Several studies investigated the reduced healing potential in hypospadias tissues, and recorded decreased expression of EGF and its receptor [4], reduced microvssel density and decreased expression of VEGF and VEGFR [16, 17]. These growth factors are crucial for angiogenesis, epithelial proliferation, and wound healing. Therefore, their deficiency might attribute to impaired wound healing and recurring complications following hypospadias surgery [17].

In hypospadias repair, the use of an interposition layer covering the neourethra has been adopted as a key strategy to reinforce the urethroplasty and serve as a waterproof layer to lower UCF rates. Various options for this interposition layer include Dartos fascia, corpus spongiosum, tunica vaginalis, dorsal preputial skin, and scrotal Dartos flaps [18].

Regardless of these techniques, complications such as compromised blood supply to nearby tissues and flap necrosis can still occur. Additionally, lack of healthy tissues and fibrosis in recurrent repairs limits the effectiveness of local flaps necessitating the use of supportive tissues that can promote better healing [5, 19].

Tissue sealants (e.g. fibrin glue) have been proposed to provide a good sealing effect following urethroplasty [20]. However, many drawbacks of fibrin sealant were reported. Allergic reactions and transmission of infection are possible risks as it is prepared from multiple plasma donors and is processed with solvent and detergent suspension. Moreover, the high cost and low commercial availability of fibrin glue reduce its practical application [7].

Research on platelet-rich plasma (PRP) has explored its effectiveness in hypospadias repair. Eryilmaz et al. utilized PRP gel to get additional coverage in mid-penile hypospadias repair, which resulted in 10% UCF, 5% urethral stenosis, and 5% wound infection rates in the PRP group. In contrast, the group without PRP experienced 25% UCF, 25% urethral stenosis, and 35% wound infection rates [21].

Nevertheless, PRP gel also has limitations, such as relatively poor durability, lengthy preparation time (including two centrifugation cycles and an incubation period), and the risk of contamination due to external additives like bovine thrombin and calcium [22].

PRF is a polymerized fibrin matrix containing large quantities of cytokines, platelets, WBCs and growth factors that are slowly released over time. Compared to older platelet concentrates like PRP and fibrin glue, PRF offers enhanced biological properties, including higher platelet concentrations and greater growth factor content. Additionally, its fibrin content gives a more durable membrane. The PRF technique is also simple, time-efficient (requiring only 10–12 min of centrifugation of the patient’s own blood), and does not involve external additives, thereby minimizing the risk of contamination [11].

Since its introduction by Choukroun et al. in 2001 [14], PRF has been commonly utilized in oral and maxillofacial surgery [7]. Its applications have expanded to include promoting soft tissue regeneration and wound healing in various surgical contexts, such as facial plastic surgery [6], recalcitrant wounds [8], chronic leg and diabetic foot ulcers [23], burn wounds and skin graft donor wounds [24]. In the field of Urology, PRF has also been tested in varied applications (e.g. urethral surgery [20], endovesical treatment of interstitial cystitis [25] and repair of vaginal prolapse [26].

PRF functions as a biological binder between skin and deep tissues, acting like glue, and preventing overlap between opposing suture lines. The substance is believed to expedite soft tissue healing by promoting angiogenesis and the connective tissue proliferation [9]. Also, it has antimicrobial properties that help in local disinfection and contamination control of wounds [10]. The fibrin matrix can regulate immune reactions, directly through its leukocyte content and growth factors, and indirectly through its angiogenic properties, aiding in the drainage of edema and inflammation [22].

In urethral surgery, a study investigated the impact of PRF on urethral defect repair. The authors suggested that PRF can enhance TGFβ and VEGF expression in urethral tissue, potentially enhancing the success of urethral repair [27]. Another case study highlighted the effective use of autologous PRF in managing a UCF following hypospadias surgery, introducing PRF as a novel option compared to traditional fistula-prevention techniques [12].

Few studies have examined PRF as a covering layer for the neourethra in hypospadias repair (Table 3). Guinot et al. were the first to apply PRF in primary hypospadias repair [15]. Similar to our study, they compared 2 groups of patients with distal hypospadias. However, they used a PRF patch only as a second layer in the first group (n = 33) and used a single dartos flap for the second (control) group (n = 72).

Elsayed et al. [28] retrospectively evaluated 20 patients (including distal and midpenile types) who received a single PRF patch between the neourethra and skin but did not include a control group. Al-awadi et al. [29] conducted a single-arm study where they applied a single layer of PRF to 30 patients undergoing TIP repair. This study included only recurrent or circumcised cases whereas a healthy preputial Dartos is lacking. Although the risk of complications is anticipated to be higher with recurrent cases (reported in up to 30%) [2], their UCF rate was only 6.7% which is comparable to our results (4.5%) as well as to the other studies: 6.1% with Guinot et al. and 10% with Elsayed et al.

While other studies used PRF membranes alone, our study combined PRF membrane with a Dartos flap, a unique approach designed to harness the benefits of both layers. This combination may explain the slightly better results observed in our study.

In our study, the addition of PRF to Dartos flap obviously reduced the rate of wound infection (0% compared to 22.7% with single Dartos flap) with a statistically significant difference (p₌0.04). Similarily, Guinot et al. did not report any case with wound infection in their study. Also, Elsayed et al. and Al-awadi et al. each reported only one case with wound infection in their studies. This can be correlated to the antimicrobial and immunomodulatory properties of PRF which seals the wound against infecting agents and reducing the risk of inflammation [10]. No cases of glans dehiscence were reported in our study nor the other studies that used PRF. So, PRF application did not prevent tension-free closure of glans wings.

The strengths of our study include its prospective randomized design with a control group. We exclusively included cases of distal primary hypospadias, all of which were operated on by the same surgeon using a standardized procedure. This design helps mitigate biases that were present in previous studies.

Despite its strengths, our study has certain limitations. First, regardless of being statistically justified, our relatively small sample may increase risk of type II errors, reduced statistical power, vulnerability to outliers and generalizability issues. To overcome these limitations in further studies, and to improve reliability and generalizability of study findings; we recommend increasing sample size, employment of meta-analyses and Bayesian statistics and facilitating replication studies. Second, the follow-up duration was brief. Thus, additional research with long-term follow-up is required to uncover any late complications. Third, the study did not evaluate the efficacy of using the PRF membrane alone without a Dartos flap for urethroplasty, and further research is recommended. Fourth, the study was conducted in a single center, therefore, multicenter studies are planned to gather more information and provide more accurate results.