Engineered Microenvironmental Cues from Fiber-Reinforced Hydrogel Composites Drive Tenogenesis and Aligned Collagen Deposition.

Effective tendon regeneration following injury is contingent on appropriate differentiation of recruited cells and deposition of mature, aligned, collagenous extracellular matrix that can withstand the extreme mechanical demands placed on the tissue. As such, myriad biomaterial approaches have been explored to provide biochemical and physical cues that encourage tenogenesis and template aligned matrix deposition in lieu of dysfunctional scar tissue formation. Fiber-reinforced hydrogels present an ideal biomaterial system toward this end given their transdermal injectability, tunable stiffness over a range amenable to tenogenic differentiation of progenitors, and capacity for modular inclusion of biochemical cues. Here, tunable and modular, fiber-reinforced, synthetic hydrogels are employed to elucidate salient microenvironmental determinants of tenogenesis and aligned collagen deposition by tendon progenitor cells. Transforming growth factor ß3 drives a cell fate switch toward pro-regenerative or pro-fibrotic phenotypes, which can be biased toward the former by culture in softer microenvironments or inhibition of the RhoA/ROCK activity. Furthermore, studies demonstrate that topographical anisotropy in fiber-reinforced hydrogels critically mediates the alignment of de novo collagen fibrils, reflecting native tendon architecture. These findings inform the design of cell-free, injectable, synthetic hydrogels for tendon tissue regeneration and, likely, that of a range of load-bearing connective tissues.

Early Outcomes Following Plantar Condylectomy and Imbrication of Plantar Plate to Metatarsal Neck for Metatarsalgia and Grade 0 Lesser Toe Metatarsophalangeal Joint Instability.

Background: Metatarsalgia and plantar plate tears are characterized by forefoot pain and toe deformity in severe cases. Conservative management may slow progression of symptoms; however, definitive treatment often requires operative intervention. The purpose of this observational study was to evaluate the combination of plantar condylectomy and surgical imbrication of the plantar plate to the metatarsal neck to repair grade 0 plantar plate injuries. Methods: We retrospectively identified 22 patients with metatarsalgia and low-grade plantar plate lesions (grade 0), operated between 2018 and 2021, who underwent operative repair involving plantar metatarsal condylectomy and proximal surgical imbrication of the plantar plate to the metatarsal neck. Fourteen patients underwent concomitant hallux valgus correction. Data collection was performed preoperatively and postoperatively and included Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) and pain interference (PI) scores. Paired Wilcoxon signed-rank tests compared PROMIS PF and PI scores at patients' preoperative, 6-9-week, 3-4-month, 5-6-month, and ≥9-month follow-up evaluations (P < .05). Results: Compared to their preoperative visit, patients demonstrated modest improvement in their PROMIS (pain and physical function) scores over the first ≥9 months postoperatively (median 13.0 months). Median preoperative and most recent PROMIS physical function scores were 40.5 (95% CI: 36-49) and 44.5 (95% CI: 40-52), respectively. Median PROMIS pain interference scores changed from 62.5 (95% CI: 56-67) to 56.0 (95% CI: 51-62). Improvement in pain and function was sustained in patients available for postoperative follow-up. Conclusion: In this small, early follow-up series, we found that plantar condylectomy and surgical imbrication of the plantar plate to the metatarsal neck was modestly helpful to treat metatarsalgia and grade 0 plantar plate injuries. Level of Evidence: Level IV, retrospective case series.

Building-Block Size Mediates Microporous Annealed Particle Hydrogel Tube Microenvironment Following Spinal Cord Injury.

Spinal cord injury (SCI) is a life-altering event, which often results in loss of sensory and motor function below the level of trauma. Biomaterial therapies have been widely investigated in SCI to promote directional regeneration but are often limited by their pre-constructed size and shape. Herein, the design parameters of microporous annealed particles (MAPs) are investigated with tubular geometries that conform to the injury and direct axons across the defect to support functional recovery. MAP tubes prepared from 20-, 40-, and 60-micron polyethylene glycol (PEG) beads are generated and implanted in a T9-10 murine hemisection model of SCI. Tubes attenuate glial and fibrotic scarring, increase innate immune cell density, and reduce inflammatory phenotypes in a bead size-dependent manner. Tubes composed of 60-micron beads increase the cell density of the chronic macrophage response, while neutrophil infiltration and phenotypes do not deviate from those seen in controls. At 8 weeks postinjury, implantation of tubes composed of 60-micron beads results in enhanced locomotor function, robust axonal ingrowth, and remyelination through both lumens and the inter-tube space. Collectively, these studies demonstrate the importance of bead size in MAP construction and highlight PEG tubes as a biomaterial therapy to promote regeneration and functional recovery in SCI.

Degree of Tendon Retraction and Younger Age Are Associated With Functional Decline Following Nonoperative Management of Complete Proximal Hamstring Ruptures.

Purpose: To characterize functional outcomes of patients with complete proximal hamstring tendon ruptures who were treated nonoperatively and determine whether there are patient characteristics associated with unfavorable outcomes. Methods: We retrospectively identified patients aged 18-80 (treated 1/2000-12/2019) who received nonoperative management of complete rupture of the hamstring tendon origin. Participants completed the Lower Extremity Functional Scale (LEFS), as well as Tegner Activity Scale (TAS), and a chart review was conducted to obtain demographic and medical information. Preinjury and postinjury TAS scores were compared, and additional models quantified associations between LEFS scores or changes in TAS scores (ΔTAS) and patient characteristics. Results: Twenty-eight subjects (mean age: 61.5 ± 1.5 years; 10 male) were included. The mean follow-up time was 5.8 ± 0.8 years (range: 2-22 years). Mean preinjury and postinjury TAS scores were 5.3 ± 0.4 and 3.7 ± 0.4, respectively, with a change of 1.5 ± 0.3 (P = .0002). Degree of tendon retraction showed a negative correlation with LEFS score (P = .003) and ΔTAS (P = .005). Increased follow-up time (P = .015) and body mass index (P = .018) were associated with lower LEFS scores. Moreover, increased follow-up time (P = .002) and younger age at injury (P = .035) were associated with more negative ΔTAS. Patients classified with an American Society of Anesthesiologists (ASA) score of 2 had a median LEFS score that was 20 points (95% CI: 6.9-33.6) lower than those classified as ASA 1 (P = .015). Conclusions: In this study, we found that increased degree of tendon retraction, increased follow-up time, and younger age at initial injury were associated with significantly worse self-reported functional outcomes. Level of Evidence: Level IV, prognostic case series.

Discoidin domain receptor 2 regulates aberrant mesenchymal lineage cell fate and matrix organization.

Extracellular matrix (ECM) interactions regulate both the cell transcriptome and proteome, thereby determining cell fate. Traumatic heterotopic ossification (HO) is a disorder characterized by aberrant mesenchymal lineage (MLin) cell differentiation, forming bone within soft tissues of the musculoskeletal system following traumatic injury. Recent work has shown that HO is influenced by ECM-MLin cell receptor signaling, but how ECM binding affects cellular outcomes remains unclear. Using time course transcriptomic and proteomic analyses, we identified discoidin domain receptor 2 (DDR2), a cell surface receptor for fibrillar collagen, as a key MLin cell regulator in HO formation. Inhibition of DDR2 signaling, through either constitutive or conditional Ddr2 deletion or pharmaceutical inhibition, reduced HO formation in mice. Mechanistically, DDR2 perturbation alters focal adhesion orientation and subsequent matrix organization, modulating Focal Adhesion Kinase (FAK) and Yes1 Associated Transcriptional Regulator and WW Domain Containing Transcription Regulator 1 (YAP/TAZ)-mediated MLin cell signaling. Hence, ECM-DDR2 interactions are critical in driving HO and could serve as a previously unknown therapeutic target for treating this disease process.

Anterior cruciate ligament graft forces are sensitive to fixation angle and tunnel position within the native femoral footprint during passive flexion.

BACKGROUND: Anterior cruciate ligament (ACL) graft position within the anatomic femoral footprint of the native ACL and the flexion angle at which the graft is fixed (i.e., fixation angle) are important considerations in ACL reconstruction surgery. However, their combined effect on ACL graft force remains less well understood. HYPOTHESIS: During passive flexion, grafts placed high within the femoral footprint carry lower forces than grafts placed low within the femoral footprint (i.e., high and low grafts, respectively). Forces carried by high grafts are independent of fixation angle. All reconstructions impart higher forces on the graft than those carried by the native ACL. STUDY DESIGN: Controlled laboratory study. METHODS: Five fresh-frozen cadaveric knees were mounted to a robotic manipulator and flexed from full extension to 90° of flexion. The ACL was sectioned and ACL force was calculated via superposition. ACL reconstructions were then performed using a patellar tendon autograft. For each knee, four different reconstruction permutations were tested: high and low femoral graft positions fixed at 15° and at 30° of flexion. Graft forces were calculated from full extension to 90° of flexion for each combination of femoral graft position and fixation angle again via superposition. Native ACL and ACL graft forces were compared through early flexion (by averaging tissue force from 0 to 30° of flexion) and in 5° increments from full extension to 90° of flexion. RESULTS: When fixed at 30° of flexion, high grafts carried less force than low grafts through early flexion bearing a respective 64 ± 19 N and 88 ± 11 N (p = 0.02). Increasing fixation angle from 15° to 30° caused graft forces through early flexion to increase 40 ± 13 N in low grafts and 23 ± 6 N in high grafts (p < 0.001). Low grafts fixed at 30° of flexion differed most from the native ACL, carrying 67 ± 9 N more force through early flexion (p < 0.001). CONCLUSION: ACL grafts placed high within the femoral footprint and fixed at a lower flexion angle carried less force through passive flexion compared to grafts placed lower within the femoral footprint and fixed at a higher flexion angle. At the prescribed pretensions, all grafts carried higher forces than the native ACL through passive flexion. CLINICAL RELEVANCE: Both fixation angle and femoral graft location within the anatomic ACL footprint influence graft forces and, therefore, should be considered when performing ACL reconstruction.

Direct comparison of angiogenesis in natural and synthetic biomaterials reveals that matrix porosity regulates endothelial cell invasion speed and sprout diameter.

Vascularization of large, diffusion-hindered biomaterial implants requires an understanding of how extracellular matrix (ECM) properties regulate angiogenesis. Sundry biomaterials assessed across many disparate angiogenesis assays have highlighted ECM determinants that influence this complex multicellular process. However, the abundance of material platforms, each with unique parameters to model endothelial cell (EC) sprouting presents additional challenges of interpretation and comparison between studies. In this work we directly compared the angiogenic potential of commonly utilized natural (collagen and fibrin) and synthetic dextran vinyl sulfone (DexVS) hydrogels in a multiplexed angiogenesis-on-a-chip platform. Modulating matrix density of collagen and fibrin hydrogels confirmed prior findings that increases in matrix density correspond to increased EC invasion as connected, multicellular sprouts, but with decreased invasion speeds. Angiogenesis in synthetic DexVS hydrogels, however, resulted in fewer multicellular sprouts. Characterizing hydrogel Young's modulus and permeability (a measure of matrix porosity), we identified matrix permeability to significantly correlate with EC invasion depth and sprout diameter. Although microporous collagen and fibrin hydrogels produced lumenized sprouts in vitro, they rapidly resorbed post-implantation into the murine epididymal fat pad. In contrast, DexVS hydrogels proved comparatively stable. To enhance angiogenesis within DexVS hydrogels, we incorporated sacrificial microgels to generate cell-scale pores throughout the hydrogel. Microporous DexVS hydrogels resulted in lumenized sprouts in vitro and enhanced cell invasion in vivo. Towards the design of vascularized biomaterials for long-term regenerative therapies, this work suggests that synthetic biomaterials offer improved size and shape control following implantation and that tuning matrix porosity may better support host angiogenesis. STATEMENT OF SIGNIFICANCE: Understanding how extracellular matrix properties govern angiogenesis will inform biomaterial design for engineering vascularized implantable grafts. Here, we utilized a multiplexed angiogenesis-on-a-chip platform to compare the angiogenic potential of natural (collagen and fibrin) and synthetic dextran vinyl sulfone (DexVS) hydrogels. Characterization of matrix properties and sprout morphometrics across these materials points to matrix porosity as a critical regulator of sprout invasion speed and diameter, supported by the observation that nanoporous DexVS hydrogels yielded endothelial cell sprouts that were not perfusable. To enhance angiogenesis into synthetic hydrogels, we incorporated sacrificial microgels to generate microporosity. We find that microporosity increased sprout diameter in vitro and cell invasion in vivo. This work establishes a composite materials approach to enhance the vascularization of synthetic hydrogels.

Magnetic Alignment of Electrospun Fiber Segments Within a Hydrogel Composite Guides Cell Spreading and Migration Phenotype Switching.

Fibrous extracellular matrix (ECM) proteins provide mechanical structure and adhesive scaffolding to resident cells within stromal tissues. Aligned ECM fibers play an important role in directing morphogenetic processes, supporting mechanical loads, and facilitating cell migration. Various methods have been developed to align matrix fibers in purified biopolymer hydrogels, such as type I collagen, including flow-induced alignment, uniaxial tensile deformation, and magnetic particles. However, purified biopolymers have limited orthogonal tunability of biophysical cues including stiffness, fiber density, and fiber alignment. Here, we generate synthetic, cell-adhesive fiber segments of the same length-scale as stromal fibrous proteins through electrospinning. Superparamagnetic iron oxide nanoparticles (SPIONs) embedded in synthetic fiber segments enable magnetic field induced alignment of fibers within an amorphous bulk hydrogel. We find that SPION density and magnetic field strength jointly influence fiber alignment and identify conditions to control the degree of alignment. Tuning fiber length allowed the alignment of dense fibrous hydrogel composites without fiber entanglement or regional variation in the degree of alignment. Functionalization of fiber segments with cell adhesive peptides induced tendon fibroblasts to adopt a uniaxial morphology akin to within native tendon. Furthermore, we demonstrate the utility of this hydrogel composite to direct multicellular migration from MCF10A spheroids and find that fiber alignment prompts invading multicellular strands to separate into disconnected single cells and multicellular clusters. These magnetic fiber segments can be readily incorporated into other natural and synthetic hydrogels and aligned with inexpensive and easily accessible rare earth magnets, without the need for specialized equipment. 3D hydrogel composites where stiffness/crosslinking, fiber density, and fiber alignment can be orthogonally tuned may provide insights into morphogenetic and pathogenic processes that involve matrix fiber alignment and can enable systematic investigation of the individual contribution of each biophysical cue to cell behavior.

Engagement of the Secondary Ligamentous and Meniscal Restraints Relative to the Anterior Cruciate Ligament Predicts Anterior Knee Laxity.

BACKGROUND: Patients with high-grade preoperative side-to-side differences in anterior laxity as assessed via the Lachman test after unilateral anterior cruciate ligament (ACL) rupture are at heightened risk of early ACL graft failure. Biomechanical factors that predict preoperative side-to-side differences in anterior laxity are poorly understood. PURPOSE: To assess, in a cadaveric model, whether the increase in anterior laxity caused by sectioning the ACL (a surrogate for preoperative side-to-side differences in anterior laxity) during a simulated Lachman test is associated with two biomechanical factors: (1) the tibial translation at which the secondary anterior stabilizers, including the remaining ligaments and the menisci, begin to carry force, or engage, relative to that of the ACL or (2) the forces carried by the ACL and secondary stabilizers at the peak applied anterior load. STUDY DESIGN: Controlled laboratory study. METHODS: Seventeen fresh-frozen human cadaveric knees underwent Lachman tests simulated through a robotic manipulator with the ACL intact and sectioned. The net forces carried by the ACL and secondary soft tissue stabilizers (the medial meniscus and all remaining ligaments, measured as a whole) were characterized as a function of anterior tibial translation. The engagement points of the ACL (with the ACL intact) and each secondary stabilizer (with the ACL sectioned) were defined as the anterior translation at which they began to carry force, or engaged, during a simulated Lachman test. Then, the relative engagement point of each secondary stabilizer was defined as the difference between the engagement point of each secondary stabilizer and that of the ACL. Linear regressions were performed to test each association (P < .05). RESULTS: The increase in anterior laxity caused by ACL sectioning was associated with increased relative engagement points of both the secondary ligaments (ß = 0.87; P < .001; R2 = 0.75) and the medial meniscus (ß = 0.66; P < .001; R2 = 0.58). Smaller changes in anterior laxity were also associated with increased in situ medial meniscal force at the peak applied load when the ACL was intact (ß = -0.06; P < .001; R2 = 0.53). CONCLUSION: The secondary ligaments and the medial meniscus require greater anterior tibial translation to engage (ie, begin to carry force) relative to the ACL in knees with greater changes in anterior laxity after ACL sectioning. Moreover, with the ACL intact, the medial meniscus carries more force in knees with smaller changes in anterior laxity after ACL sectioning. CLINICAL RELEVANCE: Relative tissue engagement is a new biomechanical measure to characterize in situ function of the ligaments and menisci. This measure may aid in developing more personalized surgical approaches to reduce high rates of ACL graft revision in patients with high-grade laxity.

Tibiofemoral Kinematics During Compressive Loading of the ACL-Intact and ACL-Sectioned Knee: Roles of Tibial Slope, Medial Eminence Volume, and Anterior Laxity.

BACKGROUND: Tibial geometry and knee laxity have been identified as risk factors for both noncontact anterior cruciate ligament (ACL) rupture and instability in the setting of ACL insufficiency via clinical studies; yet, their biomechanical relationships with tibiofemoral kinematics during compressive loading are less well understood. The purpose of this study was to identify the relative contributions of sagittal tibial slope, medial tibial eminence volume, and anterior knee laxity to tibiofemoral kinematics with axial compression in both ACL-intact and ACL-sectioned cadaveric knees. METHODS: Computed tomography (CT) data were collected from 13 human cadaveric knees (mean donor age, 45 ± 11 years; 8 male). Validated algorithms were used to calculate the sagittal slope of the medial and of the lateral tibial plateau as well as volume of the medial tibial eminence. Specimens were then mounted to a robotic manipulator. For both intact and ACL-sectioned conditions, the robot compressed the knee from 10 to 300 N at 15° of flexion; the net anterior tibial translation of the medial and lateral compartments and internal tibial rotation were recorded. Simple and multiple linear regressions were performed to identify correlations between kinematic outcomes and (1) osseous geometric parameters and (2) anterior laxity during a simulated Lachman test. RESULTS: In ACL-intact knees, anterior tibial translation of each compartment was positively correlated with the corresponding sagittal slope, and internal tibial rotation was positively correlated with the lateral sagittal slope and the sagittal slope differential (p ≤ 0.044). In ACL-sectioned knees, anterior tibial translation of the medial compartment was positively associated with medial sagittal slope as well as a combination of medial tibial eminence volume and anterior laxity; internal tibial rotation was inversely correlated with anterior knee laxity (p < 0.05). CONCLUSIONS: Under compressive loading, sagittal slope of the medial and of the lateral tibial plateau was predictive of kinematics with the ACL intact, while medial tibial eminence volume and anterior laxity were predictive of kinematics with the ACL sectioned. CLINICAL RELEVANCE: The relationships between tibial osseous morphology, anterior laxity, and knee kinematics under compression may help explain heightened risk of ACL injury and might predict knee instability after ACL rupture.

Automated, accurate, and three-dimensional method for calculating sagittal slope of the tibial plateau.

Increased posterior-inferior directed slope of the subchondral bone of the lateral tibial plateau is a risk factor for noncontact rupture of the anterior cruciate ligament (ACL). Previous measures of lateral tibial slope, however, vary from study to study and often lack documentation of their accuracy. These factors impede identifying the magnitude of lateral tibial slope that increases risk of noncontact ACL rupture. Therefore, we developed and evaluated a new method that (1) requires minimal user input; (2) employs 3D renderings of the tibia that are referenced to a 3D anatomic coordinate system; and (3) is precise, reliable, and accurate. The user first isolated the proximal tibia from computed tomography (CT) scans. Then, the algorithm placed the proximal tibia in an automatically generated tibial coordinate system. Next, it identified points along the rim of subchondral bone around the lateral tibial plateau, iteratively fit a plane to this rim of points, and, finally, referenced the plane to the tibial coordinate system. Precision and reliability of the lateral slope measurements were respectively assessed via standard deviation and intra- and inter-class correlation coefficients using CT scans of three cadaveric tibia. Accuracy was quantified by comparing changes in lateral tibial slope calculated by our algorithm to predefined in silico changes in slope. Precision, reliability, and accuracy were ≤0.18°, ≥0.998, and ≤0.13°, respectively. We will use our novel method to better understand the relationship between lateral tibial slope and knee biomechanics towards preventing ACL rupture and improving its treatment.

Anterior laxity, lateral tibial slope, and in situ ACL force differentiate knees exhibiting distinct patterns of motion during a pivoting event: A human cadaveric study.

Knee instability following anterior cruciate ligament (ACL) rupture compromises function and increases risk of injury to the cartilage and menisci. To understand the biomechanical function of the ACL, previous studies have primarily reported the net change in tibial position in response to multiplanar torques, which generate knee instability. In contrast, we retrospectively analyzed a cohort of 13 consecutively tested cadaveric knees and found distinct motion patterns, defined as the motion of the tibia as it translates and rotates from its unloaded, initial position to its loaded, final position. Specifically, ACL-sectioned knees either subluxated anteriorly under valgus torque (VL-subluxating) (5 knees) or under a combination of valgus and internal rotational torques (VL/IR-subluxating) (8 knees), which were applied at 15 and 30° flexion using a robotic manipulator. The purpose of this study was to identify differences between these knees that could be driving the two distinct motion patterns. Therefore, we asked whether parameters of bony geometry and tibiofemoral laxity (known risk factors of non-contact ACL injury) as well as in situ ACL force, when it was intact, differentiate knees in these two groups. VL-subluxating knees exhibited greater sagittal slope of the lateral tibia by 3.6 ±â€¯2.4° (p = 0.003); less change in anterior laxity after ACL-sectioning during a simulated Lachman test by 3.2 ±â€¯3.2 mm (p = 0.006); and, at the peak applied valgus torque (no internal rotation torque), higher posteriorly directed, in situ ACL force by 13.4 ±â€¯11.3 N and 12.0 ±â€¯11.6 N at 15° and 30° of flexion, respectively (both p ≤ 0.03). These results may suggest that subgroups of knees depend more on their ACL to control lateral tibial subluxation in response to uniplanar valgus and multiplanar valgus and internal rotation torques as mediated by anterior laxity and bony morphology.

New parameters describing how knee ligaments carry force in situ predict interspecimen variations in laxity during simulated clinical exams.

Knee laxity, defined as the net translation or rotation of the tibia relative to the femur in a given direction in response to an applied load, is highly variable from person to person. High levels of knee laxity as assessed during routine clinical exams are associated with first-time ligament injury and graft reinjury following reconstruction. During laxity exams, ligaments carry force to resist the applied load; however, relationships between intersubject variations in knee laxity and variations in how ligaments carry force as the knee moves through its passive envelope of motion, which we refer to as ligament engagement, are not well established. Thus, the objectives of this study were, first, to define parameters describing ligament engagement and, then, to link variations in ligament engagement and variations in laxity across a group of knees. We used a robotic manipulator in a cadaveric knee model (n=20) to quantify how important knee stabilizers, namely the anterior and posterior cruciate ligaments (ACL and PCL, respectively), as well as the medial collateral ligament (MCL) engage during respective tests of anterior, posterior, and valgus laxity. Ligament engagement was quantified using three parameters: (1) in situ slack, defined as the relative tibiofemoral motion from the neutral position of the joint to the position where the ligament began to carry force; (2) in situ stiffness, defined as the slope of the linear portion of the ligament force-tibial motion response; and (3) ligament force at the peak applied load. Knee laxity was related to parameters of ligament engagement using univariate and multivariate regression models. Variations in the in situ slack of the ACL and PCL predicted anterior and posterior laxity, while variations in both in situ slack and in situ stiffness of the MCL predicted valgus laxity. Parameters of ligament engagement may be useful to further characterize the in situ biomechanical function of ligaments and ligament grafts.

High Interspecimen Variability in Engagement of the Anterolateral Ligament: An In Vitro Cadaveric Study.

BACKGROUND: Anterolateral ligament (ALL) reconstruction as an adjunct to anterior cruciate ligament (ACL) reconstruction remains a subject of clinical debate. This uncertainty may be driven in part by a lack of knowledge regarding where, within the range of knee motion, the ALL begins to carry force (engages). QUESTIONS/PURPOSES: (1) Does the ALL engage in the ACL-intact knee; and (2) where within the range of anterior tibial translation occurring in the ACL-sectioned knee does the ALL engage? METHODS: A robotic manipulator was used to measure anterior tibial translation, ACL forces, and ALL forces in 10 fresh-frozen cadaveric knees (10 donors; mean age, 41 ± 16 years; range, 20-64 years; eight male) in response to applied multiplanar torques. The engagement point of the ALL was defined as the anterior tibial translation at which the ALL began to carry at least 15% of the force carried by the native ACL; a threshold of 15% minimized the sensitivity of the engagement point of the ALL. This engagement point was compared with the maximum anterior tibial translation permitted in the ACL-intact condition using a paired Wilcoxon signed-rank test (p < 0.05). Normality of each outcome measure was confirmed using Kolmogorov-Smirnov tests (p < 0.05). RESULTS: The ALL engaged in five and four of 10 ACL-intact knees in response to multiplanar torques at 15° and 30° of flexion, respectively. Among the nine of 10 knees in which the ALL engaged with the ACL sectioned, the ACL-intact motion limit, and ALL engagement point, respectively, averaged 1.5 ± 1.1 mm and 5.4 ± 4.1 mm at 15° of flexion and 2.0 ± 1.3 mm and 5.7 ± 2.7 mm at 30° of flexion. Thus, the ALL engaged 3.8 ± 3.1 mm (95% confidence interval [CI], 1.4-6.3 mm; p = 0.027) and 3.7 ± 2.4 mm (95% CI, 2.1-5.3 mm; p = 0.008) beyond the maximum anterior tibial translation of the ACL-intact knee at 15° and 30° of flexion, respectively. CONCLUSIONS: In this in vitro, cadaveric study, the ALL engaged in up to half of the ACL-intact knees. In the ACL-sectioned knees, the ALL engaged beyond the ACL-intact limit of anterior subluxation on average in response to multiplanar torques, albeit with variability that likely reflects interspecimen heterogeneity in ALL anatomy. CLINICAL RELEVANCE: The findings suggest that surgical variables such as the joint position and tension at which lateral extraarticular grafts and tenodeses are fixed might be able to be tuned to control where within the range of knee motion the graft tissue is engaged to restrain joint motion on a patient-specific basis.

Primary and coupled motions of the native knee in response to applied varus and valgus load.

BACKGROUND: Knowledge of the complex kinematics of the native knee is a prerequisite for a successful reconstructive procedure. The aim of this study is to describe the primary and coupled motions of the native knee throughout the range of knee flexion, in response to applied varus and valgus loads. METHODS: Twenty fresh-frozen cadaver knees were affixed to a six degree of freedom robotic arm with a universal force-moment sensor, and loaded with a 4Nm moment in varus and valgus at 0, 15, 30, 45, and 90° of knee flexion. The resulting tibiofemoral angulation, displacement, and rotation were recorded. RESULTS: For each parameter investigated, the knee joint demonstrated more laxity at higher flexion angles. Varus angulation increased progressively from zero (2.0° varus) to 90 (5.2° varus) degrees of knee flexion (p<0.001). Valgus angulation also increased progressively, from zero (1.5° valgus) to 90 (3.9° valgus) degrees of knee flexion (p<0.001). At all flexion angles, the magnitude of tibiofemoral angle deviation was larger with varus than with valgus loading (p<0.05). CONCLUSIONS: We conclude that the native knee exhibits small increases in coronal plane laxity as the flexion angle increases, and that the knee has generally more laxity under varus load than with valgus load throughout the Range of Motion (ROM). Larger differences in laxity of more than 2 to 3°, or peak laxity specifically during the range of mid-flexion, were not found in our cadaver model and are not likely to represent normal coronal plane kinematics. LEVEL OF EVIDENCE: Level V, biomechanical cadaveric study.