Comparison of Biodegradable Versus Titanium Fixation Systems in Mandibular Fractures: Systematic Review and Meta-Analysis

Abstract

Background/Objectives: Titanium fixation remains the gold standard for stabilizing mandibular fractures; however, associated complications often necessitate a second surgery for hardware removal. Consequently, biodegradable systems were introduced, though questions persist regarding their mechanical reliability and potential for tissue reactions. This systematic review and meta-analysis was conducted to compare the efficacy and morbidity of biodegradable versus titanium osteosynthesis systems for the treatment of mandibular fractures. Methods: Following PRISMA guidelines, a systematic literature search was conducted in MEDLINE, Embase, and CENTRAL. Comparative studies, such as randomized controlled trials (RCTs) and non-randomized studies, were included. The primary outcome was the rate of hardware removal; therefore, a random-effects meta-analysis was performed to calculate a pooled Odds Ratio (OR), while the risk of bias was assessed using the Cochrane RoB 2 and ROBINS-I tools. Results: Eight studies, including four RCTs, comprising a total of 369 patients, were included, with most studies judged to be at a high or serious risk of bias due to inadequate randomization, lack of blinding, and confounding co-interventions. The meta-analysis of four RCTs on hardware removal revealed no statistically significant difference between the biodegradable and titanium groups (pooled OR 0.28, 95% CI 0.04 to 1.90), with substantial and statistically significant heterogeneity observed (I² = 66.1%). Qualitative synthesis indicated that biodegradable systems were associated with higher rates of intraoperative screw breakage and longer operative times, while rates of successful bone union were comparable between the two groups. Conclusions: Biodegradable osteosynthesis systems represent a viable alternative to titanium for mandibular fracture fixation, demonstrating similar efficacy in achieving bone union, which is counterbalanced by higher rates of screw breakage and longer operative times. The decision to use a biodegradable system involves a critical trade-off that should be designed for the specific clinical scenario. The high risk of bias and significant heterogeneity limit the certainty of these findings, underscoring the imperative for future high-quality, long-term RCTs.

1. Introduction

Mandibular fractures are injuries within the maxillofacial region requiring surgical intervention to restore anatomical form and function [1,2], and because the objective of treatment is the precise reduction and stable fixation of bone segments to facilitate undisturbed primary bone healing [3], osteosynthesis systems composed of plates and screws are applied to provide the requisite stability for fracture consolidation [4].

Titanium plating systems are currently regarded as the benchmark for internal fixation of the mandible [5,6]. The combination of rigid plates and screws offers superior mechanical stability and ease of intraoperative handling, ensuring the bone segments remain immobile for optimal healing [7,8]. However, the use of permanent metallic hardware is not without drawbacks. Patients often complain of temperature sensitivity and palpability of the plates [5,9]. Furthermore, in pediatric populations, there is a risk that rigid fixation may restrict skeletal growth.

Additionally, titanium implants can create significant artifacts on CT and MRI scans, which complicates diagnostic imaging, and they can interfere with radiation delivery in oncology patients [6,10]. From a biological perspective, the high modulus of elasticity of titanium compared to bone can result in ‘stress shielding,’ leading to bone atrophy beneath the plate. There are also reports of titanium particles accumulating in local tissues and lymph nodes—a phenomenon known as metallosis—driven by oxidative stress [11,12,13]. These complications contribute to a high rate of secondary operations for symptomatic hardware removal, which imposes additional surgical risks and financial costs [4,14].

To overcome the necessity of a second surgery, biodegradable osteosynthesis systems were introduced as a viable alternative [4]. These devices, manufactured from polymers like poly-L-lactic acid (PLLA) and polyglycolic acid (PGA), are engineered to provide temporary stability. They degrade gradually in the body, transferring the mechanical load back to the healing bone over time, thereby eliminating the risk of stress shielding [4].

Biodegradable systems have limitations, including inferior mechanical properties compared to titanium, which may increase the risk of intraoperative screw breakage and could lead to fixation instability [4,5], and in some cases, degradation byproducts can elicit adverse tissue responses, including sterile abscess formation and foreign body reactions, which remain a clinical concern [1,15].

While significant advancements in titanium and biodegradable material sciences have led to improved implant designs, mechanical properties, and handling characteristics [4], newer titanium systems have been developed with altered production processes to modulate stiffness, and the composition and application of biodegradable systems have been refined to enhance strength and reduce inflammatory potential [4,5].

As a comprehensive synthesis of the current evidence is lacking to guide clinicians in selecting the optimal fixation system for mandibular fractures, this systematic review and meta-analysis was conducted to evaluate and compare the efficacy and morbidity of biodegradable versus titanium osteosynthesis systems used for the treatment of mandibular fractures, focusing on key clinical outcomes such as bone healing, postoperative complications, and the need for hardware removal.

2. Methods

2.1. Protocol and Registration

This systematic review and meta-analysis was designed and conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement (Table S1) [16]. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD420251161104, thereby ensuring transparency and methodological rigor throughout the review process.

2.2. Eligibility Criteria

Studies were included in this review based on a predefined Population, Intervention, Comparator, and Outcomes (PICO) framework, as the population of interest comprised human subjects of any age who had sustained traumatic mandibular fractures and were treated surgically with open reduction and internal fixation (ORIF). The intervention was the use of biodegradable or bioresorbable fixation systems (plates and/or screws), while the comparator group consisted of patients treated with conventional titanium fixation systems. Studies including randomized and non-randomized comparative designs such as prospective and retrospective cohort studies, were eligible for inclusion.

The primary outcome for this meta-analysis was the rate of hardware removal, which included plate rejection and reoperation for implant removal, while secondary outcomes encompassed fracture union, overall postoperative complications like infection, malunion, or hardware failure, and operative time. Studies involving fractures of facial bones other than the mandible, case series without a comparator group, in vitro or animal studies, and narrative reviews were excluded.

2.3. Information Sources and Search Strategy

A systematic search of the literature was performed across multiple electronic databases, including MEDLINE (via PubMed), Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL), to identify all relevant studies published up to the search date. The search strategy combined medical subject headings (MeSH) and free-text keywords such as “Mandibular Fracture”, “Titanium plates”, “Bioresorbable plates”, and “Biodegradable osteosynthesis”. No restrictions on language or date of publication were applied to ensure a comprehensive retrieval of the literature.

2.4. Study Selection Strategy

Following the removal of duplicate records, the titles and abstracts of the retrieved citations were screened to identify relevant studies, after which the full-text articles of these studies were obtained and assessed for final inclusion based on the predefined eligibility criteria. Any disagreements between the reviewers during the selection process were resolved through discussion and consultation with a third reviewer.

2.5. Data Extraction

A standardized data extraction form was developed and used by two independent reviewers to collect relevant information from each included study, as the extracted data included study characteristics (author, year, study design), patient demographics, fracture location, details of the intervention and comparator fixation systems, follow-up duration, and outcome data for all primary and secondary endpoints. For dichotomous outcomes, the number of events and the total number of patients in each group were extracted.

2.6. Risk of Bias Assessment

Two reviewers independently assessed the methodological quality and risk of bias of the included studies. For the randomized controlled trials (RCTs), the Cochrane RoB 2 was employed, which evaluates bias across five distinct domains: the randomization process, deviations from intended interventions, missing outcome data, measurement of the outcome, and selection of the reported result [17], while for non-randomized comparative studies, the ROBINS-I tool was used to assess bias due to confounding, selection of participants, and other relevant domains [18]. The overall risk of bias for each study was judged as “Low”, “Some Concerns”, or “High/Serious”.

2.7. Data Synthesis and Statistical Analysis

A quantitative synthesis of the primary outcome of hardware removal was performed through a meta-analysis, for which the treatment effect was calculated as an Odds Ratio (OR) with a 95% confidence interval (CI), and due to anticipated clinical and methodological diversity, a random-effects model using the DerSimonian–Laird method was chosen a priori for the analysis [19]. Statistical heterogeneity quantified using the I² statistic, where values greater than 50% indicated substantial heterogeneity, and tested for significance using Cochran’s Q test, and a continuity correction of 0.5 was applied to studies with zero events in one arm to facilitate the OR calculation, while the potential for publication bias was assessed using a funnel plot, although formal statistical tests for asymmetry were not performed due to the small number of included studies (k = 4).

All statistical analyses were conducted within the R environment for statistical computing (version 4.5.1) [20], with quantitative synthesis performed using the meta package, which was used to apply the random-effects model and generate the corresponding forest plot [21].

3. Results

3.1. Study Selection

The initial search of electronic databases and registers identified 959 records, and after the removal of 291 duplicates, 668 unique citations were screened by title and abstract, which resulted in the exclusion of 598 articles, and upon seeking retrieval for the full texts of the remaining 70 reports, 19 were assessed for eligibility, a process during which several reports were excluded for reasons including insufficient data for analysis (n = 8), the absence of a comparative control group (n = 1), or a focus on an irrelevant patient population or intervention (n = 2). A total of 8 unique studies met the eligibility criteria and were included in the qualitative and quantitative synthesis (Figure 1).

3.2. Characteristics of Included Studies

The 8 included studies comprised a total of 369 patients, as 170 patients were allocated to the biodegradable fixation group and 199 patients to the titanium fixation group. The evidence base consisted of four RCTs [22,23,24,25] and four non-randomized studies of interventions (NRSIs) [22,25,26,27]. The studies were published between 2010 and 2018 and were conducted in various geographical settings, including Europe and Asia. Clinical heterogeneity was the duration of follow-up, which varied across the studies, ranging from 8 weeks postoperatively [23] to over 5 years [24]. The biodegradable systems used were copolymers of polylactic and polyglycolic acid such as the Inion CPS system, while the control groups used standard titanium miniplate fixation systems.

Table 1. Characteristics of Included Comparative Studies.

Study	Year	Design	Country	Population (n)	Intervention Group (Biodegradable)	Comparator Group (Titanium)	Mean Age ± SD (Years) (Bio/Ti)	Sex (% Male) (Bio/Ti)	Fracture Location(s)
Gareb et al. 1 [24]	2017	RCT	Netherlands	221	Inion CPS (n = 87)	KLS Martin (n = 134)	33.0 ± 12/31.0 ± 11	52%/62%	Mixed (Mandibular, Maxillary, Zygomatic)
Bhatt et al. [23]	2010	RCT	India	40	Inion CPS (n = 19)	Synthes (n = 21)	26.6/28.7	95%/95%	Mandibular (Angle, Parasymphysis)
Ahmed et al. [22]	2013	RCT	Pakistan	69	Bonamates (n = 34)	Treu-dynamic (n = 35)	31.4 ± 11.2/34.3 ± 10.7	91%/91%	Mandibular
Kumar et al. [25]	2018	RCT	India	60	Bioresorbable (n = 30)	Titanium (n = 30)	NR	93%/93%	Mandibular
Leno et al. [26]	2017	NRSI (Cohort)	Taiwan	41	Bonamets (n = 21)	Stryker (n = 20)	26.2 ± 9.7/27.3 ± 10	41%/43%	Mandibular (Symphysis, Body, Angle)
Lim et al. [27]	2014	NRSI (Cohort)	South Korea	29	Inion CPS/Biosorb FX (n = 13)	Osteo-fit/Synthes (n = 16)	24.2 ± 6.9/28.3 ± 12.9	92%/94%	Combined Angle and Symphysis
Kumar et al. [25]	2018	NRSI (Cohort)	India	60	Bioresorbable (n = 30)	Titanium (n = 30)	29.8 ± 11.8/29.8 ± 11.8	90%/90%	Mandibular
Ahmed et al. [22]	2013	NRSI (Cohort)	Pakistan	69	Bonamates (n = 34)	Titanium (n = 35)	31.4 ± 11.2/34.3 ± 10.7	91%/91%	Mandibular

Abbreviations: Bio, biodegradable; n, number of patients; NR, not reported; NRSI, non-randomized study of intervention; RCT, randomized controlled trial; SD, standard deviation; Ti, titanium. ¹ The study by Gareb et al. [24] represents the long-term (>5 years) follow-up of a single multicenter RCT, with earlier results reported by van Bakelen et al. [28] and Buijs et al. [29]. Population numbers reflect the total treated groups for maxillofacial trauma in the trial.

provides a comprehensive overview of the design, demographics, and procedural details of the eight studies included in the systematic review.

3.3. Risk of Bias Judgement

The overall risk of bias across the studies included was judged to be considerable as among 4 RCTs, one multicenter trial was assessed as having “Some Concerns”, stemming from a high rate of long-term attrition for patient-reported outcomes and a lack of outcome assessor blinding [24,28,29], while the other 3 RCTs were judged to be at a “High Risk” of bias due to critical flaws, which included inadequate randomization methods such as allocation by “lottery” without concealment [22], the introduction of significant confounding co-interventions like prolonged maxillomandibular fixation in only the biodegradable arm [23,25], and a complete lack of blinding.

The non-randomized studies included were assessed as having a “Serious Risk” of bias due to critical confounding by indication as treatment allocation was determined by patient or surgeon preference without statistical adjustment [26,27]. A summary of the risk of bias assessment for each domain is presented in Figure 2, and the detailed judgments for each included study are shown in Figure 3.

3.4. Synthesis of Results

The primary outcome of this review was the rate of hardware removal, for which data from four RCTs comprising 369 patients were available for quantitative synthesis [22,23,24,25].

Table 2. Summary of Key Clinical Outcomes from Included Randomized Controlled Trials.

Outcome	Study	Biodegradable Group Events/Total)	Titanium Group Events/Total)	Notes and Comments
Hardware Removal	Gareb et al. [24]	23/87	22/134	Primary reason for removal in the biodegradable group was foreign body reaction; in the titanium group, it was pain/discomfort.
	Bhatt et al. [23]	0/19	4/21	All removals in the titanium group were due to reoperation for complications or patient request.
	Ahmed et al. [22]	0/34	4/35	All four removals in the titanium group were due to chronic infection or patient preference.
	Kumar et al. [25]	0/30	6/30	Complications leading to removal were not specified.
Perioperative Screw Breakage	Ahmed et al. [22]	16/216	0/208	Breakage occurred in 8% of resorbable screws inserted.
	Lim et al. [27]	2/166	0/192	Represented a 15.4% incidence of specific technical problems in the resorbable group.
Infection	Bhatt et al. [23]	0/19	1/21 (5.2%)	Low event rates in both groups.
	Ahmed et al. [22]	0/34	2/35 (5.7%)	Infections in the titanium group were managed with hardware removal.
Malunion/Malocclusion	Bhatt et al. [23]	Nonunion: 1/19 (4.2%) Malocclusion: 2/19 (11.1%)	Nonunion: 0/21 (0%) Malocclusion: 1/21 (7.7%)	Differences were not statistically significant due to small sample size.
	Ahmed et al. [22]	Malocclusion: 1/34 (2.9%)	Malocclusion: 0/35 (0%)	Low event rates overall.

details the primary and secondary clinical outcomes reported across the four RCTs included in the meta-analysis. The pooled analysis, conducted using a random-effects model, indicated no statistically significant difference in the odds of hardware removal between the bioresorbable and titanium fixation groups (Pooled [OR] = 0.28; 95% [CI] 0.04 to 1.90; p = 0.19) (

Table 3. GRADE Summary of Findings for the Primary Outcome: Hardware Removal.

Outcome	No. of Studies (Participants)	Assumed Risk (Titanium)	Corresponding Risk (Biodegradable)	Relative Effect (95% CI)	Certainty of Evidence (GRADE)	Explanation for Certainty Rating
Hardware Removal	4 RCTs (369 patients)	164 per 1000	55 per 1000 (from 7 fewer to 311 more)	OR 0.28 (0.04 to 1.90)	Very Low	Downgraded three levels: Risk of Bias: Serious risk; most studies rated as high risk. Inconsistency: Substantial and statistically significant heterogeneity (I2 = 66.1%). Imprecision: The 95% CI is very wide and includes both appreciable benefit and harm.

The Assumed Risk is the median control group event rate across the included RCTs. The Corresponding Risk is calculated by applying the pooled odds ratio to the assumed risk. Abbreviations: CI, confidence interval; GRADE, Grading of Recommendations Assessment, Development and Evaluation; OR, odds ratio; RCT, randomized controlled trial.

). Although the point estimate suggests a trend favouring a lower rate of removal for bioresorbable systems, the wide CI, which crosses the null value of 1.0, indicates that this result is inconclusive.

The analysis revealed substantial and statistically significant heterogeneity among the included studies (I² = 66.1%; Cochran’s Q = 10.84, p = 0.013), suggesting that the true effect of the intervention varies across different clinical contexts and follow-up durations, which supports the a priori decision to use a random-effects model for the analysis. A forest plot illustrating the effect estimates from individual studies and the pooled result is provided in Figure 4.

Regarding mechanical integrity, the biodegradable group exhibited a higher incidence of intraoperative mechanical failure, specifically screw breakage. Regarding adverse tissue reactions, hardware removals in the biodegradable group were attributed to sterile abscess formation, whereas titanium removals were due to subjective discomfort or cold intolerance.

3.5. Assessment of Publication Bias

A funnel plot was generated to inspect for potential publication bias by plotting the log OR against the standard error for each study. The plot displayed some asymmetry; however, with only four studies included in the meta-analysis, the power to detect true asymmetry is low, and the interpretation of the plot is therefore limited. No definitive conclusion regarding the presence or absence of publication bias could be drawn from this analysis (Figure 5).

4. Discussion

This systematic review and meta-analysis was conducted to synthesize the available evidence comparing the efficacy and morbidity of biodegradable versus titanium fixation systems for the treatment of mandibular fractures. The principal finding of this review is that while biodegradable systems demonstrate clinical union rates comparable to the titanium gold standard, they present a distinct profile of clinical trade-offs.

The meta-analysis of the primary outcome revealed no statistically significant difference in the odds of hardware removal between the two groups, but this result is qualified by substantial heterogeneity and must be interpreted with caution, while the clinical data indicates that the use of biodegradable systems is associated with a higher rate of intraoperative screw breakage and longer operative times compared to titanium systems.

The advantage of biodegradable fixation is the theoretical elimination of a secondary surgery for hardware removal, which is a procedure required in some patients with titanium implants due to complications such as pain, palpability, or temperature sensitivity [1,4]. The meta-analysis on hardware removal yielded an inconclusive result (OR 0.28, 95% CI 0.04 to 1.90), which was caused by substantial and statistically significant heterogeneity (I² = 66.1%) between the included studies. Gareb et al. [24], in a study that followed patients for over five years, reported a higher rate of symptomatic removal in the biodegradable group in contrast to smaller studies with shorter follow-up [22,23], which suggests that the true effect varies depending on clinical context, follow-up duration, and material composition.

The removal of biodegradable hardware is often required by adverse host responses such as sterile abscess formation or chronic inflammation which are linked to the degradation process of the polymer, particularly the hydrolysis of crystalline materials [4,15], while the removal of titanium hardware is caused by the presence of the permanent implant, alongside biological responses to metallic particle release such as metallosis and localized oxidative stress [4,12].

From a biomechanical standpoint, titanium systems maintain superiority in vitro, possessing significantly higher tensile strength and torsional stiffness compared to their polymeric counterparts [30]. This mechanical disparity explains the clinical finding that perioperative screw breakage was notably more frequent in the biodegradable group [22,25]. Surgeons using biodegradable systems must exercise caution, as the material demands precise technique, including the necessity of pre-tapping holes, which contributes to the longer operative times observed [5].

Despite their inferior mechanical profile, the included studies demonstrate that biodegradable systems provide sufficient stability for adequate bone healing in mandibular fractures, with rates of malunion and malocclusion that are not significantly different from titanium fixation which suggests that the mechanical strength of biodegradable systems is clinically adequate for many mandibular fractures, which are subject to load-sharing principles, even if it is not equivalent to titanium [3].

The primary strength of this systematic review is its methodology, including a registered protocol, a thorough search strategy, and the use of robust tools for risk of bias assessment, but the overall risk of bias across the included studies is high. The RCTs suffered from inadequate randomization and allocation concealment procedures [22], a lack of blinding of outcome assessors, and the presence of confounding co-interventions, such as the differential use of maxillomandibular fixation [23].

Also, the non-randomized studies were at a serious risk of bias due to confounding by indication, as the choice of implant was left to the patient or surgeon, creating systematic differences between groups that were not adjusted for in the analysis [26], which weakens the certainty of the findings and underscores that the observed effects may be distorted.

It is important to note that the included studies focused on local complications. None of the trials reported data regarding the systemic migration of degradation byproducts or their effects on distant organs such as the liver, heart, or brain. However, given the established biocompatibility of PLLA and PGA, systemic toxicity is considered rare.

Furthermore, none of the included RCTs performed a formal cost-effectiveness analysis. Biodegradable systems eliminate the cost of a second surgery for removal, but the initial implant cost and longer operating room time must be weighed against this benefit in future economic evaluations.

The findings of this review must be interpreted with caution due to several limitations, as the included studies exhibited high heterogeneity regarding the specific generation of biodegradable materials used and the duration of follow-up, which limits the generalizability of the results. Also, the total sample size (n = 369) is relatively small, reducing the statistical power to detect differences in rare adverse events. The risk of bias was considerable; most studies lacked blinding of the outcome assessors and surgeons, and non-randomized studies suffered from confounding by indication. These methodological flaws represent a significant constraint on the certainty of the current evidence.

Future research should prioritize the execution of large-scale RCTs that adhere to CONSORT guidelines, as such trials should ensure proper randomization and allocation concealment, blinding of outcome assessors, and standardized co-interventions to isolate the effect of the fixation material. A follow-up duration of at least five years is necessary to capture late-onset complications, particularly foreign body reactions associated with the final stages of polymer degradation. Also, future studies should focus on comparing specific, modern biodegradable systems (e.g., amorphous copolymers, ultrasound-welded pins) against contemporary titanium systems. Research is needed to delineate which specific fracture patterns and patient populations (e.g., pediatric vs. adult, angle vs. symphysis fractures) might benefit most from either fixation modality.

5. Conclusions

Biodegradable osteosynthesis systems represent a viable alternative to the conventional titanium standard for the fixation of mandibular fractures, demonstrating comparable efficacy in achieving successful bone union. The advantage of biodegradable implants to obviate a secondary surgery for symptomatic hardware removal is counterbalanced by intraoperative challenges, including higher rates of screw breakage and longer operative times.

This meta-analysis did not find a statistically significant difference in the odds of overall hardware removal, but this finding is constrained by substantial heterogeneity across studies, suggesting that the outcome is dependent on clinical context, material choice, and follow-up duration; therefore, the decision to use a biodegradable system involves a trade-off between avoiding the long-term risks associated with permanent titanium hardware and accepting the technical demands and material-specific complications associated with resorbable polymers.

The conclusions of this review are drawn from an evidence base with a considerable risk of bias, which limits the certainty of the findings. The selection of a fixation system should be a considered decision, designed for the specific fracture pattern, patient characteristics, and surgeon experience. Further high-quality, long-term RCTs are imperative to establish the comparative effectiveness of modern biodegradable and titanium systems and to refine their indications in the management of mandibular fractures.