Knee Model Research Articles

Adaptive Sliding Mode Feedback Control Algorithm for a Nonlinear Knee Extension Model

Functional electrical stimulation (FES) has been widely used to treat spinal cord injury (SCI) patients. Many research studies employ a closed-loop FES system to monitor the stimulated muscle response and provide a precise amount of charge to the muscle. However, most closed-loop FES devices perform poorly and sometimes fail when muscle nonlinearity effects such as fatigue, time delay response, stiffness, spasticity, and subject change happen. The poor performance of the closed-loop FES device is mainly due to discrepancies in the feedback control algorithms. Most of the existing feedback control algorithms were not designed to adapt to new changes in patients with different nonlinearity effects, resulting in early muscle fatigue. Therefore, this research proposes an adaptive sliding mode (SM) feedback control algorithm that could adapt and fine-tune internal control settings in real-time according to the current subject’s nonlinear and time-varying muscle response during the rehabilitation (knee extension) exercise. The adaptive SM feedback controller consists mainly of system identification, direct torque control, and tunable feedback control settings. Employing the system identification unit in the feedback control algorithm enables real-time self-tuning and adjusting of the SM internal control settings according to the current patient’s condition. Initially, the patient’s knee trajectory response was identified by extracting meaningful information, which included time delay, rise time, overshoot, and steady-state error. The extracted information was used to fine-tune and update the internal SM control settings. Finally, the performance of the proposed adaptive SM feedback control algorithm in terms of system response time, stability, and rehabilitation time was analysed using a nonlinear knee model. The findings from the simulation results indicate that the adaptive SM feedback controller demonstrated the best control performance in accurately tracking the desired knee angle movement by having faster response times, smaller overshoots, and lower steady-state errors when compared with the conventional SM across four reference angle settings (20°, 30°, 40°, and 76°). The adaptive feedback SM controller was also observed to compensate for muscle nonlinearities, including fatigue, stiffness, spasticity, time delay, and other disturbances.

GuiLu-ErXian Glue extract promotes mesenchymal stem cells (MSC)-Induced chondrogenesis via exosomes release and delays aging in the MSC senescence process

Ethnopharmacological relevanceThe treatment of osteoarthritis (OA) patients is a challenging problem. Mesenchymal stem cells (MSCs) are multipotent cells and play key roles in regenerative medicine for cartilage degeneration. GuiLu-ErXian Glue (GLEXG) is an herbal remedy widely used in traditional Chinese medicine to treat joint pain and disability in elderly OA patients. However, the mechanisms of how GLEXG affects MSCs-induced chondrogensis remains to be elucidated. Aim of the studyThe aim of this study was to investigate the effects of GLEXG on MSC-derived chondrogenesis, both in vitro and in vivo and its potential mechanisms. MethodsUsing human MSC (hMSCs) as in vitro model, the effects of HPLC-profiled GLEXG water extract on chondrogenic differentiation were investigated by 3D spheroid cultures under chondrogenesis-inducing medium (CIM) condition. The chondrogenesis process was evaluated by measuring the sphere sizes, chondrogenesis-related genes expression by reverse transcription real-time PCR that targeted type II/X collagens, SOX9, aggrecan, and protein expression by immunostaining. Anti-TGF-β1 neutralization antibody was used for mechanistic study. Mono-iodoacetate (MIA) induced OA joint was used to evaluate the effects of GLEXG on in vivo model. MSCs-derived exosomes were purified for proteomics study and senescence process was evaluated by cumulative population doublings and senescence-associated β-Galactosidase staining. ResultsThe results showed that GLEXG enhanced hMSCs chondrogenesis and upregulated RNA expression of type II/X collagen, SOX9 and aggrecan at 0.1 μg/mL, 0.3 μg/mL in vitro. In vivo, GLEXG at the dose of 0.3 μg intraarticular (i.a.) injection rescued the MIA-induced cartilage defect. Proteomics and ingenuity pathway analysis obtained from MSCs-released exosomes suggested that senescence pathway was less activated in GLEXG group than in vehicle group. Besides, GLEXG was able to increase cumulative population doubling and delayed hMSCs senescence process after four passages in cultures. Conclusionwe conclude that GLEXG promotes in vitro MSC-induced chondrogenesis possibly via exosomes release and delays aging in the MSC senescence process and that treatment with GLEXG (0.3 μg, i.a.) rescued cartilage defects in rat OA knee model.

Three-dimensional irradiance and temperature distributions resulting from transdermal application of laser light to human knee-A numerical approach.

The use of light for therapeutic applications requires light-absorption by cellular chromophores at the target tissues and the subsequent photobiomodulation (PBM) of cellular biochemical processes. For transdermal deep tissue light therapy (tDTLT) to be clinically effective, a sufficiently large number of photons must reach and be absorbed at the targeted deep tissue sites. Thus, delivering safe and effective tDTLT requires understanding the physics of light propagation in tissue. This study simulates laser light propagation in an anatomically accurate human knee model to assess the light transmittance and light absorption-driven thermal changes for eight commonly used laser therapy wavelengths (600-1200 nm) at multiple skin-applied irradiances (W cm-2 ) with continuous wave (CW) exposures. It shows that of the simulated parameters, 2.38 W cm-2 (30 W, 20 mm beam radius) of 1064 nm light generated the least tissue heating -4°C at skin surface, after 30 s of CW irradiation, and the highest overall transmission-approximately 3%, to the innermost muscle tissue.

Integration of statistical shape modeling and alternating interpolation-based model tracking technique for measuring knee kinematics in vivo using clinical interleaved bi-plane fluoroscopy.

A 2D fluoroscopy/3D model-based registration with statistical shape modeling (SSM)-reconstructed subject-specific bone models will help reduce radiation exposure for 3D kinematic measurements of the knee using clinical alternating bi-plane fluoroscopy systems. The current study aimed to develop such an approach and evaluate in vivo its accuracy and identify the effects of the accuracy of SSM models on the kinematic measurements. An alternating interpolation-based model tracking (AIMT) approach with SSM-reconstructed subject-specific bone models was used for measuring 3D knee kinematics from dynamic alternating bi-plane fluoroscopy images. A two-phase optimization scheme was used to reconstruct subject-specific knee models from a CT-based SSM database of 60 knees using one, two, or three pairs of fluoroscopy images. Using the CT-reconstructed model as a benchmark, the performance of the AIMT with SSM-reconstructed models in measuring bone and joint kinematics during dynamic activity was evaluated in terms of mean target registration errors (mmTRE) for registered bone poses and the mean absolute differences (MAD) for each motion component of the joint poses. The mmTRE of the femur and tibia for one image pair were significantly greater than those for two and three image pairs without significant differences between two and three image pairs. The MAD was 1.16 to 1.22° for rotations and 1.18 to 1.22 mm for translations using one image pair. The corresponding values for two and three image pairs were 0.75 to 0.89° and 0.75 to 0.79 mm; and 0.57 to 0.79° and 0.6 to 0.69 mm, respectively. The MAD values for one image pair were significantly greater than those for two and three image pairs without significant differences between two and three image pairs. An AIMT approach with SSM-reconstructed models was developed, enabling the registration of interleaved fluoroscopy images and SSM-reconstructed models from more than one asynchronous fluoroscopy image pair. This new approach had sub-millimeter and sub-degree measurement accuracy when using more than one image pair, comparable to the accuracy of CT-based methods. This approach will be helpful for future kinematic measurements of the knee with reduced radiation exposure using 3D fluoroscopy with clinically alternating bi-plane fluoroscopy systems.

Design and Evaluation of a Smooth-Locking-Based Customizable Prosthetic Knee Joint

Abstract Limb loss affects many people from a variety of backgrounds around the world. The most advanced commercially available prostheses for transfemoral amputees are fully active (powered) designs but remain very expensive and unavailable in the developing world. Consequently, improvements of low-cost, passive prostheses have been made to provide high-quality rehabilitation to amputees of any background. This study explores the design and evaluation of a smooth-locking-based bionic knee joint to replicate the swing phase of the human gait cycle. The two-part design was based on the condyle geometry of the interface between the femur and tibia obtained from magnetic resonance (MR) images of the human subject, while springs were used to replace the anterior and posterior cruciate ligaments. A flexible four-bar linkage mechanism was successfully achieved to provide not only rotation along a variable instantaneous axis but also slight translation in the sagittal plane, similar to the anatomical knee. We systematically evaluated the effects of different spring configurations in terms of stiffness, position, and relaxion length on knee flexion angles during walking. A good replication of the swing phase was achieved by relatively high stiffness and increased relaxation length of springs. The stance phase of the gait cycle was improved compared to some models but remained relatively flat, where further verification should be conducted. In addition, 3D printing technique provides a convenient design and manufacturing process, making the prosthesis customizable for different individuals based on subject-specific modeling of the amputee’s knee.

3D assessment of graft malposition after ACL reconstruction: Comparison of native and 11o'clock ligament orientations

BackgroundFemoral tunnel malposition makes up the majority of technical failures for ACL reconstructive surgery. The goal of this study was to develop adolescent knee models that accurately predict anterior tibial translation when undergoing a Lachman and pivot shift test with the ACL in the 11o’clock femoral malposition (Level of Evidence: IV). MethodsFEBio was used to build 22 subject-specific tibiofemoral joint finite element representations. To simulate the two clinical tests, the models were subject to loading and boundary conditions established in the literature. Clinical, historical control data were used to validate the predicted anterior tibial translations. ResultsA 95% confidence interval showed that with the ACL in the 11o’clock malposition, the simulated Lachman and pivot shift tests produced anterior tibial translations that were not statistically different from the in vivo data. The 11o’clock finite element knee models resulted in greater anterior displacement than those with the native (approximately 10o’clock) ACL position. The difference in anterior tibial translation between the native and 11o’clock ACL orientations was statistically significant. ConclusionClinically, by understanding the impact that ACL orientation has in anterior tibial displacement biomechanics, surgical interventions can be improved to prevent technical errors from occurring. The integration of this methodology into surgical practice not only allows for anatomical visualization prior to surgery, but also creates the opportunity to optimize graft placement, thus improving post-surgical outcomes.

Internal Rotation, Varus, and Anterior Femoral Component Malalignments Adversely Affect Patellofemoral Joint Kinematics in Patellofemoral Arthroplasty.

Patellofemoral arthroplasty (PFA) is reported to provide nearly normal PF joint kinematics but only with adequate surgical techniques. This study evaluated the effects of various femoral component settings on patellar component biomechanics. A dynamic musculoskeletal computer simulation analyzed normal knee and standard PFA models, as well as 8 femoral component malposition models: 5° internal or external rotation, 5° valgus or varus, 5° extension or flexion, and 3-mm or 5-mm anterior positioning. Mediolateral patellar translation, lateral patellar tilt, and contact force and stress at the PF joint were measured in each model during gait. The patella in the standard PFA model was shifted up to 5.0 mm laterally near heel off and was tilted up to 3.0° laterally at heel strike compared to the normal knee model. The patella in the external rotation model translated more laterally in the direction of the femoral component setting than in the standard model. However, in the internal rotation and varus alignment models, the patellar lateral shift occurred largely in the opposite direction of the femoral component setting. The patella in most models was tilted in the same direction as the femoral component setting. The PF contact force was increased, especially in the anterior femoral position models, by up to 30 MPa compared with 20 MPa in the standard model. Internal rotation, varus, and anterior femoral component settings during PFA should be avoided to reduce postoperative complications, whereas external rotation might be appropriate only for cases with lateral patellar instability.

Enoxaparin sodium bone cement displays local anti-inflammatory effects by regulating the expression of IL-6 and TNF-α

ObjectiveTo explore the roles of Enoxaparin Sodium-Polymethyl methacrylate bone cement on inflammatory factors Interleukin-6 and Tumour Necrosis Factor-α in a rabbit knee replacement model. As well as the mechanisms underlying its potential effects on lipopolysaccharide-induced endothelial cell injury. MethodsA knee replacement model was established using New Zealand rabbits. Forty rabbits were randomly divided into four groups: PMMA, ES-PMMA, sham-operated, and blank control groups (n = 10 in each group). Local tissues around the incision were taken at the 30th, 60th, and 90th minute after the surgical implantation of the corresponding bone cement. Immunohistochemistry in the surgical field was used to measure the expression of local inflammatory factors IL-6 and TNF-α. In the in vitro experiments, 1 cm3 of bone cement was immersed in 3 mL of the medium for 24 h. The bone cement was discarded and diluted to 25% with normal medium. Pre-experiments were screened for the best LPS-inducing concentration of 100 mg/mL, and the most compatible LPS concentration was used for subsequent experiments simulating the primary cultures of rats’ Inferior Vena Cava Endothelial Cells. The experiments were divided into four groups: blank control group, LPS induction group, PMMA + LPS group, and ES-PMMA + LPS group. The apoptosis rate was detected by flow cytometry, and the expression levels of TNF-α and IL-6 in the cells and supernatant were measured by ELISA, western blotting, and immunofluorescence. ResultsAccording to immunohistochemical results, IL-6-positive cells were concentrated in the tissue interstitial space. In the PMMA and sham-operated groups, the number of IL-6-positive cells gradually increased over time. At all time points, IL-6 expression in the ES-PMMA group was much lower than in the PMMA and sham-operated groups. At 30 min, TNF-α positive cells in the ES-PMMA group expressed less than those in the PMMA and sham-operated groups, with no discernible difference between the PMMA and ES-PMMA groups at 60 or 90 min. Using ELISA and flow cytometry, the expression levels of IL-6 and TNF-α were improved and the apoptosis rate was magnified in the LPS-induced group (***P < 0.001) in contrast with the blank control group. Additionally, the expression levels of IL-6 and TNF-α were reduced in the ES-PMMA + LPS group compared with the LPS-induced group (*P < 0.05) and the apoptosis rate was reduced (***P < 0.001), with statistically significant variations. Western blotting and immunofluorescence analysis confirmed that IL-6 and TNF-α protein expression in cells was upregulated in the LPS-induced group compared to the blank control group (***P < 0.001), and the mean fluorescence intensity was enlarged (***P < 0.001). Meanwhile, IL-6 and TNF-α expression in the ES-PMMA + LPS group were down-regulated (**P < 0.01 or *P < 0.05) compared with the LPS-induced group and PMMA + LPS crew protein expression, and the average fluorescence intensity of IL-6 and TNF-α was lowered in the ES-PMMA + LPS group compared to the LPS-induced group (***P < 0.001). ConclusionsES-PMMA bone cement reduced the expression levels of local inflammatory factors IL-6 and TNF-α in a rabbit knee model. ES-PMMA bone cement reduced the rate of LPS-induced endothelial cell apoptosis and diminished local inflammatory damage by regulating the secretion of inflammatory factors TNF-α and IL-6.

Comparison of side-cutting maneuvers versus low impact baseball swing on knee ligament loading in adolescent populations

BackgroundHigh impact sports are associated with an increased incidence rate for knee ligament injuries, specifically pertaining to the anterior cruciate ligament and medial collateral ligament. What is less clear is (i) the extent to which high impact activities preferentially load the anterior cruciate ligament versus the medial collateral ligament, and (ii) whether both ligaments experience similar stretch ratios during high loading scenarios. Therefore, the goal of this project was to assess how different loading conditions experienced through more at-risk sporting maneuvers influence the relative displacements of the anterior cruciate ligament and medial collateral ligament. The focus of the study was on adolescent patients – a group that has largely been overlooked when studying knee ligament biomechanics. MethodsThrough kinetic knee data obtained through motion capture experimentation, two different loading conditions (high vs low impact) were applied to 22 specimen-specific adolescent finite element knee models to investigate the biomechanical impact various sporting maneuvers place on the knee ligaments. FindingsThe high impact side cutting maneuver resulted in 102% and 47% increases in ligament displacement compared to the low impact baseball swing (p < 0.05) for both the anterior cruciate ligament and medial collateral ligament. InterpretationQuantifying biomechanical risks that sporting activities place on adolescent subjects provides physicians with insight into knee ligament vulnerability. More specifically, knowing the risks that various sports place on ligaments helps guide the selection of sports for at-risk patients (especially those who have undergone knee ligament surgery).

Enhancement of antibacterial properties and biocompatibility of Ti6Al4V by graphene oxide/strontium nanocomposite electrodepositing

Ti6Al4V is a widely used orthopedic implant material in clinics. Due to its poor antibacterial properties, surface modification is required to prevent peri-implantation infection. However, chemical linkers used for surface modification have generally been reported to have detrimental effects on cell growth. In this work, by optimizing parameters related to electrodeposition, a composite structural coating with graphene oxide (GO) compact films in the inner layer and 35 nm diameter strontium (Sr) nanoparticles in the outer layer was constructed on the surface of Ti6Al4V without using substance harmful to bone marrow mesenchymal stem cells (BMSCs) growth. The antibacterial properties of Ti6Al4V are enhanced by the controlled release of Sr ions and incomplete masking of the GO surface, showing excellent antibacterial activity against Staphylococcus aureus in bacterial culture assays. The biomimetic GO/Sr coating has a reduced roughness of the implant surface and a water contact angle of 44.1°, improving the adhesion, proliferation and differentiation of BMSCs. Observations of synovial tissue and fluid in the joint in an implantation model of rabbit knee also point to the superior anti-infective properties of the novel GO/Sr coating. In summary, the novel GO/Sr nanocomposite coating on the surface of Ti6Al4V effectively prevents surface colonization of Staphylococcus aureus and eliminates local infections in vitro and in vivo.

Augmentation of a Nonanatomical Repair of a Medial Meniscus Posterior Root Tear With Centralization Using Three Knotless Anchors May Be Associated With Less Meniscal Extrusion and Better Compressive Load Distribution in Mid-Flexion Compared With Non-Anatomical Root Repair Alone in a Porcine Knee Model

To investigate the biomechanics of the centralization augmentation using knotless soft anchors to a nonanatomicaltranstibial pull-out root repair in a porcine medial meniscus posterior root tear (MMPRT) model. Porcine knee joints (N= 10) were used to perform one of the following procedures: (1) intact; (2) MMPRT; (3) nonanatomical root repair; (4) nonanatomical root repair with centralization using 2 anchors: anchors were inserted at the posterior medial collateral ligament (MCL) border and 10 mm anterior to the posterior MCL border; and (5) nonanatomical root repair with centralization using 3 anchors: another anchor was placed 10 mm posterior to the posterior MCL border. Contact area on the medial meniscus (MM), contact pressure in the MM and tibial cartilage, and MM extrusion were evaluated at 30°, 45°, 60°, and 90° knee flexions under 200 N compressive force. MM extrusion at the posterior MCL border was significantly reduced after root repair with centralization using 3 anchors than after root repair alone at 30° (-0.063 mm vs 1.5 mm, P= .017), 45° (0.21 mm vs 1.7 mm, P= .018), and 60° (0.78 mm vs 2.3 mm, P= .019). There were no significant differences in MM extrusion between the root repair alone and root repair with centralization using 2 anchors at all flexion angles. The contact area in the middle and posterior MM was significantly greater after centralization with 3 anchors than after root repair alone at all flexion angles (except the posterior MM at 90°). The mean contact pressure in the tibial cartilage was significantly lower after centralization with 3 anchors than after root repair at all angles. Augmentation of a nonanatomical repair of a medial meniscus posterior root tear with centralization using three knotless anchors may be associated with less meniscal extrusion and better compressive load distribution between 30° and 60° flexion compared with nonanatomical root repair alone in a porcine model. This biomechanical study at time zero suggests that the addition of centralization using 3 knotless anchors may reduce MM extrusion and restore the load-distributing function of the MM.

Pre-Planning the Surgical Target for Optimal Implant Positioning in Robotic-Assisted Total Knee Arthroplasty.

Robotic-assisted total knee arthroplasty can attain highly accurate implantation. However, the target for optimal positioning of the components remains debatable. One of the proposed targets is to recreate the functional status of the pre-diseased knee. The aim of this study was to demonstrate the feasibility of reproducing the pre-diseased kinematics and strains of the ligaments and, subsequently, use that information to optimize the position of the femoral and tibial components. For this purpose, we segmented the pre-operative computed tomography of one patient with knee osteoarthritis using an image-based statistical shape model and built a patient-specific musculoskeletal model of the pre-diseased knee. This model was initially implanted with a cruciate-retaining total knee system according to mechanical alignment principles; and an optimization algorithm was then configured seeking the optimal position of the components that minimized the root-mean-square deviation between the pre-diseased and post-operative kinematics and/or ligament strains. With concurrent optimization for kinematics and ligament strains, we managed to reduce the deviations from 2.4 ± 1.4 mm (translations) and 2.7 ± 0.7° (rotations) with mechanical alignment to 1.1 ± 0.5 mm and 1.1 ± 0.6°, and the strains from 6.5% to lower than 3.2% over all the ligaments. These findings confirm that adjusting the implant position from the initial plan allows for a closer match with the pre-diseased biomechanical situation, which can be utilized to optimize the pre-planning of robotic-assisted surgery.

Quadriceps Muscle and Medial Retinaculum Combinate Effects on Patellar Instability during Knee Flexion

Background: Patellar instability can cause pain and disability. A finite element model of a healthy human knee was performed to analyze the role of quadriceps and medial retinaculum imbalance in patellar instability. Methods: The model was created by matching magnetic resonance and computed tomography images of a normal adult patient’s knee. Muscle force intensities were calculated by static optimization, considering the lower limb muscles, knee movement and the ground reaction during walking. Patellar instability was experimentally generated by progressively uncoupling muscular forces, (90 N versus 110 N), while at the same time, the load derived from the quadriceps was gradually reduced by 20%. Results: This loss in force symmetry of 10 N on the retinaculum may produce a displacement of approximately 7 mm, with an increase in patellar contact forces of approximately 44%. When the quadriceps force is reduced by 10% and the unbalanced medial retinaculum acts together, the displacements are in the order of 14 mm, and the patellar contact forces increase by 84%. Conclusion: A reduced quadriceps force alone is not able to cause significant patellar instability, while an imbalance of forces at the level of the retinaculum could lead to patellar instability, especially when the two effects are combined. A better understanding of joint relationships and muscle synergies can help to improve clinical approaches to patella instability

In Vivo Length Changes Between the Attachments of the Medial Patellofemoral Complex Fibers in Knees With Anatomic Risk Factors for Patellar Instability

Background: Medial patellofemoral complex (MPFC) reconstruction plays an important role in the surgical treatment of patellar instability. Anatomic reconstruction is critical in re-creating the native function of the ligament, which includes minimizing length changes that occur in early flexion. Anatomic risk factors for patellar instability such as trochlear dysplasia, patella alta, and increased tibial tuberosity to trochlear groove (TT-TG) distance have been shown to influence the function of the MPFC graft in cadaveric studies, but the native length change patterns of the MPFC fibers in knees with anatomic risk factors have not been described. Purpose: To describe the in vivo length changes of the MPFC fibers in knees with anatomic risk factors for patellar instability and identify the optimal attachment sites for MPFC reconstruction. Study Design: Controlled laboratory study. Methods: Dynamic computed tomography imaging was performed on the asymptomatic knee in patients with contralateral patellar instability. Three-dimensional digital knee models were created to assess knees between 0° and 50° of flexion in 10° increments. MPFC fiber lengths were calculated at each flexion angle between known anatomic attachment points on the extensor mechanism (quadriceps tendon, MPFC midpoint [M], and patella) and femur (1, 2, and 3, representing the proximal to distal femoral footprint). Changes in MPFC fiber length were compared for each condition and assessed for their relationships to morphologic risk factors (trochlear depth, Caton Deschamps Index [CDI], and TT-TG distance). Results: In 22 knees, native MPFC fibers were found to be longer at 0° than at 20° to 50° of flexion. Length changes observed between 0° and 50° increased with the number of risk factors present. In the central fibers of the MPFC (M-2), 1.7% ± 3.1% length change was noted in knees with no anatomic risk factors, which increased to 5.6% ± 4.6%, 17.0% ± 6.4%, and 26.7% ± 6.8% in the setting of 1, 2, and 3 risk factors, respectively. Nonanatomic patella-based attachments were more likely to demonstrate unfavorable length change patterns, in which length was greater at 50° than 0°. In patellar attachments, an independent relationship was found between increasing length changes and TT-TG distance, while in quadriceps tendon attachments, a trend toward a negative relationship between length changes and CDI was noted. All configurations demonstrated a strong relationship between percentage change in length and number of morphologic risk factors present, with the greatest influence found in patella-based attachments. Conclusion: The MPFC fibers demonstrated increased length changes in knees when a greater number of morphological risk factors for patellar instability were present, which worsened in the setting of nonanatomic configurations. This suggests that the function of the intact MPFC in patients with anatomic risk factors may not reflect previously described findings in anatomically normal knees. Further studies are needed to understand the pathoanatomy related to these changes, as well as the implications for graft placement and assessment of length changes during MPFC reconstruction techniques. Clinical Relevance: MPFC length change patterns vary based on the number of morphologic risk factors for patellar instability present and should be considered during reconstructive procedures.

3D Printed Models of Trochlear Dysplasia and Trochleoplasty Simulation for Trainee Education

Trochlear dysplasia is a major contributor to patellofemoral instability and subsequent failure of isolated soft tissue reconstruction procedures in the treatment of recurrent patellar dislocation and/or subluxation. Trochleoplasty procedures aim to address abnormal osseous trochlear morphologic factors that contribute to patellar maltracking. However, teaching these techniques is limited by the lack of reliable training models for trochlear dysplasia and trochleoplasty simulation. Although a cadaveric knee model of trochlear dysplasia for trochleoplasty simulation has been recently described, cadaveric knees are less amenable for use in trochleoplasty planning and surgeon training because of the absence of reliable, natural dysplastic anatomic relationships, such as suprapatellar spurs due to the rarity of dysplastic cadavers and the high cost of cadaveric specimens. Furthermore, readily available sawbone models represent “normal” osseous trochlear morphology and are difficult to modify and bend due to their material composition. Given this, we have developed a cost-effective, reliable, and anatomically accurate three-dimensional (3D) knee model of trochlear dysplasia for trochleoplasty simulation and trainee education.

Effects of millimeter-wave for preventing joint stiffness in the immobilized knee rat model

AimTo explore the effects and mechanism of millimeter-wave treatment on the development of joint stiffness in the immobilized knee rat model. MethodsTwenty-four Sprague–Dawley (SD) rats were randomly divided into the control group (O, n = 8), the surgical control group (OC, n = 8), and the millimeter-wave treatment group (MO, n = 8). After immobilized knee modeling, the knee mobility and quadriceps diameter was measured at the 6th week. Hematoxylin and eosin and Masson staining were performed to detect the pathology and fibrous lesions of the knee joint. Furthermore, the expression of TGF-β1 and Collagen I was quantified by immunohistochemical assay in the knee capsule, and Western blotting was performed to quantify the protein expression of NF-κB and MuRF1 in skeletal muscle. ResultsCompared with the O group, knee mobility, and quadriceps diameter was decreased (P < 0.01), and articular capsule fibrosis and quadriceps atrophy occurred in all rats with fixed knee joints. Compared with the OC group, millimeter-wave treatment significantly increased articular mobility and the quadriceps diameter; and improved the fibrotic lesions of the joint capsule and quadriceps atrophy. Moreover, levels of TGF-β1, Collagen I, and MuRF1 were upregulated (P < 0.01) by knee immobilization, and collagen fiber content in the articular capsule was also increased (P < 0.01). However, millimeter-wave treatment reversed it. The most noteworthy result was that NF-κB expression was not significantly different in all groups. ConclusionMillimeter-wave treatment reversed joint contracture and quadriceps atrophy caused by joint fixation, inhibited TGF-β1 and Collagen I protein expression of the joint capsule and reduced MuRF1 expression of the quadriceps muscle, thereby inhibiting the development of joint stiffness.

Inhibition of miR-182-5p Targets FGF9 to Alleviate Osteoarthritis.

The pathogenesis of osteoarthritis (OA) is complex and there is no specific drug for treatment. The aim of this study was to identify the molecular targets of OA therapy, focusing on the expression and biological functions of miR-182-5p and its target genes in OA. miR-182-5p and fibroblast growth factor 9 (FGF9) were overexpressed or knocked down in IL-1β-induced chondrocytes. An OA knee model was performed by surgically destroying the medial meniscus. The gene expression of miR-182-5p and FGF9 was calculated. The protein FGF9 was tested by western blotting. Cell counting kit-8 (CCK8), plate cloning assay, and flow cytometry were conducted to evaluate cell proliferation and apoptosis. The expression of inflammatory factors, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and interleukin (IL)-8, was evaluated using enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assays validated the targeting relationship between miR-182-5p and FGF9. Hematoxylin-eosin (HE) and safranin O-fast Green (S-O) staining were utilized to access cartilage damage. Ki67 expression in cartilage was detected using immunohistochemistry (IHC). TdT-mediated dUTP nick-end labeling (TUNEL) assays were used to calculate the apoptosis rate of cartilage. The expression of miR-182-5p was upregulated, and FGF9 was downregulated in the IL-1β-induced chondrocytes. OA chondrocytes proliferation ability in the miR-182-5p mimics group was decreased, and the apoptosis rate and inflammatory factor were increased. Transfection with miR-182-5p inhibitor increased the proliferative ability and decreased the apoptosis rate in the IL-1β-induced chondrocytes. Transfection with miR-182-5p inhibitor reversed IL-1β-induced inflammatory factor release in chondrocytes. Targeted binding sites existed between miR-182-5p and FGF9. After overexpression of FGF9, the miR-182-5p effect on OA chondrocytes was reversed. The hyaline cartilage thickness and proteoglycan content decreased in OA rats, and this was reversed by miR-182-5p inhibitor treatment. miR-182-5p expression levels were increased in OA chondrocytes and regulated chondrocyte proliferation, apoptosis, and inflammation by targeting FGF9. miR-182-5p is a potential gene for OA treatment.

Bayesian Calibration of Computational Knee Models to Estimate Subject-Specific Ligament Properties, Tibiofemoral Kinematics, and Anterior Cruciate Ligament Force With Uncertainty Quantification.

High-grade knee laxity is associated with early anterior cruciate ligament (ACL) graft failure, poor function, and compromised clinical outcome. Yet, the specific ligaments and ligament properties driving knee laxity remain poorly understood. We described a Bayesian calibration methodology for predicting unknown ligament properties in a computational knee model. Then, we applied the method to estimate unknown ligament properties with uncertainty bounds using tibiofemoral kinematics and ACL force measurements from two cadaver knees that spanned a range of laxities; these knees were tested using a robotic manipulator. The unknown ligament properties were from the Bayesian set of plausible ligament properties, as specified by their posterior distribution. Finally, we developed a calibrated predictor of tibiofemoral kinematics and ACL force with their own uncertainty bounds. The calibrated predictor was developed by first collecting the posterior draws of the kinematics and ACL force that are induced by the posterior draws of the ligament properties and model parameters. Bayesian calibration identified unique ligament slack lengths for the two knee models and produced ACL force and kinematic predictions that were closer to the corresponding in vitro measurement than those from a standard optimization technique. This Bayesian framework quantifies uncertainty in both ligament properties and model outputs; an important step towards developing subject-specific computational models to improve treatment for ACL injury.

Towards a validated musculoskeletal knee model to estimate tibiofemoral kinematics and ligament strains: comparison of different anterolateral augmentation procedures combined with isolated ACL reconstructions

BackgroundIsolated ACL reconstructions (ACLR) demonstrate limitations in restoring native knee kinematics. This study investigates the knee mechanics of ACLR plus various anterolateral augmentations using a patient-specific musculoskeletal knee model.Materials and methodsA patient-specific knee model was developed in OpenSim using contact surfaces and ligament details derived from MRI and CT data. The contact geometry and ligament parameters were varied until the predicted knee angles for intact and ACL-sectioned models were validated against cadaveric test data for that same specimen. Musculoskeletal models of the ACLR combined with various anterolateral augmentations were then simulated. Knee angles were compared between these reconstruction models to determine which technique best matched the intact kinematics. Also, ligament strains calculated by the validated knee model were compared to those of the OpenSim model driven by experimental data. The accuracy of the results was assessed by calculating the normalised RMS error (NRMSE); an NRMSE < 30% was considered acceptable.ResultsAll rotations and translations predicted by the knee model were acceptable when compared to the cadaveric data (NRMSE < 30%), except for the anterior/posterior translation (NRMSE > 60%). Similar errors were observed between ACL strain results (NRMSE > 60%). Other ligament comparisons were acceptable. All ACLR plus anterolateral augmentation models restored kinematics toward the intact state, with ACLR plus anterolateral ligament reconstruction (ACLR + ALLR) achieving the best match and the greatest strain reduction in ACL, PCL, MCL, and DMCL.ConclusionThe intact and ACL-sectioned models were validated against cadaveric experimental results for all rotations. It is acknowledged that the validation criteria are very lenient; further refinement is required for improved validation. The results indicate that anterolateral augmentation moves the kinematics closer to the intact knee state; combined ACLR and ALLR provide the best outcome for this specimen.

A digital twin framework for robust control of robotic-biological systems

Medical device regulatory standards are increasingly incorporating computational modelling and simulation to accommodate advanced manufacturing and device personalization. We present a method for robust testing of engineered soft tissue products involving a digital twin paradigm in combination with robotic systems. We developed and validated a digital twin framework for calibrating and controlling robotic-biological systems. A forward dynamics model of the robotic manipulator was developed, calibrated, and validated. After calibration, the accuracy of the digital twin in reproducing the experimental data improved in the time domain for all fourteen tested configurations and improved in frequency domain for nine configurations. We then demonstrated displacement control of a spring in lieu of a soft tissue element in a biological specimen. The simulated experiment matched the physical experiment with 0.09 mm (0.001%) root-mean-square error for a 2.9 mm (5.1%) length change. Finally, we demonstrated kinematic control of a digital twin of the knee through 70-degree passive flexion kinematics. The root-mean-square error was 2.00°, 0.57°, and 1.75° degrees for flexion, adduction, and internal rotations, respectively. The system well controlled novel mechanical elements and generated accurate kinematics in silico for a complex knee model. This calibration method could be applied to other situations where the specimen is poorly represented in the model environment (e.g., human or animal tissues), and the control system could be extended to track internal parameters such as tissue strain (e.g., control knee ligament strain). Further development of this framework can facilitate medical device testing and innovative biomechanics research.