Prevalence of complications associated with polymer-based alloplastic materials in nasal dorsal augmentation: a systematic review and meta-analysis

Various techniques with different grafts and implants have been proposed to establish a smooth and symmetric nasal dorsum with adequate function. Broadly, two categories of materials have been used in this regard: alloplastic implant materials and autograft materials. The aim of these meta-analyses is to explore the incidence of complications after dorsum augmentation surgery using alloplastic materials. After duplication removal 491 papers remained that title and abstract were assessed for eligibility. Regarding the study type, 27 observational studies were included, 21 retrospective and 6 prospective case series. A total of 3803 cases were enrolled in this systematic review and meta-analysis. Twenty-seven articles reported on complications and outcomes of dorsal augmentation rhinoplasty with synthetic materials. In a random-effects model, the weighted mean percentage was 2.75% (95% CI 1.61 to 4.17%). the weighted mean percentage were 1.91% (95% CI 0.77 to 3.54%), 0.72% (95% CI 0.316 to 1.31%), and 0.78% (95% CI 0.43 to 1.24%) respectively. The widely used alloplasts were expanded polytetrafluoroethylene (ePTFE), high-density polyethylene, and silicone. The total rates for complications, infection, deviation, irregularity, hematoma, extrusion, and overcorrection were 2.75%, 1.91%, 0.72%, 0.70%, 0.78%, and 0.49%, respectively. The revision rate, based on the random effects model, was 6.40% with 95%CI (3.84 to 9.57). This meta-analysis was registered at the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42020209644).

Yap, E. C. et al. [11] 2011 (n = 1054) e-PTFE patients stated that it became worse. 1 Conrad. K et al [27] 2009, (n = 349) Gore-Tex Godin. M et al. [32] 1995, (n = 137) Gore-Tex      ePTFE, and high-density polyethylene are an alternative. They are associated with varying incidences of infection and extrusion. Owing to their affordability, lack of any graft harvesting site and being tailorable to a particular deformity, in certain circumstances, alloplastic materials might be used [5]. In 2008, Peled et al. conducted a metaanalysis on rates of infection, extrusion, revision, and removal of different implants used in rhinoplasty surgery and mentioned that alloplastic implants have acceptable complication rates and might be used when facing limitations in using autogenous materials [7]. The aim of these meta-analyses is to explore the incidence of complications after dorsum augmentation surgery using alloplastic materials.

Protocol and registration
This meta-analysis was registered at the International Prospective Register of Systematic Reviews (https:// www. crd. york. ac. uk/ PROSPERO, registration number CRD42020209644). Also, the PRISMA 2020 Guidelines were followed in this systematic review and meta-analysis [8].

Search strategy
An electronic survey was conducted using the following databases up to and including September 2020 written in English without any time restriction: PubMed/MEDLINE, Google Scholar and the Cochrane Central Register of  Controlled Trials (Central). The searching was completed by a manual hand search of the references of all selected fulltext articles. The following search terms were screened with its appearance limited to title of the article: (a) "rhinoplasty, " (b) "nasal augmentation, " (c) "revisional rhinoplasty, " (d) "dorsum augmentation, " (e) "nasal dorsum, " (f) "alloplast, " (h) "silicone, " (i) "high-density polyethylene, " (j) "Medpor, " (k) "polytetrafluoroethylene, " and (l) "Gore-Tex" (Table 1).

Study selection
Inclusion criteria were as follows: 1. Randomized clinical trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective cohort studies, and case series with more than 10 participants which provided detailed report on complications (visible bulging of the graft, hematoma at the recipient area, graft displacement, irregularity, supra-tip depression, infection, deviation, overcorrection, insufficient augmentation, major resorption). (Report of at least one complication and revision surgery was mandatory.)

No follow-up restrictions 3. Only papers in English are included
Exclusion criteria were as follows: 1. Any cadaver studies or nonhuman studies 2. Studies reporting ratios (risk ratio, odds ratio, hazard ratio) instead of the absolute outcomes were not of our interest. 3. Any article that did not provide any detailed data regarding complication rates 4. Reports of using graft in other parts than nasal dorsum 5. Reports of using liquid alloplastic materials

Data extraction
Based on a predefined paper checklist, the following data was retrieved from the finally included studies by two reviewers (M A.V and R.G) independently and supervised by third author (Sh.R). Any disagreements were resolved by discussion with a third author (Sh.R). Data extraction included the following categories: First author, year of publication, study location, study type, mean age, mean follow-up (range), sex, number of total cases, and cases with complication, incidence of complications after dorsum augmentation with polymerbased alloplastic materials such as silicone, high-density polyethylene (Medpor), and polytetrafluoroethylene (Gore-Tex), rates of complications, revision surgical procedures, and satisfaction rate (percent). The complications assessed were as follows: visible bulging of the graft, hematoma at the recipient area, graft displacement, irregularity, supra-tip depression, infection, deviation, overcorrection, insufficient augmentation, major resorption.

Risk of bias assessment within the studies
The methodological quality and synthesis of included materials was assessed using a tool for bias assessment in case series by Murad et al. [9]. There were 8 questions in the following domains: selection, ascertainment, causality, and reporting.

Data analysis
Considering the challenges with meta-analysis in observational studies [10], we carefully checked whether included materials in hand were able to answer our clinical question (PICO). The proportion meta-analysis was performed using MedCalc version 18.9.1 (MedCalc Software Ltd., Ostend, Belgium). Both random and fixed model were used based on the heterogeneity. If the heterogeneity was significant, random model was preferred. We conducted the χ2 and I 2 tests to convey the potential heterogeneity. Potential publication biases were evaluated using funnel plots. Figure 1 shows the PRISMA flow diagram for the study selection process at different stages. 572 papers were obtained through the first search. After duplication removal, 491 papers remained that title and abstract were assessed for eligibility. Reports sought for retrieval of 77 papers. Of those, 50 papers were excluded with reason (3 reports not retrieved) and finally 27 papers remained which were included in the analysis .

Study characteristics
The characteristics of included materials are shown in Table 2. Regarding the study type, 27 observational studies were included, 21 retrospective, and 6 prospective case series. A total of 3803 cases were enrolled in this systematic review and meta-analysis. The mean age of patients was 33 (age range 10-72). Although 3 papers did not specify mean and/or age range [16][17][18][19].

Complications
The data on each complication are available in Table 3.

Other complications
Some rare complications did not meet the criteria for meta-analysis and therefore reported narratively: One case of opening of the tube the diced cartilage pieces, in a cleft lip patient, pleural tear, and air leak during rib harvesting, of strike skin necrosis (Table 3)

Publication bias
We performed funnel plot for publication bias assessment for each of variables. In the current study, some levels of bias were reported for all complications.

Discussion
One of the greatest challenges in rhinoplastic surgeries is the management of nasal dorsum augmentation. Due to the ease of use, producing ideal aesthetic results and removing needed for graft harvesting sites, alloplastic materials play an important role in typical cosmetic dorsal augmentation [1]. The use of alloplastic materials to address dorsal deficiencies is common among patients avoiding autogenous tissue harvest. Also, patients with several prior nasal operations and significant deformities are the best candidates for alloplastic materials as they mostly have depleted potential autogenous harvesting site [7]. Although there are concerns over several complications associated with synthetic materials including infection, deviation, extrusion, etc. [1]. In this systematic review and meta-analysis, we determined the complications reported for different alloplastic materials. Twenty-seven articles reported on complications and outcomes of dorsal augmentation rhinoplasty with synthetic materials. The widely used alloplasts were expanded polytetrafluoroethylene (ePTFE), high-density polyethylene, and silicone. The total rates for complications, infection, deviation, irregularity, hematoma, extrusion, and over correction were 2.75%, 1.91%, 0.72%, 0.70%, 0.78%, and 0.49%, respectively. The revision rate, based on random effects model, was 6.40% with 95% CI (3.84 to 9.57). We reported a subsequent revision of 0-21% in our included studies. The pooled rate for the need for revision surgery was 6.40%. The revision rates for the three most commonly used materials Med-pore, ePTFE, and silicone were 6.61%, 7.06%, and 7.64%, respectively. The decision for implant removal is quite controversial; although, surgical removal of infected implants followed by an immediate or delayed reconstruction has higher chances of resolution [39].
The highest revision rates were related to silicone (7.64%). A similar study reported 6.5% revision rate for silicone implants [7]. Being the most commonly used alloplastic material in Asian countries, silicone is a smooth, cost benefit, and easy-carved implant which can be easily removed in case of failure. The lack of pores leads to fibrous capsule formation around the implant within the body.
Infections and displacement are the main causes of revision surgery in silicones and therefore in order to reduce such problems aggressive modification of the natural barriers and anatomical structure should be strictly avoided [40]. If shaped appropriately according to the nasal phenotype, the extrusion rate would reduce [41]. To manage and reduce complications, this method supports alloplastic materials better for patients with thicker skin than for patients with thinner skin.
The high-density polyethylene (Medpore), with pore size range from 160 to 368 μm, and more than half of these pores are larger than 150 μm in diameter and have excellent biocompatibility. In candidates of augmentation rhinoplasty with severe over resections or severe deformities, these implants have been a useful option. Our findings for revision surgery of high-density polyethylene have been higher than previously reported rates [7]. The revision rate for polytetrafluoroethylene/expanded polytetrafluoroethylene (Gore-Tex) was 4.91%. This hydrophobic polymer with pores of up to 30 μm allows for bacterial adherence and levels of issue integration that provides implant stability with ease of removal if needed. Our results are in line with previous studies mentioning low incidence of revision rates compared with other synthetic materials. A similar previous meta-analysis (in 2008) reported the removal of 3.1% for both ePTFE and high-density polyethylene [7].
Nevertheless, our results suggested a relatively high total rate for revision rate (6.40%) compared with autogenous grafts (3.03%) [42]. This might be attributed to the fact that infection in synthetic materials, unlike autogenous grafts, conservative treatments are inapplicable and mostly require revisional surgery [42,43] The use of autograft materials in nasal dorsum augmentation is a safer treatment with fewer complications compared to the alloplastic method. Complications of using autogenous grafts materials such as diced cartilage include graft resorption, insufficient augmentation, deviation (graft displacement), infection, irregularity, supra-tip depression, over-correction, hematoma at the recipient site, and the visible bulging of the graft. According to the findings of the article, infections caused by the use of alloplastic usually require revision surgery, while most infections that occur in the autograft method can be controlled by intravenous antibiotics [42].
In fact, it can be said that the complications of the autograft method are manageable and controllable complications.
Also, the use of alloplastic materials is a risky method in comparison with autograft materials taken from the patient himself, because the use of alloplastic materials acts as a foreign body in the body and its high-risk side effects can lead to nasal deformity and aesthetic complications. Undesirability in the systematic study [44]  was reported in autograft materials, which are usually removed from the abdomen or thighs, has fewer reported complications after surgery, and in most cases, complications such as numbness gradually decrease after surgery and are completely eliminated by 3 months after surgery. In addition to the side effects of using alloplastic materials, some side effects may be preventable, such as bending along the natural convexity, bone resorption, and foreign body reactions such as fibrous capsule formation and tissue ingrowth.
Due to the fact that the complications mentioned throughout the article are not only common but also lead to major problems both during surgery and after surgery. By examining the problems and complications of this method, treatment-related techniques will be developed in the future. With the passage of time and the development of new surgical methods and materials, it shows that current methods are always associated with complications, and at no time are failures and complications announced at the same time as successes.
Current articles widely support autografts instead of using alloplastic in rhinoplasty. Surgeons describe alloplastic implants as dangerous, unpredictable, and hard to use. Therefore, the reported complications are less than 5%. Complications that require revision surgery and cause the material to be removed are 3.7%, which is a significant amount compared to the use of autografts [45], which is 1% [96]. Therefore, the use of alloplastic materials seems to be mentioned with the desire of the patient and the surgeon and acceptance of the possibility of complications (Tables 4 and 5).

Limitations and strengths
Reports of complications often come from other investigators, citing their own experience with implants inserted by other surgeons. The major limitation with current systematic review and meta-analysis was the descriptive nature of much of the current literature and lacking comparator groups. Also, a proper tool for quality assessment in case series was lacking and we had to make adaptations in domains. Some levels of bias might be caused by excluding non-English materials.
The time frame for follow-ups in this study assumed rationale for complications appearance. Having a clear understanding of complications of each material and the ways to prevent and treat them is possible by accurate disclosure of shortcoming in the literature. In the future, the development of alloplasts that approximate the ideal implant with low complication rates is warranted. The technology of prefabrication of precise three-dimensional bioactive and biocompatible implants might reduce the incidence of complications and lower the chance of failure.

Conclusion
To recapitulate, this meta-analysis suggested an acceptable rate of complications and revision surgery with synthetic materials. Synthetic materials might be a proper  A case report of ophthalmic artery emboli secondary to calcium hydroxylapatite filler injection for nose augmentation-long-term outcome [47] Not solid polymers 3. Case reports of adipose-derived stem cell therapy for nasal skin necrosis after filler injection [48] Not solid polymers 4. Complete septal extension grafts using porous high-density polyethylene sheets for the westernization of the Asian nose. [21] Not for dorsum 5. Retinal branch artery embolization following hyaluronic acid injection: a case report [49] Not solid polymers 6. Two cases of adverse reactions of hyaluronic acid-based filler injections [50] Not solid polymers 7. A newly designed minigraft to achieve angularity and projection of the nasal tip: the asymmetrical bipyramidal graft [51] Not dorsum separately