Support Oral Wound Healing

INTRODUCTION

Oral wound healing is a topic of interest for many dental professionals. Like many subjects, the research continues to provide greater insight into the effectiveness of current treatments and what may become possible in the future. In this edition of Sunstar Spotlight, Sebastiano Andreana, DDS, MS, discusses the benefits of hyaluronic acid in the wound healing process. Hyaluronic acid is a mucopolysaccharide found in the soft connective tissues and the synovial fluid of joints. It acts as a binding, lubricating, and protective agent. Hyaluronic acid-based therapies have been developed for topical use, including a mouthrinse and subgingival gel. As oral health professionals, we are committed to improving patient comfort and supporting successful oral health outcomes.Hyaluronic acid may be able to help us achieve these goals.

—Jackie L. Sanders, RDH, BS
Manager, Professional Relations Sunstar Americas Inc

Connective tissue, which is made up mostly of collagen, is one of the major components of the human body (Figure 1).^1,2 Hyaluronic acid (HA) plays a critical role in the collagen-making process (Figure 2). HA is a naturally occurring mucopolysaccharide with a long series of carbohydrates. It performs several critical functions in the body, including providing moisture and involvement in cell detachment, mitosis, migration, tumor development, and inflammation.³ Highly concentrated in soft connective tissues, HA can be used as a matrix in the support of skin matrix to encourage skin regeneration.³ According to Pini Prato et al,⁴ HA is involved in tissue repair, as demonstrated in their clinical case series assessing the outcomes of an autologous cell HA graft technique for gingival augmentation. This weak acid has a particularly
prominent presence during wound repair, embryogenesis, and whenever rapid tissue turnover and repair occur.⁵ Tissue repair can also be interpreted as wound healing.

THE COMPLEX SYSTEM OF WOUND HEALING AND WHAT IT SERVES TO ACCOMPLISH

Wound healing is a series of complex reactions initiated by the disruption of tissue architecture.⁵ In dentistry, the disruption of tissue architecture can be applied to multiple clinical situations, such as inflammation due to periodontal disease, the effects of scaling and root planing on periodontal tissues, and surgical procedures—such as periodontal, implant, and general surgeries—affecting soft tissues. HA also plays a more fundamental role depending on its molecular weight (high or low). When present in increased levels of high molecular weight, HA has immunosuppressive properties, maintains immune tolerance, and plays a role in the modulation of immune response. Furthermore, HA minimizes
the expression of cytokines during inflammatory processes. In high molecular weight, HA has an overall anti-inflammatory effect, including intrinsic antiaging and anticancer effects.⁵

The goal of wound healing is to lead to
regeneration of original tissues. Wound healing is a response to tissue damage that begins with disruption of the tissue, injury to the blood vessels, and the provision of a platelet-rich clot, followed by a cascade of events known as the inflammatory process.⁵ It culminates with the mass arrival of inflammatory cells at the injury site. HA is one of the most prevalent components at the injury site during the healing process; the increased presence of platelets contributes to high levels of HA. Additionally, endothelial cells contribute to the production and release of high levels of HA at the wound site. Once released in the damaged tissues, HA goes through a process of chemical degradation due to the presence of specific hyaluronidase enzymes and reactive oxygen species. The degradation is of particular importance in the reparative processes of the wound. The degradation products lead to interactions with in situ growth factors by stimulating their release. Following the injury, the amounts of HA in situ levels reach a
peak concentration at approximately 3 days post injury.^6,7

The outcome is tissue healing, particularly with the presence of type I collagen.⁵ Specific growth factors are part of the contemporary approach to wound healing and tissue regeneration following dental surgical procedures. Recent data suggest that an array of growth factors—such as fibroblast growth factor, transforming growth factors alpha and beta, platelet-derived growth factor, and epidermal growth factor—directly stimulate HA production and release in the tissues.^8,9

THE WOUND-HEALING PROCESS AND ITS COMPONENTS

Several events take place at the wound site following disruption of healthy tissues.⁵ The tissue-healing process begins when bleeding becomes a clot. The clot contains
platelets, which contribute to the release of HA within the fibrin clot. Fibrinogen, an HA-binding protein, is produced by platelets at the time of the initial clot formation. Together with its fibrin product, fibrinogen helps maintain a local concentration of HA. According to de la Motte et al,¹⁰ the high molecular weight HA forms the architectural matrix for deposition of the clotted fibrin.

As the healing process continues, deposition of collagen occurs, resulting from the presence of fibroblasts at the wound site (Figure 3). This leads to the granulation phase of the tissue repair, during which the fibroblasts produce and release collagen.

Wound-healing processes may be impaired in certain patient populations, such as those with diabetes, older adults, or individuals undergoing steroid treatment, which de creases the production and release of HA within the tissues. In patients with these conditions, an external source of HA may facilitate and promote the wound healing process.

OTHER ROLES FOR HYALURONIC ACID IN THE WOUND HEALING PROCESS

HA also provides anti-inflammatory properties in wound healing. Additional effects of HA include: stimulating angiogenesis; providing bacteriostatic and antiseptic properties; protecting the tissues by forming a barrier; preventing bacterial colonization; interacting with growth factors for the development of mineralized and nonmineralized tissues; and absorbing locally when applied to tissues.¹¹ As such, pharmaceutical companies across the world have tried to reproduce HA and offer it in liquid form (rinse and topical gel).

HA mouthrinses and gels have been used in dentistry for a variety of indications, each to facilitate and promote healing. A study by Sapna and Vendana¹¹ examined the use of a 0.2% hyaluronan gel for the treat ment of gingivitis. In the study, 0.2% hyaluronan gel was applied both topically and subgingivally in 28 patients with gingivitis. Each patient received four different treatments: scaling; scaling and topical hyaluronan gel; topical hyaluronan gel; and topical and intrasulcular hyaluronan gel. Gingival parameters included bleeding Index, gingival bleeding index, and plaque index. Gingival biopsies were taken to measure the inflammatory infiltrate. The results indicated that all periodontal indices improved; however, the group that received scaling and hyaluronan gel application achieved the most significant improvement compared to the other groups. Therefore, hyaluronan gel can be used as adjunct to periodontal treatment.

Another benefit of HA is its bacteriostatic properties, as demonstrated by Pirnazar et al.¹² The authors assessed the bacteriostatic effects of three different HA molecular weights in aqueous solutions, testing a low, medium, and high molecular weight HA. The bacteriostatic effect was defined as “inhibition of visible bacterial growth following an experimental condition, whereas bactericidal was defined as the absence of bacterial growth during incubation of the strain.”¹² The medium weight HA exerted the highest bacteriostatic activity on Aggregatibacter actinomycetemcomitans, Prevotella oris, and Staphylococcus aureus strains—bacteria commonly found in gingival
lesions and periodontal wounds. Pirnazar et al concluded that the use of HA as membranes or gel or sponges may reduce bacterial contamination of the surgical wound site, therefore minimizing the risk of post-surgical infection.¹²

As suggested by these two studies,^11,12 HA has dual effects, both on bacteria and the inflammatory process of the wound healing. Furthermore, recent studies on regenerative surgical procedures indicate that HA may also improve the clinical outcome of regenerative therapy at the wound site.¹³

Yet another application of HA in clinical periodontology was described by Vanden Bogaerden,¹⁴ who used HA fibers following open flap debridement and filling of the periodontal defect with HA. The 1-year results of the case series on 19 defects indicated pocket reduction of 5.8 mm and attachment gain of 3.8 mm. The author concluded that application of HA in the treatment of infra bony periodontal defects appears to be a promising method for the treatment of such periodontal defects.

Moreover, Malo et al¹⁵ described the favorable clinical effects provided by HA use during the post-surgical protocol in patients who had received implants in periodontally compromised sites. The same group of researchers has produced an interesting and clinically relevant study comparing the effects of HA vs chlorhexidine in the post-surgical phase of implant surgery. The results of this 6-month study indicated that HA produced peri-implant clinical outcomes comparable to those provided by chlorhexidine. The authors, however, recommend using HA up to 2 months following surgical procedures, and chlorhexidine between 2 months and 6 months postsurgery. This may indicate that HA was more beneficial during the woundhealing process when compared with chlorhexidine.

CONCLUSION

The use of HA-based gels and mouthrinses provides anti-inflammatory, bacteriostatic, and regenerative benefits during wound-healing proesses. HA may be useful in a variety of clinical circumstances, ranging from treating gingivitis to implant placement.

REFERENCES

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From Dimensions of Dental Hygiene. November 2015;13(11):19–22.