The Rise of Nanotech in Dentistry
Over the past few decades, it has been increasingly recognized that oral health plays a crucial role in expediting the overall health of humans. Although oral diseases are majorly preventable, several dental/oral-related diseases pose a major health burden in many countries, affecting lifestyle, discomfort, and even death. According to World Health Organization (WHO) statistics, the Global Oral Health Status Report in 2022 stated that oral-related diseases have significantly affected approximately 3.5 billion people globally, accounting for 3 out of 4 people in middle-income countries.
Tooth caries, gum-related (periodontal) diseases, and oral cancer are some of the most common issues impacting oral health. Tooth caries affected a total of 2 billion people of adults with permanent teeth and 0.5 billion of children with temporary teeth. Notably, over 40% of adults reported pain last year, and over 80% of people had at least a cavity by the age of 34. The predominant reasons for the increased rate of dental-related disorders could be untreated dental caries in permanent teeth because of expensive treatment, no health insurance coverage, and insufficient infrastructure in most low- and middle-income countries.
Dental-related issues with dentin exposure often increase the risk of developing oral diseases. The tooth has a hierarchical structure, including periodontal (superficial), orthodontic (bone-associated), and endodontic layers (dentin-pulp). Several dental-related disorders include gums-associated (gingivitis or periodontitis, and inflammation), tooth-based (dental caries, root infection, enamel erosion, tooth sensitivity, erosion, decay, and edentulous or total tooth loss), as well as overall buccal/oral-related ailments (dry mouth, bad breath, mouth sores, oral cancer, and miscellaneous bacterial infections).
Although general dental care formulations, such as antibiotic solutions, mouthwashes, and calcium constructs, have been available to improve oral health, these therapeutic options suffer from several limitations. Predominantly, the biofilms created by the bacterial colonies and acquired antibiotic resistance as defense mechanisms result in poor therapeutic outcomes, leading to further progression of oral diseases towards the loss of teeth and damage of gums.
The advent of nanotechnology has resulted in the development of various innovative nanoarchitectured composites from diverse sources to address these limitations. Nanoparticles offer advantages such as convenient synthesis, stability, ease of scale-up, and tailorable morphological and physicochemical characteristics. These ultrafine structures have gained enormous interest due to their high surface-to-volume ratio and abundant surface chemistry, facilitating the loading of diverse guest molecules.
In this comprehensive article, we will explore the role of various nanoarchitectured composites in improving oral health. We will discuss the predominant dental-related diseases, the importance of nanostructured components, and their synthesis approaches. Furthermore, we will delve into the diverse therapeutic solutions from natural (plant-, animal-, and marine-derived) and synthetic (organic- and inorganic-) precursors for enhancing dental health. Finally, we will address the challenges and future outlook for translating these innovative platforms into clinical practice.
Dental-Related Ailments: Causes, Severity, and Treatments
The major cause of various dental-related disorders is the growth of microorganisms in the oral cavity. The oral cavity acts as one of the predominant gateways for over 700 bacterial species, connecting the external environment with the gastrointestinal tract. Notably, microbiome dysbiosis plays a crucial role in oral hygiene, in which the imbalance leads to various oro-dental diseases.
The sequential progression of dental health issues and eventual tooth loss can be explained in several stages. Initially, the microbial imbalance in the oral cavity results in the bacterial biofilm formation, leading to the formation of caries or plaques on the tooth surface. The untreated plaques lead to pulpitis and apical periodontitis, resulting in local inflammation. Further, the inflammatory responses throughout the oral cavity result in highly complex gum-related diseases, such as gingivitis, periodontitis (mild or advanced), and peri-implantitis.
In addition to dental issues, several reports indicated that microbial dysbiosis inducing systemic inflammation would result in other complex ailments such as diabetes, risk of cancer, and myocardial infarction. Several other predominant direct reasons for the cause of these dental-related disorders include sugar intake, alcohol and tobacco consumption, as well as poor hygiene, among others.
Dental-related disorders have been broadly categorized into three categories: gums-related, teeth-related, and miscellaneous diseases in the buccal cavity.
Gums-Related Ailments
Gums-associated conditions are predominantly encountered, including gingivitis or periodontitis, referring to inflammation in the gums. Gingivitis is the early stage of gum-related ailments, often caused by bacterial infection. This mild periodontal ailment is initially caused by bacterial film accumulated on the teeth surface adjacent to the gums, affecting the supporting structures of the teeth. Periodontitis is the advanced stage of gums-related diseases, involving the loss of the alveolar bone and leading to tooth loss.
Tooth-Related Ailments
Tooth-related disorders include dental caries, enamel erosion, root infection, tooth sensitivity, erosion, decay, and edentulous (total tooth loss). Dental caries, often referred to as tooth decay, has emerged as the most prevalent tooth-related ailment. The microbial imbalance in the oral cavity results in bacterial biofilm formation on the surface of the tooth, leading to dental caries. The formed plaques on the tooth surface convert the consumed sugars to acids, leading to tooth demineralization and eventual destruction of the tooth.
Other minor ailments include cracked teeth, bruxism, enamel erosion, and root infection. The root canal can be infected with bacteria, resulting in tooth cavities, damaging the nerves, and ultimately developing abscesses. Tooth sensitivity can be caused by tooth decay, gum diseases, root infection, cracked tooth enamel erosion, and receding gums.
Miscellaneous Oral Ailments
In addition to specific tooth- and gums-based ailments, several other diseases in the buccal cavity influence oral hygiene, such as oral cancer, dry mouth, and bad breath. Oral cancers are often evident in the buccal cavity and gums, with excessive usage of tobacco, alcohol, and betel quid being the leading sources. Dry mouth and bad breath are also commonly seen oral disorders.
Other common ailments in the oral cavity include oro-dental trauma, noma, and oro-facial clefts. Oro-dental trauma refers to damage to teeth, the mouth, and the oral cavity during injuries. Noma is a gangrenous disease prevalent in African countries and some parts of Asia and Latin America, often affecting children aged 2-6 years due to malnutrition, dreadful infections, poor hygiene, and feeble immune system. Oro-facial clefts, also called clefts on the lip and palate, are the most common craniofacial congenital disabilities.
Common risk factors for these dental ailments include tobacco and alcohol consumption, as well as a high-sugar diet, leading to other diseases such as cardiovascular diseases, cancer, respiratory disorders, and diabetes. Maintaining oral health through public health interventions, a healthy diet, reduced alcohol consumption, increased physical activities, and regular dental check-ups play crucial roles.
The Role of Nanostructured Components in Addressing Dental Ailments
The advent of nanotechnology has opened up new avenues for addressing various dental-related issues. Nanoparticles offer several advantages, including convenient synthesis, stability, ease of scale-up, and tailorable morphological and physicochemical characteristics. These ultrafine structures have gained enormous interest due to their high surface-to-volume ratio and abundant surface chemistry, facilitating the loading of diverse guest molecules.
Nanostructured components can play a crucial role in solving various dental-related issues, such as anti-bacterial, remineralization, and tissue regeneration abilities.
Anti-Microbial Properties
Several dental-related disorders often begin with the deposition of bacteria, such as gingivitis and dental caries, in the gaps of teeth and gums. Conventional anti-microbial solutions, such as mouthwashes and other formulations with various antibiotics, have been applied to ablate the deposited bacteria on the tooth and gums and cure different tooth- and gum-related diseases.
However, these traditional formulations suffer from notable disadvantages in terms of formulation and performance aspects. Predominantly, the formulation of various dosage forms often suffers a major limitation of the poor solubility of hydrophobic drugs, limiting their successful formulation. In terms of performance, it is extremely challenging to eradicate formed biofilms, leading to increased anti-bacterial resistance and resulting in deprived therapeutic efficacy.
Nanoparticles can address these limitations by encapsulating different antibiotics or generating anti-microbial materials. These innovative nanomaterials encapsulated with antibiotics substantially improve the solubility of the hydrophobic drugs, leading to their improved performance efficacy. The nanomaterials can act through various mechanisms, including electrostatic interactions on the surface, metal ion hemostasis in the cytoplasm intracellularly, and genotoxicity and inhibition of signal transduction in the nucleus.
Remineralization Abilities
Dental caries often affect the quality of teeth, damaging the enamel and teeth subsequently due to bacterial growth. The damaged teeth portions can be fulfilled by remineralizing the hard tissues using various adhesives or resins. These adhesives or resins added with multiple biologically active nanomaterials act as remineralized anti-caries nanomaterials.
On the one hand, these nanomaterials remineralize the exposed collagen, preventing its degradation and improving bonding durability. On the other hand, the encapsulated nanoparticles can facilitate the release of highly required calcium and phosphate ions to improve strength at low pH values, promoting the remineralization of the tooth.
During the remineralization process, the root canal is cleaned with the medication referred to as the interappointment intracanal medicaments, employing anti-inflammatory and anti-microbial agents. The final step of remineralization is referred to as obturation, which is the combination of filling and sealing after the intracanal medication of a canal. Nanoparticles encapsulated with antibiotics and dispersed in the mouthwashes can provide enhanced anti-microbial action for a long time and improve mechanical properties, leading to improved remineralization.
Tissue Regeneration Abilities
Dental-related ailments often result in the loss of tissues to a great extent, specifically during tooth loss and surgical removal. The reconstruction of damaged tissues using conventional biomimetic scaffolds may pose various limitations in terms of lack of regeneration abilities. The integration of nanotechnology and encapsulation of several nanoconstructs in the biomimetic scaffolds have offered enormous potential for the functional improvement and structural restoration of tissues.
The encapsulated nanomaterials in the biomimetic scaffolds enable the improved crosstalk intercellular, enabling the regulation of mechanical signals in the extracellular matrix. In addition, the sufficiently high surface-to-volume ratio, abundant surface area, and active surface facilitate the encapsulation of various oro-protective drugs, including antibiotics.
Furthermore, stem cells have been employed for tissue regeneration applications. Human dental pulp stem cells (hDPSCs) can be employed for tissue restoration, in which these specific stem cells can be isolated from the dental pulp of permanent teeth or extracted wisdom teeth. These hDPSCs can be encapsulated in the scaffolds with the mineralized extracellular matrix-like components for their improvement of regeneration efficacy, inducing intrafibrillar mineralization of single-layer collagen fibrils.
Synthesis Approaches for Nanostructured Components
Various methods have been developed for the synthesis of nanostructured components, depending on the physicochemical properties, solubility of the precursors, dimension, size, and applicability of the end products. These synthesis methods have been broadly classified into two predominant strategies: top-down and bottom-up approaches.
Top-Down Approaches
The top-down process refers to reducing the size of initial bulk materials to nano-sized constructs using externally controlled conditions, for instance, ball milling strategy. This approach offers different mechanical actions based on the balls made of stainless steel, ceramic, or rubber, increasing the mechanical reactivity and spatial distribution of precursor components.
Bottom-Up Approaches
The bottom-up approach reduces or miniaturizes the materials to the atomic level and subsequently assembles them into nanometer-sized constructs in an organized manner. Several methods have been applied for this approach, including self-assembly, phase separation, templating, sonochemical, and miscellaneous techniques like electrospinning and microwave-assisted irradiation.
Self-assembly is one of the important processes in synthesizing materials, in which the precursors or components are either arranged spontaneously or linked to each other, systematically forming the ordered aggregates without the influence of any external stimuli.
Phase separation is the chemical segregation of a single homogeneous mixture into different forms while reducing the free energy. The liquid-based approach involves the precipitation of nanoparticles in desired particle size and altered morphological distribution through diffusion or the Ostwald ripening methods.
The template-based synthesis approach is applied to fabricate various nanometric domains using the sacrificial templates, including soft (amphiphilic surfactants and vesicles) and hard templates (copper oxide). This approach is often used to fabricate porous and non-porous constructs, in which these sacrificial templates can be removed to form mesoporous to large-sized porous and hollow architectures.
The sonochemical process utilizes ultrasound radiation to generate nanoparticles with desired morphological attributes. The sound wave strikes the precursors and results in the formation of bubbles. After breaking the bubbles due to acoustic cavitation, the microenvironment surrounding the bubbles leads to high tension, raising the local temperature and forming a high-pressure region, which activates the precursors to form nanomaterials.
In addition to these major synthetic strategies, several other methods have been discussed, including ball milling, microwave-assisted irradiation, electrospinning, and exfoliation. These techniques offer advantages and limitations in synthesizing multiple kinds of nanoparticles.
Natural and Synthetic Nanoarchitectured Composites for Improved Oral Health
Researchers have explored the generation of diverse kinds of nanoparticles based on the source of precursors, including natural (plant-, animal, and marine-life) and synthetic (organic-, inorganic-, as well as organic–inorganic) nanocomposites, for treating various oral ailments.
Natural Nanocomposites
Plant-derived extracts containing various phytochemicals (e.g., terpenoids, alkaloids, and phenolic substituents) and secondary metabolites (amino acids, vitamins, proteins, polysaccharides, enzymes, and antioxidants) can reduce metal precursors to corresponding metallic nanoparticles. These biogenic nanoparticles, such as silver nanoparticles (AgNPs), have been applied for the synthesis of anti-microbial agents and remineralizing products.
Animal tissues, such as decellularized extracellular matrix (dECM) from porcine tissues, offer a potential solution to address the desperate shortage of human tissues. These dECM-based scaffolds possess various proteins (collagen, proteoglycans, fibronectin, and glycoproteins) and exceptional growth factors, simulating the tissue environment and enabling the transmission of appropriate signaling cues.
Marine life has provided us with enormous opportunities for dental health, such as seashells, bones, and corals. These marine components offer exceptional biocompatibility and mechanical properties, displaying various functional attributes of osteoconductive and osteogenic properties, as well as anti-thrombogenic and anti-microbial activities. The abalone nacre water-soluble organic matrix and various natural polyphenols from plants have shown improved remineralization abilities for the enamel.
Synthetic Nanocomposites
Organic-based nanoparticles, such as polymeric (PLGA, PLA, chitosan, and alginate), liposomal, micellar/vesicular, collagozomes, and dendrimer-based constructs, have been synthesized for various biomedical applications, including the treatment of dental-related ailments.
These organic species can encapsulate different drugs (anti-inflammatory, anti-microbial, and anti-cancer drugs) and deliver them appropriately. They offer advantages like facile synthesis, colloidal stability, biocompatibility, and degradability. However, these constructs suffer from poor thermal stability and bioavailability issues, resulting in poor dosage-related risks.
Polymer-based hydrogels have been employed for localized drug delivery due to their exceptional hydrophilicity, tailorable shapes, mechanical characteristics, and malleability, which are of particular interest for oral-based ailments. These smart hydrogels can be designed with pH and enzyme-responsive stimuli to improve the localized delivery of various drugs.
Dendrimers, highly ordered synthetic macromolecules, have emerged as another class
