Use of Injectable Extended Platelet-Rich Fibrin as a Local Drug Delivery in the Treatment of Stage II Periodontitis Patients

Overview

The objective of the present study is to assess the clinical effectiveness of local delivery of injectable extended platelet-rich fibrin in subgingival application when used in conjunction with scaling and root planing (SRP) in the treatment of stage II periodontitis. The primary outcome includes the clinical attachment gain after 6 months, whereas the secondary outcomes include the changes of probing pocket depth, bleeding on probing percentage, plaque and gingival indices and the concentration of matrix metalloproteinase-8 (MMP-8) in gingival crevicular fluid (GCF) after 3 and 6 months.

Periodontitis is a chronic inflammatory dysbiotic disease resulting in damage of the periodontal tissue surrounding the teeth. At first, the teeth loosen, and eventually, there may be tooth loss. Periodontitis occurs due to an imbalance in the oral microbiota's natural balance and host resistance (i.e., dysbiosis). In adults, dysbiosis may be the cause of periodontitis, which can lead to inflammatory changes that affect the bone and connective tissue (1, 2). The goals of today's treatment of periodontitis are to reduce infection, resolve inflammation and create a clinical condition, which is compatible with periodontal health (3). Periodontitis is typically treated initially in a non-surgical way. Non-surgical periodontal therapy consists of scaling and root planing (SRP) combined with oral hygiene instructions. Typically, this results in clinical attachment gain due to resolution of the inflammation. However, findings revealed that in some affected areas, the standard treatment proved to be insufficient and some residual pockets remain after therapy (4). To reduce the indication of surgical invasive and technically demanding procedures, several adjuncts to SRP have been proposed such as the use of antibiotics or anti-inflammatory drugs. These adjunctive therapies improved treatment outcomes in terms of pocket depth reduction and CAL gain (5). However, their systemic administration requires the use of high dose of active drugs to reach efficient concentration at the treated site, the compliance of the patient to follow the selected administration regimen and could be associated with serious side effects. Consequently, several local treatments such as gels, fibers or chips loaded with different active molecules or drugs have been developed and evaluated in clinical settings (6). The main advantages of such treatments are the delivery of active drugs at the precise site of the lesions, the reduced risk of side effects and the possibility of 3D stabilization of the blood clot (7). Local application of medications after scaling and root planing (SRP) has shown better results than SRP alone principally in reduction of pocket depth (8). Nonetheless, some materials which are applied locally were found to induce allergic -like reactions, lack the rheological characteristics and sustained release of the active ingredient under investigation (9). To-date, platelet concentrates have been proven to promote and stimulate wound healing processes and to accelerate angiogenesis due to their concentrated growth factors content and anti-inflammatory molecules. Del Fabbro and his colleagues confirmed the use of growth factors for providing an additional stimulation to physiological healing processes (10). Platelet concentrates are classified as platelet-rich plasma (PRP) or platelet-rich fibrin (PRF). In PRP techniques, blood is collected with anticoagulant and then centrifuged, whereas in PRF techniques, blood is collected without any anticoagulant and immediately centrifuged (11). As for leukocyte- and platelet-rich fibrin (L-PRF) products, including L-PRF clots and liquid fibrinogen, platelet concentrates are obtained by centrifugation of a whole blood sample, discarding red blood cells and concentrating the components to be used, such as fibrin, platelets, growth factors, leukocytes, and other circulating cytokines and proteins (12). Nevertheless, the common demerit of current platelet concentrates is the fast resorption within 15 days inside the site of application (13). Recently, a new PRF preparation has been introduced by Richard Miron (2020) known as extended platelet- rich fibrin (e-PRF) or Albumin-PRF mixture (Alb-PRF). It consists of a combination of concentrated growth factors and denaturated albumin gel. It is postulated that it might resorb after 4-6 months; therefore, it can be used even for guided bone regeneration (14) . Extended platelet- rich fibrin (ePRF) is the latest functional and promising matrix that overcomes limitations of its predecessors. It shows many characteristics of ideal biomaterial for repair, regeneration, or facial esthetics. Here are some important characteristics: it is injectable which allows physicians to minimize access trauma to affected tissue and there is no need for sophisticated armamentarium for its production as a chairside procedure in the clinics (15). ePRF can be used as a bioactive, natural filler as it forms a "sticky" gel that can be used as a 100% natural filler and it does not easily leak out from the injury site. Its gel creates a natural scaffold allowing absorption of water that is necessary for proliferation of new cells. It does not block the space for newly formed tissue (16). Thus, the alternative hypothesis of the present study states that the injectable extended platelet rich fibrin could improve the periodontal status of patients who are suffering from stage II periodontitis.