The worldwide incidence of dry socket, which has been documented to range from 1 to 4% following normal dental extractions, is a matter of concern (1). The lower teeth have a 10 times increase in risk compared to the upper teeth, and the risk may potentially approach 45% for the removal of the mandibular third molar.(2). Dental practitioners frequently underestimate the level of pain intensity experienced by individuals with dry socket and sometimes fail to provide sufficient care to these individuals. the inflammation in the per socket sometimes extended to the buccal vestibule and sometimes towards the cheek. However, there was no increase in body temperature. This phenomenon has verified that the classical dry socket is a localized pathological condition that only affects the maxillary or mandibular alveolar process, without causing any systemic disturbance(4) .
Regardless of the kind and extent of the injury, wound healing is a complex biological process made up of interconnected steps that are classified as inflammation, angiogenesis, granulation tissue development, and tissue remodeling and regeneration. These stages are part of a biological chain reaction that results in tissue repair and healing (26).
Therefore, the inflammation score and granulation tissue formation used as parameters for healing the dry socket beside to compare the pain score and tenderness around the socket between the groups .
Socket curettage in this study caused bleeding and clotting in a damaged tooth socket that did not heal successfully after the initial attempt. Gentle socket curettage and saline irrigation aid in removing necrotic hard and soft tissue that cannot be cleared by natural physiological processes. As all the patients were healthy, their healing ability was not affected, despite an estimated delay after the formation of the new clot.
Group II is expected to benefit from the insertion of PRF clot into the socket to aid healing in the impaired socket. After curettage and saline irrigation, the PRF clot was easily inserted into the socket and stabilization carefully.
Sutures may be necessary for stabilization, especially in maxilla. It is commonly seen that dry sockets take longer to heal after receiving appropriate therapy compared to recovering sockets without complications (27). The concept of enhancing healing by the application of PRF is based on observations in the field of general surgical wound healing.
Scientifically, the application of growth factors in oral surgery generates a mixture that boosts healing in a dry socket by modulating the immune system (28) to decrease inflammation and stimulate the growth of cells needed for regeneration. Pain and sensitivity decrease, allowing for the restoration of early oral functions.
Platelet-Rich Fibrin (PRF) contains a concentrated cocktail of various growth factors trapped within its fibrin matrix. These growth factors play a crucial role in stimulating healing and tissue regeneration following tooth extraction. Here are some of the key growth factors found in PRF:
Platelet-derived growth factor (PDGF), this group of growth factors plays a vital role in promoting cell proliferation and attracting other cells involved in wound healing, including fibroblasts responsible for building granulation tissue (29).
Transforming growth factor-beta (TGF-β), this growth factor has diverse functions in wound healing. It can stimulate collagen production, which is a key component of granulation tissue, and also plays a role in regulating inflammation and cell differentiation.
Vascular endothelial growth factor (VEGF), this growth factor promotes the formation of new blood vessels, which is crucial for delivering essential nutrients and oxygen to the healing socket.
Epidermal growth factor (EGF), this growth factor stimulates the proliferation of epithelial cells, which are important for re-epithelialization, the process of forming a new surface layer over the healing socket.
Insulin-like growth factor (IGF), this growth factor has various functions in wound healing, including promoting cell proliferation, differentiation, and tissue repair.
Fibroblast growth factor (FGF), this group of growth factors plays a role in stimulating the proliferation and migration of fibroblasts, further promoting granulation tissue formation.
In addition to these major growth factors, PRF may also contain other beneficial molecules like cytokines and interleukins that modulate the inflammatory response and support the healing process. Our results showed the Patients in group II, which decreased to 1 at range [0–4] on day 4. Clinical observations showed rapid remission of perisocket inflammation and reduction in discomfort by day 4 in all sockets. Granulation tissue rapidly filled the socket by day 4, and by day 7, all four sockets were fully covered by granulation tissue. By day 4, tenderness around the infected socket decreased as the granulation tissue invaded the socket, resulting in a reduction of pain symptoms and lowering the visual analogue scale (VAS) pain score to zero. for every socket by the seventh day. the results of our study agree to many previous study such as Pavlovic et al. 2021. Which stated that PRF release the growth factor along time which have significant effect on wound healing and regeneration of tissue. Benzaquén et al 2020 which provided a comprehensive overview of PRF, including a table summarizing the various growth factors found within it, such as PDGF, TGF-β, VEGF, EGF, and IGF.
Chenchev et. al. 2017 worked on alveolar osteitis using platelet rich fibrin (PRF). They claimed that PRF can successfully treat dry socket by reducing pain symptoms and expedite wound closure and epithelialization. King et al. worked on PRP as plasma rich in growth factors, to treat alveolar osteitis in 2018. They claimed that plasma rich in growth factors indeed has considerable advantages. Choukroun et al.2019 who highlight the potential applications of PRF in dentistry and mentions the presence of growth factors like PDGF, TGF-β, VEGF, and IGF within PRF that contribute to its wound healing properties. By Chou et al. [4] This review discusses the use of PRF in oral and maxillofacial surgery and emphasizes the role of its concentrated growth factors, including PDGF, TGF-β, VEGF, and EGF, in promoting tissue regeneration.
According to Simonpieri et al 2016 study that explores the scientific evidence for PRF's effectiveness in various clinical applications. It mentions the presence of growth factors like PDGF, TGF-β, VEGF, and IGF-1 within PRF and their potential impact on wound healing processes (31). Barrientos et al. [2] founded the role of various growth factors in wound healing, including those found in PRF like PDGF, TGF-β, VEGF, and FGF. It explores how these growth factors influence cellular processes crucial for repair and regeneration.
Granulation tissue is young connective tissue possessing microscopic blood vessels which is formed on the surface of a wound during the healing process, forming a protective layer, and resistant to microbial invasion. It is friable and may be easily damaged, but PRF seems to promote the formation and protection of granulation tissue in a compromised wound. This could be the main reason for the dry socket healing expedition and reduction of pain.
Autologous platelet concentrates, is easy to prepare, is of low cost, and has minimal risk for the patient [49].
In a group III, the use of LLLT because of there are many benefits that based on its photo-biostimulation effects including promoting wound healing, anti-inflammatory effects, and reduction of pain by stimulating tissues without producing any irreversible changes (32). These mechanisms are achieved by stimulation of natural biological processes, dose-dependent reduction of tumor necrosis factor-alpha concentration in acute phase of inflammation, change in size and permeability of vessel lumen, and alteration of neurotransmitter activity (33). These efficacies of LLLT have been proven to accelerate dermal wound healing in the medical fields by numerous studies(34) .
Low-level laser therapy (LLLT) is thought to improve granulation tissue formation in the socket through several potential mechanisms:
Cellular proliferation, LLLT might stimulate fibroblasts, the cells responsible for building granulation tissue, to reproduce more rapidly. This can lead to a quicker formation of the granulation tissue that fills the socket after a tooth extraction (35).
Increased blood flow, LLLT may improve blood circulation in the treated area. This increased blood flow can deliver essential nutrients and oxygen to the healing socket, promoting the growth of granulation tissue (35).
Anti-inflammatory effects, as mentioned earlier, LLLT might reduce inflammation. This is crucial because excessive inflammation can hinder tissue healing. By reducing inflammation, LLLT creates a more favorable environment for granulation tissue formation (36).
Growth factor production, LLLT may stimulate the production of growth factors, which are signaling molecules that play a vital role in tissue repair and regeneration. Increased growth factors can further enhance the formation of granulation tissue (37).
Dry sockets that had a new clot developed after curettage were treated with low-level laser therapy on their whole buccal, occlusal, and lingual surfaces. The median perisocket inflammation decreased to 1 at range [0–1] on day 4, and perisocket pain decreased to 1 at range [1–2] on day 4. The socket depth decreased to 4 at range [1–5] by the seventh day. By day 7, all sockets, with the exception of two, have fully healed, discomfort and tenderness have decreased, and patients have returned to their regular diet.
Pain and sensitivity decrease, allowing for the restoration of early oral functions. Low-level laser therapy (LLLT) has been implemented in dental surgery within the past 20 years. Initially, it was used in the orofacial area for cosmetic purposes, as low intensity laser light could penetrate the skin and stimulate fibroblast, collagen synthesis, and hyaluronic acid production to rejuvenate the face. Oral wound healing mechanisms are enhanced through biostimulation at the cellular and molecular levels, promoting the activity of growth factors such as platelet-derived growth factor and insulin-like growth factor on fibroblast proliferation and collagen formation. LLLT stimulates the growth and movement of human gingival fibroblast cells, along with inducing various biological effects such protein synthesis and growth factor release (36)(38).
Identifying treatment solutions for dry socket is challenging due to the unclear understanding of its pathophysiology. The study indicates that traditional treatment for dry socket, which depends on the body's natural healing mechanism, is less effective than treatments including regeneration molecular or light stimulation. PRF and LLLT have shown improved results in improving dry socket wound healing compared to conventional techniques by lowering inflammation, promoting tissue growth, and alleviating pain.
Angiogenesis is a crucial stage in the mechanism of wound healing. The current research demonstrated a beneficial effect of Low-Level Laser Therapy (LLLT) at 660 and 808 nm on the angiogenesis of extracted sockets (39). Angiogenesis is an essential step in tissue regeneration that includes artery sprouting, endothelial cell proliferation, and tube creation. This process supplies oxygen and nutrients to the developing tissue, promoting cell growth, movement, and protein production. Prior research has also shown the reliable effectiveness of LLLT in promoting the development of new blood vessels (36).
The power dose needs and setting parameters are simply understood, and the operation is sterile and painless, unlike PRF, which requires at least 9 mL of blood to be taken to create the growth factor-rich gel. Yet, the high cost of laser technology and the requirement to follow Laser Protection Protocol may hinder its widespread use in surgical settings. Furthermore, there is a need to determine the optimal LLLT irradiation parameters for oral surgical operations to effectively stimulate cell regeneration (40). The variation in parameter settings has resulted in different assertions regarding the clinical results of low-level laser therapy (LLLT) in wound healing approaches PRF and LLLT both expedite the production of granulation tissue in dry socket. The study demonstrates that the level of discomfort experienced in the healing dry socket is inversely related to the quantity of granulation tissue production. Granulation tissue is a fresh reddish connective tissue along with microscopic blood vessels that develops at the bottom of the dry socket as part of the healing process. It is the primary clinical indicator used to evaluate the body's response to the damage. Hyper granulation may arise due to excessive granulation tissue production, the existence of endogenous growth factor inhibitors at the PRF implantation site could hinder the binding of growth factors to their receptors, therefore obstructing cell proliferation and perhaps slowing down the production of granulation tissue during wound healing (41).
As observed in day 4 that LLLT groups overcome the PRF groups by granulation tissue formation. These include of epidermal growth factor receptor inhibitor (EGFR-I), PDGF-I, and VEGF-I. Novel exogenous growth factor delivery systems are currently under development to transport, deliver, and regulate the precise timing and location of growth factors needed for the efficient and safe utilization of growth factors in regenerative therapies in medical settings, as well as to counteract the impact of natural growth factor inhibitors(42).
This may emphasis our results why the LLLT exceed the PRF Group in day fourth in granulation tissue formed this result was in different with result show by Kemal et al 2020 that show the growth factor exceed the LLLT in GT formation.
The conventional therapy group I required more than 7 days to reach the healing phase of group II PRF treated socket and group III LLLT-exposed socket, as shown by the comparison of healing rates in this study (p < 0.05). When comparing the healing rates of Platelet-Rich Fibrin (PRF) and Low-Level Laser Therapy (LLLT). The PRF treated socket outperformed LLLT in achieving a 75% greater granulation tissue and full pain elimination by day 7 (p = 0.001).
there are many limitation of the study such as small sample size, no finding of histological study to recorded precisely the amount and number of cells formed, also we need further study on effect of LLLT according type, dose, power. Also the followed up of the study was more difficult especially after 7 days. but from another hand the PRF was less expensive and easy to prepare.