Key Findings

The Chitosan Complex (chitosan/ASAP and chitosan/ASAP/β-TCP) developed, tested, analyzed, and characterized provide valuable insights into the properties and potential applications in biomedical applications broadly and periodontal therapy and dental implants, specifically.

The Chitosan Complex possess favorable biocompatibility and bioactive properties, making it a promising candidate for use in tissue engineering, regenerative medicine, and periodontal therapy and dental implants, specifically.

Introduction

The development of new materials incorporating bioactive molecules for tissue regeneration is a growing area of interest. We at ChitoLytic are excited to review a recent paper that highlights the innovative applications of the Chitosan-based bioactive complex (Chitosan Complex). The technology is developed, and the paper is authored by a Brazilian consortium of professors and researchers and departments from the Universidade Federal do Rio Grande do Sul (UFRGS), Universidade Luterana do Brasil (ULBRA), and the Stem Cell Research Institute. The paper explores the multifaceted uses of the technology they developed for regenerative biomedical applications. The positive results from their extensive experiments and analysis using ChitoLytic chitosan underscores the quality and reliability of our products.

To get deeper insights into the study, we reached out to Dr. Luciano Pighinelli, one of the co-developers of the technology and co-author to get his input.

While the research paper covers a broader range of regenerative bone and skin applications, this blog narrows its scope to emphasize the practical and immediate advantages for dental professionals. This targeted approach aims to showcase the Chitosan Complex’s and method to obtain, a potential to advance dental care. And more specifically, it highlights the most impactful and clinically relevant uses of the Chitosan Complex in periodontal therapy and dental implants. These areas address significant unmet clinical needs, such as chronic periodontitis and implant failure, where the Chitosan Complex’s unique properties demonstrate it can confer the substantial benefits of enhanced tissue regeneration and antimicrobial activity.

The Study

The objective of this study was to develop a novel Chitosan Complex specifically designed for bone and skin tissue engineering, by combining chitosan, ascorbic acid-2-magnesium phosphate (ASAP), and β-tricalcium phosphate (β-TCP). The chitosan and the complexes chitosan/ASAP and chitosan/ASAP/β-TCP were prepared in membrane form, macerated to a particulate format, and then subjected to characterization through Fourier transform infrared (FTIR) spectroscopy, optical and scanning electron microscopy (SEM), zeta potential, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Cell viability was evaluated through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and with fluorescein diacetate (FDA) and propidium iodide (PI) staining in stem cells obtained from deciduous teeth. Statistical analyses were performed using analysis of variance (ANOVA), followed by Tukey’s test.

Results

The FTIR results indicated the characteristic bands in the chitosan group and the complexation between chitosan, ASAP, and β-TCP. Microscopic characterization revealed a polydisperse distribution of micrometric particles. Zeta potential measurements demonstrated a reduction in surface charge upon the addition of ASAP and β-TCP to the chitosan matrix. TGA and DSC analyses further indicated complexation between the three components and the successful formation of a cross-linked structure in the chitosan matrix. Stem cells cultured with the particulate biomaterials demonstrated their biocompatibility. Statistical analysis revealed a significant increase in cell viability for the chitosan/ASAP and chitosan/ASAP/β-TCP groups compared to the chitosan control.
  • Fourier transform infrared spectroscopy (FTIR) to elucidate the nature of the chemical interactions. It indicated the characteristic bands in the chitosan group and the complexation between chitosan, ASAP, and β-TCP.
  • Optical and scanning electron microscopy (SEM) to ascertain irregular morphology. This Microscopic characterization revealed a polydisperse distribution of micrometric particles.
  • Zeta potential measurements to uncover alterations in the surface characteristics when ASAP and β-TCP were conjugated to chitosan. Zeta potential measurements demonstrated a reduction in surface charge upon the addition of ASAP and β-TCP to the chitosan matrix.
  • Thermogravimetric analysis (TGA) and Differential scanning calorimetry (DSC) to determine thermal stability and complexation. Both the TGA and DSC analyses further indicated complexation between the three components and the successful formation of a cross-linked structure in the chitosan matrix.
  • Viability testing to assess the biological compatibility of mesenchymal stem/stromal cells derived from dental pulp.
  • Stem cells cultured with particulate biomaterials demonstrated their biocompatibility.
  • Statistical analysis revealed a significant increase in cell viability for the chitosan/ASAP and chitosan/ASAP/β-TCP groups compared to the chitosan control.

Study Conclusion

The chitosan/ASAP complex demonstrated potential for skin regeneration, while the chitosan/ASAP/β-TCP formulation showed promise as a biomaterial for bone regeneration due to the presence of β-tricalcium phosphate.
The findings of this paper highlight the significant potential of chitosan in addressing some of the critical challenges in healthcare. Michel Lockhart, Chitolytic CEO says, “we are proud to see our product contributing to such groundbreaking research. As we continue to innovate and improve our chitosan manufacturing and supply processes, we look forward to supporting more studies like this to that explore new and exciting applications of this versatile biopolymer”.
Chitosan is a linear polysaccharide derived from the deacetylation of chitin. It is a versatile that has shown significant promise in various dental applications due to its unique properties such as biocompatibility, biodegradability, antimicrobial activity, and ability to promote tissue regeneration. When integrated with ASAP and β-TCP, the resulting complex demonstrates enhanced regenerative capabilities, making it a versatile material for both soft and hard tissue engineering. The inclusion of ASAP, a potent antioxidant, promotes collagen synthesis and cellular proliferation, while β-TCP, a well-known osteoconductive material, supports bone regeneration and mineralization.
To provide deeper insights into the study, Dr. Luciano Pighinelli, one of the researchers and authors of the paper was contacted for his input. Here are some of his thoughts:

“Chitosan’s versatility is truly remarkable. Our research has shown that it can be effectively used in many biomedical application areas offering sustainable solutions.”

“It is important to highlight that the process of obtaining the complexes was only possible due to the characteristics obtained in the manufacturing process and the physical and chemical parameters defined by Chitolytic and the researchers.” 

“The quality of Chitolytic chitosan played a crucial role in our experiments. Its purity and consistency ensured reliable results across various applications.”

Luciano Pighinelli, PhD, Professor
These properties of the Chitosan Complex enables several innovative uses in dentistry including;
Periodontal Therapy
Dental Implants
Osseointegration

Bone Grafting

Endodontics

Root Canal Therapy

Caries Prevention and Treatment

Oral Cancer Treatment

Etc.
Periodontal therapy and dental implants have been selected for detailed discussion due to the advantages presented by the Chitosan Complex and its ability to address the unmet clinical needs in both areas.

Periodontal Therapy

Periodontal disease, including gingivitis and periodontitis, is a significant public health issue in the United States and throughout the world. According to data from the National Institute of Dental and Craniofacial Research (NIDCR) and the Centers for Disease Control and Prevention (CDC):
  • The prevalence of periodontitis is approximately 42.2% of adults 30 years or older have some form of periodontitis.1
  • Severe periodontitis affects about 7.8% of adults.2
  • Nonsevere periodontitis (mild and moderate) affects 34.4% of adults.3
Periodontal failure is also of critical concern as it often results in tooth loss.  Periodontitis is a leading cause of tooth loss among adults.4 This failure can be attributed to several factors, including poor oral hygiene, smoking, uncontrolled diabetes, and genetic predispositions.5 Periodontal disease can be an unmet clinical need since current treatments often fail to fully regenerate the damaged periodontal tissues.  All these facts and statistics underscore the importance of effective periodontal therapy and the need for ongoing research and innovation in treatment methods to address this widespread health issue. The Chitosan Complex holds promise for addressing the unmet clinical need in periodontal disease due to its
  • Enhanced Regeneration: The Chitosan Complex promotes the regeneration of periodontal tissues, including gums, periodontal ligament, and alveolar bone, which are often damaged in periodontitis.
  • Antimicrobial Properties: The natural antimicrobial properties of chitosan help reduce bacterial load, which is crucial in managing periodontal infections without relying heavily on antibiotics.

Dental Implants

The need for dental implants in the United States is substantial, driven by the high prevalence of missing teeth among adults. While dental implants generally have a high success rate, certain factors can contribute to their failure. Understanding these factors and addressing them through careful patient selection and advanced surgical techniques can help improve outcomes.

  • Over 150 million people in the U.S. have at least one missing tooth.6
  • Nearly 70% of adults aged 35-44 have lost at least one permanent tooth due to gum disease, decay, or trauma.7
  • Among adults aged 65 and older, 26% have lost all their permanent teeth.8
  • More than 500,000 dental implants are performed each year in the U.S. 9

Unmet Clinical Need: Implant failure can be a significant challenge in dental implantology when implants do not properly integrate with the jawbone, leading to implant loosening or rejection.

How the Chitosan Complex Addresses This Need:

  • Improved Osseointegration: The β-TCP component of the complex enhances the integration of implants with the bone, promoting stable and long-lasting implant placement.
  • Bone Regeneration: The chitosan-based complex supports bone growth around the implant site, which is essential for the success of dental implants, especially in patients with insufficient bone volume.

In the realm of dental science, the quest for innovative materials that can address complex clinical challenges is continual. The Chitosan Complex presents as a promising advancement in that can not only address significant clinical challenges, but also offers innovative solutions that improve patient outcomes and quality of life.

Understanding the Chitosan-Based Complex

Chitosan, a linear polysaccharide derived from the deacetylation of chitin, exhibits remarkable biocompatibility, biodegradability, and antimicrobial properties. When integrated with ASAP and β-TCP, the resulting complex demonstrates enhanced regenerative capabilities, making it a versatile material for both soft and hard tissue engineering. The inclusion of ASAP, a potent antioxidant, promotes collagen synthesis and cellular proliferation, while β-TCP, a well-known osteoconductive material, supports bone regeneration and mineralization.

Applications in Periodontal Therapy

1. Periodontal Regeneration

Periodontitis, a chronic inflammatory condition characterized by the destruction of periodontal tissues, poses a significant challenge in dental practice. Traditional treatments, such as scaling and root planing, often fail to fully regenerate the damaged tissues, leading to persistent inflammation and progressive tissue loss.

Mechanism of Action:

  • Antimicrobial Properties: Chitosan’s cationic nature enables it to interact with the negatively charged bacterial cell membranes, disrupting their integrity and leading to cell death. This antimicrobial action is crucial in reducing the bacterial load in periodontal pockets.
  • Tissue Regeneration: The bioactive molecules in the complex, particularly ASAP, enhance the synthesis of collagen and other extracellular matrix components, promoting the regeneration of periodontal ligament and alveolar bone. β-TCP provides a scaffold that supports the attachment and proliferation of osteoblasts, facilitating bone regeneration.
In clinical settings, the complex can be applied to periodontal pockets following debridement to support the regeneration of damaged tissues. This approach not only reduces bacterial load but also promotes the healing and regeneration of periodontal structures, improving clinical outcomes for patients with periodontitis.

2. Applications in Dental Implants can provide improved Osseointegration

The success of dental implants hinges on their ability to integrate with the surrounding bone, a process known as osseointegration. Factors such as poor bone quality and insufficient bone volume can compromise implant stability and longevity.

Mechanism of Action:

  • Osteoconductive Properties: β-TCP serves as an osteoconductive scaffold, facilitating the attachment, proliferation, and differentiation of osteoblasts. This promotes the formation of new bone around the implant, enhancing its stability.
  • Biocompatibility: Chitosan’s biocompatibility ensures minimal inflammatory response and supports the integration of the implant with the host tissue. The presence of ASAP further enhances cellular proliferation and differentiation, contributing to the overall success of the implant.
The complex can be used as a coating for dental implants to improve their integration with the bone. This approach enhances osseointegration, reducing the risk of implant failure and improving patient outcomes.

3. Bone Grafting

Bone grafting is often necessary to ensure sufficient bone volume for implant placement, particularly in cases of bone loss due to trauma, disease, or prolonged edentulism.

Mechanism of Action:

  • Bone Regeneration: The chitosan-based complex provides a conducive environment for new bone formation. Chitosan’s scaffold properties support the attachment and proliferation of osteoblasts, while β-TCP enhances mineralization and bone formation.
  • Bioactive Molecules: ASAP promotes the synthesis of collagen and other extracellular matrix components, essential for the formation of new bone tissue.

In cases of bone loss, the complex can be used to fill the defect and promote the growth of new bone. This not only facilitates the placement of dental implants but also ensures their long-term stability and success.

Here on the following page is a table comparing the Chitosan Complex with traditional materials in dental applications:

Conclusion

The Chitosan Complex developed by the research group represents a significant advancement in dental biomaterial for regenerative medicine. The Chitosan Complex developed and analyzed was a conjugate of i) chitosan/ASAP, which combines chitosan with L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (ASAP), and ii) chitosan/ASAP/β-TCP, which conjugates β-tricalcium phosphate (β-TCP) to enhance bone regeneration potential. The primary objective was to develop materials for the regeneration of bone and skin tissue, utilizing the biocompatibility and bioactive properties of chitosan, ASAP, and β-TCP.
The Chitosan Complex offers a comprehensive solution to the challenges faced in periodontal therapy and dental implants. Its unique properties make it a promising alternative to traditional materials and other biopolymers, with the potential to improve patient outcomes and address unmet clinical needs in dentistry. The Chitosan Complex was extensively tested, characterized, and analyzed utilizing a variety of methods. The results points to the Chitosan Complex’s effectiveness in enhancing osseointegration, providing antimicrobial protection, and supporting tissue regeneration.
This blog utilized these findings to apply them to promising advancements in dental applications, particularly in periodontal therapy and dental implants. This innovative material demonstrates superior biocompatibility and controlled biodegradability, minimizing adverse reactions and supporting tissue integration. Enhanced by ascorbic acid-2-magnesium phosphate (ASAP), the complex promotes cellular proliferation and differentiation, further improving biocompatibility and tissue regeneration; all enabling potential clinical benefits in dentistry.
When compared to traditional materials, the Chitosan Complex can offer significant advantages in dental applications when its composite attributes are considered, i.e., superior biocompatibility, natural antimicrobial properties, enhanced regenerative capabilities, and consistent clinical outcomes. These combined make it a promising alternative for addressing unmet clinical needs in dentistry.
The Chitosan Complex offers significant advantages over traditional materials in dental applications. Its superior biocompatibility, natural antimicrobial properties, enhanced regenerative capabilities, and consistent clinical outcomes make it a promising alternative for addressing unmet clinical needs in dentistry. As research and development continue, the potential of this innovative technology to transform dental care becomes increasingly evident. By leveraging the unique properties of chitosan, ASAP, and β-TCP, these complexes provide a multifaceted approach to improving dental health and patient outcomes.

References

  1. https://www.nidcr.nih.gov/research/data-statistics/periodontal-disease/adults
  2. https://impressionsdental.com/blog/dental-implant-statistics/
  3. https://www.2740consulting.com/dental-implant-statistics/

https://www.mdpi.com/2673-9879/4/4/46

Maurmann, N., et al. (2024). Innovative Applications of Chitosan in Biomedical and Environmental Fields. Future Pharmacol. 2024, 4(4), 873-891.