The Effect of Injectable Platelet Rich Fibrin on Apical Lesion Healing

Although conventional endodontic approaches generally achieve high success rates in the treatment of periapical lesions, treatment outcomes may vary depending on several factors. In particular, lesion size, the patient's systemic condition, and the treatment protocol employed may directly influence the healing process and treatment success. Healing may be prolonged, and the response to treatment may be more limited in cases involving large lesions or immunocompromised individuals. In this context, the adjunctive application of injectable platelet-rich fibrin (i-PRF) alongside conventional root canal treatment may offer a biologically innovative contribution to existing treatment protocols.

The use of autologous therapies in dentistry has increased in recent years because of their potential to facilitate natural healing, accelerate tissue regeneration, and improve postoperative patient comfort. Platelet-rich fibrin (PRF) and platelet-rich plasma (PRP) are among the autologous products used for this purpose. Platelets play an important role in wound healing. Upon activation, they release various growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-beta (TGF-β), and insulin-like growth factor I (IGF-I), which stimulate cell proliferation. In 2014, injectable platelet-rich fibrin (i-PRF) was developed by modifying centrifugation parameters. Centrifugation of blood at lower speeds in non-glass centrifuge tubes results in the formation of a fluid PRF product known as i-PRF. Owing to its growth factors and bioactive proteins, i-PRF may promote tissue regeneration, enhance angiogenesis and local blood supply, and modulate the inflammatory response, potentially contributing to the reduction of symptoms such as pain and swelling.

In addition to releasing growth factors and cytokines derived from platelets and leukocytes, which play critical roles in healing processes such as collagen matrix formation and neovascularization, PRF may also support immune responses and tissue epithelialization. The fibrin component of PRF serves as a scaffold, while leukocytes, macrophages, neutrophils, and platelets help recruit and accumulate regenerative cells at defect sites. Furthermore, fibrin acts as a reservoir for growth factors, allowing their gradual release over a period of approximately 10-14 days.

PRF has also been reported to exert antimicrobial effects through the secretion of pro-inflammatory and anti-inflammatory cytokines. Its application has been associated with reduced postoperative pain scores. Studies using the visual analogue scale (VAS) have demonstrated statistically significant reductions in pain following PRF application.

In a study by Sitamahalakshmi et al., i-PRF was applied during flap surgery for the treatment of infrabony defects. The authors reported an increase in bone levels at 6 months compared with baseline. These findings suggest a potential beneficial effect of i-PRF on bone healing and support the rationale underlying our hypothesis. However, unlike that study, the present investigation does not involve a surgical procedure.

Faour et al. investigated individuals with thin gingival phenotypes and used a 30-gauge microneedle, as in our study. They reported an increase in gingival thickness at 3 months. These findings suggest that i-PRF may have beneficial effects on local tissues. Unlike that study, the primary outcomes of our investigation are periapical lesion volume reduction and increased bone trabeculation. Nevertheless, an increase in the thickness of the soft tissues surrounding the tooth may have implications for the supporting periodontal tissues and potentially contribute to long-term tooth preservation.

In an ex vivo study conducted by Panda et al. in 2024, both leukocyte- and platelet-rich fibrin (L-PRF) and i-PRF were shown to increase the number of dental pulp stem cells. The study also demonstrated that PRF groups produced an extracellular matrix containing calcium-rich deposits through osteoblast activity. Based on these findings, we hypothesize that i-PRF injected into the periapical region may contribute to the repair of the periapical bone defect through similar biological mechanisms.

The minimally invasive nature of microneedle-based administration, the possibility of monitoring healing using objective methods such as radiographic and fractal analyses, and its potential to support both endodontic and periodontal healing represent clinically relevant features of this approach. In particular, i-PRF-assisted treatment protocols may warrant further investigation as a potential adjunctive approach in complex clinical situations, including cases involving extensive periapical defects, lesions that respond poorly to conventional treatment, and situations requiring bone regeneration before implant placement. The findings of this study are expected to contribute to the development of more effective, biologically based approaches to the treatment of periapical lesions.

Study Hypothesis Based on the aforementioned evidence, the hypothesis of this study is that the administration of i-PRF injections as an adjunct to conventional root canal treatment will result in greater periapical healing and increased bone trabeculation than conventional root canal treatment alone, owing to the growth factors and other bioactive components contained in i-PRF.

Originality and Novelty of the Project Although i-PRF has previously been used in endodontic treatment through intracanal application, the present study will investigate its injection into the tissues surrounding the periapical lesion.

To the best of our knowledge, the needle gauge and length planned for use in this study have previously been reported in the context of periodontal treatment, specifically microneedling to increase the width of keratinized gingiva, rather than for the treatment of periapical lesions.

To the best of our knowledge, the use of an ultrafine, short needle (30 G, 4 mm) to deliver i-PRF atraumatically into the periapical region, with the aim of promoting healing of lesions that might otherwise be considered for surgical intervention while minimizing local tissue irritation, has not previously been reported in the literature.

To the best of our knowledge, this will be the first study to investigate the injection of i-PRF into the tissues surrounding a periapical lesion through an apical approach.

Despite being an exploratory investigation of a novel approach, the study has been designed to incorporate a comprehensive assessment of healing. In addition to evaluating radiographic outcomes using cone-beam computed tomography (CBCT), one of the most detailed imaging modalities available for assessing periapical lesions, the study will record clinical parameters, including the width of keratinized gingiva, VAS pain scores, percussion sensitivity, tooth mobility, and periodontal probing depth at the tooth under investigation. By integrating detailed radiographic assessment with relevant clinical parameters, this study aims to provide preliminary evidence regarding a novel adjunctive treatment approach for periapical lesions and to inform the design of future clinical investigations.