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.
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.
In locked plate fixation of proximal humerus fractures, the calcar is an important anchor point for screws providing much-needed medial column support. Most locking plate implants utilize a ...fixed-trajectory locking screw to achieve this goal. Consequently, adjustments of plate location to account for patient-specific anatomy may result in a screw position outside of the calcar. To date, little is known about the consequences of “missing” the calcar during plate positioning. This study sought to characterize the biomechanics associated with proximal and distal placement of locking plates in a two-part fracture model.
This experiment was performed twice, first with elderly cadaveric specimens and again with osteoporotic sawbones. Two-part fractures were simulated and specimens were divided to represent proximal, neutral, and distal plate placements. Non-destructive torsional and axial compression tests were performed prior to an axial fatigue test and a ramp to failure. Torsional stiffness, axial stiffness, humeral head displacement and stiffness during fatigue testing, and ultimate load were compared between groups.
Cadavers: Proximal implant placement led to trends of decreased mechanical properties, but there were no significant differences found between groups. Sawbones: Distal placement increased torsional stiffness in both directions (p = 0.003, p = 0.034) and axial stiffness (p = 0.018) when compared to proximal placement. Distal placement also increased torsional stiffness in external rotation (p = 0.020), increased axial stiffness (p = 0.024), decreased humeral head displacement during fatigue testing, and increased stiffness during fatigue testing when compared to neutral placement.
The distal and neutral groups had similar mechanical properties in many cadaveric comparisons while the proximal group trended towards decreased construct stiffness.
from the Sawbones model were more definitive and provided further evidence that proximal calcar screw placements are undesirable and distal implant placement may provide improved construct stability.
Successful proximal humerus fracture reconstruction is inherent upon anatomic fracture reduction coupled with medial column support. Results from this experiment suggest that missing the calcar proximally is deleterious to fixation strength, while it is safe, and perhaps even desirable, to aim slightly distal to the intended target.
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 m
) 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.
The biological mechanisms regulating tenocyte differentiation and morphological maturation have not been well-established, partly due to the lack of reliable in vitro systems that produce highly ...aligned collagenous tissues. In this study, we developed a scaffold-free, three-dimensional (3D) tendon culture system using mouse tendon cells in a differentially adherent growth channel. Transforming Growth Factor-β (TGFβ) signaling is involved in various biological processes in the tendon, regulating tendon cell fate, recruitment and maintenance of tenocytes, and matrix organization. This known function of TGFβ signaling in tendon prompted us to utilize TGFβ1 to induce tendon-like structures in 3D tendon constructs. TGFβ1 treatment promoted a tendon-like structure in the peripheral layer of the constructs characterized by increased thickness with a gradual decrease in cell density and highly aligned collagen matrix. TGFβ1 also enhanced cell proliferation, matrix production, and morphological maturation of cells in the peripheral layer compared to vehicle treatment. TGFβ1 treatment also induced early tenogenic differentiation and resulted in sufficient mechanical integrity, allowing biomechanical testing. The current study suggests that this scaffold-free 3D tendon cell culture system could be an in vitro platform to investigate underlying biological mechanisms that regulate tenogenic cell differentiation and matrix organization.
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 (OA). In small animal models, ...progressive degenerative changes occur with the 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 the disease has not yet been defined in these models. Thus, the goal of this study is to develop and validate a large animal model of surgically induced DMM and to use multimodal (mechanical, histological, and magnetic resonance imaging) and multiscale (joint to tissue level) quantitative measures to evaluate degeneration in both the meniscus and cartilage. DMM was achieved using an arthroscopic approach in 13 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 3 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 1 month compared to sham‐operated animals; these deleterious changes persisted through 3 months. Over this same time course, meniscus remodeling was evident through decreased proteoglycan staining in DMM compared to sham menisci at both 1 and 3 months. These findings support that arthroscopic DMM results in joint degeneration in the Yucatan minipig and provide a new large animal testbed in which to evaluate therapeutics and interventions to treat post‐traumatic OA that originates from a meniscal injury.
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.
Mucopolysaccharidosis (MPS) I is a lysosomal storage disorder characterized by deficient alpha‐l‐iduronidase activity, leading to abnormal accumulation of glycosaminoglycans (GAGs) in cells and ...tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a strong clinical need for improved treatment approaches that specifically target joint tissues; however, their development is hampered by poor understanding of underlying disease pathophysiology, including how pathological changes to component tissues contribute to overall joint dysfunction. Ligaments and tendons, in particular, have received very little attention, despite the critical roles of these tissues in joint stability and biomechanical function. The goal of this study was to leverage the naturally canine model to undertake functional and structural assessments of the anterior (cranial) cruciate ligament (CCL) and Achilles tendon in MPS I. Tissues were obtained postmortem from 12‐month‐old MPS I and control dogs and tested to failure in uniaxial tension. Both CCLs and Achilles tendons from MPS I animals exhibited significantly lower stiffness and failure properties compared to those from healthy controls. Histological examination revealed multiple pathological abnormalities, including collagen fiber disorganization, increased cellularity and vascularity, and elevated GAG content in both tissues. Clinically, animals exhibited mobility deficits, including abnormal gait, which was associated with hyperextensibility of the stifle and hock joints. These findings demonstrate that pathological changes to both ligaments and tendons contribute to abnormal joint function in MPS I, and suggest that effective clinical management of joint disease in patients should incorporate treatments targeting these tissues.
Treatment of proximal humerus periprosthetic fractures is challenging. It remains difficult to achieve robust fixation of the proximal fragment to the locking plate using cerclage wiring and/or ...unicortical screws. Use of polyaxial tangentially directed bicortical locking screws increases screw purchase, but it is unclear if this option provides robust fixation. This biomechanical study compares fixation of constructs using cerclage wires, bicortical locking screws, and a hybrid method utilizing both methods.
Uncemented humeral stems were implanted into synthetic humeri and Type C periprosthetic fractures were simulated with a 1 cm transverse osteotomy. Distal ends of locking plates were secured with bicortical non-locking screws. The proximal ends were supported by either isolated cerclage wires, polyaxial locking screws, or a hybrid combination of both (n = 6 for each group). A universal test frame was used for non-destructive torsion and cyclic axial compression tests. 3-D motion tracking was employed to determine stiffnesses and relative interfragmentary motions.
Isolated screw constructs showed significantly increased resistance against torsional movement, bending, and shear, (p < 0.05) in comparison to cerclage constructs. The hybrid construct provided no significant changes in stability over the isolated screw construct.
Addition of cerclage wires in this synthetic bone model of Type C periprosthetic humerus fractures did not add significant stability to proximal bicortical locking plate fixation. Considering risks of tissue stripping and nerve injury, usage of cerclage wires in a similar clinical setting should be chosen carefully, especially when bicortical fixation around the prosthetic stem can be achieved.
•It is difficult to create robust reconstructions for periprosthetic humeral fractures.•Cerclage wiring, screw fixation, and a hybrid method were biomechanically tested.•Isolated bicortical screw fixation provided resistance against bending, shear, and torsional motion.•Addition of cerclage wiring to bicortical screw fixation offered no biomechanical advantage.
Model-based estimation of in vivo contact forces arising between components of a total knee replacement is challenging because such forces depend upon accurate modeling of muscles, tendons, ...ligaments, contact, and multibody dynamics. Here we describe an approach to solving this problem with results that are tested by comparison to knee loads measured in vivo for a single subject and made available through the Grand Challenge Competition to Predict in vivo Tibiofemoral Loads. The approach makes use of a "dual-joint" paradigm in which the knee joint is alternately represented by (1) a ball-joint knee for inverse dynamic computation of required muscle controls and (2) a 12 degree-of-freedom (DOF) knee with elastic foundation contact at the tibiofemoral and patellofemoral articulations for forward dynamic integration. Measured external forces and kinematics were applied as a feedback controller and static optimization attempted to track measured knee flexion angles and electromyographic (EMG) activity. The resulting simulations showed excellent tracking of knee flexion (average RMS error of 2.53 deg) and EMG (muscle activations within ±10% envelopes of normalized measured EMG signals). Simulated tibiofemoral contact forces agreed qualitatively with measured contact forces, but their RMS errors were approximately 25% of the peak measured values. These results demonstrate the potential of a dual-joint modeling approach to predict joint contact forces from kinesiological data measured in the motion laboratory. It is anticipated that errors in the estimation of contact force will be reduced as more accurate subject-specific models of muscles and other soft tissues are developed.