Keywords
Allograft, Autograft, Anterior Cruciate Ligament
We conducted this meta-analysis to evaluate the clinical outcomes of the two procedures using a pooled analysis of multiple scales, as there has been dispute among the research on the use of autografts or allografts.
We searched PubMed, Scopus, and Web of Science databases for articles that fulfilled our aim. The search strategy was based on three main keywords: “Autograft”, “Allograft”, and “Anterior Cruciate Ligament. The resulting articles were collected and uploaded to Rayyan. All statistical procedures were performed using Review Manager software version 5.4. We conducted a pooled analysis of continuous variables using mean difference (MD), while for dichotomous variables, we used the pooled analysis of odds ratio (OR) by extraction of event and total.
Autograft showed better outcomes regarding IKDC score compared to allograft with MD of 1.89 (95%CI: 0.37, 3.42. p=0.02), and I2=66%, p=0.002. It was also associated with better Lysholm and Tegner scores with MD of 1.48 (95%CI: 0.19, 2.77, p=0.02), and 0.32 (0.15, 0.49, p=0.0003), respectively, with no significant heterogeneity in both. Autografts were associated with a higher OR of grade 0 in the Lachmann score with an OR of 2.6 (95%CI: 1.26, 5.38, p=0.01), while allografts had higher odds of having grades 2 and 3 (OR, 0.53 (95%CI, 0.31, 0.93; p=0.03), and 0.48 (95%CI: 0.27, 0.84, p=0.01), respectively
Compared to allografts, the use of autografts in ACL reconstruction is associated with better functional, structural, stability, and satisfaction outcomes, as observed by statistically significant differences in IKDC, Tegner, Lachmann, Pivot shift test, and Lysholm. However, no differences were observed in ROM, Daniel’s one-leg hop test, or Harner’s vertical jump.
Allograft, Autograft, Anterior Cruciate Ligament
Anterior cruciate ligament (ACL) tears are common injuries that affect over 250,000 people annually in the US.1,2 A comprehensive study conducted in New Zealand revealed an incidence of 36.9 injuries per 100,000 person-years.3 Conservative care and repair are insufficient for healing ACL tears. As a result, ACL repair is thought to be the typical surgical method used to treat ACL tears.4,5
When treating ACL injuries, conservative care is preferred over surgical intervention. However, ineffective treatment for these injuries can result in meniscal tears, articular cartilage degradation, and early onset osteoarthritis. Consequently, surgery has become the preferred treatment course for young individuals with a high demand for ACL injuries. ACL repair success depends on several factors, including the right patient selection, right tunnel location, right graft, stable graft fixation, and sufficient rehabilitation.6
Graft selection has been identified as a modifiable extrinsic factor influencing ACL reconstruction failure.7–9 Autografts and allograft tissues are the two main categories of graft options in ACL surgery. The most popular autograft among ACL surgeons globally is the hamstring tendon autograft, followed by bone–patellar tendon–bone, and quadriceps tendon autografts.10 Because allografts prevent donor site morbidity and require less time during surgery than autografts when they are available, they are an appealing alternative to autografts. There are several sources of allografts, ranging from the tendon bone to soft tissue.
Autografts can cause donor-site morbidity despite their advantages of quicker integration, lack of rejection, and lack of disease transmission. Allografts have the benefit of being readily available, avoiding donor-site morbidity, requiring less time for surgery and rehabilitation, and having a shorter recovery period.11,12 Its main drawbacks, however, include increased graft costs, spread of illness, delayed graft assimilation, and worse functional results.13 It is possible to avoid allograft-related infections using gamma irradiation. Nonetheless, a number of investigations have shown that the biomechanical and biochemical characteristics of allografts are significantly altered by this sterilization technique.14 We conducted this meta-analysis to evaluate the clinical outcomes of the two procedures using a pooled analysis of multiple scales, as there has been dispute among the research on the use of autografts or allografts.
We used the Cochrane Handbook for Systematic Reviews and Meta-Analyses (Preferred) guidelines for systematic reviews and meta-analyses.15
We searched PubMed, Scopus, and Web of Science databases for articles that fulfilled our aim. The search strategy was based on three main keywords: “Autograft”, “Allograft”, and “Anterior Cruciate Ligament. The resulting articles were gathered and uploaded to Rayyan.16
We included randomized controlled trials (RCTs) that compared the use of autografts and allografts in ACL surgery. Reviews, observational studies, and case reports were excluded. We conducted title and abstract screening to determine whether the articles met our criteria. This process was followed by a full-text screening to ensure that the articles included in the previous step were eligible for inclusion.
We extracted the baseline data of the included studies, including study ID, country, sample size, age, and sex of the included patients. The following outcomes were extracted: International Knee Documentation Committee (IKDC) score, Lysholm, Tegner, subjective IKDC, range of motion (ROM), Harner’s vertical jump test, Daniel’s one-leg hop test, Lachman test, pivot shift test, and anterior drawer test (ADT).
This process was conducted using Cochrane’s Risk of Bias Assessment 2 tool (Rob-2).17 Random sequence creation, allocation concealment, participant and staff blinding, outcome assessor blinding, incomplete outcome data, selective result reporting, and additional bias (fund and baseline balance) were components of the evaluation. Every field was classified as having a low risk of bias, high risk of bias, or some bias issues.
All statistical procedures were performed using Review Manager software version 5.4.18 We conducted a pooled analysis of continuous variables using mean difference (MD), while for dichotomous variables, we used the pooled analysis of odds ratio (OR) by extraction of event and total. We used the random effects model for heterogeneous outcomes and the fixed effects model for homogeneous outcomes, with a confidence interval (CI) of 95% and a p-value of 0.05. I2 was used to measure the heterogeneity at a p-value of 0.05.
The search process yielded a total of 1223 studies and after removal of duplicates, 754 articles were eligible for title and abstract screening. After which, 20 articles were included for full-text screening, and finally 14 articles6,19–31 were included in our meta-analysis ( Figure 1).
Regarding the risk of bias assessment of the included RCTs based on Rob-2, eight studies had a low risk of bias, two had a high risk of bias, and four had some concerns (Supplementary Figure 1).
Most of the included studies were conducted in China, with 1339 patients undergoing surgery using autografts and 1519 patients undergoing surgery using allografts. The mean age of the participants ranged from 24 to 32.8 years old ( Table 1).
Autograft showed better outcomes regarding IKDC score compared to allograft with MD of 1.89 (95%CI: 0.37, 3.42. p=0.02), and I2=66%, p=0.002 ( Figure 2). It was also associated with better Lysholm and Tegner scores with MD of 1.48 2 (95%CI: 0.19, 2.77, p=0.02), and 0.32 (0.15, 0.49, p=0.0003), respectively, with no significant heterogeneity ( Figures 3, and 4).
Autografts were associated with a higher OR of grade 0 in the Lachmann score with an OR of 2.6 (95%CI: 1.26, 5.38, p=0.01), while allografts had higher odds of having grades 2 and 3 (OR, 0.53 (95%CI, 0.31, 0.93; p=0.03), and 0.48 (95%CI: 0.27, 0.84, p=0.01), respectively (Supplementary Figure 2).
In addition, autograft was associated with higher odds of grade 0 in the Pivot shift test with OR of 2.41 (95%CI: 1.64, 3.55, p<0.00001), while allograft was associated with higher odds of grades 1, and 2 with OR of 0.52 (95%CI: 0.35, 0.77, p=0.001), and 0.22 (95%CI: 0.07, 0.65, p=0.006), respectively (Supplementary Figure 3).
Moreover, autograft was associated with a higher chance of grade 0 in the ADT group with an OR of 3.09 (95%CI: 1.19, 8.03, p=0.02) compared to allograft, which was associated with a higher chance of grade 2 with an OR of 0.36 (95%CI: 0.15, 0.88, p=0.02) (Supplementary Figure 4).
On the other hand, no statistically significant differences were observed when comparing the subjective IKDC, ROM, Daniel’s one-leg hop test, and Harner’s vertical jump test between autografts and allografts (Supplementary Figures 5,6, 7 and 8).
The current study aimed to comprehensively gather evidence from RCTs comparing the role of autografts and allografts in ACL surgeries. Our findings demonstrated that autografts were associated with better outcomes than allografts based on the IKDC score, Lysholm score, Tegner score, Lachmann scale, pivot shift test, and ADT. However, no difference was observed in the different grades of subjective IKDC, ROM, Daniel’s one-leg hop test, and Harner’s vertical jump test between the autograft and allograft groups.
This shows a better profile of the autograft regarding the functional outcomes (IKDC and Tegner), in addition to the levels of satisfaction (Lysholm). In addition, the stability improved more in autografts than in allografts, as shown by the significant differences observed in the pivot shift test.
Research reports varying rates of clinical failure following ACL restoration; allografts experience a higher percentage of clinical failure than autografts. For instance, Prodromos et al.32 found that the failure rate for autografts was 5%, whereas the failure rate for allografts was 14%. In their group, autograft failure rates were 3.5% and allograft failure rates were 8.9% according to Kaeding et al.33 In a meta-analysis by Kan et al.,34 the autograft group experienced significantly less clinical failures. Previous studies by Prodromos et al.,32 Yao et al.,35 and Zeng et al.36 revealed that autografts experienced much lower rates of clinical failure than allografts. There was no discernible difference in clinical failure between autografts and allografts according to a prior study by Hu et al.37 The inclusion of multiple nonrandomized controlled trials by Hu et al. may account for the discrepancy in the results between their meta-analysis and that of Kan et al. Previous research has shown that the risk of graft failure is higher in younger individuals with ACL allograft restoration.33 However, Kan et al.34 found no association between clinical failure and the mean age. Additional studies involving individuals in their late teens and early 20s are necessary to confirm the outcomes of autograft versus allograft ACL restorations.
The impact of preservation and sterilization methods on the structural integrity of allograft ligaments is a topic of debate. In addition to some cutting-edge commercial tissue disinfection and sterilization procedures, such as the BioCleanse tissue processing system (RTI Surgical, Alachua, FL), these methods include irradiation, cryopreservation, and freeze-drying. The use of radiation is the most contentious subject. Similar results of ACL reconstruction with autograft versus non-irradiated allograft were obtained in a study by Zeng et al.,36 where subgroup analyses based on whether irradiation was used were performed. Comparatively, noted differences were insignificant in the overall IKDC level, Lysholm score, clinical failure rate, pivot-shift test, Lachman test, Daniel 1-leg hop test, instrumented laxity test, or Tegner score. These findings imply that non-irradiated allografts for ACL restoration can be considered viable substitutes for autografts. McGuire and Hendricks38 also found no evidence of a substantial difference between systemic and local immune responses that could have a negative impact on clinical outcomes and graft healing. In addition, Rihn et al.39 reported no unfavorable clinical outcomes. However, numerous studies have also asserted that patients bear intolerable dangers from unsterilized grafts.40 Sterilization, whether it involves radiation or not, is thought to have a significant impact on the results of allogeneic ACL restoration. In terms of the Lysholm score, clinical failure rate, pivot-shift test, Lachman test, instrumented laxity test, and Tegner score, autografts outperformed irradiation allografts in terms of clinical outcomes in the study by Zeng et al.,36 which is similar to our findings. With regard to knee stability and function, autografts outperformed irradiation allografts in clinical trials. One argument could be that when such a graft is utilized to rebuild the ACL, the biomechanical characteristics altered by radiation could be harmful to the graft function and have an impact on the clinical results. Researchers have focused a lot of attention on the major drawbacks of non-irradiated allograft disease transmission. For human immunodeficiency virus (HIV) and hepatitis C, the estimated chances of infection were 1 in 421,000 and 1 in 1.6 million, respectively.41 Despite the low infection rate, once an infection develops, its consequences are severe. Thus, it is desirable to have alternate sterilization methods that do not interfere with the biomechanical qualities of grafts and offer total protection against viral and bacterial infections. When compared to electron beam and gamma irradiation alone, Hoburg et al.42 discovered that the fractionation of high-dose electron beam irradiation could considerably enhance the viscoelastic and structural characteristics of bone-patellar tendon-bone grafts while preserving the degree of non-irradiated control. This technology could be used as a significant substitute for standard procedures for sterilizing soft tissue allografts.
This study included all available RCTs that compared allografts with autografts for ACL construction. We also included all structural, functional, stability, and satisfaction outcomes measured by different scales, which showed the superiority of the autograft. However, some limitations exist, including different types of allografts and autografts, in addition to limited data regarding the effect of age and different techniques on the success rate of the procedures. Therefore, large future RCTs are required to investigate these issues and provide deep insights into their associated factors.
Compared to allografts, the use of autografts in ACL reconstruction is associated with better functional, structural, stability, and satisfaction outcomes, as observed by statistically significant differences in IKDC, Tegner, Lachmann, Pivot shift test, and Lysholm. However, no differences were observed in ROM, Daniel’s one-leg hop test, or Harner’s vertical jump.
No data are associated with this article.
figshare: Autografts versus Allografts for Anterior Cruciate Ligament (ACL) reconstruction: Comparison of clinical outcomes by pooled meta-analysis of randomized controlled trials, https://doi.org/10.6084/m9.figshare.27894315.v2.43
This project contains the following extended data:
• Figure 1: PRISMA flow diagram of database searching and screening
• Figure 2: Comparison between autograft and allograft regarding IKDC
• Figure 3: Comparison between autograft and allograft regarding Lysholm score
• Figure 4: Comparison between autograft and allograft regarding Tegner score
• Supplementary figure 1: Risk of bias assessment of the included randomized controlled trial using Rob-2 tool
• Supplementary figure 2: Comparison between autograft and allograft regarding Lachmann score
• Supplementary figure 3: Comparison between autograft and allograft regarding Pivot shift test
• Supplementary figure 4: Comparison between autograft and allograft regarding Anterior drawer test
• Supplementary figure 5: Comparison between autograft and allograft regarding IKDC grades
• Supplementary figure 6: Comparison between autograft and allograft regarding range of motion grades
• Supplementary figure 7: Comparison between autograft and allograft regarding Daniel’s one-leg hop test
• Supplementary figure 8: Comparison between autograft and allograft regarding Harner’s vertical jump test
• Figures: All figures in Microsoft word file
• Supplementary figures: All supplementary figures in Microsoft word file
• Tables: Contains Table 1 (Baseline characteristics of the included studies)
• PRISMA_2020_Checklist: PRISMA Checklist
• Protocol: Our protocol
Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).
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