Introduction

Guided tissue regeneration (GTR) is a pivotal technique in periodontal therapy, aimed at regenerating lost periodontal structures, including bone, periodontal ligament, and cementum. Since its introduction in the 1980s, GTR has become a widely accepted method for promoting tissue regeneration, particularly in the treatment of periodontal defects. The principle behind GTR is the use of a barrier membrane that selectively inhibits the migration of epithelial and connective tissue cells into the defect site, thus allowing slower-growing cells from the periodontal ligament and bone to repopulate the area. This method has demonstrated its efficacy in regenerating tissues that are otherwise difficult to repair using conventional techniques (1).

The success of GTR heavily depends on the biomaterials used to construct the barrier membrane. Biomaterials are selected based on their ability to support the regeneration process without causing adverse immune reactions. Ideally, these materials should be biocompatible, promote cell attachment and proliferation, and be resorbable over time to avoid the need for surgical removal (2). Over the years, several types of biomaterials have been developed, ranging from non-resorbable materials, such as expanded polytetrafluoroethylene (ePTFE), to resorbable materials, including collagen-based membranes and synthetic polymers. The choice of biomaterial often depends on the specific clinical situation and the properties required for optimal tissue regeneration (3).

Collagen, a natural component of the extracellular matrix, is one of the most commonly used resorbable biomaterials in GTR. Collagen membranes are favored for their biocompatibility and ability to promote cell attachment. However, despite their widespread use, these materials have limitations, such as varying degradation rates and susceptibility to infection. Other materials, such as synthetic polymers, offer greater control over degradation rates and mechanical properties but may lack the biological cues that promote tissue regeneration (4). This review aims to evaluate the various biomaterials used in GTR, focusing on their properties, clinical performance, and future directions.

Review

The selection of biomaterials in GTR plays a critical role in determining the success of the regenerative process. Over the years, the development of both natural and synthetic biomaterials has expanded treatment options for clinicians. Natural biomaterials, such as collagen-based membranes, are often favored for their biocompatibility and ability to promote cell attachment. These materials mimic the natural extracellular matrix, facilitating cellular processes essential for tissue regeneration. However, their variability in degradation rates and susceptibility to bacterial infection remain key limitations (5). On the other hand, synthetic biomaterials, such as polylactic acid (PLA) and polyglycolic acid (PGA), offer more predictable degradation rates and can be engineered to meet specific mechanical and biological requirements. These synthetic polymers provide greater structural support during the early phases of healing, which is particularly advantageous in larger defects. Despite their advantages, some synthetic materials may elicit foreign body reactions, which can hinder the regenerative process (6). In recent years, advancements in biomaterial engineering, including the development of composite membranes, have shown promise in overcoming the limitations of both natural and synthetic materials. These composite membranes aim to combine the favorable properties of different biomaterials, providing better control over degradation and enhanced bioactivity, thus improving clinical outcomes.

Types of Biomaterials Used in Guided Tissue Regeneration

Biomaterials used in GTR can be broadly classified into non-resorbable and resorbable categories, each offering distinct advantages and challenges. Non-resorbable membranes, such as ePTFE, were among the first materials introduced in GTR. These materials provide excellent mechanical support, effectively creating a physical barrier to prevent epithelial migration into the defect site. The high tensile strength and chemical stability of ePTFE membranes contribute to their long-term durability, allowing extended healing periods. However, non-resorbable materials require a second surgical procedure for removal, increasing patient morbidity and the risk of infection (7).

In contrast, resorbable biomaterials, such as collagen-based membranes, have become increasingly popular due to their ability to degrade naturally over time, eliminating the need for removal. Collagen, as a natural protein found in connective tissues, is highly biocompatible and promotes cell attachment, making it a favorable choice for GTR applications. Collagen membranes also have chemotactic properties, attracting fibroblasts and other cells necessary for tissue regeneration. Despite these advantages, collagen membranes can degrade unpredictably, sometimes too quickly, which may compromise the regenerative process, particularly in larger defects (8).

Synthetic resorbable biomaterials, including PLA, PGA, and their copolymer polylactic-co-glycolic acid (PLGA), offer greater control over degradation rates. These materials are engineered to degrade over a specific time frame, allowing them to provide support during the early stages of healing while gradually being absorbed by the body. PLA and PGA membranes have been shown to support periodontal regeneration effectively, with predictable degradation profiles. However, the breakdown of these synthetic materials can sometimes lead to acidic byproducts, which may induce local inflammation and affect the surrounding tissues (9).

Composite membranes have emerged as a novel approach, combining the benefits of both natural and synthetic biomaterials. These membranes are designed to provide the biocompatibility of natural materials, like collagen, while incorporating synthetic components that offer controlled degradation and enhanced mechanical properties. Such hybrid membranes aim to overcome the limitations of traditional materials by providing a balance between bioactivity and structural support. This combination holds promise for improving clinical outcomes in GTR by optimizing both tissue regeneration and material stability throughout the healing process. In Table 1, there is a summary of different types of biomaterials and their characteristics.

Biocompatibility and Degradation Properties of Biomaterials

Biocompatibility is a crucial factor in the selection of biomaterials for GTR as it directly affects the success of the regenerative process. A biomaterial's ability to integrate into the host tissue without eliciting an adverse immune response is essential to ensure that the healing process is not disrupted. Natural biomaterials like collagen are highly biocompatible due to their resemblance to the extracellular matrix components. These materials promote cellular attachment and proliferation, making them particularly effective in periodontal regeneration. However, despite their biocompatibility, collagen-based membranes can degrade unpredictably, and the rapid breakdown of these materials may hinder effective tissue regeneration, especially in complex or large defects (10-12).

The degradation properties of biomaterials are equally significant, as they determine how long the material can provide mechanical support during healing. Resorbable biomaterials, such as PLGA, are designed to degrade over a set period, gradually being absorbed by the body. The degradation rate of these synthetic materials can be tailored to match the healing requirements of the tissue. However, one potential issue with synthetic polymers is the accumulation of acidic byproducts during degradation, which can lead to localized inflammation and tissue irritation. These byproducts may interfere with cell proliferation and tissue formation, complicating the healing process (13). In contrast, non-resorbable materials like ePTFE do not degrade and remain intact throughout the healing period. This ensures that the mechanical support is maintained for a prolonged period, allowing sufficient time for tissue regeneration. However, their permanence also necessitates a second surgical procedure for removal, increasing the risk of infection and patient discomfort. The need for removal and the associated complications have led to a decline in the use of non-resorbable materials in favor of resorbable alternatives (14, 15).

To address the limitations of both resorbable and non-resorbable materials, researchers have developed hybrid or composite materials that combine the biocompatibility of natural biomaterials with the controlled degradation properties of synthetic ones. These composite materials offer a balance between providing mechanical support and facilitating tissue integration, with degradation profiles that can be customized to match the healing dynamics of the target tissue. As the field of biomaterials advances, the focus on improving both biocompatibility and degradation properties continues to be a priority for enhancing clinical outcomes in GTR.

Clinical Applications and Effectiveness in Periodontal Regeneration

The clinical application of GTR has been a cornerstone in the treatment of periodontal defects, particularly in cases where significant bone and soft tissue loss occurred. GTR has shown remarkable effectiveness in promoting periodontal regeneration, with its most common use being in the treatment of infrabony defects, furcation defects, and gingival recession. The technique's primary goal is to regenerate lost periodontal structures, including the alveolar bone, periodontal ligament, and cementum, which are often compromised due to periodontal disease. Numerous studies have demonstrated the success of GTR in achieving these objectives when appropriately used in conjunction with suitable biomaterials (16).

Infrabony defects, which are characterized by vertical bone loss, are among the most challenging periodontal defects to treat. GTR has been widely used in these cases due to its ability to facilitate new bone formation and prevent epithelial downgrowth into the defect. Both resorbable and non-resorbable membranes have been utilized in treating infrabony defects, with studies showing that collagen-based membranes, in particular, have yielded favorable outcomes by promoting cell adhesion and proliferation (17). However, the effectiveness of GTR in these cases often depends on the size and shape of the defect, as well as the patient's individual healing capacity. Furcation defects, which occur when periodontal disease leads to the loss of bone between the roots of multi-rooted teeth, are another key indication for GTR. These defects present a significant challenge due to the complex anatomy of the root structures. Clinical studies have reported varying degrees of success in treating furcation defects with GTR, with better outcomes typically observed in Class II furcation defects, where partial bone loss has occurred. In these cases, the use of GTR has been shown to regenerate periodontal ligament fibers and bone, leading to improved tooth stability and long-term prognosis (18).

Gingival recession, often associated with traumatic brushing or periodontal disease, can also be effectively treated using GTR. By placing a barrier membrane over the exposed root surface, GTR can facilitate the regeneration of new attachment, reducing root sensitivity and improving esthetic outcomes. Research has shown that GTR, when combined with grafting materials such as connective tissue grafts, can significantly enhance the clinical results by promoting more predictable root coverage and tissue regeneration in recession defects.

Challenges and Future Directions in Biomaterial Development

Despite significant advancements in the development of biomaterials for GTR, several challenges persist that limit their widespread clinical success. One of the primary challenges is achieving a balance between mechanical stability and bioactivity. While non-resorbable membranes such as ePTFE provide robust mechanical support, they require a second surgical procedure for removal, which increases the risk of infection and patient discomfort. Resorbable membranes, on the other hand, offer a more patient-friendly alternative but often lack the necessary mechanical strength to maintain space during the critical early stages of healing (19).

Another key challenge lies in the predictability of degradation rates, particularly for resorbable materials. Natural biomaterials like collagen degrade unpredictably, which can compromise tissue regeneration if the membrane resorbs too quickly before adequate tissue formation has occurred. On the contrary, synthetic biomaterials such as PLA and PGA can be engineered with controlled degradation rates, but their breakdown can sometimes lead to the accumulation of acidic byproducts, causing localized inflammation and delaying the healing process (20). Addressing these issues requires the development of biomaterials that not only have predictable degradation profiles but also supports the regenerative process by promoting cellular attachment and proliferation.

One promising area of research involves the incorporation of bioactive agents, such as growth factors and stem cells, into GTR membranes. These bioactive agents can enhance the regenerative capacity of the biomaterials by stimulating cellular responses necessary for tissue formation. For example, growth factors like bone morphogenetic proteins have been shown to promote bone regeneration when incorporated into GTR membranes. However, the controlled release of these bioactive agents remains a challenge, as rapid or uncontrolled release can lead to undesirable effects, such as ectopic tissue formation (21).

Looking to the future, the development of composite biomaterials is seen as a potential solution to many of the current challenges. By combining the favorable properties of natural and synthetic materials, composite membranes can offer both mechanical strength and biological activity. Additionally, advances in nanotechnology have the potential to revolutionize the design of GTR membranes. Nanoscale modifications to the surface of biomaterials can enhance cell attachment, proliferation, and differentiation, leading to improved regenerative outcomes. Future research will likely focus on creating smart biomaterials that respond to the dynamic healing environment by adjusting their degradation rates and releasing bioactive agents in a controlled manner.

Conclusion

The evolution of biomaterials for guided tissue regeneration has significantly improved the outcomes of periodontal therapies, but challenges such as degradation predictability and biocompatibility remain. Advancements in bioactive agents and composite materials offer promising solutions, while ongoing research in nanotechnology may further optimize biomaterial performance. Future innovations must focus on creating smart, adaptive biomaterials that provide both mechanical support and enhanced biological activity to promote efficient tissue regeneration. Continued exploration in this field is essential for overcoming current limitations and improving clinical success.

Disclosure

Conflict of interest

There is no conflict of interest.

Funding

No funding

Ethical Consideration

Not applicable.

Data availability

Data that support the findings of this study are embedded within the manuscript.

Author Contribution

The authors contributed to conceptualizing, data drafting, collection and final writing of the manuscript.