Systematic Review of Case Reports and Case Series Published Between 2015 and 2025 on the Use of Biomaterials for Closure of Oroantral Fistula

Introduction

Oroantral fistulas (OAF) are abnormal communications between the oral cavity and the maxillary sinus that primarily occur as a complication of posterior teeth extraction or as the secondary outcome of trauma, sinus infections, and other soft and hard tissue pathology [1]. These dental and maxillofacial defects can affect quality of life and lead to symptoms such as nasal regurgitation, sinusitis, and discomfort. Restoring patients’ quality of life and preventing subsequent complications requires a competent OAF closure [2]. Small-sized or intermittent OAFs may close/heal spontaneously, but persistent and larger fistulas require surgical interventions, either with or without the use of intermediate biocompatible material. Local flaps and the use of bone grafts have been traditionally used for OAF surgical closures [3]. Digitization technologies incorporating the combined use of bioprinting, computer-assisted designing, and artificial intelligence have resulted in modern tissue engineering and regenerative medicine [4]. These technological shifts have also brought promising alternative biomaterials for closing OAF and related defects, thereby substantially improving healing, and include biomaterials such as platelet-rich fibrin (PRF), collagen-based products, bone grafts, and various membranes [5]. Many biomaterials that are currently used for OAF closures have been primarily developed for other oral and maxillofacial or general surgical applications rather than having been specifically engineered for OAF management; however, their favorable healing properties have led to their adaptations for OAF closures. OAF closures, unlike their use in other non-OAF conditions, present additional challenges, including promoting mucosal and bone healing in potentially infected environments, serving as a barrier between the maxillary sinus and oral cavity, integrating dual tissues (sinus lining and oral mucosa), and withstanding the mechanical stresses associated with oral functions [6]. Given the rapid evolution of bioengineered biomaterials and surgical techniques and the various clinical conditions associated with OAF closure, a systematic review of the current literature is essential to estimate relative success rates, evaluate patient outcomes, identify potential complications, and guide advancements in patient care and oral surgical practice. Case reports and relevant case series, although limited by their study design, do provide valuable educational resources, hypothesis generation, and rare condition documentation, in addition to providing invaluable information about the early clinical application and patient-related outcomes of OAF biomaterials in actual clinical settings. Moreover, in the context of personalized medicine, which involves highly individualized treatments, case reports and series provide additional insights into individual variations, whether related to tissue responses or potential complications [7]. By systematically examining the reported outcomes, complications, and determinants of success associated with different biomaterials used in OAF closure, this review would present clinicians with a current comprehensive understanding of the effectiveness, competency, and safety profile of modern biomaterials in the treatment of OAFs. The conclusions drawn from this comprehensive review will also serve to inform evidence-based clinical practice and direct forthcoming research endeavors concerning the advancement, applications, and precautions of biomaterials for OAF closure. This systematic review was aimed at evaluating the clinical outcomes and challenges of various biomaterials that were originally developed for periodontal regeneration, sinus augmentation, and general wound healing for affecting the clinical closure of OAFs and oroantral communication. The review focused particularly on case reports and series documenting infection-prone environments, dual-tissue barrier functions, and mechanical stresses associated with oral function..

This systematic review follows the standardized recommendations for reporting the findings of systematic reviews as outlined in Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [8]. The purpose of this review is to present a comprehensive and transparent methodology along with the relevant findings, to ensure future reproducibility and reliability.

Methods

RESEARCH QUESTION AND STUDY DESIGN:

For this systematic review, the research question addressed was “What recent biomaterials have been used for closing an OAF, as reported in case reports and series published between 2015 and 2025?” As per the requirements, the protocol for this study was prospectively registered with PROSPERO, with reference number CRD420251089886.

INCLUSION CRITERIA:

Case reports and series involving the reporting of 1 or more OAF cases exclusively describing the use of biomaterials for surgical closure of OAF and published from January 1, 2015, till February 28, 2025, were included for the systematic review. Studies were included if they were published in peer-reviewed journals. Cases with clearly defined outcome measures, including complete fistula closure, were included.

EXCLUSION CRITERIA:

Studies were excluded if they failed to report the outcomes of OAF closure. Review articles of any type, editorials, and letters to the editor were also excluded. Studies conducted on animal models were excluded. Studies that did not involve the use of any biomaterials were excluded.

SEARCH STRATEGY:

A comprehensive search was conducted in the following electronic databases: PubMed, Scopus, Web of Science, and the Cochrane Library. The following search terms were used, combined with Boolean operators: “(“Oroantral fistula” OR “oroantral communication”) AND (“collagen” OR “PRF” OR “platelet-rich fibrin” OR “bone graft” OR “hydroxyapatite” OR “titanium mesh” OR “amniotic membrane” OR “CAD-CAM” OR “scaffold” OR “materials”) AND (“case report” OR “case series”)”. To ensure a thorough search, we also hand-searched the relevant individual journals, confirmed dates of publication, reviewed the reference lists of included studies, and consulted with experts in the field.

SCREENING PROCESS:

Two independent reviewers (FMA, NO) conducted the required screening process. First, the reviewers screened respective titles and abstracts (structured and unstructured) to identify the potentially relevant studies to be included in the systematic review. Then, the selected studies were independently reviewed to further establish their eligibility against the predetermined inclusion and exclusion criteria. All disagreements between the reviewers were comprehensively resolved through proper discussion between reviewers; when a consensus was not reached, a third reviewer (AMM) was consulted for determination of including or excluding the relevant article.

DATA EXTRACTION:

A standardized data extraction form was used to collect relevant information from the included studies. The extracted data included study characteristics (author, year, journal), patient demographics (age, sex, medical history), OAF characteristics (etiology, size, location), and a description of the biomaterial(s) used. The primary outcome was OAF closure (success or failure). The secondary outcomes were healing time, complications, recurrence, and patient-reported outcomes.

QUALITY ASSESSMENT:

The quality of the included case reports was assessed using a validated tool, the Joanna Briggs Institute (JBI) critical appraisal tool for case reports and case series [9]. Two reviewers conducted the quality assessment of the studies (FMA, NO). Disagreements between reviewers were resolved through discussion or consultation with a third reviewer (AMM).

DATA SYNTHESIS:

A narrative synthesis of the findings was performed. The data were synthesized by categorizing biomaterials and techniques used for OAF closure, describing the outcomes and complications reported in the studies, and exploring potential factors influencing the success of OAF closure.

STUDY SELECTION:

This systematic review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, adapted for case reports and case series (Figure 1).

Results

STUDY CHARACTERISTICS:

This review was conducted by using PubMed, Scopus, Web of Science, and the Cochrane Library. The initial search yielded 189 case records, which were subsequently refined through the removal of duplicates, using the screening of titles and abstracts. After a comprehensive evaluation of the full texts, 18 studies (Table 1) satisfied the inclusion criteria and were thus integrated into the review [10–27]; alternately, 6 studies were excluded, primarily due to divergences in their primary objectives or because they used only flap techniques without any biomaterial application.

PATIENT DEMOGRAPHICS:

The population under investigation exhibited a broad age spectrum, ranging from 20 to 77 years, with a calculated mean age of 46 years (Table 1) [10–27]. The available sex distribution was 12 male and 7 female treated patients (Table 1) [10–27]. Reported patient factors included smoking and documented systemic conditions, such as multiple myeloma, pericarditis, long-term steroid use, and squamous cell carcinoma.

OAF ETIOLOGY AND CHARACTERISTICS:

Post-extraction complications were reported to be the most common cited cause for OAF formation, constituting 50% (9/18) of the overall documented instances. Other causes of OAF included sinus graft infections (18.75%, 3/16), outcomes from radicular cyst treatment, removal of dental osseointegrated implants, implant explantation, projectile wounds from gunshot injuries, and osteoradionecrosis. OAF dimensions (size), when specified, varied from 4 mm to over 20 mm, with descriptors such as “large”, “extensive”, and “chronic” also used. The maxillary posterior dentition was the primary site of OAFs, and specific tooth numbers were identified in most cases.

BIOMATERIALS AND TREATMENT MODALITIES:

A wide range of mucosal and bone biomaterial types, along with different treatment modalities, were clinically utilized in the included studies. PRF [10,15,16,19,23] and advanced PRF [10] were used in 5 (31.25%) of a total of 18 studies, thereby indicating the higher prevalence and use of autologous materials. Combination therapies involving multiple biomaterials were frequently observed [15,16,19,23,24]. Other materials included computer-aided design–computer-aided manufacturing (CAD-CAM) allogenic bone blocks [11], collagen cones and membranes [27], cortical bone shell grafts [13], hydroxyapatite and ribose [14], sinus bone grafts and allografts [13,17], chin grafts [21], buccal fat pads [16,21], buccal advancement flaps [14–19,21], and human amniotic membranes [25].

FOLLOW-UP AND PATIENT OUTCOMES:

Follow-up periods observed were 7 days [12,14,16,25,27], 1 to 2 weeks [19], 1 month [11,15], and 3 to 6 months [17,21], with 7 days being the most common follow-up duration. Consistently, patient-based outcomes indicated successful OAF closure. Patients in these case reports and series had frequently reported symptom relief [10,12,14–16,19], with subsequent pain and/or discomfort alleviation when pain/discomfort was associated [10,14–16,19], the cessation of nasal regurgitation [10,12,14–16,19,25], and the resolution of air leakage [12,15,16,19,25]. Several cases reported describing the healing process as completely “uneventful” [11,12,14–17,19,21,25,27], thereby indicating a more favorable patient response attributed to the diverse treatment modalities used.

GEOGRAPHIC DISTRIBUTION:

The studies considered, published between 2015 and 2025, encompassed a wide geographical scope, including Poland [10], Egypt [11], Bulgaria [12], South Korea [13,15,17], Colombia [14], India [16,21,25], the United States [18,22], Iraq [19], Taiwan [20], Saudi Arabia [23], Brazil [24], and Russia [26].

VARIABILITY IN REPORTING:

Although positive outcomes were generally observed, there were reporting variations for the size (length and sample size), clinical location, and periodic follow-up durations for OAF closures. This indicates that there must be standardized documentation in future studies that will improve and enhance reproducibility and comparability, thus strengthening the reliability and validity of these studies.

JBI CRITICAL APPRAISAL:

The reported quality of the included case reports and case series was evaluated using the standard JBI critical appraisal checklists [9]. The relative findings from this critical appraisal are presented in Table 2, which evaluates individual studies across 7 key areas: patient attributes, causal relationship, condition presentation, intervention/exposure, outcomes, alternative explanations, and key conclusions.

OVERALL QUALITY ASSESSMENT:

All 18 included studies had adequately addressed the vital clinical categories of patient attributes, underlying causal relationship, planned intervention/exposure, relative outcomes, and significant conclusions, prompting a consistent “yes” score in these categories. The studies also demonstrated clear descriptions of patient characteristics, a plausible link between the exposure and the outcome, detailed information about the interventions, well-defined outcomes, and relevant clinical implications.

CONDITION PRESENTATION:

All the studies (18/18) offered a clear and transparent presentation of the patient’s condition, thereby scoring a “yes” in this domain.

ALTERNATIVE EXPLANATIONS:

A common limitation across the included studies was how well they dealt with their respective alternative explanations. All 18 studies received an “unclear” rating in this area. This suggests that the studies did not fully explore or discuss possible alternative explanations for the results they found. This is a common issue in case reports and case series, mainly because of their specific research design.

KEY CONCLUSIONS:

The JBI critical appraisal indicated that the incorporated studies largely conformed to the essential standards for reporting case reports and case series. These studies presented lucid patient information, established causal links, described interventions in detail, reported outcomes, and communicated pertinent conclusions. Nevertheless, the recurring “unclear” rating concerning alternative explanations underscores a notable constraint. Although the studies definitely offered valuable clinical perspectives, there is still further scope for enhancing the accounting for potential confounding variables while at the same time offering exhaustive, detailed, and comprehensively specific clinical presentations.

Discussion

LIMITATIONS:

The findings of this systematic review require cautious interpretation owing to several methodological limitations of the involved studies. These findings cannot be generalized, which stems from their basis, which was a singular or narrowly focused case study. Additionally, the observational nature of these studies prevents the determination of causal relationships, as patient attributes and concurrent treatments introduce significant confounding variables that vary among populations and across geographical areas. Reporting bias is inherent to case reports and series, with most studies favoring positive clinical outcomes. Furthermore, the synthesis of data is hampered by heterogeneity and inconsistent reporting quality, as demonstrated by JBI appraisals that expose ambiguous demographic information or statistical approaches. Ultimately, the possibility of over-interpretation presents a challenge, whereby atypical cases could skew perceptions of biomaterial efficacy within complex scenarios, such as those involving infection or mechanical strain.

FUTURE DIRECTIONS:

Although the results of this systematic review have limitations, they provide insight into future research directions. Future research needs to focus on conducting randomized controlled clinical trials to determine and compare the efficacy of different biomaterials and their relative surgical techniques for OAF closure. Standardized outcome measures and long-term follow-up protocols also need to be implemented, which will provide a more robust and reliable clinical evidence. Studies should also explore the potential role of certain novel biomaterials and tissue engineering approaches that were not mentioned in these studies, for broadening the scope of OAF management.

Conclusions

This systematic review in general emphasizes the use of a diverse range of mucosal and bone biomaterials for OAF closure, with PRF and advanced PRF being among the most frequently reported biomaterial types, either individually or in combination with other compatible biomaterial. Overall, most of the studies included in this systematic review reported favorable clinical outcomes. However, the variability in individual reporting indicates the need for standardized documentation and higher-quality studies to improve comparability, reliability, and validity and to guide evidence-based clinical decision-making.