Introduction

Active oxygen-releasing gels are used in various dental treatments due to their antibacterial properties and ability to promote healing. These gels release oxygen in a controlled manner, which helps in eradicating anaerobic bacteria and promoting the recovery of healthy oral flora. Active oxygen-releasing gels typically contain compounds such as hydrogen peroxide, carbamide peroxide, or percarbonate. When these compounds decompose, they release oxygen radicals. One notable application is in the treatment of medication-related osteonecrosis of the jaw (MRONJ). For instance, blue®m oral gel has been used successfully to treat MRONJ, showing significant improvement in wound healing and bone recovery (references available in book). Additionally, these gels have been compared to traditional treatments like 0.2% chlorhexidine gel in managing chronic periodontitis, where they have shown better results in reducing probing pocket depth and improving clinical attachment levels (references available in book).

Historical aspect of research on active oxygen-releasing gels

The development and application of active oxygen-releasing gels have evolved over the past few decades, driven by advancements in materials science, chemistry, and periodontal therapy. During early 1950’s, hydrogen peroxide began to be recognized for its antimicrobial properties and was initially used as a mouth rinse and for wound disinfection. However, its unstable nature and rapid decomposition limited its efficacy. In 1970’s carbamide peroxide which releases hydrogen peroxide more slowly, was introduced and used primarily in tooth whitening gels. Its controlled release properties made it a candidate for further exploration in periodontal applications. The gel formulations were introduced in early 1990’s when researchers began experimenting with gel formulations to stabilize hydrogen peroxide and carbamide peroxide. Gels allowed for localized delivery and sustained release, enhancing the practical use of peroxides in periodontal therapy. Early clinical trials explored the efficacy of peroxide gels in treating gingivitis and mild periodontitis. These studies showed promising results in reducing microbial load and inflammation. The first commercial products containing peroxide gels for periodontal use were introduced in early 2000’s. These included formulations combining peroxides with other antimicrobial agents, such as chlorhexidine, to enhance their effectiveness. During this time period, significant research was focused on optimizing the stability, release kinetics, and patient tolerability of these gels. Advances in polymer science led to the development of more effective gelling agents and stabilizers. During 2010’s new innovations in gel composition, including the use of more sophisticated gelling agents like Carbopol and hydroxyethyl cellulose, improved the stability and efficacy of peroxide gels were introduced. The incorporation of additional therapeutic agents, such as anti-inflammatory compounds and growth factors, further enhanced their benefits. Active oxygen-releasing gels began to be used more widely in various periodontal treatments, including post-surgical care, maintenance therapy, and implantology. Clinical studies provided robust evidence supporting their efficacy and safety. At present, the ongoing research aims to refine these gels further, focusing on nano-encapsulation techniques to control the release of ROS more precisely. Studies also explore the synergistic effects of combining active oxygen-releasing gels with other novel therapies, such as probiotics and bioactive materials. Along with this, advances in personalized medicine are leading to the development of customized gel formulations tailored to individual patient needs, considering factors like specific periodontal pathogens present and the patient’s unique oral microbiome. Several active oxygen-releasing gel formulations have received regulatory approvals, validating their safety and efficacy for periodontal applications.

Composition of Active Oxygen-Releasing Gels

Active oxygen-releasing gels are typically formulated with the following key components:

Peroxide Compounds:

Hydrogen Peroxide (H2O2): Commonly used for its strong oxidative properties.

Carbamide Peroxide: A compound that releases hydrogen peroxide upon decomposition.

Sodium Percarbonate: Another source of hydrogen peroxide.

Gel Base:

Carbopol: A common gelling agent providing a viscous consistency.

Hydroxyethyl Cellulose: Used to stabilize the gel and control the release of active ingredients.

Stabilizers and pH Adjusters:

Phosphoric Acid: Maintains an optimal pH for stability and activity.

Ethylenediaminetetraacetic Acid (EDTA): Prevents degradation of peroxide compounds by chelating metal ions.

Additional Components:

Antimicrobial Agents: Chlorhexidine or other antimicrobial agents may be added to enhance the antimicrobial spectrum.

Humectants: Glycerin or propylene glycol to retain moisture and improve gel texture.

Preservatives: Ensure long-term stability and prevent contamination.

Mechanism of action of active oxygen releasing gels

Active oxygen-releasing gels work through a combination of oxygen release and antibacterial action. These gels perform their biological functions by following mechanisms,

Oxygen Release: These gels release oxygen in a controlled manner. Upon application, the peroxide compounds decompose to release reactive oxygen species (ROS) such as hydroxyl radicals (•OH) and superoxide anions (O2•−). This process can be catalyzed by contact with tissues, enzymes, or through pH changes. The oxygen helps in several wound healing processes, including oxidative killing of bacteria, re-epithelialization, angiogenesis (formation of new blood vessels), and collagen synthesis.

Antibacterial Action: The release of oxygen creates an environment that is hostile to anaerobic bacteria, which are common in periodontal diseases. This helps in reducing bacterial load and infection. ROS exhibit strong antimicrobial properties by causing oxidative damage to microbial cell membranes, proteins, and DNA. This leads to cell lysis and death, effectively reducing the bacterial load in periodontal pockets.

Biofilm Disruption: The oxidative action of ROS disrupts the extracellular matrix of biofilms, which are protective layers that harbor periodontal pathogens. This makes the microbes more susceptible to antimicrobial agents and the host immune response.

Hydrogen Peroxide and Lactoferrin: Some formulations also release hydrogen peroxide and lactoferrin. Hydrogen peroxide has strong antibacterial properties, while lactoferrin stimulates bone cells and aids in healing. The decomposition of peroxide compounds releases oxygen into the local environment. Increased oxygen levels promote aerobic metabolism and enhance the function of immune cells, aiding in the healing and regeneration of periodontal tissues.

Inflammation Reduction: By reducing bacterial load and promoting healing, these gels help in reducing inflammation and associated symptoms like bleeding and exudation. ROS can also modulate inflammatory responses, reducing inflammation and promoting tissue repair. Controlled levels of ROS have been shown to stimulate the production of growth factors and cytokines involved in wound healing.

Formulations of active oxygen-releasing gels

Here are some common formulations of active oxygen-releasing gels,

Blue®m Gel: This gel contains sodium peroxoborate, which releases oxygen and hydrogen peroxide. It also includes lactoferrin, which stimulates bone cells and aids in healing.

Carbopol-Based Gels: These gels often use Carbopol as a gelling agent, sometimes combined with other polymers like HPMC (Hydroxypropyl Methylcellulose) or sodium CMC (Carboxymethyl Cellulose) to enhance drug release and stability.

Cellulose-Based Gels: Formulations may include cellulose and glycerol, which help in maintaining the gel’s consistency and effectiveness. Sodium peroxoborate is often used as the oxygen-releasing agent.

Future Directions

Nanotechnology and Smart Gels:

Future developments may include “smart” gels that respond to environmental triggers, such as pH changes or microbial activity, to release active oxygen in a more targeted and controlled manner. The stimuli-responsive hydrogels are designed to respond to specific environmental triggers such as pH, temperature, light, or the presence of certain biomolecules. This responsiveness allows for controlled and targeted release of oxygen and other therapeutic agents. Nanogels are tiny hydrogel particles that can deliver oxygen and drugs more efficiently. They offer improved penetration and distribution within tissues, making them highly effective for medical applications.

Combination Therapies:

Ongoing research is likely to explore the combination of active oxygen-releasing gels with other therapeutic modalities, such as laser therapy, to enhance overall treatment outcomes. Combining active oxygen-releasing gels with SRP has shown significant improvements in periodontal health. Studies have demonstrated that these gels, when used as an adjunct to SRP, result in better clinical outcomes compared to traditional treatments like 0.2% chlorhexidine gel (references available in book). Active oxygen-releasing gels can be used alongside systemic or local antibiotics to enhance antibacterial effects. This combination helps in reducing bacterial load more effectively and promotes faster healing. In procedures involving bone grafts, such as DFDBA (Demineralized Freeze-Dried Bone Allograft), the use of oxygen-releasing gels can enhance the integration and healing of the graft by promoting angiogenesis and reducing infection risk. For dental implants, including zygomatic and pterygoid implants, these gels can be used to improve osseointegration and reduce peri-implantitis. The controlled release of oxygen helps in maintaining a healthy peri-implant environment.

Conclusion

The active oxygen-releasing gel formulations are designed to provide a sustained release of oxygen, which helps in reducing bacterial load, promoting healing, and improving clinical outcomes in periodontal treatments. The history of active oxygen-releasing gels is marked by continuous innovation and a growing understanding of their potential in periodontal therapy. As research progresses, these gels are expected to become even more integral to advanced periodontal treatment strategies. These gels are increasingly recognized in clinical guidelines and protocols for the management of periodontal diseases, highlighting their role as an adjunctive therapy.

References

References are available in the hardcopy of the website “Periobasics: A Textbook of Periodontics and Implantology”.