Introduction
Tympanoplasty using a temporalis fascia graft is a mainstay surgical approach for the management of tympanic membrane perforation due to chronic otitis media, where the aim is to create a dry and non-infected environment in the ear, repair the perforated membrane, eradicate infection, and restore hearing loss.Reference Zollner1–Reference Asghari, Mohseni, Daneshi, Nasoori, Rostami and Balali4 Although use of temporalis fascia in initial tympanoplasties has been associated with high surgical success rates (93–97 per cent),Reference Singh, Kumar, Aggarwal, Garg, Arora and Kumar5 post-operative outcomes are largely unpredictable given the structural composition of fascia temporalis, which exhibits irregular elastic fibres and fibrous connective tissue.Reference Cabra and Monux6 Thus, various types of graft materials (e.g. cartilage, fat and vein) have been tested in tympanoplasty surgery in recent years, to achieve better and more predictable post-operative outcomes. These materials have been tested in the context of continuous advances in techniques and biomaterials (e.g. absorbable gelatine film, paper patches, hyaluronic acid, autologous serum enriched with growth factors, and basic fibroblast growth factor) for reconstructive middle-ear surgery.Reference Jalali, Motasaddi, Kouhi, Dabiri and Soleimani7–Reference Arora, Passey, Agarwal and Bansal9
The regeneration of a perforated tympanic membrane is a complex biological process involving epithelial proliferation and migration, fibroblast proliferation, angiogenesis, and tissue remodelling.Reference Wang, Shen, Wang, Eikelboom and Dilley10 Given the recent recognition of platelet involvement in traditional haemostasis, as well as in wound healing and immunomodulation,Reference Sanchez, Sheridan and Kupp11,Reference Fernandez-Moure, Van Eps, Cabrera, Barbosa, Medrano Del Rosal and Weiner12 the topical use of platelet concentrates, such as platelet-rich plasma, leucocyte-rich plasma, platelet-rich fibrin and leucocyte-rich fibrin, has emerged as a potential adjuvant therapy. These concentrates have been tested in many different clinical applications for improving the healing of surgical wounds and injuries.Reference Fernandez-Moure, Van Eps, Cabrera, Barbosa, Medrano Del Rosal and Weiner12,Reference Dohan Ehrenfest, Rasmusson and Albrektsson13
Platelet-rich fibrin is a novel platelet concentrate, consisting of a matrix of autologous fibrin. It has several advantages over platelet-rich plasma, including simpler preparation, without the need for chemical modification of the blood.Reference Dohan, Choukroun, Diss, Dohan, Dohan and Mouhyi14,Reference Borie, Olivi, Orsi, Garlet, Weber and Beltran15 Platelet-rich fibrin is regarded as a biomaterial with remarkable potential for improved wound healing and soft tissue repair, primarily in the context of oral and maxillofacial surgery.Reference Borie, Olivi, Orsi, Garlet, Weber and Beltran15 Moreover, applications in microsurgery and plastic surgery have been suggested. Platelet-rich fibrin might also improve the post-operative outcomes of tympanic surgical procedures.Reference Choukroun, Braccini, Diss, Giordano, Doglioli and Dohan16 Given the scarcity of data regarding the use of platelet-rich fibrin for tympanic membrane repair, this study was designed to evaluate the impact of platelet-rich fibrin in tympanoplasty type 1 surgery on graft survival and hearing outcomes in patients with tympanic membrane perforation due to chronic otitis media.
Materials and methods
Study population
A total of 91 patients with tympanic perforation due to chronic otitis media, who underwent tympanoplasty type 1 surgery at our clinic between October 2016 and January 2018, were included in this retrospective study. Patients who had cholesteatoma, adhesive otitis media, attic perforation, ossicular chain erosion or a history of tympanoplasty were excluded. All included patients had inactive mucosal chronic otitis media.
Patients were randomised into two groups: temporal fascia graft alone (n = 55) and temporal fascia graft plus platelet-rich fibrin therapy (n = 36) groups.
Patients were informed about the surgical techniques and provided their consent for the application of platelet-rich fibrin during surgery. The study was conducted in full compliance with local Good Clinical Practice guidelines and current legislation; permission was obtained from our institutional ethics committee for the use of patient data for publication purposes.
Study parameters
Data were obtained on: patient demographics (age and sex), side and type of perforation, graft status and survival (at one, three and six months post-operatively), and outcomes of frequency-specific hearing at six months post-operatively (pure tone averages, air conduction thresholds at 0.5–4 kHz and air–bone gap).
The impact of graft material on functional (hearing improvement) and anatomical (graft survival) outcomes was compared between the temporal fascia graft alone and temporal fascia graft plus platelet-rich fibrin therapy groups, and a subgroup of graft-intact patients. Cases of graft failure were excluded from subgroup analysis.
Tympanoplasty
In all patients, type 1 tympanoplasty was performed under general anaesthesia by harvesting graft tissue from the areolar tissue layer above the temporalis fascia via a post-auricular incision. This was followed by elevation of the tympanomeatal flap to gain access to the tympanic cavity. Following thorough elimination of inflamed and infected tissue in the tympanic cavity, graft tissue was placed on the undersurface of the tympanomeatal flap to reconstruct the tympanic membrane. If ossicular chain defects were observed during surgery, concomitant ossiculoplasty was performed. Finally, the middle ear and external ear canals were packed with an absorbable gelatine sponge (Gelfoam; Pfizer, New York, USA).
All patients received broad-spectrum antibiotic treatment for one week. In patients with ongoing otorrhoea, middle-ear mucosal oedema and active infection, medical treatment was initiated to maintain dryness of the perforated ear for at least three months pre-operatively.
Platelet-rich fibrin preparation
In the temporal fascia graft plus platelet-rich fibrin therapy group, 8–10 ml of peripheral venous blood was drawn from each patient and collected into plastic tubes without anticoagulant (10 ml per tube). The tubes were immediately centrifuged for 12 minutes at 2700 revolutions per minute, as described by Choukroun in 2001 (cited in Gur et al.Reference Gur, Ensari, Ozturk, Boztepe, Gun and Selcuk17). This allowed the separation of blood into three layers, including a base layer of red blood cells, a middle layer of platelet-rich fibrin and a top layer of acellular plasma (Figure 1).
Fig. 1. Layers of centrifuged blood.
The platelet-rich fibrin clot (Figure 2), in a thin membranous form, was placed on the temporal fascia with support from the tympanomeatal flap and sponges (Figure 3). The middle ear and external ear canals were then packed with an absorbable gelatine sponge (Gelfoam; Pfizer). All patients received broad-spectrum antibiotic treatment for one week.
Fig. 2. Platelet-rich fibrin clot.
Fig. 3. Platelet-rich fibrin clot spread over temporal fascia.
Audiological assessment
All patients underwent pure tone audiometry to evaluate pre- and post-operative hearing status. The mean hearing level and air–bone gap of each patient were measured by averaging their hearing thresholds at 0.5, 1, 2 and 4 kHz. Pure tone audiometry was performed using an ascending–descending method in 5 dB steps. The threshold was defined as the lowest decibel hearing level at which responses occurred in at least half of a series of ascending trials.
Statistical analysis
Statistical analysis was performed using SPSS Statistics for Windows software (version 17.0; IBM, Armonk, New York, USA). Continuity-corrected chi-square tests were used to compare categorical data. Student's t-test and paired t-tests were used to compare parametric variables. Data are expressed as mean ± standard deviation (SD), minimum–maximum, or percentages, as appropriate. A p-value of less than 0.05 was considered statistically significant.
Results
Demographic and clinical characteristics
In the temporal fascia graft plus platelet-rich fibrin therapy group, relative to the temporal fascia graft alone group, patients were older (mean age ± SD, 34.5 ± 9.2 vs 29.7 ± 8.2 years; p = 0.011), and more likely to show bilateral perforation (52.8 vs 23.6 per cent, p = 0.009) and more than 50 per cent perforation (63.9 vs 32.7 per cent, p = 0.007). Central perforation (11.1 vs 41.8 per cent, p = 0.004) was less common in the temporal fascia graft plus platelet-rich fibrin therapy group (Table 1).
Table 1. Patient demographics and clinical characteristics
*n = 55; †n = 36. ‡Indicates statistical significance (p < 0.05). **Student's t-test; §continuity-corrected chi-square test; #Fisher's exact test. TFG = temporal fascia graft; PRF = platelet-rich fibrin therapy; SD = standard deviation
Graft survival rates
The graft survival rate was significantly higher in the temporal fascia graft plus platelet-rich fibrin therapy group than in the temporal fascia graft alone group at one (100.0 vs 85.5 per cent, p = 0.020), three (97.2 vs 80.0 per cent, p = 0.024) and six months post-operatively (94.4 vs 74.5 per cent, p = 0.031; Table 2). Re-perforations were mostly observed in patients who had more than 50 per cent perforation pre-operatively (Table 3). During the first month post-operatively, platelet-rich fibrin significantly increased the graft survival rate in patients with large perforations (p = 0.030; Table 3).
Table 2. Post-operative graft survival data
Data represent numbers (and percentages), unless indicated otherwise. *n = 55; †n = 36. ‡Indicates statistical significance (p < 0.05). **Fisher's exact test; §continuity-corrected chi-square test. TFG = temporal fascia graft; PRF = platelet-rich fibrin therapy
Table 3. Post-operative evaluation of perforation status according to pre-operative perforation type
*Indicates statistical significance (p < 0.05). TFG = temporal fascia graft; PRF = platelet-rich fibrin therapy
Hearing outcomes
In the temporal fascia graft alone group, a significant improvement was found in post-operative pure tone averages at 0.5–4 kHz, as well as in the corresponding air–bone gaps (all p < 0.001; Table 4). In contrast, significant improvements were observed at 2 and 4 kHz in the temporal fascia graft plus platelet-rich fibrin therapy group (p < 0.001; Table 4). Pre-operatively, pure tone averages and air–bone gaps at 0.5–4 kHz were higher in the temporal fascia graft plus platelet-rich fibrin therapy group than in the temporal fascia graft alone group (p < 0.001; Table 4). Air–bone gaps significantly decreased post-operatively in both groups (p < 0.05). Hearing gain tended to be greater in the temporal fascia graft plus platelet-rich fibrin therapy group, but the difference between groups was not statistically significant (p > 0.05; Table 4).
Table 4. Pre- and post-operative hearing outcomes
Data represent mean ± standard deviation values (in decibels), unless indicated otherwise. *Indicates statistical significance (p < 0.05). TFG = temporal fascia graft; PRF = platelet-rich fibrin therapy
Discussion
In our retrospective cohort of patients with chronic otitis media related tympanic perforation, higher rates of graft survival were noted in the temporal fascia graft plus platelet-rich fibrin therapy group than in the temporal fascia graft alone group within six months post-operatively. Pre-operative examinations revealed that the number of large perforations was higher in the temporal fascia graft plus platelet-rich fibrin therapy group than in the temporal fascia graft alone group. In patients with large perforations, the use of platelet-rich fibrin increased the rates of graft survival. There was a significant improvement in frequency-specific hearing outcomes related to post-operative pure tone averages at 0.5–4 kHz, as well as in the corresponding air–bone gaps, in both the temporal fascia graft alone and temporal fascia graft plus platelet-rich fibrin therapy groups. The difference in hearing gain between groups was not significant.
Similarly, in a retrospective study of 108 patients who underwent middle-ear surgery involving the application of platelet-rich fibrin, the success rate of tympanic membrane repair was 93.8 per cent; one-year post-operative hearing improvements of at least 10 dB were observed at 1–2 kHz and 4 kHz.Reference Garin, Mullier, Gheldof, Dogne, Putz and Van Damme18 Notably, the use of platelet-rich plasma during tympanoplasty was associated with closure success rates of 88.5–100.0 per cent, along with functional improvement at six weeks post-operatively.Reference Ayala-Montes de Oca, Alla and López-Valdés19,Reference Navarrete Alvaro, Ortiz, Rodriguez, Boemo, Fuentes and Mateo20
In an experimental rat study on the repair of perforated tympanic membranes, use of platelet-rich fibrin was associated with a significantly shorter healing time than in the control group (mean, 10.3 vs 17.0 days). This highlights the potential utility of platelet-rich fibrin membranes for the clinical repair of tympanic membrane perforation and wound healing.Reference Ensari, Gur, Ozturk, Suren, Selcuk and Osma21
In a study comparing platelet-rich fibrin and paper patch repair of traumatic tympanic membrane perforations, closure rates were 93 per cent and 83 per cent, respectively, while the improvement in the mean air–bone gap was 14.1 dB and 12.4 dB at 45 days post-operatively.Reference Gur, Ensari, Ozturk, Boztepe, Gun and Selcuk17 Accordingly, those authors suggested that platelet-rich fibrin afforded more rapid healing, and better audiological results for tympanic membrane repair, relative to the paper patch method.Reference Gur, Ensari, Ozturk, Boztepe, Gun and Selcuk17
In another study, in which endoscopic inlay butterfly myringoplasty with (n = 25) or without (n = 25) autologous platelet-rich fibrin was used in 50 patients with a dry central perforation, the graft survival rate was significantly higher with versus without platelet-rich fibrin (96.0 vs 76 per cent), and hearing outcomes were satisfactory.Reference Hosam, Shaker and Aboulwafa22 Those results emphasised the association between the topical application of platelet-rich fibrin and an improved success rate of inlay butterfly cartilage myringoplasty for the repair of small to medium sized tympanic membrane perforations.Reference Hosam, Shaker and Aboulwafa22 Furthermore, in a study on the use of platelet-rich fibrin in myringoplasties (n = 152), the surgical success rates with and without the use of platelet-rich fibrin were 96 per cent and 85 per cent, respectively.Reference Braccini, Tardivet and Dohan Ehrenfest23
• Platelet concentrates may improve wound healing and immunomodulation, which are crucial for tympanic membrane closure
• Platelet-rich fibrin increased graft survival rates relative to fascia graft use alone, but did not significantly affect hearing outcomes
• Platelet-rich fibrin can increase graft survival rates after tympanoplasty, especially in patients with large perforations
• The application of platelet-rich fibrin to fascia grafts may increase perforation closure rate after tympanoplasty
The outcomes in our temporal fascia graft alone group are consistent with those of previous studies reporting an association between tympanoplasty with temporalis fascia and improvements in the following parameters: air–bone gap (from 20.40 dB pre-operatively to 8.12 dB post-operatively);Reference Dundar, Kulduk, Soy, Aslan, Hanci and Muluk24 hearing (average gain of 12.4 dB);Reference Indorewala, Pagare, Aboojiwala and Barpande3 and air–bone gap (average gains of 19, 18, 19 and 23 dB at 0.5, 1, 2 and 4 kHz, respectively).Reference Hashemi, Sohrabi and Bohranifard25 However, it should be noted that a much higher surgical success rate (91.6 per cent) and greater air–bone gap improvement (18.5 dB) were reported for type 1 tympanoplasty with fascia temporalis alone, in a retrospective study of 320 patients over a 10-year period.Reference Kouhi, Khorsandi Ashthiani and Jalali26
The association of the use of platelet-rich fibrin with a higher surgical success rate and improved hearing gains in our patients who underwent type 1 tympanoplasty surgery seems to support the previously suggested role of platelet-rich fibrin in providing mechanical and inflammatory protection to the tympanic graft, as well as in the acceleration of cell proliferation and matrix remodelling.Reference Braccini, Tardivet and Dohan Ehrenfest23 In addition, given that platelet-rich fibrin is an inexpensive and easily prepared autologous material with advantages in terms of biocompatibility and safety,Reference Garin, Mullier, Gheldof, Dogne, Putz and Van Damme18 our findings emphasise that platelet-rich fibrin may have utility for tympanoplasty surgery in routine clinical practice, by promoting graft survival, tympanic healing and hearing restoration.Reference Garin, Mullier, Gheldof, Dogne, Putz and Van Damme18,Reference Braccini, Tardivet and Dohan Ehrenfest23 We observed higher rates of graft survival with platelet-rich fibrin, but hearing outcomes were better in the temporal fascia graft alone group. Platelet-rich fibrin may negatively affect the elasticity of the tympanic membrane and fascia graft, which may have contributed to poorer hearing outcomes. This hypothesis should be investigated in a future study.
In our retrospective cohort of chronic otitis media patients, platelet-rich fibrin combined with temporal fascia graft in type 1 tympanoplasty was associated with more favourable post-operative outcomes than temporal fascia graft alone, both in terms of tympanic membrane healing and graft survival; hearing restoration outcomes were similar. Our findings emphasise the potential utility of platelet-rich fibrin-based type 1 tympanoplasty for the management of chronic otitis media without cholesteatoma.
Competing interests
None declared
