A review of new generation of dental restorative resin composites with antibacterial, remineralizing and self-healing capabilities

Abstract

Dental restorative resin composites are widely used to repair tooth decay owing to attractive esthetics, adequate mechanical properties and minimally invasive tooth structure preparations. Nevertheless, dental restorative resin composites still face challenges because of their relatively high failure rate and short lifespan caused by secondary caries and bulk fracture. Thus, attempts have been carried out to explore a new generation of dental restorative resin composites with antibacterial, remineralizing, and self-healing capabilities to inhibit bacteria and lengthen the lifetime of the restorations. Such novel restorative composites can inhibit bacterial activity, reduce acid production, promote mineral regeneration and present a renewable advantage to achieve a higher performance, which are inspiring and provide support for further basic and clinical research. In this review, antibacterial dental restorative resin composites are first introduced, followed by remineralizing, self-healing, and multifunctional dental resin composites with two or more of the functions mentioned above. Meanwhile, we explain the mechanism of the corresponding dental restorative resin composites and describe their characteristics. Finally, we conclude and put forward prospects. This review will attract both researchers and clinicians in this field and help to provide innovative ideas to design new restorative resin composites for biomedical applications.

Graphical abstract

Introduction

Dental caries is a prevalent dental disease in the worldwide, which can cause serious damage to teeth and affect human health greatly. Dental restorative resin composites which are mainly composed of resin monomers, inorganic filler and coupling agent have been applied extensively to restore the cavities in direct restorations owing to the tooth-colored appearance, adequate mechanical characteristics and less removal of sound tissue as compared with the dental amalgams [1–5]. The properties of dental restorative resin composites have been greatly optimized since bisphenol A-glycidyl methacrylate (BisGMA) was introduced by Bowen in 1962 [1, 6, 7]. There are also bio-based resins which act as renewable dental materials in current research. Isosorbide materials were widely used to replace bisphenol A-based dental materials, with the potential to become a renewable alternative for BisGMA-based dental restorative resin composites [8, 9]. However, there exist higher failure rates in resin composite restorations when compared to amalgam [10]. One research retrospected 8 studies which were published between 1992 and 2013, and reported the mean rate of survival which is 92.8% for amalgams and 86.2% for resin composites [11]. Secondary caries and fracture are primary factors which can lead to failure in resin composite restorations when it comes to posterior teeth, while esthetic concerns are the primary causes in anterior teeth [12]. From the perspective of material properties, the limited lifetime of dental restorative resin composites is primarily related to the complicated interaction of several factors such as low fracture toughness, polymerization shrinkage induced strain and stress, and high surface bacterial biofilm accumulation tendency [13].

Efforts have been made to face the dilemma mentioned above and expand the longevity of dental restorative resin composites. In the last few decades, scientific research was mainly concentrated on the mechanical enhancement and polymerization shrinkage reducing in achieving the higher performance of composites [12, 14–17]. During the past decade, there has been growing attention in exploring a new generation of dental restorative resin composites possessing antibacterial activity, remineralizing effect and self-healing capacity [13, 18–21]. Leachable antibacterial agents, contact-killing antibacterial agents and the agents with synergistic antibacterial effect were used to develop antibacterial dental restorative resin composites. The antibacterial dental restorative resin composites can inhibit bacterial adhesion, biofilm formation and the occurrence of recurrent caries. As a kind of regenerative resin material, the remineralizing dental restorative resin composites provide an exogenous mineralized ion source such as calcium orthophosphates (CaP), fluoride and bioactive glass (BG) to compensate for the early demineralization of caries and enhance the tooth strength. The self-healing dental restorative resin composites have the renewable advantage to heal microcracks autonomically. Different shell materials and healing liquid were used to prepare microcapsules to improve its self-healing efficiency.

In this review, we introduce dental restorative resin composites with antibacterial, remineralizing, self-healing capabilities. We explain the mechanism of the dental restorative resin composites and discuss their corresponding characteristics. In the end, we draw a conclusion and propose future prospects. We hope this review will assist in optimizing the performance of dental restorative resin composites and promote their development.

Antibacterial dental restorative resin composites

In comparison with other dental materials such as amalgam and glass ionomer, dental restorative resin composites are more likely to accumulate dental plaque on the material surfaces [22]. The bacteria could produce acids and enzymes that cause tooth demineralization and material degradation, leading to subsequent restoration failures [23, 24]. Therefore, enduing dental restorative resin composites with antibacterial effect is of great interest to both academic research and clinical practice [25]. It is extensively used to develop resins with antibacterial properties by adding antibacterial agents to the composites [26–30]. This strategy has attracted considerable interests since Colton et al. [31] imparts bactericidal effect to dental resins in 1953. Herein, we mainly divide the antibacterial agents into three types: leachable antibacterial agents, contact-killing antibacterial agents and the agents with synergistic antibacterial effect. Several selected examples were summarized in Table 1.

Table 1.

The summary of studies on different types of dental restorative resin composites

Different types of dental restorative resin composites	Authors	Functional component	Significant results
Antibacterial dental restorative resin composites	Ren et al. [32]	AgNPs	A 0.20 wt% silver salt concentration provided significant antibacterial properties without compromising mechanical strength or biocompatibility
	Barot et al. [33]	HNT/Ag	The incorporation of HNT/Ag (5%) into dental restorative resin composites resulted in enhanced mechanical strength and significant antibacterial activity against S. mutans
	Alansy et al. [34]	BNNSs/ZnO	The antibacterial efficacy of the modified composites significantly increased compared to those without BNNSs/ZnO, reaching 98% with the addition of 0.5 wt% BNNSs/ZnO
	Bai et al. [35]	Zn-MSNs	The composites doped with 15 wt% zinc mesoporous silica nanoparticles (Zn-MSNs) exhibited a 100% antibacterial rate and a significantly enhanced mechanical strength
	Yang et al. [36]	SiO2–ZrO2–ZnO CNCs	The composites containing SiO2–ZrO2–ZnO CNCs at a ratio of 56:10:4 demonstrated superior antibacterial properties compared to the other formulations
	Fu et al. [37]	QAMEMT-x	The resins cured with 5 wt% of QAMEMT-x demonstrated antibacterial activity against S. mutans, achieving a maximum antibacterial efficiency exceeding 99% when the alkyl chain length was extended to 16
	Cao et al. [38]	AgBr/BHPVP	Even with just 1.0 wt% AgBr/BHPVP content, the material exhibited adequate antimicrobial properties and retained its antimicrobial activity following a one-month water aging test
Remineralizing dental restorative resin composites	Zhang et al. [39]	NACP	The composites are capable of continuously releasing calcium and phosphorus ions for 42 days without the need for recharging
	Niu et al. [40]	Pchi/ACP	A resin composite containing 25 wt% Pchi/ACP is suitable for use as a novel regenerative dental material, capable of enhancing remineralization while maintaining sufficient overall performance
	Lukomska-Szymanska et al. [41]	CaF2	Composites containing 1.5 wt% CaF2 demonstrated the most effective inhibition of bacterial growth
	Mitwalli et al. [42]	nCaF2	The release of F and Ca ions remained constant after being recharged/released 6 times, and the composites demonstrated the ability to continuously re-release for 42 days
	Dai et al. [43]	nCaF2cpsd	After being submerged in water for 84 days, the nanocomposites with 20 wt% nCaF2 cpsd exhibited an accumulative fluorine release 65 times greater and a long-term fluorine release ratio 77 times higher than those of the commercial counterpart
	Par et al. [44]	BG	Composites with 10 wt% BG remained fairly stable across all aging conditions
Self-healing dental restorative resin composites	Wertzberger et al. [45]	PUF microcapsules	A repair rate of 57% of the original fracture toughness can be attained without compromising mechanical properties
	Then et al. [46]	Melamine-modified UF microcapsules	Melamine-modified UF microcapsules exhibited excellent adhesion to the dental host material, and the minimal addition of these microcapsules did not compromise the performance of the matrix material
	Wu et al. [47]	PUF microcapsules	The resin with 15 wt% microcapsules exhibited excellent self-healing efficiency and cellular cytotoxicity without compromising mechanical properties
	Ning et al. [48]	PUF microcapsules	The healing efficiency of flowable composites embedding microcapsules grows with rising microcapsule dimensions and concentrations, as well as the concentration of the initiator
	Althaqafi et al. [49]	PUF microcapsules	Except for a drastic decrease in flexural strength with increasing microcapsule concentrations (> 10 wt%) in the composites, other mechanical properties remained largely unaffected
	Huynh et al. [50]	Melamine-reinforced and silanized PUF microcapsules	The functionalization process maintained the structural integrity and volume of the microcapsules, enhancing healing efficiency with TEOS/MPTMS-functionalized microcapsules reaching up to 35% toughness recovery
Multifunctional dental restorative resin composites	Xie et al. [51]	DMAHDM, MPC, NACP	The composites with 3% MPC and 3% DMAHDM demonstrated superior bactericidal efficacy. Additionally, these composites with biofilm culture sustained a pH above 6.5 in contrast to the commercial group exhibiting a cariogenic pH of 4.2 within the biofilm culture medium
	Yao et al. [52]	Nanoparticle-modified MC with a NIF containing a quaternary ammonium salt	The inclusion of M-10 microcapsules can decrease bacterial levels by 2–3 orders of magnitude compared to the control group. Dental resins that include 7.5 wt% of M-10 microcapsules can achieve a renewable efficiency of nearly 69%
	Wu et al. [53]	DMAHDM, NACP, PUF microcapsules	The original fracture toughness of the material was recovered by 65–81%. If the microcapsule content does not exceed 7.5%, the addition of antibacterial agents and remineralization agents is compatible with the self-healing ability of the composite

Leachable antibacterial agents

Leachable antibacterial agents include antibiotics, chlorhexidine (CHX), chitosan, metal nanoparticles and their oxide materials [24, 54, 55]. Dental restorative resin composites containing such agents can release antibacterial agents which are pre-loaded in the restorative materials into the environment to kill bacteria over time. Leachable antibacterial agents have less systemic toxicity compared with systemic drug delivery due to their high release amount at specific sites. Recently, with continual advances in nanotechnology, the applications of metal nanoparticles and their oxide materials have steadily increased in the medical fields. These nanoparticles have the advantages of small particle size, high specific surface area, adequate properties of physicochemical and satisfactory antibacterial activity.

Silver nanoparticles (AgNPs) were a focal point of tremendous studies over the last few decades [24]. Although the exact antibacterial mechanism of AgNPs has not been very clear and needs more investigations, several antibacterial ways have been proposed through the ways of destroying cell walls and membrane, inhibiting protein synthesis and DNA replication, and denaturing enzymes, as shown in Fig. 1 [56, 57]. Despite its high antibacterial activity, there are several concerns for the addition of AgNPs into resins, involving its poor dissoluvability in the hydrophobic monomers, easy agglomeration, and biocompatibility. Several works have been reported to solve these problems through a new method of synthesizing AgNPs in-situ in resins [32, 58–60]. In 2015, Cheng et al. [59] dissolved the Ag salt in the TBAEMA (2-(tertbutylamino)ethyl methacrylate) monomer, which was subsequently added into dental monomers containing BisGMA and TEGDMA (triethylene glycol dimethacrylate). The Ag ions were reduced to Ag when the monomers underwent photopolymerization. Compared with the mechanical addition of AgNPs into resins, such method could greatly reduce the possibility of agglomerations and promot the dissolution of silver salts in the resin monomers. In 2019, Ren et al. [32] synthesized AgNPs successfully by the in-situ method in resins and proposed that the proper concentration of silver salt was 0.20 wt%, which showed a significant antibacterial effect without impacting the mechanical properties and biocompatibility. In 2020, Barot et al. [33] attached silver nanoparticles to Halloysite nanotubes (HNTs) to create a novel filler. The addition of HNT/Ag (5%) in dental restorative resin composites presented the improved mechanical strength and significant antibacterial activity against Streptococcus mutans (S. mutans). In 2022, Azhar et al. [61] synthesized Diethylaminoethyl (DEAE)-Dextran AgNPs to limit the aggregation of AgNPs in dental restorative resin composites and enhanced their blending capacity. After testing against Enterococcus faecalis, S. mutans and oral microcosm, it was found that the antibacterial effect of composites prepared with DEAE-Dextran AgNPs was greatly enhanced compared with the group reinforced by AgNPs. Another concern of AgNPs is that excess silver is reported to accumulate in tissues and organs such as skin, liver, kidneys, spleen, and gingival [62], which can influence the biocompatibility. In 2011, Durner et al. [63] investigated and discovered that silver can increase the amount of elutable substances from photocuring resins at tiny doses, thus reducing the biocompatibility of the silver-containing materials. In 2016, Safari et al. [64] provided evidence that AgNPs can induce oxidative stress and damage the antioxidant enzyme glutathione peroxidase in the rat brain. Treating by silver nanoparticles also resulted in a substantial decline in the levels of neurotransmitters such as dopamine, suggesting the treated animals may have changed their behavior. In 2017, Ghooshchian et al. [65] observed a higher level of Bax/Bcl-2 ratio in rat hippocampal cells exposed to AgNPs, implying cell apoptosis and neurotoxicity.

Fig. 1.

The antibacterial mechanism of AgNPs. Reprinted with permission from Ref. [57]

It seems that ZnO nanoparticles are also one kind of promising candidates in the development of antibacterial fillers owing to the advantage of broad-spectrum antibacterial properties, aesthetic appearance and good biological compatibility [34, 66]. ZnO nanomaterials can interact with bacterial cells from both chemically and physically to exert antibacterial effects [67]. The chemical reaction of ZnO nanomaterials with bacterial cells can result in the light-induced generation of reactive oxygenated species (ROS), the H₂O₂ production and Zn²⁺ releasing. By comparison, the physical interaction shows the biocidal effects through membranolysis, internalization of cells or mechanical damage. However, the direct incorporation of ZnO nanoparticles could not effectively enhance the mechanical strength [16]. As a result, Wang et al. [68] fabricated cellulose nanocrystal/zinc oxide (CNC/ZnO) nanohybrids by introducing them into resins in 2019, showing that the nanohybrids combined the enhancement function of CNC and the antibacterial effect of ZnO together. The prepared dental restorative resin composites added with 2 wt% nanohybrids exhibit superior compressive strength and flexural modulus compared with the group without the additives. In 2020, Bai et al. [35] introduced mesoporous silica nanoparticles (MSN), an ideal carrier of antibacterial active ingredients, as effective fillers of dental restorative resin composites. The antibacterial rate of the composites with 15 wt% zinc doped mesoporous silica nanoparticles (Zn-MSNs) can reach up to 100% and the mechanical strength was improved considerably. In 2022, Alansy et al. [34] synthesized boron nitride nanosheets modified with ZnO nanoparticles (BNNSs/ZnO) as the filler to obtain a novel antibacterial dental restorative resin composite. The antibacterial capacity of the modified composites was greatly improved in comparison with the group without adding BNNSs/ZnO, achieving 98% when 0.5 wt% BNNSs/ZnO was incorporated. At the same year, Yang et al. [36] constructed SiO₂–ZrO₂ complex nanoparticle clusters (CNCs) by a three-fluid nozzle spray dryer (Fig. 2), which is of high efficiency. Then the SiO₂–ZrO₂–ZnO CNCs was constructed in the same way. The result showed that the dental restorative resin composites added with SiO₂–ZrO₂–ZnO CNCs at a rate of 56:10:4 exhibited the excellent antibacterial properties compared with others. In 2024, Lee et al. [28] evaluated the effects of incorporating 0–20 wt% tetrapod-shaped zinc oxide (tZnO) whiskers on the mechanical, antibacterial, and cytotoxic properties of experimental dual-cure resin composites. It can be found that the addition of silanized tZnO in dual-cure resin composites can reach up to 20 wt% without compromising mechanical properties. Meanwhile, it can significantly enhance the antibacterial activity against S. mutans without inducing cytotoxicity in stem cells from human exfoliated deciduous teeth (SHED). However, in 2020, Arun et al. [69] suggested that there are less obvious clinical advantages for ZnO nanoparticle composites because of the short-lived duration of the observed antibacterial effects, which showed inferior effect against multi-species biofilms in some vitro studies.

Fig. 2.

Fabrication procedure of SiO₂–ZrO₂ CNCs by a two-fluid nozzle or a three-fluid nozzle spray dryer. Reprinted with permission from Ref. [36]

The antibacterial effects of silver and zinc nanoparticles have been well-explored while little research was conducted to investigate the application of copper particles in dental resin composites [70]. Studies indicate that the antibacterial mechanism of copper nanoparticles (CuNPs) is primarily to produce ROS and cause damage to the DNA of bacteria. In 2020, Pasha et al. [71] prepared drug-decorated copper particles (DDCP) using the available drug named Augmentin containing amoxicillin., It was shown that the addition of DDCP endowed resin composites with anti-cariogenic properties, which can be maintained for one month without adverse impact on physicochemical behaviors of the material.

Other leachable antibacterial agents such as chlorhexidine have also been extensively explored in the dental restorative resin composites [72–74], which will not be discussed here in details.

Contact-killing antibacterial agents

While there are a lot of advantages about leachable antibacterial agent, there still exists some defects. The drawback of quick ion release can lead to short effective reaction time of active agents [23]. Furthermore, the mechanical strength of composites may be influenced because the release of antibacterial agents will generate nanopores or interfacial delamination [4]. To overcome the shortcomings of ion releasing, an immobilized contact-killing agent has been developed, which can be considered as a more bio-sustainable approach [4] and exhibit long-term antibacterial activity [23]. In this strategy, polymers such as quaternary ammonium compounds (QACs) containing insoluble positively charged species have been widely explored [67]. For QACs, their antibacterial mechanisms are not clear yet, but it is widely accepted that the main form of action is ‘contact killing’ (Fig. 3). The positively-charged (N⁺) sites of QA molecules can interact with the negatively-charged bacterial membrane. This interaction disrupts the structures and functions of the cell membrane, causing the bacterial cells to burst under their own osmotic pressure finally [35, 36, 68]. In 1994, Imazato et al. [75] synthesized 12-methacryloyloxy dodecyl pyridinium bromide (MDPB) by integrating an antibacterial agent with methacryloyl group, which was the first time to use quaternary ammonium monomer (QAM) in antibacterial dental resins. Subsequently, generous explorations about the use of other kinds of QAMs on antibacterial dental restorative composites have been carried out. In 2018, Zhang et al. [76] synthesized QAMs with different chain lengths and investigated their influence on the biofilm and mechanical strength of nanocomposites. The metabolic activity and acid generation of the dental plaque were decreased by tenfold and the colony-forming units (CFUs) of overall microorganisms, total streptococci, and mutans streptococci were decreased by 2 orders of magnitude when the chain length was increased from 3 to 16. In 2022, Fu et al. [37] synthesized polymerizable quaternarized thiazole salts (QAMEMT-x) with different alkyl chain lengths (12, 14, and 16) and incorporated them into dental resins. The result showed that the cured resins with 5 wt% of QAMEMT-x exhibited antibacterial effects against S. mutans with the maximum antibacterial efficiency over 99% when increasing the length of alkyl chain to 16.

Fig. 3.

Antibacterial QA surfaces (left) compared with the pristine surface (right). Reprinted with permission from Ref. [77]

One potential shortage of QAMs is that the formation of salivary proteins on the composite surfaces could influence the effect of ‘contact inhibition’ [55, 78]. In 2015, Zhang et al. [78] incorporated 2-Methacryloyloxyethyl phosphorylcholine (MPC) into dental resins to solve the problem. MPC was a common biological compatible and hydrophilous biomedical polymer with superior performance to resist the protein adsorption and reduce bacterial attachment. The result indicated that  the incorporation of MPC into composites at 3 wt% can significantly decrease the protein adsorption, the adhesion of bacteria and biofilm CFUs, without impact on mechanical strength. After that, Koyama et al. [79] fabricated an MPC polymer that can be in situ bonded on the resin composite surfaces in 2019. The treated surface exhibited distinct resistance to the protein adsorption and bacterial attachment even when brushing it with a tooth brush.

Agents with synergistic antibacterial effect

As mentioned above, although restorative resin composites containing releasing antibacterial agents or contact-killing agents have been investigated, neither of the two ways has been completely successful owing to their respective shortages [55]. Thus, composite resins containing agents with synergistic antibacterial effect have been introduced recently to achieve augmented antibacterial properties. In 2015, Zhang et al. [80] added MPC and quaternary ammonium dimethylaminohexadecyl methacrylate (DMAHDM) into the material to fabricate composites with protein-repellent and antibacterial capabilities. The results indicated that the prepared composite with incorporation of 3 wt% MPC + 1.5 wt% DMAHDM bhad a superior effect on reducing the growth of biofilm than the one added with MPC or DMAHDM alone. Biofilm CFU counts on the composites containing 3 wt% MPC + 1.5 wt% DMAHDM were decreased by over 3 orders of magnitude than that of commercial one. In 2017, Cherchali et al. [81] further explored this method by mixing dimethyl-hexadecyl-methacryloxyethyl-ammonium iodide (DHMAI) and the MPC into dental composites. Either DHMAI or MPC was added alone or together at various amounts. The composites containing 7.5 wt% DHMAI showed a strong inhibited effect on the microorganism and improved conversion degree, as well as adequate stress-bearing abilities. In 2017, Cao et al. [38] designed a new antibacterial material containing lightcurable core–shell AgBr/cationic polymer nanocomposites (AgBr/BHPVP) with synergistic antibacterial effect. Combining the contact-killing biocidal effect of polymers and the releasing-killing effect of Ag⁺ ions, the overall antibacterial activity of the resins containing AgBr/BHPVP was improved with strong bactericidal effect against S. mutans as shown in Fig. 4. Even at a tiny content of 1.0 wt% AgBr/BHPVP, the material showed sufficient antimicrobial activity and maintained the antimicrobial activity even after water aging test for one month.

Fig. 4.

A CFU counts of S. mutans growing on different composites surfaces; B CFU counts of S. mutans growing on resin disks made with 1.0% AgBr/BHPVP at different incubation times; C Live/dead bacterial staining assay of biofilms attached to the layered disks. Reprinted with permission from Ref. [38]

To develop novel dental composites with synergistic antibacterial effect and stronger antibacterial activity, further studies should be investigated to combine more effective antibacterial agents. Besides, longer lasting and biosafe agents should be explored to maintain or strengthen the fundamental material properties. In the future, it is necessary to establish a standardized testing process to precisely evaluate the safety profile and effectiveness of the antibacterial resin composites in inhibiting dental caries.

Remineralizing dental restorative resin composites

Dental caries is a complicated disease in which demineralization as a undermining process and remineralization as a regenerative process happen simultaneously or alternately [82]. It was observed that demineralization is crystal dissolution, whereas remineralization is shown as the recovery of partially dissolved crystals, the growing of the remaining crystals and the deposition of regenerative crystals [82–87]. Prolonging and repeating demineralization results in the net loss of mineral, which can lead to hard tissue dissolution and the formation of caries lesions that can be seen clinically [88, 89].

The fluctuations in pH caused by metabolic activity of bacteria in the biofilm always have an effect on de-and re-mineralization processes [88]. pH above 6 is relatively secure while pH 6–5.5 is possibly cariogenic and pH 5.5–4 is considered to be cariogenic [90]. Plaque buffering capacity and its supersaturated degree, relating to calcium and phosphates, will be impacted if exposure to a low pH environment repeatedly for a long period, causing tooth structure demineralization ultimately [91]. In addition, the rate and degree of minerals dissolution are related to the concentration of ions shown in Eq. (1) [92]. Thus, it is a good choice to inhibit the demineralization of hard tissue by increasing the content of calcium, phosphate, and fluoride ions [93]. Several selected examples were summarized in Table 1.

$$\begin{array}{c}{\text{Ca}}_{10-\text{x}}{\text{Na}}_{\text{x}}{({\text{PO}}_4)}_{6-\text{y}}{({\text{CO}}_3)}_z{\left(\text{OH}\right)}_{2-\text{u}}{\text{F}}_{\text{u}}+3{\text{H}}^{+}\to \left(10-\text{x}\right)\\ {\text{Ca}}^{2+}+{\text{xNa}}^{+}+\left(6-\text{y}\right)\left({\text{HPO}}_4^{2-}\right)+\text{z}\left({\text{HCO}}_3^{-}\right)+{\text{H}}_2\text{O}+{\text{uF}}^{-}\\ \end{array}$$ 1

It is well known that calcium orthophosphates (CaP) have been widely explored in the mineral regeneration of enamel and dentin [94]. In the 1990s, restorative resin composites containing amorphous calcium phosphate (ACP) particles have been used to accelerate enamel remineralization [95], but not until in the last decade did there produced a wealth of information including using various CaP phases as co-fillers in the prepared composites [96, 97]. In 2011, Xu et al. [98] firstly developed nanocomposite comprising ACP nanoparticles. Compared with commercial composites with little ion release, the flexural strength of the prepared ones was greatly enhanced and twofold higher, which can significantly increase the ion release when these ions would be most needed to prevent caries at a pH of 4. For purpose of achieving long-term prevention of dental decay, Zhang et al. [39] further developed a new composite comprising nanoparticles of amorphous calcium phosphate (NACP) with rechargeable capability in 2016. The composites can re-release calcium and phosphorus ions for 42 days continuously without recharging. In 2021, Niu et al. [40] incorporated phosphorylated chitosan/amorphous calcium phosphate nanocomplex (Pchi/ACP) into the composite resin and evaluated their corresponding mechanical strength and dentin remineralization effect. In the study, the resin composite added with 25 wt% Pchi/ACP is adoptable as a new regenerative dental material to promote remineralization with adequate comprehensive performance.

In addition, Huang et al. [99] explored the performance of restorative resin composites with respect to the size of calcium phosphate particles in 2021. Resin composites containing micrometer-sized tricalcium phosphate (TCP) particles showed a similar buffering effect compared with the much smaller grinding TCP-G particles. It is slightly beneficial for the integrated TCP particles to release Ca²⁺/PO₄³⁻, which has less impact on the long-term bending performance. Furthermore, the mineral regeneration effect was tested by two different pretreatments (Fig. 5A). After immersion in acidic solution for 3 days at 37 °C, plenty of crystals were discovered at the interface between dentin and 15 wt% TCP-G composites, leading to a closure of the gap (Fig. 5C), compared with scattered and isolated mineral precipitation or particulate fillers in other groups (Fig. 5B, D), and hardly identified mineral deposition in commercial resin composites denoted as the control group (Fig. 5E). In brief, the 15% TCP-G resin composites can promote remineralization and gap-closing more effectively. In 2021, Skaria et al. [100] synthesized a new methacrylate-functionalized calcium phosphate (MCP) to be used as a bioactive dental composite. It was found that the content of MCP in a composite composition is directly connected with the deposition of hydroxyapatite on the material surface and MCP containing composite was considered to be a promising regenerative material for mineral regeneration. In 2023, Shafqat et al. [101] investigated the in vitro bioactivity of novel dental resin composites based on polypropylene glycol (PPG) with calcium phosphate fillers and chlorhexidine (CHX). The composites were immersed in simulated body fluid (SBF) for 7, 14, and 28 days to assess bioactivity through surface morphology and elemental analysis using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). The results showed that the composites with higher levels of calcium phosphate fillers formed an apatite layer after 28 days in SBF, indicating the enhanced bioactivity due to the presence of polypropylene glycol dimethacrylate (PPGDMA) and CHX.

Fig. 5.

Remineralization of the dentin − material interfaces. A schematic diagram of the remineralization assessments in vitro. Scheme A: Unpretreated samples were placed in the acid artificial saliva for 3 days and the solution was replaced daily; scheme B: samples etched with 37% phosphoric acid gel were placed in the artificial saliva for 10 days. Typical SEM images of samples of undemineralized dentin exposed to B 15% TCP, C 15% TCP-G, D glass ionomer cement, and E a commercial resin composite (SonicFill, SF) in the acid artificial saliva for 3 days with the pretreatment in scheme A. Reprinted with permission from Ref. [99]

Fluoride, as an anticariogenic agent, is extensively applied in dental treatment [102–104]. The mechanism of the anticaries functions includes: promoting remineralization and preventing demineralization of hard tooth tissues, inhibiting the formation of pellicles and biofilm, and hindering the growing and metabolic activity of bacteria [105]. In 2014, Tammaro et al. [106] first prepared the modified hydrotalcite inserted with fluoride ions as the filler through ion exchange procedure. Fluoride was released relatively constant for a period with no initial toxic burst effect. In 2019, Wei Su et al. [107] found an optimized method in the release and recharge capability of fluoride in the restorative resin composites containing LiAl-F layered double hydroxide (LDH). Besides, it can be observed that discrepant sizes of the LDH fillers can result in different fluoride releasing properties. Smaller particles endow with more and faster fluoride release in initial period owing to their large surface area. Lukomska-Szymanska et al. [41] assessed the antibacterial property of composites modified with CaF₂ against caries-related microbes, such as S. mutans and L. acidophilus in 2016. One regular photocurable composite resin consisting of fluoride ions and two regular flowable photo-curing composite resins (Flow Art and X-Flow) added with 1.5, 2.5, and 5.0 wt% anhydrous CaF₂ were selected in this research. It can be found that the composites added with 1.5 wt% CaF₂ exhibited the best effect on inhibiting bacteria growth (Fig. 6). In 2022, Mitwalli et al. [42] developed a novel rechargeable nanocomposite containing calcium fluoride nanoparticles (nCaF₂) and investigated the F and Ca recharge and re-release abilities. It is found that the nanocomposites realized the optimal integration of original mechanical strength, the F and Ca ion recharge and re-release abilities. The release of F and Ca ions did not decrease after recharge/rerelease for 6 times, and the composites can exhibit continuous re-release for 42 days.

Fig. 6.

Distribution of S. mutans (A) and L. acidophilus (B) in 1 mL solution for composite specimens (F2, Flow Art, and X-Flow). Reprinted with permission from Ref. [41]

Attempts have been carried out to improve the mechanical strength and the F ion release levels of composites. In 2021, Cao et al. [108] used CaF₂/SiO₂ core–shell nanoparticles (CaF₂/SiO₂ NPs) as new fillers to endow resin composites with continuous release of F and great mechanical performance. In this study, the mechanical performance of the restorative resin composites filled with CaF₂/50SiO₂ NPs reached the highest value when the filling amount was 50 wt%. Moreover, the fluorine releasing ratio and long-term fluorine releasing rate of resin composites incorporated with CaF₂/50SiO₂ NPs were respectively much lower than those incorporated with CaF₂ NPs, showing that the former was more stable and sustainable in the fluorine release process than the latter. In 2021, Dai et al. [43] synthesized CaF₂ nanoparticles by ‘co-precipitation + spray-drying’ (cpsd) method. The composites containing nCaF₂cpsd with the smaller particle size and narrower distribution showed greater mechanical strength than composites containing CaF₂cp and the commercial group. After immersion in water for 84 days, the nanocomposites added with 20 wt% nCaF₂cpsd had 65 times higher accumulative fluorine release and 77 times greater long period fluorine release ratio, than those of commercial one.

Bioactive glass (BG), mainly consisting of SiO₂–Na₂O–CaO–P₂O₅ system [109], is another category of bioactive filler material for stimulating mineral regeneration due to its high bioactivity [110]. The first BG named Bioglass 45S5 was used in 1969. Subsequently, multiple types of BGs were explored and their primary compositions are close to 45S5 with slightly different contents [56]. Although the BGs present inferior mechanical strength compared with the typical range of glass fillers, they can be added into dental restorative resin composites to promote mineral regeneration of hard tooth tissues, exhibiting desirable biological compatibility [111–114]. In 2018, Jang et al. [115] evaluated the regenerative effect of composites containing bioactive glass on dentin. It is found that the micro-hardness of the neighboring demineralized dentin was greatly increased and the surface containing deposits sectionally blocked the dentin tubules, concluding that the demineralized dentin close to a resin composite containing bioactive glass could be partially remineralized. To estimate the influence of bioactive glass 45S5 in composites on mechanical properties and material reliability after artificial aging in water and ethanol, Par et al. [44] added 0–40 wt% of BG into prepared composites containing a full filler fraction of 70 wt% in 2019. It is found that as the unsilanized BG amount added from 0 to 40 wt%, the mechanical properties of dental composites deteriorated gradually and a further deterioration was exhibited in the process of artificial aging. Among them, composites containing 10 wt% BG were fairly stable throughout all aging regimes. In 2020, Odermatt et al. [116] compared the influence of different particle sizes of bioactive glass 45S5 on the chemical and physical performance of the composite and proposed that lessening the bioactive glass 45S5 fillers to nano-size can improve the hydroxyapatite-forming ability of composites without impacting their fundamental performance. Regarding the effect of BG on the mechanical strength of the prepared composites, the discrepancy findings were yielded in two studies [117, 118].

To improve the incompatibility of BG with hydrophobic resin matrix, the BG fillers were hydrophobically modified [96, 119–121]. Nevertheless, the surface of BG should be contacted with saliva directly to promote the formation of hydroxyapatite, which limits the degree of hydrophobic modification. Thus, an alternative method is expected to avoid the dilemma. In 2019, Li et al. [122] conducted bioactive amphiphilic raspberry-like composite nanoparticles (BRPs) which were added as fillers to disperse well in the resin matrix (Fig. 7). The restorative resin composites exhibited the enhanced mechanical performance and improved resistance to water absorption and solubility with the effect of the amphiphilic surface. Moreover, the addition of bioactive fillers endowed restorative resin composites with bioactivity, forming apatite on composites after immersion in artificial saliva for 7 days. It can lead to denser mineral precipitated on the surface of dentin (Fig. 8) compared to the groups of BT (Bis-GMA/TEGDMA resin system) and BT/BG.

Fig. 7.

Schematic illustration of the production of dental resin composites containing BRP and the succeeding hydroxyapatite formation on the surface of dentin. Reprinted with permission from Ref. [122]

Fig. 8.

SEM image of mineral regeneration of dentin induced by different dental composites after reacting with artificial saliva within 30 days (the arrows point towards the BG fillers). Reprinted with permission from Ref. [122]

However, there are still some problems that need to be further discussed, such as the ideal ratio of the remineralized particles to the resin matrix, the performance of the ion recharging cycle, and the influence on the material properties of adding remineralized ingredients. Further research is supposed to be concentrated on improving the mechanical strength and biological activity of restorative composite resins containing remineralized components, so that the restorative composite resins can react to occlusal force during mastication and continuously release ions to promote tooth remineralization.

Self-healing dental restorative resin composites

Bulk fracture is one of the main factors for the failure of composite restorations. It is observed that above 25% of the alternatives of composite resins were caused by certain types of fracture [123]. Previous studies have made efforts to improve the fracture toughness [124–129], including increasing the composition of filler materials, employing nano-sized silica fillers, adding reinforcing fillers such as whiskers, fibers and nanotubes, improving interfacial bonding between resins and fillers, modificating monomer chemistry and enhancing the polymerization reactions. Nevertheless, fracture and failure still occur frequently and deserve further study and improvements.

Enlightened by the capability of natural organisms to heal nonfatal wounds by themselves, researchers developed self-healing materials that have a renewable effect and can repair the damages automatically [130–132]. Among the developed materials, microcapsule-based type has drawn widespread concern [133, 134]. Several selected examples were summarized in Table 1. White et al. [135] first proposed self-healing microcapsules owning the renewable ability to repair cracks autonomically in 2001. A healing agent of dicyclopentadiene and a catalyst were incorporated into microcapsules composed of a urea–formaldehyde shell. When the microcapsules break up, the agent was released into the crack plane by capillary effect, triggering reaction once the agent meets the catalyst (Fig. 9), thus the crack areas were bonded together. In 2010, Wertzberger et al. [45] introduced White’s self-healing approach to dental restorative resin composites to evaluate the renewable ratio of self-healing highly contained composite and the physical performance of a model dental composite. It can be found that 57% mean repairing rate of the initial fracture toughness can be achieved without compromising the mechanical properties. For purpose of reinforcing the physical properties of the capsule, Then et al. [46] modified the initial urea–formaldehyde (UF) shell with melamine in 2011. The prepared sample showed the excellent bonding between microcapsules and the host material, which is vital to maintain good mechanical performance of the dental restorative composites endowing with renewable capacity. Besides, it is proved that 6 wt% UF/DCPD microcapsules is adequate to incorporate into the original material and the mechanical strength of the dental matrix was not influenced when the urea in the capsule shell was substituted by melamine up to 5 wt%.

Fig. 9.

Self-healing mechanism of microcapsules

In 2016, Wu et al. [47] prepared a novel dental resin composite comprising microcapsules with (TEGDMA)-N, N-dihydroxyethyl-p-toluidine (DHEPT) and poly(urea–formaldehyde) (PUF) shells by in-situ polymerization. The renewable efficiency showed 65% recovery of the initial fracture toughness when 15 wt% microcapsules were added (Fig. 10C, D). There was no obvious harmful impact on the elastic modulus and flexural strength of the resins when the microcapsule concentration was less than 15 wt% (Fig. 10A, B). The self-healing resins added with microcapsules also showed great cytotoxicity in vitro. Subsequently, they investigated the influence of water-aging on mechanical performance and renewable efficacy of the composites [136]. It can be observed that after water-aging at 37 ℃ for 1 day to 6 months, the renewable efficiency didn’t decrease (p > 0.1). Thus, this new self-healing composite is prospective for increasing the durability and longevity of dental restorative materials.

Fig. 10.

A Flexural strength, B elastic modulus, C fracture toughness, D self-healing efficiency of resin containing microcapsules of various concentrations. Reprinted with permission from Ref. [47]

In addition, Ning et al. [48] systematically investigated the relationship between the self-healing effect of dental restorative resin composites, and microcapsule and resin parameters in 2021. The results showed that the fracture toughness of renewable dental restorative composites substantially improved when the microcapsule size and concentration were increased (2 wt% BPO, p < 0.05). The renewable efficiency reached the highest value of 76% with microcapsules sized 198 ± 43 µm. In 2022, Althaqafi et al. [49] explored the relationship between the mechanical properties of a self-healing dental composite model composed of SiO₂ nanoparticles and the content of microcapsules containing TEGDMA monomer and DHEPT amine. All of measured properties were not greatly affected except flexural strength decreasing from 80 to 55 MPa when the amount of microcapsules reached 10 wt%.

In 2024, Huynh et al. [50] optimized the physicochemical interactions between microcapsules and the resin matrix to improve the self-healing capability of dental restorative resin composites. The microcapsules utilized in this study are composed of poly(urea–formaldehyde) (PUF) reinforced with melamine and surface-functionalized with silane agents, including 3-aminopropyltriethoxysilane (APTES) and (3-mercaptopropyl)trimethoxysilane (MPTMS). Furthermore, a bilayer functionalization strategy was implemented, integrating tetraethyl orthosilicate (TEOS) with either APTES or MPTMS. It was confirmed that the functionalization process did not compromise the structural integrity of the microcapsules or the volume of the healing agent. The functionalized microcapsules exhibited improved healing efficiency with the TEOS/MPTMS-functionalized microcapsules, achieving the highest performance and recovering up to 35% of toughness.

In summary, the self-healing materials exhibit promising advantage to solve some of the most limiting shortage of dental resin composites: microcracking and possible fracture. However, there are still a host of problems to be solved. Whether the material can maintain renewable effects in the long term is still a problem. Up to now, the optimum parameter of microcapsules such as addition ratio and diameter in resins was still not clear. In addition, the biological compatibility of the released substances of microcapsules is supposed to be further tested and verified.

Multifunctional dental restorative resin composites

In recent years, increasing numbers of research on bioactive and multifunctional dental materials have been reported [137]. Several selected examples were summarized in Table 1. Xie et al. [51] incorporated DMAHDM and MPC into new rechargeable NACP composites in 2016. The composites containing 3% MPC + 3% DMAHDM exhibited the high bactericidal performance, which can reduce CFU of biofilm by 3 logs in comparison with the commercial group (p < 0.05) when they have a similar flexural strength. The composites comprising 3% MPC + 3% DMAHDM with biofilm culture kept a pH value over 6.5, compared with the commercial composites owning a cariogenic pH of 4.2 in the biofilm culture medium. This method can be widely applied to develop a range of CaP rechargeable and antibacterial dental composites to decrease bacterial accumulation and prevent caries. In addition, Mitwalli et al. [138] incorporated DMAHDM and nCaF₂ together to create a novel bioactive material with regenerative and antibacterial effects in 2021. The new nanocomposite showed strong antibacterial effect against salivary bacterium, and achieved high levels of F and Ca ion release with the advantage for remineralization without sacrificing the mechanical properties. In 2021, Montoya et al. [139] first proposed the application of piezoelectric nanoparticles of barium titanate (BaTiO₃) as a multifunctional bioactive filler in dental composites with the combinative effects of antibacterial and regenerative (Fig. 11). It is observed that a substantial decline in the growing of biofilm (up to 90%) and new minerals can be formed in the piezoelectric composites in comparison with the control groups.

Fig. 11.

Application of BaTiO₃ as a multifunctional bioactive filler in dental resin composites. Reprinted with permission from Ref. [139]

In previous studies, ingredients with antibacterial properties were incorporated into microcapsules to add in the restorative resin composites. Ahangaran et al. [140] developed a new self-healing dental composite containing poly(methyl methacrylate) (PMMA) microcapsules in 2022. TEGDMA as a healing agent and PMMA as a microcapsule shell were used to prepare microcapsules via solvent evaporation method. The results indicated that the incorporation of PMMA microcapsules has the advanced self-healing effect varying from 78 to 121% without significant impact on flexural properties. Besides, it is also found that the prepared self-healing dental composite presents impressive antibacterial activity against S. mutans without cytotoxicity effects. In 2022, Yao et al. [52] synthesized a modified microcapsule with a nano-antibacterial inorganic filler (NIF) comprising a quaternary ammonium salt. The roughness, modulus and hardness of microcapsules were all enhanced after adding NIFs. In addition, the incorporation of M-10 (mass fractions of NIFs was 10%) microcapsules can reduce bacteria by 2–3 orders of magnitude in comparison with the control group. The dental resins comprising 7.5 wt% M-10 microcapsules can reach renewable efficiency near 69% without greatly affecting the survival rate of cell. The antibacterial property was improved without compromising self-healing capability of the microcapsule. In 2023, Zhang et al. [141] developed and assessed a novel multifunctional dental resin composites characterized by minimal polymerization shrinkage, antibacterial effects, and self-healing functionalities. This resin was made by integrating a mixture of 20 wt% of two resin monomers and self-healing antibacterial microcapsules with different mass fractions into the base material. Notable outcomes revealed that the resin with 20 wt% of two resin monomers and 7.5 wt% microcapsules exhibited 30.12% decrease in polymerization volumetric shrinkage as compared to the control sample. Additionally, the resin showed strong antibacterial activity and self-healing efficiency of 71% with maintaining mechanical integrity and cell viability.

Compared to dental restorative resin composites with double benefits as mentioned above, Wu et al. [53] first introduced dental composites with triple functions of antibacterial activity, remineralization capability and self-healing ability after fracture in 2015. DMAHDM for antibacterial activity and NACP for regenerative potential were added to microcapsules, which were synthesized with PUF shells comprising TEGDMA and DHEPT as the healing liquid. 65–81% renewable recovery in the virgin fracture toughness was achieved, thus regaining the load-bearing ability of a cracked composite. Compared with the control group without DMAHDM, the new composite exhibited the high antibacterial property, inhibiting biofilm activity and acid production, and decreasing CFU by 3–4 orders of magnitude. The mechanical properties of this composite were not influenced when the incorporation of microcapsules reached 7.5 wt%. This indicates that the addition of antimicrobials and remineralizers is compatible with self-healing ability when the microcapsule content is no more than 7.5%.

With deepening the research, the synthesis of multifunctional restorative resin composites and the improvement of their corresponding properties have always been the research hotspot of dental restorative materials. In the existing synthesis method, different antibacterial agents and remineralizing agents were added to the dental resin composites to endow the resins with antibacterial and remineralizing ability. Regarding multifunctional dental resin composites with self-healing properties, nano-antibacterial inorganic fillers were incorporated into the shell of microcapsules and then mixed into the resin matrix in general. Additionally, antibacterial agents and remineralizing agents along with microcapsules can also be directly added to the resin matrix. However, some limitations exist in the synthesis methods mentioned above. For example, the additive amount of microcapsules will affect the mechanical strength of the composites. Besides, the specific binding mechanism between the nano-antibacterial inorganic filler and the microcapsules is unknown, and the long-term effect of the antibacterial agent and the remineralization agent in the self-healing resin material has not been verified.

When aiming to synthesize dental resin composites with self-healing capabilities without compromising other key properties, some considerations should be taken into account. It is crucial to choose healing agents, catalysts and the additive amount of microcapsules that are biocompatible and do not interfere with the original mechanical properties of the materials. The silanized microcapsules had the least effect on the mechanical properties. The choice of antibacterial agents should ensure to remain active during the self-healing process and maintain the antibacterial effect. The selection of remineralization agents should guarantee their ability to release remineralized ions during the self-healing process, thereby promoting tooth remineralization. In the future, more efforts should be made for the compatibility of multiple functions of composite resins and determine their effects under conditions that mimic the oral environment.

Conclusions

Repairing tooth defects with dental restorative resin composites remains to be an important method before achieving the regeneration of hard tissue of damaged teeth through tissue engineering. Therefore, it’s beneficial to endue dental restorative resin composites with antibacterial, remineralizing and self-healing capabilities to serve for a long time. However, it is difficult to optimize dental restorative composite formulations because the reinforcement of different properties may contrast each other negatively. In brief, the incorporation of the functional ingredients is supposed to endue the resin composites with superior new performance without sacrificing the other performances. Exploring the appropriate amount of each functional ingredient can be a good solution to synthesize resin materials with excellent properties. It is equally important that these new materials should have the ability to face more challenges in comparison with long-term in vitro experiments to survive in the complicated oral environment. In the future, more in vivo studies and clinical research are supposed to be conducted to investigate the effectiveness of the new generation of dental restorative resin composites and their interaction with oral microorganisms.

Author contributions

Study conception and design: S. Z. and J. Z.; Writing-review & editing: S. Z., J. Z., Y. Y., Y. C., J. W., D. S.; Draft manuscript preparation: J. Z., S. Z., X. C., A. L.; Supervision and funding acquisition: S. Z. All authors reviewed the manuscript and approved the final version of the manuscript.

Funding

This work was supported by National Natural Science Foundation of China (Grant No. 82101070); the Key Research and Development Program of Anhui Province (Grant No. 2022e07020051); College Young and Middle-Aged Teachers Training Action Project of Anhui Education Department (Grant No. YQZD2023024); Research Fund of Anhui Institute of Translational Medicine (Grant No. 2021zhyxC51); Natural Science Foundation of Anhui Province (Grant No. 2008085QH374); Anhui Medical University Basic and Clinical Collaborative Research Enhancement Program (Grant No. 2019xkjT019); Grants for Scientific Research of BSKY (Grant No. XJ201918) from Anhui Medical University; 2023 Disciplinary Construction Project in the School of Dentistry, Anhui Medical University (Grant No. 2023xkfyts02); 2022 Disciplinary Construction Project in the School of Dentistry, Anhui Medical University (Grant No. 2022xkfyts09); 2021 Disciplinary Construction Project in the School of Dentistry, Anhui Medical University (Grant No. 2021kqxkFY17) and Research Improvement Program in Stomatologic Hospital & College of Anhui Medical University (Grant No. 2020kqkyT02).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Competing interests

The authors declare no competing interests.