Quantifying the differential functional behavior between the medial and lateral meniscus after posterior meniscus root tears.

Meniscus tears of the knee are among the most common orthopedic knee injury. Specifically, tears of the posterior root can result in abnormal meniscal extrusion leading to decreased function and progressive osteoarthritis. Despite contemporary surgical treatments of posterior meniscus root tears, there is a low rate of healing and an incidence of residual meniscus extrusion approaching 30%, illustrating an inability to recapitulate native meniscus function. Here, we characterized the differential functional behavior of the medial and lateral meniscus during axial compression load and dynamic knee motion using a cadaveric model. We hypothesized essential differences in extrusion between the medial and lateral meniscus in response to axial compression and knee range of motion. We found no differences in the amount of meniscus extrusion between the medial and lateral meniscus with a competent posterior root (0.338mm vs. 0.235mm; p-value = 0.181). However, posterior root detachment resulted in a consistently increased meniscus extrusion for the medial meniscus compared to the lateral meniscus (2.233mm vs. 0.4705mm; p-value < 0.0001). Moreover, detachment of the posterior root of the medial meniscus resulted in an increase in extrusion at all angles of knee flexion and was most pronounced (4.00mm ± 1.26mm) at 30-degrees of knee flexion. In contrast, the maximum mean extrusion of the lateral meniscus was 1.65mm ± 0.97mm, occurring in full extension. Furthermore, only the medial meniscus extruded during dynamic knee flexion after posterior root detachment. Given the differential functional behaviors between the medial and lateral meniscus, these findings suggest that posterior root repair requires reducing overall meniscus extrusion and recapitulating the native functional responses specific to each meniscus.

Introduction

The menisci are fibrocartilage structures that distribute load across the knee joint’s articular cartilage during activity [1]. Tears of the meniscus are among the most common orthopedic knee injuries, with an annual incidence of approximately 61 per 100,000 persons [2]. Posterior root tears (PRTs) are a specific type of meniscus tear resulting in the detachment of the posterior root ligament resulting in extrusion of the meniscus from between the femur and tibia [3]. Previous studies demonstrate biomechanical alterations of the knee after PRT resulting from increased meniscus extrusion leading to subsequent osteoarthritis (OA) [4-6]. Posterior root repair offers a promise of restoring normal contact forces across the articular cartilage [5] and improving clinical outcomes in the short term [7]. However, a critical challenge to be resolved is the recapitulation of native meniscus function and prevention of knee OA [8-10]. There have been considerable efforts to minimize meniscus extrusion by improving surgical techniques and fixation strength of the suture repair; however, there remains a high rate of postoperative meniscus extrusion [4, 11–14].

Furthermore, recent studies suggest that there are essential differences in PRTs between the medial and lateral meniscus. For instance, medial meniscus PRTs are associated with degenerative changes and advanced age [15], while lateral meniscus PRTs are most commonly associated knee trauma, such as anterior cruciate ligament ruptures [16]. In a recent clinical study comparing the medial and lateral meniscus PRTs, Koo et al. found a higher rate and increased amount of meniscus extrusion of the medial meniscus compared to the lateral meniscus on static magnetic resonance imaging (MRI) after PRTs [1].

To demonstrate the effects of knee activity on meniscus motion, here we compared meniscus extrusion of the medial and lateral meniscus during axial compression and dynamic motion before and after detachment of the posterior root. The objective of this study was to understand essential differences in response to PRTs between the medial and lateral meniscus.

Materials and methods

Cadaveric dissection and posterior root detachment

The University of Wisconsin-Madison Institutional Review Board approved the study under 2016–1316, and as a cadaveric study with anonymous data analysis, written consent was not required. Human knees were obtained from the Anatomic Gifts Registry. Knee specimens were cleared of soft tissue leaving the capsule intact as previously described by Allaire et al [8]. The femur length was reduced to 6-inches and the tibia length to 4-inches to accommodate testing. Holes were drilled through the distal end of the bones for pin placement to help fixate the potting to the bone. Shafts were pinned with 3.2-mm steel pins and potted in tubular molds using auto body filler. The molds were 44-mm in diameter for the femur and 56-mm for the tibia to fit in custom fabricated grips. The condition of a torn posterior meniscus root was simulated by transection of the meniscus within 1-cm of the root attachment using an arthroscopic meniscus knife as described by LaPrade et al [17]. For the lateral meniscus, the meniscal femoral ligaments were left intact.

Equipment and setup

Custom fabricated grips were attached to an MTS 858 Bionics servo-hydraulic test system (Fig 1). The lower grip was fabricated using an axle system to release the knee rotational (medial/lateral) degree of freedom. The axle system was then mounted on two crossed roller slides (Deltron NBT-6160A) in an X-Y arrangement to allow degree of freedom release of the medial/lateral and anterior/posterior planes (Fig 1A). Data acquisition included the specimen load, actuator displacement, and meniscus displacement, using a Lord Microstrain model M-DVRT-6 transducer (M-DVRT-6, 6.0mm stroke micro-miniature DVRT linear displacement Transducer, and DEMOD-DC, Miniature DC input, DC output signal conditioner, LORD Corporation, 459 Hurricane Lane, Suite 102, Williston, Vermont 05495) (Fig 1B). Data were acquired using a Data Translation 16-bit digital to analog converter. The force generated during each testing protocol was recorded in real-time. The upper grip was fabricated to allow positioning the knee in the range of zero to one hundred degrees of flexion for mechanical testing during a dynamic range of motion (Fig 1C).

Fig 1

Photographs of MTS testing setup.

(A) Custom base (yellow bidirectional arrow) allowed for three degrees of freedom, and femoral potting (top) allowed for control of knee flexion. (B) Photograph of cadaveric testing. A displacement sensor (white arrow) was placed at the posterior meniscus root attachment 1-cm from the insertional footprint and in the tibia’s periosteum at the knee’s midline (capsule reflected only for demonstration purposes). (C) Photograph demonstrating testing setup during knee range of motion. An electronic goniometer arm (red star) captured real-time (60 Hz) knee angle during range of motion testing. (D) Photograph of the calibrated femoral potting (top) used for axial compression testing.

Testing protocols

Protocols simulated clinical knee activities during weight-bearing, including axial compression loading and passive non-weight-bearing dynamic range of motion. The amount of load delivered across the knee simulated that of a 75-kg person [18-20]. Specimens were tested in the following sequence: posterior root intact and posterior root detached. Axial compression load: Testing was performed in load control in the axial direction. A ramp to a constant load was completed to simulate a load from 25-N preload to full weight-bearing (1800-N) at 0.1-second ramp to set load, with a manual return to preload in full knee extension (0-degrees of knee flexion). A sinusoidal cyclic load to simulate a walking gait at 20-cycle compressive ½ cycle sine wave, 25-N to set load with 1-sec cycle (0.3-second down, 0.3-second up, 0.4-second pause to stimulate swing phase of gait). This test was performed across 0-, 30-, 45-, 60- and 90-degrees of knee flexion. Dynamic non-weight-bearing range of motion: Each knee was taken through a range of motion from 0- to 100-degrees of flexion. Meniscus extrusion was linked to range of motion data detected with a calibrated custom electronic goniometer in real-time.

Statistical analysis

Means and standard deviations or standard error of the means were calculated. Between group comparisons were performed using a Student’s t-test for two groups and analysis of variance (ANOVA) for more than two groups. Pairwise comparisons and post-hoc adjustments were performed if the ANOVA model was statistically significant. Linear regression was used to model the relationship between knee flexion and meniscus extrusion. A p-value < 0.05 was considered statistically significant. Calculations were performed using GraphPad Prism 9.0.1 for Mac (San Diego, CA, USA).

Priori power analysis

Based upon our preliminary data demonstrating a variance of 3.0-mm between groups and a variance of 1.27-mm within groups, a total of 3.27 meniscus roots per group would need to be tested to achieve 80% with a balanced one-way ANOVA with a 5% significance level.

Results and discussion

This study used a total of eleven cadaveric specimens (six for testing the medial meniscus and five for testing the lateral meniscus). There were six males and five females, seven right knees and four left knees, with a mean age of 69.7 years (range: 36–84 years) (S1 Table). The overall amount of extrusion with a competent posterior meniscus root did not differ between the medial and lateral meniscus. However, overall medial meniscus extrusion was increased compared to the lateral meniscus in response to detachment of the posterior root (Table 1). Data is available at doi:10.5061/dryad.1ns1rn8v9 [21].

Table 1

Summary data for medial and lateral posterior root extrusion.

Condition	Medial Meniscus	Lateral Meniscus	p-valueb
Intact	0.338 ± 0.296	0.235 ± 0.242	0.181
Torn	2.233 ± 1.270	0.4705 ± 0.566	0.001

a Data represents mean ± standard deviation. n = 11 aggregated across all testing conditions.

b Student’s t-test comparing medial meniscus and lateral meniscus displacement. Bold indicates statistical significance.

With a competent posterior root, a constant axial compressive load across the knee in full extension result in a mean extrusion of 0.436mm (± 0.459mm) for the medial meniscus and 0.270mm (± 0.250mm) for the lateral meniscus (p-value = 0.893). Detachment of the posterior meniscus root resulted in increased meniscus extrusion for both the medial (Fig 2A) and lateral meniscus (Fig 2B). Extrusion of the medial meniscus was increased compared to the lateral meniscus after posterior root detachment (Fig 2C).

Fig 2

Comparison of meniscus extrusion between the medial and lateral meniscus under constant axial compression load.

(A) Meniscus extrusion comparing intact versus detached condition for the medial meniscus. (B) Meniscus extrusion comparing intact versus detached condition for the lateral meniscus. (C) Comparison of meniscus extrusion between the medial and lateral meniscus. n = 5 cadavers aggregated in triplicate. ns = not statistically significant; **** p-value < 0.0001.

To test the hypothesis that meniscus extrusion is a function of knee flexion, knees were subjected to cyclic axial compression loading at knee flexion angles at 0-, 30-, 45-, 60-, and 90-degrees. Overall, the mean extrusion of an intact medial meniscus was seen at 45-degrees of knee flexion (0.7235mm ± 0.298mm). However, the mean extrusion of an intact medial meniscus was not dependent on the degree of knee flexion (p-value = 0.304). Conversely, detachment of the posterior root resulted in an increase in extrusion of the medial meniscus across all tested degrees of knee flexion (Fig 3A). The greatest extrusion was recorded at 30-degrees of knee flexion (4.000 ± 01.259mm; p-value = 0.015). Loading the knee in axial compression at various degrees of knee flexion resulted in no difference in extrusion of an intact lateral meniscus (p-value = 0.787). Knee flexion of 45-degrees resulted in the greatest extrusion of an intact lateral meniscus (0.235mm ± 0.007mm). In agreement with the previous findings of extrusion of the lateral meniscus after posterior root detachment under constant axial compression loading in full knee extension, cyclic loading resulted in an increase in lateral meniscus extrusion after posterior root detachment at 0-degrees of knee flexion. However, none of the other knee flexion categories resulted in increased extrusion of a detached posterior lateral meniscus root compared to an intact root (Fig 3B). Although there was no difference in extrusion of an intact medial meniscus posterior root compared to a lateral meniscus, detachment of the posterior root resulted in increased extrusion of the medial meniscus compared to the lateral meniscus at all degrees of knee flexion (Fig 3C). Thirty-degrees of knee flexion resulted in the greatest difference between the medial and lateral meniscus extrusion of a torn posterior root (3.805mm ± 0.0.505mm; p-value < 0.0001).

Fig 3

The effects of knee flexion on meniscus extrusion during axial compression loading.

(A) Comparison of meniscus extrusion between intact and detached posterior meniscus root of the medial meniscus. (B) Comparison of meniscus extrusion between intact and detached posterior meniscus root of the lateral meniscus. (C) Comparison of meniscus extrusion between medial and lateral meniscus. n = 5. Titles represent the angle of knee flexion in degrees. ns = not statistically significant; * p-value < 0.05; ** P-value < 0.01; **** p-value < 0.0001.

To test the hypothesis that cyclic range of knee motion without axial compression load results in an increase in meniscus extrusion, cadaveric knees were subjected to dynamic range of motion from full extension to maximum allowable flexion capturing meniscus extrusion and range of motion with an electric goniometer in real-time. There was a direct linear relationship between increasing knee flexion and meniscus extrusion with an intact posterior root for both the medial and lateral meniscus (Fig 4A). However, detachment of the posterior root resulted in a direct nonlinear relationship between increasing knee flexion and meniscus extrusion for the medial meniscus with a maximum of 4.59mm of extrusion occurring at 19.4-degrees of knee flexion and 2.69mm occurring at 63.8-degrees of knee flexion for the lateral meniscus (Fig 4B). In comparison, detachment of the lateral meniscus posterior root resulted in increased variability in meniscus extrusion, but a direct linear relationship between knee flexion and meniscus extrusion was preserved (Fig 4B). Means and standard deviations were calculated and compared between the medial and lateral meniscus for each 10-degrees of knee flexion (Fig 4C). The mean extrusion of an intact posterior medial root was greater than an intact posterior lateral root for knee flexion greater than 40-degrees, although this did not reach the threshold of statistical significance. However, detachment of the posterior root resulted in increased extrusion of the medial meniscus compared to the lateral meniscus for knee flexion greater than 10-degrees.

Fig 4

The effects of cyclic range of motion without axial compression on meniscus extrusion.

(A) Scatterplot of the relationship of knee range of motion and meniscus extrusion for the medial and lateral meniscus with an intact posterior root. (B) Scatterplot of the relationship of knee range of motion and meniscus extrusion for the medial and lateral meniscus with the posterior root detached. (C) Comparison of meniscus extrusion between the medial and lateral meniscus. n = 5. Top left: Regression equation represented by the red line. **** p-value < 0.0001.

Tears of the posterior meniscus roots account for up to 21% of all meniscus tears [3]. PRTs of the medial meniscus treated with partial meniscectomy have a conversion rate to total knee replacement of up to 35% [22], and PRTs of the lateral meniscus are associated with anterior crucial ligament tears [1, 16]. The stark association between PRT and clinically progressive disease is purportedly due to the functional consequences, namely meniscus extrusion and the resultant abnormal contact stresses across the knee joint [8, 23]. For example, one study found that a PRT of the medial meniscus caused a 25% increase in peak contact pressure compared to an intact meniscus [8]. A more recent study used a finite element analysis to demonstrate that a PRT of the lateral meniscus caused maximum contact pressure and contact stress values approaching that found after total lateral meniscectomy [23].

Although medial meniscus PRTs treated without repair are associated with progressive joint degeneration, results of surgical repair are not uniformly superior. For example, after medial meniscus repair, MRI evaluation has demonstrated continued meniscus extrusion [24] and low healing rates [25]. Similarly, the paucity of research regarding the clinical implications of PRTs of the lateral meniscus demonstrates lax healing of up to 21% [26], and a recent systematic review was unable to conclude whether root repair restored the functional hoop stress characteristics required of the meniscus to distribute compression forces across the knee evenly [27]. Furthermore, a recent study found characteristic clinical differences between the medial and lateral meniscus PRTs, including the association of trauma in lateral meniscus PRTs, and older age and higher grade of OA changes of the knee in medial meniscus PRTs [1]. Although surgical repair strategies can repair the posterior root to the tibia, the recapitulation of meniscus function remains a significant challenge in clinical orthopedics. Here we examined the behavior of the meniscus in response to both axial compression load and dynamic range of motion of the knee.

Our model successfully captured the amount of meniscus extrusion under axial compression and knee motion, as evidenced by the increased extrusion amount after detachment of the posterior root in both medial and lateral menisci. Interestingly, the findings of increased meniscus extrusion after detachment of the posterior root in both the medial and lateral meniscus suggest the loss of structural integrity and the possibility of compromised resistance to hoop stress after PRTs of both medial and lateral meniscus. Indeed, the detection of meniscus extrusion of MRI has been reported to be evident after PRT clinically [1, 4, 28]. Moreover, the degree of extrusion is associated with the progression of articular cartilage damage for the medial meniscus [10].

Here, we found no difference in meniscus extrusion with an intact posterior root between the medial and lateral meniscus under a constant axial compression load across a fully extended knee. However, detachment of the posterior root resulted in a significant increase in both the medial and lateral meniscus extrusion compared to an intact posterior root. Interestingly, extrusion of the medial meniscus was increased compared to the lateral meniscus after posterior root detachment. These results are consistent with Koo et al., who reviewed MRIs of patients with PRTs and found mean meniscal extrusion of 4.2mm for the medial meniscus and 0.9mm for the lateral meniscus [1].

The effects of knee flexion on meniscus extrusion are not well described. Previous clinical research has examined MRI findings after PRTs [1, 4, 28–30], and biomechanical protocols aim to test suture repair constructs in a fixed knee position [5, 12, 31–35]. Again, we found small amounts of extrusion when the posterior root was intact with no difference between the medial and lateral meniscus regardless of knee flexion angle. Similarly, there were differences in the medial and lateral meniscus behavior after detachment of the posterior root. The medial meniscus extrusion increased after posterior root detachment at every knee flexion angle. The greatest amount of extrusion was found at 30 degrees of knee flexion (mean 4.00mm ± 1.26mm). However, the lateral meniscus extruded the greatest amount after posterior root detachment in full extension (mean 1.645mm ± 0.971mm). Moreover, we found that lateral meniscus extrusion did not increase significantly after posterior root detachment when subjected to axial compression load at greater angles of knee flexion. Compared to the lateral meniscus, the medial meniscus demonstrated increased extrusion at all knee flexion angles (mean difference 2.49mm ± 0.90mm). These findings suggest that compared to the lateral meniscus, extrusion of the medial meniscus may increase during axial compression load with the knee flexed, such as what may occur during ambulation. Moreover, static MRI protocols with the knee in full extension may underestimate the degree of extrusion in PRTs of the medial meniscus. On the other hand, these data suggest that axial compression load in flexed knee angles results in less extrusion in PRTs of the lateral meniscus.

While this model successfully demonstrates that PRTs increase meniscus extrusion, particularly in the medial meniscus, under axial compression load, we also examined the behavior of the meniscus when subjected to dynamically flexing the knee. Similar to axial compression load testing results, dynamic flexion of the knee resulted in differing behavior of the medial compared to the lateral meniscus with an incompetent posterior root. We found that when the posterior root was intact and competent, there was a direct linear relationship between knee flexion and meniscus extrusion for both the medial and lateral meniscus. Detaching the posterior root resulted in a nonlinear relationship between knee flexion and meniscus extrusion for the medial meniscus. Although this relationship is complex, it is clear that across lower degrees of knee flexion, meniscus extrusion increases rapidly and plateaus at knee flexion angles greater than about 50 degrees. The lateral meniscus responded differently after posterior root detachment. Although there was more scatter and an increase in the average extrusion during knee range motion with an incompetent posterior root, a direct linear relationship was preserved. Furthermore, compared to the medial meniscus, the amount of extrusion was significantly less for the lateral meniscus at knee flexion angles greater than 10-degrees.

Together these findings suggest that PRTs compromise the functional integrity of both menisci and result in an increase in meniscus extrusion compared to a competent posterior root consistent with previous biomechanical studies. For example, Camarda et al. found that using three single loops enhanced the biomechanical behavior for suture repair [31]. Similarly, Daney et al. used a cadaveric model and found that using a centralization suture reduced extrusion and restored tibiofemoral contact mechanics [12]. However, we found that the behavior of meniscus extrusion differed between the medial and lateral meniscus. Indeed, these findings suggest that while reducing meniscus extrusion is a requirement of suture repair, it may not be sufficient to recapitulate native function.

Here, we identified that the essential differences after PRTs between the medial and lateral meniscus are the extrusion and behavior of extrusion during motion. This study is the first to directly compare the extrusion between the medial and lateral meniscus with both a competent and incompetent posterior root condition. Moreover, we demonstrate that a nonlinear relationship exists in response to PRTs in the medial meniscus, which may be critical in optimizing repair following PRTs. Finally, we also demonstrate that the extrusion of the lateral meniscus is variable and results in significantly less extrusion in response to PRTs. The clinical significance of these findings are that PRTs of the lateral meniscus may not result in the same biomechanical changes as is found after PRTs of the medial meniscus, assuming a stable ACL and meniscofemoral ligament. While cadaveric tissue may not replicate that of living tissue, our model had no occurrences of tissue failure.

Similarly, we recognize that this is a “time-zero” study and does not directly consider the effects of any biologic healing, concomitant surgical procedures (e.g., anterior cruciate ligament reconstruction), or lower extremity alignment variability. However, at present, the characterization of meniscus extrusion in vivo is limited. Despite these limitations, this study further demonstrates the need to improve the fixation of posterior meniscus roots, particularly following medial root tears.

Conclusions

Minimal extrusion occurs with a competent posterior meniscus root for both the medial and lateral menisci. The functional behavior associated with a detached posterior meniscus root are different between the medial and lateral meniscus. While strictly limiting the amount of meniscus extrusion after PRTs is necessary, it may not be sufficient to recapitulate native meniscus function.

Descriptive data of tested specimens.

yr = age of the specimen in years.

(DOCX)

Click here for additional data file.

3 Sep 2021

PONE-D-21-16714Quantifying the Functional Consequences Between the Medial and Lateral Meniscus After Posterior Meniscus Root TearsPLOS ONE

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Reviewer #1: Comment on the manuscript Number PONE-D-21-16714

Quantifying the Functional Consequences Between the Medial and Lateral Meniscus After Posterior Meniscus Root Tears

• The idea of the research is interesting for the readers of the journal. The authors used a cadaveric model to compare the effect of the meniscal root detachment of the medial and lateral meniscus on the meniscal extrusion. Using a cadaveric model, the test was carried out on both medial and lateral menisci during constant axial compression load, simulated axial load in various knee flexion angles (0-90°) as well as simulated non-weightbearing ROM (0-100°). The test was repeated while the meniscal root intact and after detaching the posterior meniscal roots.

• The study methodology is very clear. The results are reported in sufficient details. The statistical analysis used in the study is sound.

• The article is written in a clear and simple English language. I did not found any spelling or grammatical mistakes.

• With exception of figure 1, the included Diagrams and table are informative.

• The abstract is short and comprehensive and summarizes the important points of the article.

• The authors reported the weak points and the limitation of the study.

• Only few improvement suggestions:

­ line 195: I think the authors meant lateral meniscus not medial.

­ Figure 1 is of low quality and very low resolution/Pixel. For example you cannot read the flexion angle written in part C. I recommend to replace with pictures of higher resolution.

• Decision:

According to the guidelines of the critical appraisal, I recommend to accept this Article for publication after considering the previously mentions improvement recommendations.

Reviewer #2: Quantifying the Functional Consequences Between the Medial and Lateral Meniscus

After Posterior Meniscus Root Tears

Aim of the study:

The objective of this study was to understand essential differences in the response to posterior root tears (PRTs ) between the medial and lateral meniscus.

the authors conducted a cadaveric study to quantify the subluxation of both medial and lateral meniscus both with intact and with torn posterior root. This quantification was performed in 3 different settings; 1: axial compression load, 2: varying degrees of flexion (0-90°) with sinusoidal loading to mimic gait 3: dynamic flexion with no load (non weight bearing). The degree of subluxation was compared both between the intact and torn posterior horn within each meniscus and across both menisci.

This is a novel work with interesting findings. They provided a good introduction. The methodology was described in details. Statistical analysis was also described. Power calculation for sample size was conducted. The results are detailed and discussed adequately. Limitations of the study were also discussed.

points to be improved.

The title should be modified for example : Quantifying the differential Functional Consequences Between the Medial and Lateral Meniscus

After Posterior Meniscus Root Tears.

The abstract could be more simple and highlight the novelty of this work. It should be more attractive to let the reader continue into the article. The conclusion that functional consequences of extrusion are more significant

for the medial meniscus than that of the lateral meniscus however can not be simply made based on the degree of meniscus subluxation. Other factors that were not measured in this work such as changes in stress distribution across the joint surface with PRT could make such conclusion possible.

The software used for statistical analysis should be mentioned

In the results section, how was the overall subluxation in table 1 measured? Please provide a supplementary table with all measures for all specimens.

Line 176, 177 : The greatest extrusion was recorded at 30-degrees of knee flexion (4.000 ± 01.259mm), please add the statistical significance . also in the same paragraph ensure that the statistical significance of each difference (which can be luckily found in the figures) is always mentioned

Line 195: lateral meniscus instead of medial ?

In the conclusion, as mentioned above in the comment on the abstract, no functional consequences of extrusion were tested here, as for example the differential stress distribution across the joint in response to this measured meniscus subluxation. So the authors can not make this assumption. The direct fact that can be concluded here is obviously the significant subluxation of medial meniscus in the different given testing situations in comparison to the lateral meniscus.

**********

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Reviewer #1: Yes: Ayman F. AbdelKawi

Reviewer #2: Yes: Dr. Mohammad Masoud

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26 Sep 2021

Rebuttal

Manuscript ID # PONE-D-21-16714

Title: Quantifying the Differential Consequences Between the Medial and Lateral Meniscus After Posterior Meniscus Root Tears

We would like to thank the reviewers for their insightful comments and suggestions. We have taken the suggestions into consideration and revised the manuscript accordingly to address each of the reviewers’ questions and concerns.

Editor Comments:

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf.

Author’s Response:

We appreciate the editor’s critical feedback of the formatting requirements and we have reviewed the requirements provided in the above link. To address the concern, we have revised the manuscript accordingly.

Author’s Action:

We have changed the title to sentence case, added the location of the laboratory where the experiments were performed, removed the symbols denoting ‘current address’ as it is the same as the affiliation denoted by the numerical superscripts, and we have removed the corresponding author’s name and replaced it with ‘* Corresponding author,’ as described in the formatting requirement template.

2. Please include your full ethics statement in the ‘Methods’ section of your manuscript file. In your statement, please include the full name of the IRB or ethics committee who approved or waived your study, as well as whether or not you obtained informed written or verbal consent. If consent was waived for your study, please include this information in your statement as well.

Author’s Response:

We appreciate the editor’s critical feedback of the requirements for IRB or ethics approval. To address the concern, we have revised the manuscript by including the IRB approval and waiver of informed consent.

Author’s Action:

While the IRB approval organization and number was provided in the ethics statement in ‘editor manager,’ we have added the following to the beginning of the materials and methods section: “The University of Wisconsin-Madison Institutional Review Board approved the study under 2016-1316 and as a cadaveric study with anonymous data analysis written consent was not required.”

3. We note that the grant information you provided in the ‘Funding Information’ and ‘Financial Disclosure’ sections do not match.

When you resubmit, please ensure that you provide the correct grant numbers for the awards you received for your study in the ‘Funding Information’ section.

Author’s Response:

We appreciate the editor’s critical feedback of the requirements for the Funding Information and Financial Disclosure and we understand the importance of this information. To address this concern, we have revised the information accordingly and apologize for this confusion.

Author’s Action:

We have removed the funding information within the text of the manuscript that was previously under ‘Acknowledgements’ to comply with the formatting described within the pdf provided titled, “MANUSCRIPT BODY FORMATTING GUIDELINES.” The funding information provided within the online submission system is appropriate funding for this study. The additional funding information can be found in the revised cover letter.

4. Thank you for stating the following in the Acknowledgments Section of your manuscript:

Dr. Walczak was supported by NIH UW T32 AG000213-26, NIH UW TL1 TR000429, NIH UW UL1 TR000427, and UW-Madison Department of Orthopedic Surgery’s Freedom of Movement Award. No conflicts of interest, financial or otherwise, are declared by the authors.”

We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form.

Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows:

“B.E.W. was supported by NIH UW T32 AG000213-26, NIH UW TL1 TR000429, NIH UW UL1 TR000427, and UW-Madison Department of Orthopedic Surgery’s Freedom of Movement Award.”

Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

Author’s Response:

Again, we appreciate and thank the editorial review process for this critical feedback and again we understand this importance of this information, both in regards to accuracy and format. To address this concern, we have revised the information accordingly and apologize for this confusion.

Author’s Action:

We have removed the funding information within the text of the manuscript that was previously under ‘Acknowledgements’ to comply with the formatting described within the pdf provided titled, “MANUSCRIPT BODY FORMATTING GUIDELINES.” We have placed in the ‘Acknowledgements’ section the person who assisted the work and she has approved her recognition in the acknowledgement section. Furthermore, the following is how we would like the Funding Statement to read, and is listed as ordered in the Funding Information section of the online submission site, “B.E.W. was supported by National Center for Advancing Translational Sciences under award numbers: UL1 TR000427, TL1 TR000429, and TL1 TR002375, National Institute on Aging under award number: T32 AG000213, and the Department of Orthopedic Surgery of the University of Wisconsin-Madison’s Freedom of Movement Award. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.”

5. Thank you for stating the following in the Competing Interests section:

“I have read the journal's policy and the authors of this manuscript have the following competing interests: B.E.W. is a consultant for AlloSource and G.S.B. is a consultant for Conmed.”

Please confirm that this does not alter your adherence to all PLOS ONE policies on sharing data and materials, by including the following statement: ""This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). If there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include your updated Competing Interests statement in your cover letter; we will change the online submission form on your behalf.

Author’s Response:

Again, we appreciate and thank the editorial review process for this critical feedback regarding competing interests. We also want full transparency with any and all potential competing interests.

Author’s Action:

We have added the confirmation that any competing interests declared do not alter adherence to the PLOS ONE policies on sharing data and materials. We have also added into our cover letter the updated competing interest section as described and includes the following additional statement which accurately the author’s relationships, "This does not alter our adherence to PLOS ONE policies on sharing data and materials.”

6. Thank you for stating the following in the Competing Interests section:

“I have read the journal's policy and the authors of this manuscript have the following competing interests: B.E.W. is a consultant for AlloSource and G.S.B. is a consultant for Conmed.”

We note that one or more of the authors are employed by a commercial company: Conmed

a. Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form.

Please also include the following statement within your amended Funding Statement.

“The funder provided support in the form of salaries for authors B.E.W but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.”

If your commercial affiliation did play a role in your study, please state and explain this role within your updated Funding Statement.

b. Please also provide an updated Competing Interests Statement declaring this commercial affiliation along with any other relevant declarations relating to employment, consultancy, patents, products in development, or marketed products, etc.

Within your Competing Interests Statement, please confirm that this commercial affiliation does not alter your adherence to all PLOS ONE policies on sharing data and materials by including the following statement: ""This does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests) . If this adherence statement is not accurate and there are restrictions on sharing of data and/or materials, please state these. Please note that we cannot proceed with consideration of your article until this information has been declared.

Please include both an updated Funding Statement and Competing Interests Statement in your cover letter. We will change the online submission form on your behalf.

Author’s Response:

Again, we appreciate and thank the editorial review process for this critical feedback regarding competing interests. We also want full transparency with any and all potential competing interests.

Author’s Action:

We have added revisions to the cover letter as follows: “I have read the journal's policy and the authors of this manuscript have the following competing interests: B.E.W. is a consultant for AlloSource and G.S.B. is a consultant for Conmed. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The commercial affiliates had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors did not receive payment or renumeration in any form for any efforts related to this work.”

7. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

Author’s Response:

We thank the editor’s response for repository information regarding the data. We have addressed the concerns and provided the relevant DOIs.

Author’s Action:

We have submitted the data to DRYAD and the data for this manuscript can be accessed by linking the following DOI: https://doi.org/10.5061/dryad.1ns1rn8v9.

8. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

Author’s Response:

We understand and have revised the manuscript accordingly.

Author’s Action:

We added the ethical approval of this study in the first sentence in the methods section and removed from any other section.

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Author’s Response:

We thank the reviewer for the positive comment.

Reviewer #2: Partly

Author’s Response:

We thank the reviewer for the essential feedback and address this concern below.

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Author’s Response:

We thank the reviewer for the positive comment.

Reviewer #2: I Don't Know

Author’s Response:

We thank the reviewer for their review.

Author’s Action:

To make complete assurances regarding the analyses, we have published the data from this study and it can be downloaded from the link provided above https://doi.org/10.5061/dryad.1ns1rn8v9.

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Author’s Response:

We thank the reviewer for the positive comment.

Reviewer #2: No

Author’s Response:

We thank the reviewer for the feedback and we have now provided all data to DRYAD and is accessible on DOI: https://doi.org/10.5061/dryad.1ns1rn8v9.

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Author’s Response:

We thank the reviewer for the positive comment.

Reviewer #2: Yes

Author’s Response:

We thank the reviewer for the positive comment.

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Comment on the manuscript Number PONE-D-21-16714

Quantifying the Functional Consequences Between the Medial and Lateral Meniscus After Posterior Meniscus Root Tears

• The idea of the research is interesting for the readers of the journal. The authors used a cadaveric model to compare the effect of the meniscal root detachment of the medial and lateral meniscus on the meniscal extrusion. Using a cadaveric model, the test was carried out on both medial and lateral menisci during constant axial compression load, simulated axial load in various knee flexion angles (0-90°) as well as simulated non-weightbearing ROM (0-100°). The test was repeated while the meniscal root intact and after detaching the posterior meniscal roots.

Author’s Response:

We thank the reviewer for the positive comment.

• The study methodology is very clear. The results are reported in sufficient details. The statistical analysis used in the study is sound.

Author’s Response:

We thank the reviewer for the positive comment.

• The article is written in a clear and simple English language. I did not found any spelling or grammatical mistakes.

Author’s Response:

We thank the reviewer for the positive comment.

• With exception of figure 1, the included Diagrams and table are informative.

Author’s Response:

We thank the reviewer for the positive comment.

• The abstract is short and comprehensive and summarizes the important points of the article.

Author’s Response:

We thank the reviewer for the positive comment.

• The authors reported the weak points and the limitation of the study.

Author’s Response:

We thank the reviewer for the positive comment.

• Only few improvement suggestions:

­ line 195: I think the authors meant lateral meniscus not medial.

Author’s Response:

We thank the reviewer for their critical review of this. The typo is now corrected.

­ Figure 1 is of low quality and very low resolution/Pixel. For example you cannot read the flexion angle written in part C. I recommend to replace with pictures of higher resolution.

Author’s Response:

We thank the reviewer for their feedback and understand the concern and agree that the photographs can be improved.

Author’s Action:

Figure 1 has been revised with photographs of higher resolution for clarity. Additionally, we have added a high-resolution photo of the electronic goniometer capturing real-time angular measurements associated with meniscus extrusion. The figure legend has also been improved with more detail to illustrate the novel methods of this research.

• Decision:

According to the guidelines of the critical appraisal, I recommend to accept this Article for publication after considering the previously mentions improvement recommendations.

Author’s Response:

We thank the reviewer for their positive review.

Reviewer #2: Quantifying the Functional Consequences Between the Medial and Lateral Meniscus

After Posterior Meniscus Root Tears

Aim of the study:

The objective of this study was to understand essential differences in the response to posterior root tears (PRTs ) between the medial and lateral meniscus.

the authors conducted a cadaveric study to quantify the subluxation of both medial and lateral meniscus both with intact and with torn posterior root. This quantification was performed in 3 different settings; 1: axial compression load, 2: varying degrees of flexion (0-90°) with sinusoidal loading to mimic gait 3: dynamic flexion with no load (non weight bearing). The degree of subluxation was compared both between the intact and torn posterior horn within each meniscus and across both menisci.

This is a novel work with interesting findings. They provided a good introduction. The methodology was described in details. Statistical analysis was also described. Power calculation for sample size was conducted. The results are detailed and discussed adequately. Limitations of the study were also discussed.

points to be improved.

The title should be modified for example : Quantifying the differential Functional Consequences Between the Medial and Lateral Meniscus

After Posterior Meniscus Root Tears.

Author’s Response:

We welcome the reviewer’s critique and after considering the comments agree that the title should be modified to both more precisely characterize the purpose of this research and the findings.

Author’s Action:

To address this concern, we have revised the title to more precisely characterize the purpose of the research and subsequent findings. The title has been modified to, “Quantifying the differential functional behavior between the medial and lateral meniscus after posterior meniscus root tears.”

The abstract could be more simple and highlight the novelty of this work. It should be more attractive to let the reader continue into the article. The conclusion that functional consequences of extrusion are more significant

for the medial meniscus than that of the lateral meniscus however can not be simply made based on the degree of meniscus subluxation. Other factors that were not measured in this work such as changes in stress distribution across the joint surface with PRT could make such conclusion possible.

Author’s Response:

We thank the reviewer for their comments and agree that the abstract could better highlight the novelty of the work and be more attractive to reader to continue into the paper. We have revised the abstract in response to address this concern.

Author’s Action:

We have simplified the abstract to highlighting the novelty of the research and encouraging the reader to find details within the paper. Additionally, we have clarified the conclusion stating that there is a differential functional behavior in extrusion between the medial and lateral meniscus and this must be accounted for in posterior root repair.

The software used for statistical analysis should be mentioned

Author’s Response:

We agree that the software used for statistical analysis should be mentioned and we thank the reviewer for the suggestion.

Author’s Action:

We have added the software used for statistical analysis at the end of the ‘Statistical analysis’ subsection of the ‘Materials and methods’ section.

In the results section, how was the overall subluxation in table 1 measured? Please provide a supplementary table with all measures for all specimens.

Author’s Response:

We thank the reviewer for pointing out an area of needed clarification. We have revised the manuscript to provide full access to the data and the first paragraph in the ‘Results’ section was expanded to clarify how the overall subluxation was calculated.

Author’s Action:

To address this comment, we have provided the data using DRYAD accessible through https://datadryad.org/stash/share/XR2diRRfUYUd5cDw_d79mYO_i3iaJu0S5EW-FgcuMw8 and the manuscript was revised to include the doi number linked to the DRYAD repository where the full data is deposited and accessible upon publication of the research article in PLOS ONE at the end of the first paragraph in the ‘Results’ section. Table 1’s footnote was expanded to clarify the measurements of the Summary data.

Line 176, 177 : The greatest extrusion was recorded at 30-degrees of knee flexion (4.000 ± 01.259mm), please add the statistical significance . also in the same paragraph ensure that the statistical significance of each difference (which can be luckily found in the figures) is always mentioned

Author’s Response:

We agree with the reviewer that the narrative could be improved for clarity. We have revised the paragraph for the results regarding meniscus extrusion and knee flexion.

Author’s Action:

We have revised the figure 3 results narrative adding the statistical significance next to the point estimates and variation to augment the data provided in Figure 3.

Line 195: lateral meniscus instead of medial ?

Author’s Response:

We thank the reviewer for their critical review of this. The typo is now corrected.

In the conclusion, as mentioned above in the comment on the abstract, no functional consequences of extrusion were tested here, as for example the differential stress distribution across the joint in response to this measured meniscus subluxation. So the authors can not make this assumption. The direct fact that can be concluded here is obviously the significant subluxation of medial meniscus in the different given testing situations in comparison to the lateral meniscus.

Author’s Response:

We thank the reviewer for bringing up this point. We agree that in general the stress distribution across the joint is a useful piece of data. However, there are technical challenges in adding a sensor to measure stress distribution using this model, and we found that the sensor actually inhibited the dynamic motion of the meniscus in response to axial compression and range of motion, which was the focus of this work. Moreover, it is known that stress distribution and pressure is altered after detachment of the posterior root as many previous studies have demonstrated. For example, a seminal article showed that peak contact pressure after posterior root tear was similar to a total meniscectomy (Allaire et al., The Journal of Bone and Joint Surgery, 2008). A more recent study used a finite element analysis and demonstrated increased contact pressure and contact stress after posterior root avulsion (Wang et al., Journal of Orthopaedic Surgery and Research, 2021).

Author’s Action:

The discussion section was revised by adding a discussion point of what is known regarding the stress distribution and pressure changes associated with posterior root avulsions. We have also simplified the conclusion to highlight that focus of the work regarding the influence of knee motion and axial compression on the differential meniscus extrusion between the medial and lateral meniscus.

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Ayman F. AbdelKawi

Reviewer #2: Yes: Dr. Mohammad Masoud

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

25 Oct 2021

Quantifying the differential functional behavior between the medial and lateral meniscus after posterior meniscus root tears

PONE-D-21-16714R1

Dear Dr. Walczak,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Osama Farouk

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: The authors have made all the needed and recommended changes to the article. I have no further comments.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Ayman F. AbdelKawi

Reviewer #2: Yes: Dr. Mohammad Masoud

29 Oct 2021

PONE-D-21-16714R1

Quantifying the differential functional behavior between the medial and lateral meniscus after posterior meniscus root tears

Dear Dr. Walczak:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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on behalf of

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PLOS ONE