Mechanical Properties Of Ligaments Research Articles

Mechanical response of human thoracic spine ligaments under quasi-static loading: An experimental study

PurposeThis study aimed to investigate the geometrical and mechanical properties of human thoracic spine ligaments subjected to uniaxial quasi-static tensile test. MethodsFour human thoracic spines, obtained through a body donation program, were utilized for the study. The anterior longitudinal ligament (ALL), posterior longitudinal ligament (PLL), capsular ligament (CL), ligamenta flava (LF), and the interspinous ligament and supraspinous ligament complex (ISL + SSL), were investigated. The samples underwent specimen preparation, including dissection, cleaning, and reinforcement, before being immersed in epoxy resin. Uniaxial tensile tests were performed using a custom-designed mechanical testing machine equipped with an environmental chamber (T = 36.6 °C; humidity 95%). Then, the obtained tensile curves were averaged preserving the characteristic regions of typical ligaments response. ResultsGeometrical and mechanical properties, such as initial length and width, failure load, and failure elongation, were measured. Analysis of variance (ANOVA) revealed significant differences among the ligaments for all investigated parameters. Pairwise comparisons using Tukey's post-hoc test indicated differences in initial length and width. ALL and PLL exhibited higher failure forces compared to CL and LF. ALL and ISL + SSL demonstrated biggest failure elongation. Comparisons with other studies showed variations in initial length, failure force, and failure elongation across different ligaments. The subsystem (Th1 – Th6 and Th7 – Th12) analysis revealed increases in initial length, width, failure force, and elongation for certain ligaments. ConclusionsVariations of both the geometric and mechanical properties of the ligaments were noticed, highlighting their unique characteristics and response to tensile force. Presented results extend very limited experimental data base of thoracic spine ligaments existing in the literature. The obtained geometrical and mechanical properties can help in the development of more precise human body models (HBMs).

Identification of the periodontal ligament material parameters using response surface method

The orthodontic treatment can be guided by the finite element (FE) simulation of periodontal ligament (PDL) mechanical properties, and the biomimetic degree of FE simulation can be primarily affected by the material properties of the PDL. According to the principle of parameter inverse, a method: response surface (RS) method and FE inverse method were proposed to identify the material parameters of PDL. The Prony series viscoelastic FE model was established based on the relaxation experiment. With root mean square error of simulation results and experimental results as the objective function, the optimal parameter combination was obtained by RS method, and the FE simulation result were compared with the experimental result. The result showed that the optimal parameters of the PDL were elastic modulus: 3.791 MPa, Poisson's ratio: 0.42, temperature: 29.294°C separately, and the simulation result of optimal combination maintained consistency with experiment with the correlation coefficient of 0.97258, indicating that the method proposed in this paper could well identify of PDL material parameters. The parameter identification method used in this paper can significantly improve the calculation efficiency, and reduce the parameter identification error compared with the simple FE inverse method, which has scientific significance and theoretical value.

Sacrospinous and sacrotuberous ligaments influence in pelvis kinematics.

The alteration in mechanical properties of posterior pelvis ligaments may cause a biased pelvis deformation which, in turn, may contribute to hip and spine instability and malfunction. Here, the effect of different mechanical properties of ligaments on lumbopelvic deformation is analyzed via the finite element method. First, the improved finite element model was validated using experimental data from previous studies and then used to calculate the sensitivity of lumbopelvic deformation to changes in ligament mechanical properties, load magnitude, and unilateral ligament resection. The deformation of the lumbopelvic complex relative to a given load was predominant in the medial plane. The effect of unilateral resection on deformation appeared to be counterintuitive, suggesting that ligaments have the ability to redistribute load and that they play an important role in the mechanics of the lumbopelvic complex.

Opposite Effect of Cyclic Loading on the Material Properties of Medial Collateral Ligament at Different Temperatures: An Animal Study.

In traffic accidents, the medial collateral ligament (MCL) injury of the knee joint of pedestrians is common. Biofidelic material is important to realize MCL’s native biomechanics in simulations to clarify the injury mechanisms of pedestrians. Pedestrians’ MCLs usually experience cyclic loading at the intra-articular temperature of the knee joint before accidents. Temperature influences the material behaviors of ligaments. However, the mechanical properties of ligaments under cyclic loading have been widely evaluated only at room temperature rather than physiological temperature. Therefore, this study aimed to determine whether the difference between room and intra-articular temperatures influences the effect of cyclic loading on the mechanical properties of MCL. We measured the tensile properties of 34 porcine MCLs at room temperature (21–23°C) and intra-articular temperature (35–37°C), with either 10 cycles or 240 cycles of cyclic loading, a total of four different conditions. The structural responses and geometric data were recorded. After 240 cycles of cyclic loading, stiffness increased by 29.0% (p < 0.01) at room temperature and decreased by 11.5% (p = 0.106) at intra-articular temperature. Material properties were further compared because the geometric differences between samples were inevitable. At room temperature, after 240 cycles of cyclic loading, elastic modulus increased by 29.6% (p < 0.001), and failure strain decreased by 20.4% (p < 0.05). By contrast, at intra-articular temperature, after 240 cycles of cyclic loading, modulus decreased by 27.4% (p < 0.001), and failure strain increased by 17.5% (p = 0.193), insignificant though. In addition, there were no significant differences between the four groups in other structural or material properties. The results showed that temperature reversed the effect of cyclic loading on the mechanical properties of MCL, which may be caused by the high strength and thermally stable crosslinks of MCL. Therefore, for improving the fidelity of knee joint simulations and elucidating the injury mechanism of pedestrians, it is better to measure the mechanical properties of MCL at intra-articular temperature rather than room temperature.

Modelling and evaluating periodontal ligament mechanical behaviour and properties: A scoping review of current approaches and limitations.

This scoping review is intended to synthesize the techniques proposed to model the tooth-periodontal ligament-bone complex (TPBC), while also evaluating the suggested periodontal ligament (PDL) material properties. It is concentrated on the recent advancements on the PDL and TPBC models, while identifying the advantages and limitations of the proposed approaches. Systematic searches were conducted up to December 2020 for articles that proposed PDL models to assess orthodontic tooth movement in Compendex, Web of Science, EMBASE, MEDLINE, PubMed, ScienceDirect, Google Scholar and Scopus databases. Although there have been many studies focused on the evaluation of PDL material properties through numerous modelling approaches, only a handful of approaches have been identified to investigate the interface properties of the PDL as a complete dynamical system (TPBC models). Past reviews on the analytical and experimental determination of the PDL properties already show a concerning range in reported output values-some nearly six orders of magnitude in difference-that strongly suggested the need for further investigation. Surprisingly, it has not yet been possible to determine a narrower range of values for the PDL material properties. Moreover, very few scientific approaches address the TPBC as an integrated complex system model. In consequence, current methods for capturing the PDL material behaviour in a clinical setting are limited and inconclusive. This synthesis encourages more systematic, pragmatic and phenomenological research in this area.

Effect of impact velocity and ligament mechanical properties on lumbar spine injuries in posterior-anterior impact loading conditions: a finite element study.

Traumatic events may lead to lumbar spine injuries ranging from low severity bony fracture to complex fracture dislocation. Injury pathomechanisms as well as the influence of loading rate and ligament mechanical properties were not yet fully elucidated. The objective was to quantify the influence of impact velocity and ligament properties variability on the lumbar spine response in traumatic flexion-shear conditions. An L1-L3 finite element spinal segment was submitted to a posterior-anterior impact at three velocities (2.7, 5, or 10m/s) and for 27 sets of ligament properties. Spinal injury pathomechanism varied according to the impact velocities: initial osseous compression in the anterior column for low and medium velocities versus distraction in the posterior column for high velocity. Impact at 2.7 and 5m/s lead to higher extent of bony injury, i.e., volume of ruptured bone, compared to the impact at 10m/s (1140, 1094, and 718mm3 respectively), lower L2 anterior displacement (2.09, 5.36, and 7.72mm respectively), and lower facet fracture occurrence. Ligament properties had no effect on bony injury initiation but influenced the presence of facet fracture. These results improve the understanding of lumbar injury pathomechanisms and provide additional knowledge of lumbar injury load thresholds that could be used for injury prevention. Graphical abstract Stress distribution analysis at the injury initiation and final injury pattern identification for a lumbar segment submitted to a traumatic posterior-anterior impact.

Ultrasound Shear Wave Elastography of the Elbow Ulnar Collateral Ligament: Reliability Test and a Preliminary Case Study in a Baseball Pitcher

Overhead throwing athletes are at high risk of the elbow ulnar collateral ligament (UCL) injury, and there is a need for clinical tools to objectively diagnose severity of injury and monitor recovery. Mechanical properties of ligaments can potentially be used as biomarkers of UCL health. The objectives of this study are to evaluate the reliability of shear wave ultrasound elastography (SWE) for quantifying UCL shear modulus in 16 healthy nonthrowing individuals and use this technique to evaluate the difference in UCL shear modulus between the injured and uninjured elbows in a baseball pitcher with UCL tear. In the reliability test, the UCL shear modulus of both elbows of each participant was evaluated by SWE for five trials. The same procedures were repeated on two different days. The intra-day and day-to-day reliabilities were determined by the five measurements on the first day and two averages on the two days, respectively. In the case study, each elbow of the baseball pitcher with UCL tear was tested for five trials, and the average was calculated. The intra-day (intraclass correlation coefficient (ICC) = 0.715, Cronbach's alpha = 0.926) and day-to-day (ICC = 0.948, Cronbach's alpha = 0.955) reliabilities were found to be good. There was no difference between both sides. In the case study, the UCL shear modulus of the injured elbow (186.45 kPa) was much lower than that of the uninjured elbow (879.59 kPa). This study shows that SWE could be a reliable tool for quantifying the mechanical properties and health status of the UCL.

The influence of ligament modelling strategies on the predictive capability of finite element models of the human knee joint

In finite element (FE) models knee ligaments can represented either by a group of one-dimensional springs, or by three-dimensional continuum elements based on segmentations. Continuum models closer approximate the anatomy, and facilitate ligament wrapping, while spring models are computationally less expensive. The mechanical properties of ligaments can be based on literature, or adjusted specifically for the subject. In the current study we investigated the effect of ligament modelling strategy on the predictive capability of FE models of the human knee joint. The effect of literature-based versus specimen-specific optimized material parameters was evaluated. Experiments were performed on three human cadaver knees, which were modelled in FE models with ligaments represented either using springs, or using continuum representations. In spring representation collateral ligaments were each modelled with three and cruciate ligaments with two single-element bundles. Stiffness parameters and pre-strains were optimized based on laxity tests for both approaches. Validation experiments were conducted to evaluate the outcomes of the FE models.Models (both spring and continuum) with subject-specific properties improved the predicted kinematics and contact outcome parameters. Models incorporating literature-based parameters, and particularly the spring models (with the representations implemented in this study), led to relatively high errors in kinematics and contact pressures. Using a continuum modelling approach resulted in more accurate contact outcome variables than the spring representation with two (cruciate ligaments) and three (collateral ligaments) single-element-bundle representations. However, when the prediction of joint kinematics is of main interest, spring ligament models provide a faster option with acceptable outcome.

The exercise-induced biochemical milieu enhances collagen content and tensile strength of engineered ligaments.

Exercise stimulates a dramatic change in the concentration of circulating hormones, such as growth hormone (GH), but the biological functions of this response are unclear. Pharmacological GH administration stimulates collagen synthesis; however, whether the post-exercise systemic milieu has a similar action is unknown. We aimed to determine whether the collagen content and tensile strength of tissue-engineered ligaments is enhanced by serum obtained post-exercise. Primary cells from a human anterior cruciate ligament (ACL) were used to engineer ligament constructs in vitro. Blood obtained from 12 healthy young men 15 min after resistance exercise contained GH concentrations that were ∼7-fold greater than resting serum (P < 0.001), whereas IGF-1 was not elevated at this time point (P = 0.21 vs. rest). Ligament constructs were treated for 7 days with medium supplemented with serum obtained at rest (RestTx) or 15 min post-exercise (ExTx), before tensile testing and collagen content analysis. Compared with RestTx, ExTx enhanced collagen content (+19%; 181 ± 33 vs. 215 ± 40 μg per construct P = 0.001) and ligament mechanical properties - maximal tensile load (+17%, P = 0.03 vs. RestTx) and ultimate tensile strength (+10%, P = 0.15 vs. RestTx). In a separate set of engineered ligaments, recombinant IGF-1, but not GH, enhanced collagen content and mechanics. Bioassays in 2D culture revealed that acute treatment with post-exercise serum activated mTORC1 and ERK1/2. In conclusion, the post-exercise biochemical milieu, but not recombinant GH, enhances collagen content and tensile strength of engineered ligaments, in association with mTORC1 and ERK1/2 activation.

A quantitative study of the relationship between the distribution of different types of collagen and the mechanical behavior of rabbit medial collateral ligaments.

The mechanical properties of ligaments are key contributors to the stability and function of musculoskeletal joints. Ligaments are generally composed of ground substance, collagen (mainly type I and III collagen), and minimal elastin fibers. However, no consensus has been reached about whether the distribution of different types of collagen correlates with the mechanical behaviors of ligaments. The main objective of this study was to determine whether the collagen type distribution is correlated with the mechanical properties of ligaments. Using axial tensile tests and picrosirius red staining-polarization observations, the mechanical behaviors and the ratios of the various types of collagen were investigated for twenty-four rabbit medial collateral ligaments from twenty-four rabbits of different ages, respectively. One-way analysis of variance was used in the comparison of the Young's modulus in the linear region of the stress-strain curves and the ratios of type I and III collagen for the specimens (the mid-substance specimens of the ligaments) with different ages. A multiple linear regression was performed using the collagen contents (the ratios of type I and III collagen) and the Young's modulus of the specimens. During the maturation of the ligaments, the type I collagen content increased, and the type III collagen content decreased. A significant and strong correlation () was identified by multiple linear regression between the collagen contents (i.e., the ratios of type I and type III collagen) and the mechanical properties of the specimens. The collagen content of ligaments might provide a new perspective for evaluating the linear modulus of global stress-strain curves for ligaments and open a new door for studying the mechanical behaviors and functions of connective tissues.

The Muscle Stretch Reflex throughout the Menstrual Cycle

The significant sex disparity in sports-related knee injuries may be due to underlying differences in motor control. Although the development of sex-specific movement patterns is likely multifactorial, this study specifically focuses on the potential modulatory role of sex hormones. This study aimed to investigate the muscle stretch reflex (MSR) across the menstrual cycle. We hypothesized that the MSR would fluctuate throughout the menstrual cycle and that the lowest response would correspond with peak concentrations of estrogen. Nineteen healthy women age 18-35 yr participated in this study: 8 eumenorrheic women and 11 women taking oral contraceptives. Serum estradiol and progesterone concentrations, anterior knee laxity (AKL), and the MSR response of the quadriceps muscles were measured three times during the menstrual cycle. The MSR response of the rectus femoris (RF) varied significantly across the menstrual cycle in both groups. Specifically, the RF MSR response was 2.4 times lower during the periovulatory phase when compared with the luteal phase (P = 0.007). The same trend was seen in the vastus medialis, but this did not reach statistical significance (P = 0.070). The MSR response of the vastus lateralis did not change significantly across the menstrual cycle (P = 0.494). A mixed model comparison did not show an association between endogenous concentrations of estradiol and progesterone, exposure to hormonal contraceptives or AKL, and the MSR response for any muscle. Our results demonstrate that the RF MSR response varies throughout the menstrual cycle with the lowest response around the time of ovulation. Additional research is needed to clarify the exact relationship between sex hormones, AKL, and MSR response and to determine the specific origin of the change along the monosynaptic reflex arc.

Strain rate dependent properties of younger human cervical spine ligaments

The cervical spine ligaments play an essential role in limiting the physiological ranges of motion in the neck; however, traumatic loading such as that experienced in automotive crash scenarios can lead to ligament damage and result in neck injury. The development of detailed neck models to evaluate the response and the potential for injury requires accurate ligament mechanical properties at relevant loading rates.The objective of this study was to measure the mechanical properties of the cervical spine ligaments, by performing tensile tests at elongation rates relevant to car crash scenarios, using younger specimens (≤50 years), in simulated in vivo conditions, and to provide a comprehensive investigation of gender and spinal level effects.The five ligaments investigated were the anterior longitudinal ligament, posterior longitudinal ligament, capsular ligament, ligamentum flavum, and interspinous ligament. Ligaments were tested in tension at quasi-static (0.5 s−1), medium (20 s−1) and high (150–250 s−1) strain rates. The high strain rates represented typical car crash scenarios as determined using an existing cervical spine finite element model.In total, 261 ligament tests were performed, with approximately even distribution within elongation rate, spinal level, and gender. The measured force–displacement data followed expected trends compared to previous studies. The younger ligaments investigated in this study demonstrated less scatter, and were both stiffer and stronger than comparable data from older specimens reported in previous studies. Strain rate effects were most significant, while spinal level effects were limited. Gender effects were not significant, but consistent trends were identified, with male ligaments having a higher stiffness and failure force than female ligaments.

CSM 2010 Orthopaedic Section Platform Presentations (Abstracts OPL1-OPL67)

CSM 2010 Orthopaedic Section Platform Presentations (Abstracts OPL1-OPL67)

Verification of predicted specimen-specific natural and implanted patellofemoral kinematics during simulated deep knee bend

Verified computational models represent an efficient method for studying the relationship between articular geometry, soft-tissue constraint, and patellofemoral (PF) mechanics. The current study was performed to evaluate an explicit finite element (FE) modeling approach for predicting PF kinematics in the natural and implanted knee. Experimental three-dimensional kinematic data were collected on four healthy cadaver specimens in their natural state and after total knee replacement in the Kansas knee simulator during a simulated deep knee bend activity. Specimen-specific FE models were created from medical images and CAD implant geometry, and included soft-tissue structures representing medial–lateral PF ligaments and the quadriceps tendon. Measured quadriceps loads and prescribed tibiofemoral kinematics were used to predict dynamic kinematics of an isolated PF joint between 10° and 110° femoral flexion. Model sensitivity analyses were performed to determine the effect of rigid or deformable patellar representations and perturbed PF ligament mechanical properties (pre-tension and stiffness) on model predictions and computational efficiency.Predicted PF kinematics from the deformable analyses showed average root mean square (RMS) differences for the natural and implanted states of less than 3.1° and 1.7mm for all rotations and translations. Kinematic predictions with rigid bodies increased average RMS values slightly to 3.7° and 1.9mm with a five-fold decrease in computational time. Two-fold increases and decreases in PF ligament initial strain and linear stiffness were found to most adversely affect kinematic predictions for flexion, internal–external tilt and inferior–superior translation in both natural and implanted states. The verified models could be used to further investigate the effects of component alignment or soft-tissue variability on natural and implant PF mechanics.

Healing ligament mechanical properties are improved by repair with interpositional allografts but not by concomitant treatment with hyaluronic acid

Healing ligaments have inferior mechanical properties compared to normal ligaments during early healing intervals. The purpose of this study was to investigate if in vivo ligament repair with an interpositional allograft and treatment with hyaluronic acid (HA) would improve the mechanical properties of a medial collateral ligament (MCL) healing from a gap injury. Twenty rabbits were assigned equally to either a donor or recipient group. A gap injury of the MCL was created in both hindlimbs of 10 recipient animals. The right hindlimb was treated with allograft plus HA while the left hindlimb was treated with allograft only. Low-load and high-load mechanical properties, including laxity, relaxation and failure, and histology were evaluated after 6 weeks of healing. Mechanical results were compared to previously published normal MCL and MCL gap scar data. MCL allografts had greater initial force during cyclic relaxation testing and maximum force during failure testing than MCL scars, but were weaker than normal MCLs. Failure stress was the only parameter to demonstrate a statistically significant effect of treatment with HA on the allografts. However, the failure stress of the HA-treated MCL allografts was not different than MCL scars and was less than normal MCLs. In conclusion, interpositional allografts could enhance some mechanical properties of ligament healing but HA, in the way we applied it, did not produce an obvious improvement.

Tissue Engineering Options for Ligament Healing

The anterior cruciate ligament (ACL) is one of five ligaments in the knee that are important for stability and kinematics. It is also the most commonly injured ligament of the knee and due to its poor healing potential, severe damage warrants surgical intervention including complete replacement. Ligaments are longitudinally arranged, complex tissues; the mechanical properties of ligaments are a direct result of their components and the arrangement of these components in the tissue. It is these mechanics that have made ligaments so difficult to replace. Past ACL replacements have had many limitations that prevented their extensive use. These limitations range from mechanical fatigue over time to fraying of the device after implantation. In light of these problems, investigators have begun to pursue a host of new techniques to create a range of viable options for the repair, replacement, and/or regeneration of the ACL. These options include tissue engineered scaffolds with novel designs and specially treated transplanted tissues. In this article, the composition, arrangement, and mechanics of the ACL will be discussed in order to elucidate important aspects of ACL repair; past replacements will also be discussed. Afterwards, novel replacement options that look to solve problems faced by older replacement options will be presented. These devices use a wide variety of materials and designs to replicate ligament mechanics and allow for new tissue regeneration.

Contribution to the optimisation of artificial ligament mechanical properties

In this work, artificial anterior cruciate ligaments were manufactured using braiding process. The mechanical behaviour of circular braids under tensile loads was studied. These braids were manufactured from different yarns and materials. A study of the effect of yarns characteristics and the machine parameters on the braid mechanical properties was done. Predictive models of the braid mechanical response based on the constituent yarn characteristics and the machine parameters have been developed. The last part of this study has been devoted to optimise the braid mechanical properties to be close to those of native ligament.

Subject-specific models of the hindfoot reveal a relationship between morphology and passive mechanical properties

The morphology of the bones, articular surfaces and ligaments and the passive mechanical characteristics of the ankle complex were reported to vary greatly among individuals. The goal of this study was to test the hypothesis that the variations observed in the passive mechanical properties of the healthy ankle complex are strongly influenced by morphological variations. To evaluate this hypothesis six numerical models of the ankle joint complex were developed from morphological data obtained from MRI of six cadaveric lower limbs, and from average reported data on the mechanical properties of ligaments and articular cartilage. The passive mechanical behavior of each model, under a variety of loading conditions, was found to closely match the experimental data obtained from each corresponding specimen. Since all models used identical material properties and were subjected to identical loads and boundary conditions, it was concluded that the observed variations in passive mechanical characteristics were due to variations in morphology, thus confirming the hypothesis. In addition, the average and large variations in passive mechanical behavior observed between the models were similar to those observed experimentally between cadaveric specimens. The results suggest that individualized subject-specific treatment procedures for ankle complex disorders are potentially superior to a one-size-fits-all approach.

Cervical facet capsular ligament yield defines the threshold for injury and persistent joint-mediated neck pain

The cervical facet joint has been identified as a source of neck pain, and its capsular ligament is a likely candidate for injury during whiplash. Many studies have shown that the mechanical properties of ligaments can be altered by subfailure injury. However, the subfailure mechanical response of the facet capsular ligament has not been well defined, particularly in the context of physiology and pain. Therefore, the goal of this study was to quantify the structural mechanics of the cervical facet capsule and define the threshold for altered structural responses in this ligament during distraction. Tensile failure tests were preformed using isolated C6/C7 rat facet capsular ligaments ( n=8); gross ligament failure, the occurrence of minor ruptures and ligament yield were measured. Gross failure occurred at 2.45±0.60 N and 0.92±0.17 mm. However, the yield point occurred at 1.68±0.56 N and 0.57±0.08 mm, which was significantly less than gross failure ( p<0.001 for both measurements). Maximum principal strain in the capsule at yield was 80±24%. Energy to yield was 14.3±3.4% of the total energy for a complete tear of the ligament. Ligament yield point occurred at a distraction magnitude in which pain symptoms begin to appear in vivo in the rat. These mechanical findings provide insight into the relationship between gross structural failure and painful loading for the facet capsular ligament, which has not been previously defined for such neck injuries. Findings also present a framework for more in-depth methods to define the threshold for persistent pain and could enable extrapolation to the human response.

Low-Intensity Pulsed Ultrasound Accelerates and a Nonsteroidal Anti-inflammatory Drug Delays Knee Ligament Healing

Background Low-intensity pulsed ultrasound and nonsteroidal anti-inflammatory drugs are used to treat ligament injuries; however, their individual and combined effects are not established. Hypotheses Low-intensity pulsed ultrasound accelerates ligament healing, a nonsteroidal anti-inflammatory drug delays healing, and the nonsteroidal anti-inflammatory drug inhibits the beneficial effect of low-intensity pulsed ultrasound. Study Design Controlled laboratory study. Methods Sixty adult rats underwent bilateral transection of their knee medial collateral ligaments. Animals were divided into 2 drug groups and treated 5 d/wk with celecoxib (5 mg/kg) mixed in a vehicle solution (NSAID group) or vehicle alone (VEH group). One to 3 hours after drug administration, all animals were treated with unilateral active low-intensity pulsed ultrasound and contralateral inactive low-intensity pulsed ultrasound. Equal numbers of animals from each drug group were mechanically tested at 2 weeks (n = 14/group), 4 weeks (n = 8/group), and 12 weeks (n = 8/group) after injury. Results Ultrasound and drug intervention did not interact to influence ligament mechanical properties at any time point. After 2 weeks of intervention, ligaments treated with active low-intensity pulsed ultrasound were 34.2% stronger, 27.0% stiffer, and could absorb 54.4% more energy before failure than could ligaments treated with inactive low-intensity pulsed ultrasound, whereas ligaments from the NSAID group could absorb 33.3% less energy than could ligaments from the VEH group. There were no ultrasound or drug effects after 4 and 12 weeks of intervention. Conclusions Low-intensity pulsed ultrasound accelerated but did not improve ligament healing, whereas the nonsteroidal anti-inflammatory drug delayed but did not impair healing. When used in combination, the beneficial low-intensity pulsed ultrasound effect was cancelled by the detrimental nonsteroidal anti-inflammatory drug effect. Clinical Relevance Low-intensity pulsed ultrasound after ligament injury may facilitate earlier return to activity, whereas nonsteroidal anti-inflammatory drugs may elevate early reinjury risk.