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Hydrogels that provide mechanical support and sustainably release therapeutics have been used to treat tendon injuries. However, most hydrogels are insufficiently tough, release drugs in bursts, and require cell infiltration or suturing to integrate with surrounding tissue. Here we report that a hydrogel serving as a high-capacity drug depot and combining a dissipative tough matrix on one side and a chitosan adhesive surface on the other side supports tendon gliding and strong adhesion (larger than 1,000 J msup-2/sup) to tendon on opposite surfaces of the hydrogel, as we show with porcine and human tendon preparations during cyclic-friction loadings. The hydrogel is biocompatible, strongly adheres to patellar, supraspinatus and Achilles tendons of live rats, boosted healing and reduced scar formation in a rat model of Achilles-tendon rupture, and sustainably released the corticosteroid triamcinolone acetonide in a rat model of patellar tendon injury, reducing inflammation, modulating chemokine secretion, recruiting tendon stem and progenitor cells, and promoting macrophage polarization to the M2 phenotype. Hydrogels with 'Janus' surfaces and sustained-drug-release functionality could be designed for a range of biomedical applications.

Conventional treatment for intervertebral disc herniation alleviates pain but does not repair the annulus fibrosus (AF), resulting in a high incidence of recurrent herniation and persistent disfunction. The lack of repair and the acute inflammation that arise after injury further compromises the disc and can result in disc-wide degeneration in the long term. To address this clinical need, we developed tension-activated repair patches (TARPs) for annular repair and the local delivery of bioactive anti-inflammatory factors. TARPs transmit physiologic strains to mechanically-activated microcapsules (MAMCs) embedded within, which activate and release encapsulated biomolecules in response to physiologic loading. Here, we demonstrate that the TARP design modulates implant biomechanical properties and regulates MAMC mechano-activation. Next, the FDA-approved anti-inflammatory molecule, interleukin 1 receptor antagonist, Anakinra, was loaded in TARPs and the effects of TARP-mediated annular repair and Anakinra delivery was evaluated in a model of annular injury in the goat cervical spine. TARPs showed robust integration with the native tissue and provided structural reinforcement at the injury site that prevented disc-wide aberrant remodeling resulting from AF detensioning. The delivery of Anakinra via TARP implantation improved the retention of disc biochemical composition through increased matrix deposition and retention at the site of annular injury. Anakinra delivery additionally attenuated the inflammatory response associated by scaffold implantation, decreasing osteolysis in adjacent vertebrae and preserving disc cellularity and matrix organization throughout the AF. These results demonstrate the translational and therapeutic potential of this novel TARP system for the treatment of intervertebral disc herniations.One Sentence SummaryTension-activated repair patches delivering bioactive anti-inflammatory factors improve healing in an in vivo goat cervical disc injury model.

Given its complex shape and relatively small size, the trapezium surface at the trapeziometacarpal (TMC) joint is a particularly attractive target for anatomic biologic joint resurfacing, especially given its propensity to develop osteoarthritis, and the limited and sub-optimal treatment options available. For this to advance to clinical translation, however, an appropriate large animal model is required. In this study, we explored the porcine accessory carpal bone (ACB) as a model for the human trapezium. We characterized ACB anatomy, geometry, joint and tissue-scale mechanics, and composition across multiple donors. We showed that the ACB is similar both in size, and in the saddle shape of the main articulating surface to the human trapezium, and that loads experienced across each joint are similar. Using this information, we then devised a fabrication method and workflow to produce patient-specific tissue-engineered replicas based on CT scans, and showed that when such replicas are implanted orthotopically in an ex vivo model, normal loading is restored. Data from this study establish the porcine ACB as a model system in which to evaluate function of engineered living joint resurfacing strategies. STATEMENT OF SIGNIFICANCE: Biologic joint resurfacing, or the replacement of a joint with living tissue as opposed to metal and plastic, is the holy grail of orthopaedic tissue engineering. However, despite marked advances in engineering native-like osteochondral tissues and in matching patient-specific anatomy, these technologies have not yet reached clinical translation. Given its propensity for developing osteoarthritis, as well as its small size and complex shape, the trapezial surface of the trapeziometacarpal joint at the base of the thumb presents a unique opportunity for pursuing a biologic joint resurfacing strategy. This work establishes the porcine accessory carpal bone as an animal model for the human trapezium and presents a viable test-bed for evaluating the function of engineered living joint resurfacing strategies.

Background This study compared stiffness between two constructs for talonavicular arthrodesis: a dorsomedial plating system and two partially threaded cannulated cancellous screws. We hypothesized that the plate would exhibit greater stiffness and resistance to deformation during cyclic loading. Methods The constructs were implanted in eight matched pairs of cadaveric feet and subjected to axial torsion, cantilever bending in two directions, and cyclic loading to failure. Results The two-screw constructs were significantly stiffer in plantar-dorsal bending (p = .025) and trended towards a higher number of cycles before failure than the plate group (p = .087). No significant differences were observed in internal torsion (p = .620), external torsion (p = .165), or medial-lateral bending (p = .686). Conclusions This study provided the first biomechanical assessment of a plating system with an integrated compression screw, which was significantly less stiff than a two-screw construct when loaded from plantar to dorsal.

Background and AimsGlisson’s capsule is the interstitial connective tissue that surrounds the liver. As part of its normal physiology, it withstands significant daily changes in liver size. The pathophysiology of the capsule in disease is not well understood. The aim of this study was to characterize the changes in capsule matrix, cellular composition, and mechanical properties that occur in liver disease and to determine whether these correlate with disease severity or etiology.Methods10 control, 6 steatotic, 7 moderately fibrotic and 37 cirrhotic patient samples were collected from autopsies, intraoperative biopsies and liver explants. Matrix proteins and cell markers were assessed by staining and second harmonic generation imaging. Mechanical tensile testing was performed on a test frame.ResultsCapsule thickness was significantly increased in cirrhotic samples compared to normal controls irrespective of disease etiology (69.62 ± 9.99 and 171.269 ± 16.65 µm respectively), whereas steatosis and moderate fibrosis had no effect on thickness (62.15 ± 4.97 µm). Changes in cirrhosis included an increase in cell number (fibroblasts, vascular cells, infiltrating immune cells and biliary epithelial cells). Key matrix components (collagens 1 and 3, hyaluronan, versican and elastin) were all deposited in the lower capsule although only the relative amounts per area of hyaluronan and versican were increased. Organizational features including crimping and alignment of collagen fibers were also altered in cirrhosis. Unexpectedly, capsules from cirrhotic livers had decreased resistance to loading in comparison to controls.ConclusionsThe liver capsule, like the parenchyma, is an active site of disease, demonstrating changes in matrix and cell composition as well as mechanical properties.Lay summaryWe assessed the changes in composition and response to stretching of the liver outer sheath, the capsule, in human liver disease. We find an increase in key structural components and numbers of cells as well as a change in matrix organization of the capsule in the later stages of disease. This allows the diseased capsule to stretch more under any given force, suggesting it is less stiff than healthy tissue.Graphical abstractHighlightsThe capsule is an active site of disease: thickness and cellularity increase markedly in cirrhosisExtracellular matrix composition and organization change in cirrhosisThe cirrhotic capsule stretches more and is less stiff

The meniscus plays a central load bearing role in the knee joint. Unfortunately, meniscus injury is common and can lead to joint degeneration and osteoarthritis. In small animal models, progressive degenerative changes occur with unloading of the meniscus via destabilization of the medial meniscus (DMM). However, few large animal models of DMM exist and the joint-wide initiation of disease has not yet been defined in these models. Thus, the goal of this study was to develop and validate a large-animal model of surgically-induced destabilization of the medial meniscus and to use multi-modal (mechanical, histological, and MRI) and multi-scale (joint to tissue level) quantitative measures to evaluate degeneration in both the meniscus and cartilage. DMM was achieved using an arthroscopic approach in thirteen Yucatan minipigs. One month after DMM, joint contact area decreased and peak pressure increased, indicating altered load transmission as a result of meniscus destabilization. By three months, the joint had adapted to the injury and load transmission patterns were restored to baseline, likely due to the formation and maturation of a fibrovascular scar at the anterior aspect of the meniscus. Despite this, we found a decrease in the indentation modulus of the tibial cartilage and an increase in cartilage histopathology scores at one month compared to Sham operated animals; these deleterious changes persisted through three months. Over this same time course, meniscus remodeling was evident through decreased proteoglycan staining in DMM compared to Sham menisci at both one and three months. These findings support that arthroscopic DMM results in joint degeneration in the Yucatan minipig and provides a new large animal test bed in which to evaluate therapeutics and interventions to treat post-traumatic osteoarthritis (PTOA) that originates from meniscal injury.

Background: The docking technique is widely used to perform ulnar collateral ligament (UCL) reconstructions because of its high failure torque and reliable clinical outcomes. A double–cortical button technique was recently described, with advantages including the ability to tension the graft at the ulnar and humeral attachments and the creation of single bone tunnels. Purpose/Hypothesis: To compare the biomechanics between the docking and double-button UCL reconstruction techniques using cadaveric specimens. We hypothesized that there would be no difference in postoperative stiffness or maximum strength between the techniques. Study Design: Controlled laboratory study. Methods: Eight matched pairs of cadaveric elbow joints underwent controlled humeral valgus torsion cycles in a test frame. Toe region stiffness, elastic region stiffness, and maximum torque were measured during a 4-step protocol: intact, injured, reconstructed (10 and 1000 cycles), and ramp to failure. Graft strains were calculated using 3-dimensional motion capture. Results: After 10 cycles, intact ligaments from the docking and double-button groups exhibited mean ± SD elastic torsional stiffness of 1.60 ± 0.49 and 1.64 ± 0.35 N·m/deg ( P = .827), while docking (1.10 ± 0.39 N·m/deg) and double-button (1.05 ± 0.29 N·m/deg) reconstructions were lower ( P = .754). There were no significant differences in maximum torque between the docking (3.45 ± 1.35 N·m) and double-button (3.25 ± 1.31 N·m) groups ( P = .777). Similarly, differences in maximum graft strains were not significant between the docking (8.1% ± 7.2%) and double-button (5.5% ± 3.1%) groups ( P = .645). The groups demonstrated similar decreases in these measures after cyclic loading. Ramp-to-failure testing showed no significant differences in ultimate torque between the docking (8.93 ± 3.9 N·m) and double-button (9.56 ± 3.5 N·m) groups ( P = .739). Conclusion: The biomechanical behavior of the double-button technique was not significantly different from that of the docking technique. Both reconstruction techniques restored joint stability, but neither fully recapitulated preinjury joint stiffness. Clinical Relevance: With its procedural advantages, results preliminarily support the use of the double-button reconstruction technique for UCL reconstruction as a reliable single-tunnel technique for primary or revision cases.

Rib fractures and chest flail injuries are life threatening injuries that often require surgical treatment using metal (e.g. titanium) fracture reconstruction plates and screws. Current implant designs do not account for the variable stiffness present in human ribs and are much stiffer than the native bone, causing undesirable clinical outcomes. In this preliminary study, groups of latticed test plates were designed with a body centered cubic (BCC) lattice and porosities ranging from 36–86%. Porosity was altered by changing lattice strut thickness between 0.225–0.425 mm and unit cell length between 1, 2, and 3 mm. The test plates were fabricated using an established laser powder bed fusion additive manufacturing process. Flexural strength (4-point bending) tests were performed at a strain rate of 1.3 mm/min to characterize changes in bending stiffness and strength. It was found that implant stiffness could be decreased by 15.7% (p = 0.068) by decreasing strut thickness from 0.425 to 0.225 mm and increasing unit cell length from 1 to 3 mm. The results of this preliminary experiment serve as guidelines for the design of full-sized rib fracture reconstruction plates that contain a gradient lattice with varied mechanical properties to better match the behavior of intact ribs.

This systematic review explores the differences in the intrinsic biomechanical properties of different graft sources used in anterior cruciate ligament (ACL) reconstruction as tested in a laboratory setting.Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two authors conducted a systematic review exploring the biomechanical properties of ACL graft sources (querying PubMed, Cochrane, and Embase databases). Using the keywords "anterior cruciate ligament graft," "biomechanics," and "biomechanical testing," relevant articles of any level of evidence were identified as eligible and included if they reported on the biomechanical properties of skeletally immature or mature ACL grafts solely and if the grafts were studied in vitro, in isolation, and under similar testing conditions. Studies were excluded if performed on both skeletally immature and mature or non-human grafts, or if the grafts were tested after fixation in a cadaveric knee. For each graft, failure load, stiffness, Young's modulus, maximum stress, and maximum strain were recorded.Twenty-six articles were included. Most studies reported equal or increased biomechanical failure load and stiffness of their tested bone-patellar tendon-bone, hamstring, quadriceps, peroneus longus, tibialis anterior and posterior, Achilles, tensor fascia lata, and iliotibial band grafts compared to the native ACL. All recorded biomechanical properties had similar values between graft types.Most grafts used for ACL reconstruction are biomechanically superior to the native ACL. Utilizing a proper graft, combined with a standard surgical technique and a rigorous rehabilitation before and after surgery, will improve outcomes of ACL reconstruction.

Current surgical fracture treatment paradigms, which use rigid metallic constructs to heal bones, provide reasonable clinical outcomes; however, they do not leverage recent advances in our understanding of bone healing and mechanotransduction throughout bone healing. The objective of this review was to investigate the efficacy and potential clinical applicability of surgical techniques and implants that deliberately introduce interfragmentary motion throughout the healing process.The authors searched PubMed and Google Scholar databases for articles reporting on fracture repair using dynamic locking plates, dynamized surgical techniques, and reverse dynamization. Data collection also included assessment of additively manufactured (AM) implants that provide dynamic mechanical behaviors.Forty articles were included for final review. It was found that accelerated rates of fracture healing can be achieved with staged 2-part surgeries or dynamic implant designs. Temporal dynamization, where static fixation of bones is followed by the introduction of micromotion and controlled loading, has been shown to improve callus volume and accelerate the healing response. Reverse dynamization, where micromotion is encouraged during early callus formation and arrested later, may represent a significant advance for the treatment of critical defect injuries. Advances in AM techniques will likely provide the ability to create high-resolution implants capable of dynamized and reverse dynamized modalities.There is no one-size-fits-all approach to optimization of fracture healing. However, it has been clearly demonstrated that fracture treatment can be enhanced by systematically altering the construct stiffness throughout the different phases of healing, which may be achieved with AM implant designs.

Biomechanical testing of long bones can be susceptible to errors and uncertainty due to malalignment of specimens with respect to the mechanical axis of the test frame. To solve this problem, we designed a novel, customizable alignment and potting fixture for long bone testing. The fixture consists of three-dimensional-printed components modeled from specimen-specific computed tomography (CT) scans to achieve a predetermined specimen alignment. We demonstrated the functionality of this fixture by comparing benchtop torsional test results to specimen-matched finite element models and found a strong correlation (R2 = 0.95, p

Achieving satisfactory fracture fixation in osteoporotic patients with unstable proximal humerus fractures remains a major clinical challenge. Varus collapse is one of the more prominent complications that may lead to screw cutout. This aim of this study was to compare the fixation provided by conventional locking plates with novel design concepts that are only feasible through additive manufacturing (AM) techniques. In addition to reversed engineered implants, two novel implant designs with integrated struts were included in the study to provide medial support to humeral head. The medial strut was either solid or included a porous lattice structure intended to promote bone ingrowth. Biomechanical tests were performed using low density synthetic bones with simulated 3-part comminuted fractures. Nondestructive torsion and compression were performed, followed by increasing cyclic loading. The relative displacements between the bone fragments were determined using a 3D motion capture system. The AM manufactured implants with medial strut showed significant reduction of varus displacement during the increasing cyclic loading when compared to conventional designs. AM reversed-engineered locking plates showed similar mechanical behavior to conventional plates with identical geometry. This study demonstrates the feasibility and potential of employing alternative design via AM for fixation of unstable comminuted proximal humerus fractures to reduce fragment displacement.

The purpose of this study was to systematically quantify distal radioulnar joint stability with a cadaveric model, using radiographic and joint contact force measurements. Six fresh-frozen cadavers underwent sequential ulnar styloid osteotomies. Posteroanterior and lateral stress radiographs were obtained and joint contact forces and areas were measured. Posteroanterior radiographs showed a significant increase in the distal radioulnar joint gap after osteotomy of the base of the ulnar styloid. Contact force and contact area measurements were not significantly different. We conclude that fractures that involve the ulnar styloid base should be considered for operative fixation when carrying out open reduction and internal fixation of fractures of the distal radius.

Achilles tendon ruptures have been linked with detrimental changes in muscle-tendon structure, which may help explain long-term functional deficits. However, the causal effects of muscle-tendon structure on joint function have not been tested in a controlled setting. Therefore, the purpose of this study was to test the implications of muscle-tendon unit parameters on simulated single-leg heel raise height. We hypothesized that muscle fiber length and resting ankle angle - a clinical surrogate measure of tendon slack length - would predict single-leg heel raise height more strongly than other parameters. To test this hypothesis, we developed a two-part simulation paradigm that recreated clinically relevant muscle-tendon scenarios and then tested these parameters on single-leg heel raise height. We found that longer muscle fibers had the greatest positive effect on single-leg heel raise height. However, tendon slack length, determined by simulating resting ankle angles in a secondary analysis, revealed a stronger negative correlation with heel raise height. Our findings support previous clinical observations that both muscle fascicle length and resting tendon length are important muscle-tendon parameters for patient function. In addition to minimizing tendon elongation following rupture, treatment plans should focus on preserving plantarflexor muscle structure to mitigate functional loses following Achilles tendon ruptures.

Background: A previous study has demonstrated an increase in mechanical properties of acellular canine bone after topical raloxifene exposure. The goal of this study was to determine if similar treatment yields the same results in bovine bone and whether this translates into a difference in screw pull-out strength in human cadaveric tissue. Methods: Matched pairs of bone specimens were submerged in solutions of either raloxifene (20 µM) or phosphate-buffered saline as a control for 7 days. In the first experiment, cancellous bone from fetal bovine distal femora underwent quasi-static four-point bending tests. In the second experiment, 3.5 mm unicortical cancellous screws were inserted to a 30 mm depth in human osteoporotic cadaveric humeral heads and quasi-static screw pull-out tests were performed. Results: In the four-point bending tests, there were no significant differences between the raloxifene and control groups for any of the mechanical properties - including stiffness (p = 0.326) and toughness (p = 0.850). In the screw pull-out tests, the raloxifene soaked samples trended towards a higher load at failure, without statistical significance (p = 0.099). Failure loads were 122 ± 74.3 N and 89.5 ± 63.8 N for the raloxifene and control groups, respectively.Conclusions: Biologic solutions that address the acute improvement of bone quality during the fracture healing timeframe are an important area of future research and untapped potential for reducing construct failure in osteoporotic fracture fixation. The bovine samples did not demonstrate an increase in toughness with raloxifene treatment, which is in contrast to previously published data. In vivo experiments are likely required to determine whether topical use of raloxifene will improve implant fixation.

Current implants for clavicle fractures are known to cause poor cosmesis and irritation, which may require implant removal. Low-profile shape-memory staples provide an attractive alternative, but their biomechanical utility in clavicle reconstruction is unknown. We hypothesized that shape-memory reconstructions would be more compliant compared to traditional constructs but would also outperform conventional plates during cyclic loading to failure.This study was performed with 36 synthetic clavicles and 12 matched pairs of cadaveric specimens. The synthetic study tested four reconstructions: a single superiorly placed staple (n = 6), a single anteroinferiorly-placed staple (n = 6), a 3.5 mm reconstruction plate (n = 12), and two orthogonally placed staples (n = 12). The cadaveric study tested three constructs: reconstruction plate (n = 8), two orthogonal staples (n = 8), and a 2.7 mm reconstruction plate combined with a superior staple (n = 8). Non-destructive 4-point bending, compression, and torsion assays were performed prior to destructive cantilever bending and cyclic torsion tests.The single staple and double staple groups demonstrated significantly decreased resistance to bending (p 0.001) and torsion (p ≤ 0.027) when compared to reconstruction plate groups. The double staple group sustained significantly fewer cycles to failure than the reconstruction plate group in cyclic torsional tests (p = 0.012). The synthetic models produced higher stiffness and failure mechanisms that were completely different from cadaveric specimens.Shape memory alloy implants provided inadequate stiffness for clavicle fixation but may have utility in other orthopaedic applications when used as a supplementary compression device in conjunction with traditional plated constructs. Synthetic bones have limited capacity for modeling fragility fractures.

OBJECTIVES To make direct comparisons of the biomechanical properties of a control (CTL) group and implants that were augmented with far cortical locking (FCL), bone substitute material (BSM), and a combination of both (ALL) to determine which fixation is most effective in reducing implant failure. METHODS The constructs were tested with osteopenic cadaveric specimens in a two-part fracture model. Specimens were subjected to a battery of nondestructive torsion and axial compression tests, followed by a cyclic test. Construct stiffness and cycles to failure were documented, pre- and post-test fluoroscopy was performed, and implant and bone kinematics were quantified. RESULTS During nondestructive testing, the BSM group exhibited significantly increased torsional and axial stiffness compared with the FCL (P = 0.006, P < 0.001) group and ALL group (P < 0.001, P = 0.006). There were no significant differences in resistance to cyclic loading between groups. Fluoroscopic analysis indicated significant differences in the motions of nonlocked cannulated screws (used in BSM and ALL) versus locked screws (used in CTL and FCL). CONCLUSIONS Patients with poor bone quality and proximal humerus fracture may necessitate added compliance or rigidity to achieve fixation. Both have exhibited favorable biomechanical characteristics in this cadaveric 2-part proximal humerus fracture model.

Background: Tendon injuries are common problems among athletes. Complete recovery of the mechanical structure and function of ruptured tendons is challenging. It has been demonstrated that upregulation of glycolysis and lactate production occurs in wounds, inflammation sites, and cancerous tumors, and these metabolic changes also control growth and differentiation of stem and progenitor cells. Similar metabolic changes have been reported in human healing tendons. In addition, lactate production has increased in progenitors isolated from injured tendons after treatment with IL-1β. It is thought that the metabolic changes play a role in tendon healing after injury. Hypothesis: Glucose metabolism is altered during tendon injury and healing, and modulation of this altered metabolism improves tendon repair. Study Design: Controlled laboratory study. Methods: The authors used the tendon injury model involving a complete incision of the Achilles tendon in C57BL/6J female mice and studied alterations of glucose metabolism in injured tendons with [U-13C]glucose and metabolomics analysis 1 and 4 weeks after surgery. They also examined the effects of dichloroacetate (DCA; an indirect lactate synthesis inhibitor) treatment on the recovery of structure and mechanical properties of injured tendons 4 weeks after surgery in the same mouse model. Results: Significant changes in glucose metabolism in tendons after injury surgery were detected. 13C enrichment of metabolites and intermediates, flux through glycolysis, and lactate synthesis, as well as tricarboxylic acid cycle activity, were acutely increased 1 week after injury. Increased glycolysis and lactate generation were also found 4 weeks after injury. DCA-treated injured tendons showed decreased cross-sectional area and higher values of modulus, maximum stress, and maximum force when compared with vehicle-treated injured tendons. Improved alignment of the collagen fibers was also observed in the DCA group. Furthermore, DCA treatment reduced mucoid accumulation and ectopic calcification in injured tendons. Conclusion: The findings indicate that injured tendons acutely increase glycolysis and lactate synthesis after injury and that the inhibition of lactate synthesis by DCA is beneficial for tendon healing. Clinical Relevance: Changing metabolism in injured tendons may be a therapeutic target for tendon repair.

Superior capsular reconstruction has received increased attention as a surgical technique to address massive "irreparable" rotator cuff tears; however, the functional limitations and surgical techniques associated with this repair have yet to be sufficiently explored. The goal of this study was to utilize a multidisciplinary approach to characterize the biomechanics of this repair by: (i) identifying activities of daily living that may overburden the graft; and (ii) optimizing surgical techniques used during implantation. This experiment was completed in three phases. First, graft failure mechanics were characterized by performing an in vitro experiment. Second, in vivo shoulder kinematics associated with various activities were recorded with 3-D motion capture techniques. Finally, an in silico model was used to assess graft strains. Results show that motions involving posterior shoulder rotation, such as back washing, lead to graft strains that may cause failure. Output from the optimization suggests that orienting the humerus in approximately 25° abduction, and 20° internal rotation during implantation will result in optimal graft performance. Clinical Significance: The novel paradigm used in this study demonstrates the utility of coupling in vitro, in vivo, and in silico modeling techniques in one cohesive experiment. This paradigm presents an additional tool, aside from clinical studies and cadaveric experimentation, to better predict and understand the strengths and limitations of superior capsular reconstruction. This approach has potential to be translated to other soft tissue repairs and may provide valuable information to clinicians and rehabilitative specialists to manage patient expectations and guide rehabilitation. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2789-2796, 2018.

Background: The corrective procedures for meniscal injury are dependent on tear type, severity, and location. Vertical longitudinal tears are common in young and active individuals, but their natural progression and impact on osteoarthritis (OA) development are not known. Root tears are challenging and they often indicate poor outcomes, although the timing and mechanisms of initiation of joint dysfunction are poorly understood, particularly in large-animal and human models. Purpose/Hypothesis: In this study, vertical longitudinal and root tears were made in a large-animal model to determine the progression of joint-wide dysfunction. We hypothesized that OA onset and progression would depend on the extent of injury-based load disruption in the tissue, such that root tears would cause earlier and more severe changes to the joint. Study Design: Controlled laboratory study. Methods: Sham surgeries and procedures to create either vertical longitudinal or root tears were performed in juvenile Yucatan mini pigs through randomized and bilateral arthroscopic procedures. Animals were sacrificed at 1, 3, or 6 months after injury and assessed at the joint and tissue level for evidence of OA. Functional measures of joint load transfer, cartilage indentation mechanics, and meniscal tensile properties were performed, as well as histological evaluation of the cartilage, meniscus, and synovium. Results: Outcomes suggested a progressive and sustained degeneration of the knee joint and meniscus after root tear, as evidenced by histological analysis of the cartilage and meniscus. This occurred in spite of spontaneous reattachment of the root, suggesting that this reattachment did not fully restore the function of the native attachment. In contrast, the vertical longitudinal tear did not cause significant changes to the joint, with only mild differences compared with sham surgery at the 6-month time point. Conclusion: Given that the root tear, which severs circumferential connectivity and load transfer, caused more intense OA compared with the circumferentially stable vertical longitudinal tear, our findings suggest that without timely and mechanically competent fixation, root tears may cause irreversible joint damage. Clinical Relevance: More generally, this new model can serve as a test bed for experimental surgical, scaffold-based, and small molecule–driven interventions after injury to prevent OA progression.

Design and processing capabilities of additive manufacturing (AM) to fabricate complex geometries continues to drive the adoption of AM for biomedical applications. In this study, a validated design methodology is presented to evaluate AM as an effective fabrication technique for reconstruction of large bone defects after tumor resection in pediatric oncology patients. Implanting off-the-shelf components in pediatric patients is especially challenging because most standard components are sized and shaped for more common adult cases. While currently reported efforts on AM implants are focused on maxillofacial, hip and knee reconstructions, there have been no reported studies on reconstruction of proximal humerus tumors. A case study of a 9-year-old diagnosed with proximal humerus osteosarcoma was used to develop a patient-specific AM prosthesis for the humerus following tumor resection. Commonly used body-centered cubic (BCC) structures were incorporated at the surgical neck and distal interface in order to increase the effective surface area, promote osseointegration, and reduce the implant weight. A patient-specific prosthesis was fabricated using electron beam melting method from biocompatible Ti-6Al-4V. Both computational and biomechanical tests were performed on the prosthesis to evaluate its biomechanical behavior under varying loading conditions. Morphological analysis of the construct using micro-computed tomography was used to compare the as-designed and as-built prosthesis. It was found that the patient-specific prosthesis could withstand physiologically-relevant loading conditions with minimal permanent deformation (82 μm after 105 cycles) at the medial aspect of the porous surgical neck. These outcomes support potential translation of the patient-specific AM prostheses to reconstruct large bone defects following tumor resection.

Objectives This study sought to examine fatigue characteristics of 2 polyaxial locking screw designs: locking cap (LC) and cross-threaded (CT). The goal was to compare LC and CT implants at 0, 10, and 15 degrees of angulation to determine the effect of locking mechanism on screw-plate interface failure. The hypothesis was that LC implants would have superior fatigue properties in comparison to CT designs and that increased angulation of the screw would have a negative impact on the fatigue life of CT implants, but would not have any effect on LC implants. Methods A total of 72 screws were tested in 4 upper extremity implants. Implants were subjected to cyclic shear loads and subsequent ramp to failure. Performance characteristics were statistically compared using nonparametric statistical methods. Results Fatigue testing demonstrated that LC designs were consistently able to sustain a significantly higher number of cyclic loads than CT designs. There were no significant differences in the number of cycles sustained by LC designs because of changes in screw angle, but CT implants exhibited decreases in screw stability with increasing angulation. Conclusions Likely because of the spherical screw head geometry, LC fatigue characteristics are not influenced by the orientation of the screw relative to the plate. Application of an LC in the operating room requires additional time, but provides significantly more robust fixation of the screw, especially at oblique angles to the plate and provides a more predictable and consistent biomechanical result.

Achilles tendon disorders are among the most difficult sports-related injuries to predict with current diagnostic tools. The purpose of this study was to identify a clinically useful marker for early tendon damage. We hypothesized that alterations in mean echogenicity are linked with changes in vitro tendon mechanics. To test our hypothesis, we harvested Achilles tendons from 10 fresh-frozen cadaveric feet and cyclically fatigued them using a universal test frame while we continuously acquired ultrasound images. Throughout this fatigue protocol, we applied 2 stress tests every 500 loading cycles to quantify changes in ultrasound imaging echogenicity. We continued this fatigue protocol until each tendon either failed completely or survived 150,000 cycles. Tendons that failed during the fatigue loading (6/10) underwent greater changes in mean echogenicity compared to tendons that did not fail (P = 0.031). These tendons that failed during fatigue loading demonstrated greater changes in mean echogenicity that surpassed 1.0%; whereas survivor tendons exhibited less than 0.5% changes in mean echogenicity. We found that changes in mean echogenicity measured with ultrasound increased proportionally with increased tendon damage. The magnitude of these changes was relatively small (Level of evidenceControlled laboratory experiment

Achilles tendon disorders are among the most difficult sports-related injuries to predict with current diagnostic tools. The purpose of this study was to identify a clinically useful marker for early tendon damage. We hypothesized that alterations in mean echogenicity are linked with changes in vitro tendon mechanics. To test our hypothesis, we harvested Achilles tendons from 10 fresh-frozen cadaveric feet and cyclically fatigued them using a universal test frame while we continuously acquired ultrasound images. Throughout this fatigue protocol, we applied 2 stress tests every 500 loading cycles to quantify changes in ultrasound imaging echogenicity. We continued this fatigue protocol until each tendon either failed completely or survived 150,000 cycles. Tendons that failed during the fatigue loading (6/10) underwent greater changes in mean echogenicity compared to tendons that did not fail (P = 0.031). These tendons that failed during fatigue loading demonstrated greater changes in mean echogenicity that surpassed 1.0%; whereas survivor tendons exhibited less than 0.5% changes in mean echogenicity. We found that changes in mean echogenicity measured with ultrasound increased proportionally with increased tendon damage. The magnitude of these changes was relatively small (1.5% change in mean echogenicity) but may be an effective predictor of tendon failure. Mean echogenicity is a promising marker for quantifying fatigue damage in cadaveric Achilles tendons during a stress test. Although these changes cannot be detected with the naked eye, computer-based predictive models may effectively assess risk of tendon damage in physically active adults.

Internal fixation with the use of locking plates is the standard surgical treatment for proximal humerus fractures, one of the most common fractures in the elderly. Screw cut-out through weak cancellous bone of the humeral head, which ultimately results in collapse of the fixed fracture, is the leading cause of failure and revision surgery. In an attempt to address this problem, surgeons often attach the plate with as many locking screws as possible into the proximal fragment. It is not thoroughly understood which screws and screw combinations play the most critical roles in fixation stability. This study conducted a detailed finite element analysis to evaluate critical parameters associated with screw cut-out failure. Several clinically relevant screw configurations and fracture gap sizes were modeled. Findings demonstrate that in perfectly reduced fracture cases, variation of the screw configurations had minor influence on mechanical stability of the fixation. The effects of screw configurations became substantial with the existence of a fracture gap. Interestingly, the use of a single anterior calcar screw was as effective as utilizing two screws to support the calcar. On the other hand, the variation in calcar screw configuration had minor influence on the fixation stability when all the proximal screws (A-D level) were filled. This study evaluates different screw configurations to further understand the influence of combined screw configurations and the individual screws on the fixation stability. Findings from this study may help decrease the risk for screw cut-out with proximal humerus varus collapse and the associated economic costs.

Background: Although anterior cruciate ligament (ACL) tears have received the most attention, the medial collateral ligament (MCL) is thought to be the most commonly injured knee ligament overall. The lateral collateral ligament (LCL) and posterior collateral ligament (PCL) are less frequently compromised but can be involved in severe multiligament injuries. The paucity of information on the native properties of these ligaments in the pediatric population hinders the overall optimization of treatment for these injuries. Purpose: To characterize the mechanical and microstructural properties of pediatric MCLs, LCLs, and PCLs using a rare cadaveric cohort (mean age, 9.2 years). Study Design: Descriptive laboratory study. Methods: MCLs, LCLs, and PCLs were harvested from 5 fresh-frozen pediatric knee specimens (3 male, 2 female) and were subjected to a tensile loading protocol. A subset of contralateral tissues from a single donor was analyzed using bright-field, polarized light, and transmission electron microscopy to measure collagen fiber morphology. Results: The pediatric MCL exhibited values for ultimate stress (11.7 ± 6.7 MPa), ultimate strain (18.2% ± 6.8%), and the Young modulus (93.7 ± 56.5 MPa) that were similar to values for the LCL (11.4 ± 11.5 MPa, 27.7% ± 12.9%, and 64.4 ± 76.6 MPa, respectively). The PCL demonstrated decreased ultimate stress (4.2 ± 1.8 MPa), increased ultimate strain (28.8% ± 11.9%), and a decreased Young modulus (19.8 ± 10.4 MPa) when compared with the MCL and LCL. All 3 ligaments had similar mean crimp wavelengths (MCL, 32.8 ± 3.6 µm; LCL, 27.2 ± 3.5 µm; PCL, 25.8 ± 3.5 µm) and collagen fibril diameters (MCL, 88.0 ± 26.0 nm; LCL, 93.3 ± 34.6 nm; PCL, 90.9 ± 34.0 nm); however, the fibril distribution profiles exhibited different modalities. Conclusion: The pediatric MCL and LCL possessed similar mechanical properties, while the pediatric PCL was weaker but capable of withstanding higher amounts of strain. All 3 of these pediatric structures were weaker than what has been reported in studies with adult cohorts. Clinical Relevance: Results from this study can be considered preliminary mechanical and microstructural data for healthy pediatric collateral and posterior cruciate ligaments that can be used to guide further laboratory and clinical research.

Adequate glenoid baseplate fixation in reverse total shoulder arthroplasty (rTSA) is important to achieve, but may prove challenging in the context of glenoid bone loss or osteopenia. Current rTSA testing standards rely upon synthetic bone surrogates, but it is unclear if these models accurately recapitulate the mechanics of osteoporotic bone. Additionally, it also unknown if the use of a central screw effectively provides resistance to micromotion in the milieu of poor quality bone. The purpose of this experiment was to create a novel cyclic load test protocol that elicited clinically relevant failures, so that comparisons of relative motion between baseplates and bones could be made with: (1) synthetic bones and poor quality cadaveric bones, and (2) the use or omission of a central screw. rTSA components were implanted into cadaveric and synthetic bones with and without a central screw. To model a range of loads that may be experienced during abduction, increasing cyclic loads were applied to shoulder joints in 30° of humeral abduction. Cycles and loads prior to permanent deformation exceeding 150 µm, 1 mm, and joint failure were determined using measurements from the test frame and from 3-D motion analysis. Synthetic bones demonstrated significantly more resistance to micromotion in comparison to cadaveric bones. Use of the central screw improved resistance to dislodgement, which was only observed in the cadaveric specimens. This study highlights the need for biomechanical testing with cadaveric specimens, especially when assessing osteopenic or osteoporotic populations.

Background The saline load test has previously been shown to be an effective tool to diagnose traumatic arthrotomies, but no studies have assessed the test's efficacy in the wrist. The purpose of this study was to investigate the amount of fluid required during a saline load test to detect intra-articular wrist involvement of traumatic wounds with high sensitivity. Methods A cadaveric study was conducted using 7 thawed, fresh-frozen forequarter amputations from 7 different donors (3 male, 4 female). Specimen age (mean: 67.7 y, range: 52 to 80 y), laterality (1 right, 6 left), body weight (mean: 164.3 lbs, range: 100 to 223 lbs), and wrist range of motion (ROM) was assessed before testing. The wrist capsule was punctured with an 11-blade scalpel through the 6R radiocarpal portal site under fluoroscopic guidance to ensure the injury was intra-articular. A 19-G needle was then placed through the 3,4 radiocarpal portal site and confirmed with fluoroscopy to ensure intra-articular placement. Normal saline was then injected at a steady rate into the 3,4 radiocarpal portal site until extravasation of the saline was observed from the 6R radiocarpal arthrotomy site. The volume of saline required for extravasation from the 6R radiocarpal arthrotomy was recorded as the volume required to detect the arthrotomy. A plot of saline volumes (by percentile) was created, and a logarithmic distribution was calculated. A Wilcoxon rank-sum test was used to compare injection volumes between male and female specimens, and Pearson Coefficients were used to determine any correlations between injection volume and ROM. Results The average amount of saline that resulted in extravasation was 4 mL (range: 2 to 7 mL). In order to identify 75%, 90%, 95%, and 99% of the simulated wrist arthrotomies, 5 (95% confidence interval: 3-7), 6 (4-9), 7 (4-10), and 9 (5-14) mL were required, respectively. Pretest ROM did not correlate with saline volume. Conclusions This study demonstrates the efficacy of the saline load test in detecting traumatic arthrotomies of the wrist joint with 95% sensitivity after loading 7 mL of saline. Prompt and accurate diagnosis of traumatic arthrotomies is paramount to guide management and optimize postinjury outcomes.

A cadaveric study was performed to investigate the external mechanical forces required to fracture maxillary fourth premolar teeth in domestic dogs and describe a clinically relevant model of chewing forces placed on functionally important teeth in which fracture patterns are consistent with those defined by the American Veterinary Dental College (AVDC). Twenty-four maxillary fourth premolar teeth were harvested from dog cadavers. Samples consisted of teeth with surrounding alveolar bone potted in polycarbonate cylinders filled with acrylic. The cylinders were held by an aluminum device at an angle of 60° with respect to the ground. An axial compression test was performed, creating a force upon the occluso-palatal aspects of the main cusps of the crowns of the teeth. The highest compressive force prior to failure was considered the maximum force sustained by the teeth. Results showed the mean maximum force (± SD) sustained by the tested teeth at the point of fracture was 1,281 N (± 403 N) at a mean impact angle (± SD) of 59.7° (± 5.2°). The most common fracture type that occurred among all samples was a complicated crown fracture (n = 12), followed by an uncomplicated crown fracture (n = 6), complicated crown-root fracture (n = 5), and uncomplicated crown-root fracture (n = 1). There was no statistically significant correlation between dog breed, age, weight, impact angle, crown height or crown diameter, and the maximum force applied at the point of fracture. The only independent variable that remained significantly associated with maximum force was the crown height to diameter ratio (p = 0.005), suggesting that a decreased ratio increases tooth fracture resistance. The methodology described herein has been successful in creating a pattern of fracture of maxillary fourth premolar teeth consistent with that defined by the AVDC under angled compression at forces within the maximum chewing capability of the average domestic dog.

Recent advancements in additive manufacturing (AM) have motivated researchers to consider this fabrication technique as a solution for challenges in patient-specific orthopaedic needs. Although there is an increasing trend in the applications of AM in medical fields, there is a critical need to understand the biomechanical performance of AM implants. In particular, design opportunities, anisotropic material properties and resulting stability of AM implant constructs for large bone defects such as osteosarcoma, comminuted fractures and infections are unexplored. This study aims to evaluate metal AM for complex fracture fixation using both computational and experimental methods. In addition, this research highlights the role of AM in the entire workflow to fabricate metal AM fixation plates for treatment of comminuted proximal humerus fractures. A new AM-centric patient-specific implant design for reducing common postoperative complications such as varus collapse and screw cutout is investigated. Biocompatible 316L stainless steel specimens processed in laser-powder bed fusion (L-PBF) is subjected to tensile testing and post-hoc microhardness to obtain orthotropic material properties of the AM implants. Subsequently, risk of screw cut-out is evaluated using finite element modelling (FEM) of AM implant-bone constructs. Parallel experiments included synthetic bones that are evaluated using a 3D motion capture system. The biomechanical tests are analyzed to quantify the medial fracture gap displacement among study groups subject to different loading conditions. The outcomes of this study suggest that the proposed AM-centric fixation plate design reduces average varus collapse (i.e. medial fracture gap displacement) by 47.2 % and risk of screw cut-out by 14.6 % when compared to the conventional plate design. Findings from this study can be extended to other patient anatomy, loading conditions, and AM processes.

Half of the women who sustain a hip fracture would not qualify for osteoporosis treatment based on current DXA-estimated bone mineral density criteria. Therefore, a better approach is needed to determine if an individual is at risk of hip fracture from a fall. The objective of this study was to determine the association between radiation-free MRI-derived bone strength and strain simulations compared to results from direct mechanical testing of cadaveric femora. Imaging was conducted on a 3-Tesla MRI scanner using two sequences: one balanced steady-state free precession sequence with 300 μm isotropic voxel size and one spoiled gradient echo with anisotropic voxel size of 234 × 234 × 1500 μm. Femora were dissected free of soft-tissue and 4350-ohm strain-gauges were securely applied to surfaces at the femoral shaft, inferior neck, greater trochanter, and superior neck. Cadavers were mechanically tested with a hydraulic universal test frame to simulate loading in a sideways fall orientation. Sideways fall forces were simulated on MRI-based finite element meshes and bone stiffness, failure force, and force for plastic deformation were computed. Simulated bone strength metrics from the 300 μm isotropic sequence showed strong agreement with experimentally obtained values of bone strength, with stiffness (r = 0.88, p = 0.0002), plastic deformation point (r = 0.89, p 0.0001), and failure force (r = 0.92, p 0.0001). The anisotropic sequence showed similar trends for stiffness, plastic deformation point, and failure force (r = 0.68, 0.70, 0.84; p = 0.02, 0.01, 0.0006, respectively). Surface strain-gauge measurements showed moderate to strong agreement with simulated magnitude strain values at the greater trochanter, superior neck, and inferior neck (r = -0.97, -0.86, 0.80; p ≤0.0001, 0.003, 0.03, respectively). The findings from this study support the use of MRI-based FE analysis of the hip to reliably predict the mechanical competence of the human femur in clinical settings.

Achilles tendon ruptures lead to reduced ankle function and often limits recreational activity. Single-leg heel raises are often used clinically to characterize patient function. However, it is unclear how the structure of the Achilles tendon and plantarflexor muscles affects single-leg heel raise function. Therefore, the purpose of this study was to develop a musculoskeletal model in order to simulate the effects of muscle-tendon unit (MTU) parameters on peak plantarflexion during this clinically-relevant task. The ankle joint was plantarflexed by two MTUs that represented the soleus and gastrocnemius muscles. The optimal fiber length, maximal muscle force, muscle pennation, tendon stiffness, and resting ankle angle – a surrogate measure of tendon slack length – were iteratively adjusted to test the combined effects of each of these MTU parameters. Single-leg heel raises were simulated by maximally exciting the two plantarflexor MTUs for each model configuration (N = 161,051 simulations). Optimal muscle fiber and tendon slack lengths had the greatest effect on peak plantarflexion during simulated single-leg heel raises. Simulations that were unable to produce at least 30 degrees of plantarflexion had muscle fibers that were shorter than healthy muscle and longer tendon slack lengths. These findings highlight the importance of preserving muscle fascicle and tendon length following Achilles tendon injuries.Fundingno funding has been provided for this researchAcknowledgementsthe Authors have no acknowledgementsConflict of interestthe Authors have no conflicts of interest that are relevant to this work

BackgroundLocked plating of displaced proximal humerus fractures is common, but rates of subacromial impingement remain high. Computational predictions of implant impingement have yet to be sufficiently explored in proximal humerus fixation. The goal of this study was to utilize a multidisciplinary approach to elucidate the relationships between common surgical parameters, anatomical variability, and the likelihood of plate impingement.MethodsThe experiment was completed in three phases. First, a controlled in vitro experiment was conducted to simulate impingement. Second, a dynamic in silico musculoskeletal model was developed to simulate changes to implant geometry, surgical techniques, and acromial anatomy, where a collision detection algorithm was used to simulate contact between the plate and acromion. Finally, in vivo shoulder kinematics were recorded for nine activities of daily living and motions that created a high likelihood of impingement were identified.ResultsImpingement was measured at 73.3±14.5° abduction in the cadaveric model and 92.0°±34.0° with computational simulations. Impingement events were limited to ranges of motion between 10–40° of cross-body adduction. Activities of daily living, such as combing one’s hair, lifting and object overhead, and reaching behind one’s head are likely to cause impingement.Discussion and ConclusionThis multidisciplinary experiment quantified key preoperative factors to assist with implantation decisions. Results demonstrated that proximal implant placement, superior translation of the humeral center of rotation, increases in plate thickness, and increases in acromial tilt all increase the likelihood of impingement. Careful preoperative planning that includes these factors could help guide operative decision making and improve clinical outcomes.Level of Evidence: V

BackgroundOver the last several decades there has been a steady increase in pediatric ACL tears, particularly in young female basketball and soccer players. Because allograft tissue for pediatric ACL reconstruction (ACLR) has shown high rates of failure, autograft tissue may be the best option for ACLR in this population. However, the differences in structure and mechanical behavior of these tissues are not clear.PurposeThis study sought to characterize mechanical and microstructural properties in pediatric ACLs and autograft tissues using a rare cadaveric cohort (mean age 9.2 years).Study DesignDescriptive laboratory study.MethodsACLs, patellar tendons, quadriceps tendons, semitendinosus tendons, and iliotibial bands (ITBs) were harvested from five fresh-frozen pediatric knee specimens (3M, 2F) and subjected to a tensile loading protocol. A subset of contralateral tissues were analyzed using brightfield, polarized light, and transmission electron microscopy.ResultsPatellar tendons exhibited values for ultimate stress (5.2±3.1 MPa), ultimate strain (35.3±12.5%), and Young’s Modulus (27.0±8.0 MPa) that were most similar to the ACL (5.2±2.2 MPa; 31.4±9.9%; 23.6±15.5 MPa). Semitendinosus tendons and ITBs were stronger but less compliant than the quadriceps or patellar tendons. ITBs exhibited crimp wavelengths (24.3±3.1 um) and collagen fibril diameters (67.5±19.5 nm) that were most similar to the ACL (24.4±3.2 um; 69.7±20.3 nm).ConclusionThe mechanical properties of the patellar tendon were almost identical to that of the ACL. The ITB exhibited increased strength and similar microstructure to the native ACL. These findings are not entirely congruent to studies examining adult tissues.Clinical RelevanceResults suggest that ITB tissue may be the preferable choice as an autograft tissue in pediatric ACL reconstructions.Key TermsPediatric, ACL reconstruction, mechanical properties, microstructural properties, patella tendon grafts, quadriceps tendon grafts, hamstring graftsWhat is Known about the SubjectDue to the extreme rarity of pediatric cadaveric specimens, very little is known about these tissues.What this Study Adds to Existing KnowledgeThis suite of data can be used to further optimize the design and selection of grafts for reconstruction and may provide insight into the development of constitutive musculoskeletal models.

Background: Plantarflexor structure is an important predictor of function in healthy, athletic, and some patient populations. Computational simulations are powerful tools capable of testing the isolated effects of muscle-tendon structure on gait function. Research Question: The purpose of this study was to characterize the sensitivity of plantarflexor muscle function based on muscle-tendon unit (MTU) parameters. We hypothesized that plantarflexor metabolics and shortening dynamics would be sensitive to MTU parameters. Methods: Stance phase of gait was simulated using a musculoskeletal model and computed muscle control algorithm. Optimal muscle fiber length, resting ankle angle, and tendon stiffness parameters were systematically changed to test these effects on plantarflexor metabolics, activation, and power. Dorsiflexor metabolics were also measured to determine the impact of the action of the antagonist muscle group. Results and Significance: Plantarflexor metabolic demands were 1.5 and 2.7 times more sensitive to optimal fiber length and resting ankle angle, respectively, compared to the effect of tendon stiffness. Increased resting ankle plantarflexion induced a large passive plantarflexion moment during early stance, which required non-physiologic dorsiflexor contractions. Conversely, longer optimal fiber and more neutral resting ankle angles increased the shortening demands of the plantarflexors. These findings highlight the importance of carefully selecting MTU parameters when modeling gait with musculoskeletal models, especially in pathologic or high-performance athlete populations.