital pulp tissue and the pulp capping material [50]. This necrotic zone acts as a barrier between the alkaline substance pH and the pulp cells beneath it. Additionally, a reparative dentin bridge will form adjacent to it. Furthermore, Biodentine has been observed to release silicon ions into the surrounding dentin. It is hypothesized that these silicon ions produced by Biodentine aid in the formation of dentin bridges and accelerate mineralization [42]. Studies have shown that after applying Biodentine for DPC, a complete dentin bridge forms, accompanied by a less inflammatory pulpal response and well-arranged layers of odontoblasts and odontoblast-like cells [51].

Clinical application of biodentine in dentin-pulp regeneration

The clinical application of Biodentine in dentin and pulp restoration has been extensively studied. Research has compared the efficacy of Biodentine as a direct DPC material with that of MTA. In a 6-month evaluation, 24 teeth with carious pulp exposure were treated with MTA or Biodentine, resulting in overall success rates of 91.7% and 83.3%, respectively. Another experiment involving 68 teeth with carious pulp exposure in 54 patients showed that after 6 months of treatment, both MTA and Biodentine exhibited overall success rates of 93.5% and 93.1%, respectively. After a duration of 12 months, the achievement rates of MTA and Biodentine were 100% and 96%, respectively. A subsequent 3-year study revealed overall success rates for MTA and Biodentine of 96% and 91.7%, respectively. These findings imply that when used as materials for dental pulp coverage in fully mature permanent teeth with carious exposure, both Biodentine and MTA demonstrate favorable and comparable success rates. However, the long-term achievement of dental pulp coverage may depend on the amount of remaining healthy dental structure and the resistance of the coronal restoration [52]. Nevertheless, further evidence from clinical trials with extended follow-up periods is needed to thoroughly evaluate the effectiveness of Biodentine in covering exposed dental pulp.

Pulpotomy and partial pulpotomy: Biodentine has been shown to be effective in pulpotomies, where it is applied in the pulp chamber to preserve the vitality of the affected pulp tissue. Significant success rates have been demonstrated in pulpotomies with Biodentine, with reparative dentin formation and a favorable pulpal response.

Direct pulpal sealing: In cases of direct pulp exposure during cavity preparations, Biodentine has been used for direct pulpal sealing. Its sealing capacity and compatibility with pulp tissues have been noted [6, 26].

Direct pulpal capping: In situations of indirect pulp exposure, Biodentine has been applied as a direct pulp capping material, yielding positive pulpal responses and reactive dentin formation when used as a direct capping agent [26].

The efficacy and prognosis of this therapy depend on variables such as age, type of exposure, site of exposure, and degree of pulp exposure. It is worth noting that MTA has undergone more extensive evaluation as a direct pulp capping substance compared to Biodentine. Furthermore, prevailing research on Biodentine has involved a smaller number of participants compared to MTA research [42].

2.2.3 BioAggregate

BioAggregate is a bioinductive tricalcium cement [48], composed of tricalcium silicate, dicalcium silicate, monobasic calcium phosphate, amorphous silica, and tantalum oxide acting as a radiopacifier [34, 53]. Accumulated evidence suggests that when used as an apical filling material, BioAggregate exhibits exceptional sealing capabilities and superior biocompatibility compared to MTA. Additionally, recent research has provided empirical evidence indicating that BioAggregate outperforms MTA in terms of its ability to promote odontoblastic differentiation and mineralization when employed as a pulp capping material [54].

Composition and properties

BioAggregate, an advanced iteration of MTA, lacks aluminum. Instead, it is primarily composed of tantalum oxide, which replaces bismuth oxide and calcium phosphate. The removal of aluminum from its chemical composition leads to a reduction in adverse effects on inflammatory cellular response [34]. However, the effects of BioAggregate on dental pulp tissues have not been thoroughly investigated.

Indications

BioAggregate is used for dentin-pulp complex regeneration in the following cases:

• Irreversible pulp lesions: BioAggregate can be used to alleviate pain and inflammation in cases of irreversible pulp lesions.

• Irreversible pulp lesions with pulp exposure: BioAggregate can be used to protect exposed dental pulp from infections and inflammation.

• Irreversible pulp lesions with pulp exposure and apical root fracture: BioAggregate can be used to restore dental pulp function in cases of irreversible pulp lesions with pulp exposure and apical root fracture [54].

Efficacy

The efficacy of BioAggregate in dentin-pulp complex regeneration has been evaluated in various clinical research studies. Overall, these studies have demonstrated that BioAggregate is effective in stimulating dental pulp regeneration in cases of irreversible pulp lesions. Recent findings have indicated that MTA has exhibited significantly higher levels of thicker hard tissue development compared to BioAggregate. However, BioAggregate also showed substantial and uniform hard tissue barrier formation. Further examination is required to determine if BioAggregate could function as a suitable substitute for pulp capping materials [54].

2.2.4 Super MTA paste

It is composed of Portland cement, with the addition of TBB (tributyl borane) as a polymerization initiator, eliminating the need for photopolymerization [13]. It provides biocompatibility as a pulp-capping material and is capable of inducing the formation of a uniform dentin bridge. It is composed of:

• Zinc oxide, which has antimicrobial and antifungal properties.

• Bismuth oxide, with radiopaque properties, making it visible on radiographs.

• Tricalcium silicate, with cementing and bioactive properties.

• Bismuth orthosilicate, with cementing and antifungal properties [13, 29].

Properties:

• Biocompatibility with human tissues.

• Bioactivity, stimulating the regeneration of the dental pulp complex.

• Biodegradability, naturally decomposing in the body.

• Mechanical strength: The paste exhibits high mechanical strength, suitable for use in stress-prone areas [29].

Clinical indications:

• Indirect pulp therapy: Used to seal the pulp chamber and protect the dental pulp from infections.

• Pulp Regenerative Therapy: Can be used as a base for applying dental pulp or periodontal ligament stem cells.

• Direct pulp capping: To protect exposed dental pulp from infections.

• Sealing an open apex of a tooth [27, 29, 55].

Efficacy:

Super MTA paste has demonstrated therapeutic efficacy comparable to TheraCal LC when applied to exposed pulp. However, further clinical trials are needed to validate its efficacy in both short- and long-term clinical outcomes [27, 55].

2.3 Resin-based MTA: TheraCal LC

Composition and properties:

TheraCal LC (Bisco, Schaumburg, IL, USA) [32], considered as a resin-based biomaterial, is composed of calcium silicate and can be used as a pulp-capping agent and as a protective lining combined with restoration materials [22]. Its composition includes type I collagen, hydroxyapatite, fibronectin, and growth factors. The collagen matrix provides a solid framework for dentin-pulp complex restoration. Hydroxyapatite acts as a supportive scaffold for dentin and blood vessel formation. Fibronectin helps facilitate cellular adhesion and migration, while growth factors serve as catalysts for the dentin-pulp complex regeneration process. In order to address the limitations of the original MTA, certain resin-modified MTAs have been introduced with the aim of reducing setting time [32].

TheraCal LC has effectively demonstrated its ability to release calcium ions, which are essential in stimulating and differentiating human dental pulp cells and odontoblasts, as well as aiding in the formation of new mineralized hard tissues [23, 47, 56].

Applications:

TheraCal LC is used in dentin-pulp complex regeneration in cases of irreversible pulp lesions and can be employed to protect exposed dental pulp from infections and inflammation [18, 47].

Efficacy:

The efficacy of TheraCal LC in stimulating dentin-pulp complex regeneration has been evaluated in various clinical research studies and has shown success in promoting dental pulp regeneration in cases of irreversible pulp lesions. Clinical success rates of TheraCal LC have been evaluated and compared with other substances over a short period of time [57]. It has been determined that there is no statistically significant difference in success rates among TheraCal, Biodentine, and MTA when compared with each other, leading to the recommendation of TheraCal LC as a substance for dentin-pulp complex restoration [32, 57].

2.4 Collagen hydrogels

Collagen hydrogels are biomaterials composed of a collagen matrix and a liquid substance. Collagen is a protein naturally found in the human body and possesses biocompatible, bioactive, and biodegradable properties. The liquid substance can be water, blood serum, or saline solution [58, 59, 60, 61].

Indications:

Collagen hydrogels are used for various clinical indications in dentistry, including pulp regeneration, promoting regeneration in cases of irreversible lesions, closure of open apices, in regenerative pulp therapy as a base for the application of dental pulp or periodontal ligament stem cells, and as a direct pulp-capping material to protect exposed dental pulp from infections [58, 60].

2.5 Another material DPC

Eugenol Zinc Oxide (ZOE): It has been mentioned as another material for dental pulp capping, possessing bactericidal properties similar to those of CH cements and calcium silicate [10]. However, the release of eugenol from this material is highly toxic to cells [16]. A study revealed that coating dental pulp with ZOE did not result in pulp healing but rather in chronic inflammation and absence of dentin bridge formation after 12 weeks [10]. Consequently, ZOE is not recommended for dental pulp coating [10, 11].

Glass Ionomer (GI) and Resin-Modified Glass Ionomer (RMGI): While CH and calcium silicate cements are alkaline in nature, GI, RMGI cements retain their initial acidity at a low pH for an extended period, which could have an adverse impact on pulp tissue [11]. Compared to CH and GI/RMGI, CH has been shown to significantly promote pulp healing, while GI/RMGI resulted in chronic inflammation and absence of dentin bridge formation after 10 months. Therefore, GI/RMGI should not be used for dental pulp coating [9].

2.5.1 Bioactive glass

Bioactive glass (BG) is a novel material that has gained significant prominence in regenerative dentistry due to its unique properties. Composed primarily of silica, calcium, and phosphorus, BG stimulates beneficial cellular responses, promoting the formation of hydroxyapatite and facilitating tissue regeneration. Its capacity to release ions and its intrinsic bioactivity make it a promising candidate for various dental applications [38, 62].

Clinical applications of bioactive glass:

1. Direct pulp capping: BG is utilized to promote the formation of reparative dentin and safeguard pulp vitality. It fosters the creation of a barrier between the pulp and the restorative material. BG reduces the need for pulp extirpation.

2. Repair of bone defects: BG is employed in osseous regeneration surgeries to repair bone defects, including those associated with implant dentistry. Research has demonstrated the efficacy of BG in promoting the formation of new bone tissue and integration with surrounding dental structures. BG increases the success rate of dental implants [62].

3. Regenerative endodontics: BG has shown potential in stimulating the regeneration of the dentin-pulp complex. Studies have explored its application in pulpotomies and pulpectomies, highlighting its ability to promote the formation of dentin-pulp tissue. BG offers a more conservative alternative to tooth extraction [62].

Considerations regarding the use of adhesive materials:

While resin adhesive materials have been recommended for their bonding ability [38]. However, despite their similarity to GI and RMGI in terms of their acidic nature and lack of bactericidal properties, adhesive resins have been found to have unsatisfactory results in terms of pulp healing and dentin bridging compared to CH [63, 64, 65]. Interestingly, studies have shown that directly coating the pulp with non-acidic adhesive resin or resin composite tends to elicit a better pulp response compared to the use of acidic primers or adhesives. Therefore, it is advisable to avoid the use of dental adhesive in DPC [9, 11].

While adhesive resin has shown promising results in experimental models during the early stages after DPC, its use in humans has revealed a lack of biocompatibility and consistent formation of reparative dentin [66].

3. Clinical protocol for direct pulp capping

3.1 Diagnosis

Implementation of DPC treatment is recommended and is performed after a comprehensive diagnosis. To accurately determine the extent of caries and fractures in the affected tooth, intraoral radiographs should be obtained. Patient history and reports, radiographic evidence, clinical evaluation, and sensitivity testing should be considered before treatment decisions are made. Once the clinical evaluation is completed and pulp exposure is confirmed, the initial pulp diagnosis can be confirmed [61].

3.2 Caries removal

In situations where there are cases of pulp exposure, it is of utmost importance to completely remove the caries to eradicate the infected tissues [61]. When managing deep caries lesions, it is necessary to remove demineralized enamel and infected dentin. If infected tissue is left behind, chronic inflammatory cells have been observed to infiltrate and subclinical pulp inflammation can compromise pulp vitality [25]. The use of caries detectors can be beneficial during the caries removal process, especially when working in close proximity to the pulp cavity [67, 68].

3.3 Use of hemostatic agent

The use of a hemostatic agent is advised in order to effectively control bleeding arising from the exposed pulp. A variety of hemostatic solutions and techniques are recommended to achieve this goal. These include, among others, sodium hypochlorite (NaOCl), chlorhexidine, hydrogen peroxide, ferric sulfate, and other similar options. Among these alternatives, the most efficient hemostatic solution for direct pulp exposure in the dental field is 2.5% NaOCl [69]. This particular solution serves as an antimicrobial agent that not only facilitates hemostasis but also disinfects the dentin-pulp interface, eradicates biofilm, chemically removes blood clots and fibrin, as well as removes dentin chips and damaged cells from the mechanically exposed site [31]. To achieve hemostasis in the exposed pulp, two main approaches have been proposed: direct passive irrigation or the use of NaOCl-soaked cotton pellets [70]. Despite the availability of multiple hemostatic options, NaOCl can be administered directly to the pulp tissue at different concentrations without compromising the integrity of the pulp itself [71]. It is of utmost importance to control bleeding prior to application of an appropriate biomaterial, as this facilitates clinical assessment of inflammation levels and identification of potential necrotic tissue.

3.4 Use of biomaterials

The use of biomaterials plays an important role in the successful treatment of direct pulp capping DPC. The use of calcium silicate-based materials in DPC procedures has become increasingly popular in recent years, as demonstrated by numerous studies [17, 32, 34, 72, 73, 74]. These materials have consistently demonstrated their clinical effectiveness, with MTA being one of the most widely used and investigated biomaterials in DPC [11, 73, 75]. Furthermore, compared to CH-based materials, calcium silicate-based materials have been shown to create higher quality mineralized tissue barriers and consistent mineralized tissue formation and long-term preservation of pulp vitality [76].

3.5 Final restoration

Final restoration of the tooth represents a fundamental phase in DPC procedures. A higher level of success is observed when teeth undergo DPC treatment using calcium silicate-based cements and are restored quickly [11, 41]. Immediate restoration confers numerous benefits, such as prevention of microleakage, protection of the biomaterial layer, mitigation of postoperative sensitivity, and improved thermal conductivity.

The results of pulpal complex regeneration (PCR) vary according to the type of lesion, the biomaterial used, the application technique, and the clinical conditions of the patient [76].

4. Factors affecting the results of PCR

1. Type of lesion: The severity of the pulp lesion is a crucial factor affecting the results of PCR. Mild lesions are more likely to respond positively to PCR compared to severe lesions.

2. Biomaterial used: The type of biomaterial used can also affect the results of PCR. Biomaterials that promote dentin and blood vessel formation are more likely to result in complete regeneration.

3. Application technique: The technique used to apply the biomaterial may influence the PCR results. Techniques that ensure biomaterial stability are more likely to lead to successful regeneration.

4. Clinical conditions of the patient: Patient clinical conditions, including age, general health and oral hygiene, can also affect PCR results. Young, healthy patients with good oral hygiene are more likely to respond positively to PCR [13].

5. Types of PCR results

1. Complete regeneration: Ideal outcome of CRP characterized by the formation of new dental pulp, including odontoblasts, dentin, and blood vessels.

2. Partial repair: Less favorable PCR outcome characterized by the formation of new dental pulp but lacking odontoblasts or blood vessels.

3. Failure: The least favorable outcome of PCR characterized by the absence of dental pulp regeneration or repair [13].

6. Conclusions

Dentin-pulp complex regeneration (DPCR) research is progressing rapidly. New biomaterials, techniques, and cell therapies could make DPCR a viable option for all patients in the future. DPCR is an area of research in dentistry with great potential to improve the preservation of natural teeth. New biomaterials, techniques and cell therapies are being developed that could improve regeneration outcomes. Advances in DPCR could allow dentists to preserve natural teeth in cases where extraction would have been previously indicated. This has the potential to improve patients’ quality of life and decrease the costs associated with medical care. However, there are still challenges that must be overcome before DPCR becomes a viable option for all patients. These challenges include:

• The need to develop more biocompatible, bioactive, and biodegradable biomaterials.

• The need to develop more precise and efficient techniques for the application of biomaterials.

• The need to better understand the regeneration mechanisms of the dentin-pulp complex.

Traditionally, pulp inflammation has been considered only as an undesirable side effect. However, recent research indicates that it actually plays a crucial role in the pulp healing process as it leads to cell multiplication, facilitates pulp cell attachment and stimulates the proliferation of various cell types that transform into odontoblast-like cells, thus promoting the development of mineralized tissue at the site of exposure. Although calcium hydroxide has been extensively studied as a biomaterial with positive clinical results, calcium silicate-based materials currently demonstrate the highest efficacy among biomaterials used in DPCR. In addition, MTA and Biodentine have shown superior clinical results compared to other materials used in DPCR.

Thanks

We would like to thank the Universidad Católica de Cuenca for their support in the execution of this Book Chapter, as it stems from a research project entitled PERFIL EPIDEMIOLOGICO BUCAL DE LA PROVINCIA DEL CAÑAR from the 5th call with Code PICV18-31.