Healthy Knee Research Articles

A Machine Learning based Approach for Detection of Osteoarthritis using Thermal Images

Osteoarthritis (OA) of the knee is a common disorder that contributes to physical decline and activity limitation. Early OA diagnosis and treatment can stop the disease's progression. The assessment of a physician's visual examination is impartial, subject to different interpretations, and highly dependent on their level of experience. Therefore, a system that employs machine learning techniques to automatically determine the degree of knee OA has been proposed in this study. At first, a specifically created one stage YOLOv2 network is employed to estimate the size of the kneecap according to the distribution of knee joints in low contrast thermal images. To be more specific, the knee Kellgren-Lawrence (KL) grading assignment is ordinal; therefore, a harsher penalty is provided for misrepresentation with a larger gap between the anticipated and actual KL grade. A machine learning architecture is then constructed and extensive tests are performed to demonstrate how texture properties affect diagnostic performance. Thermal images are used to determine if they might be used to distinguish between radiographs of diseased and healthy knees. The outcomes of machine learning features and manually extracted features are compared. Finally, a stacked model that combines second-level machine learning with predictions of patellar texture and clinical characteristics is provided.

Atlas-based finite element analyses with simpler constitutive models predict personalized progression of knee osteoarthritis: data from the osteoarthritis initiative

New technologies are required to support a radical shift towards preventive healthcare. Here we focus on evaluating the possibility of finite element (FE) analysis-aided prevention of knee osteoarthritis (OA), a disease that affects 100 million citizens in the US and EU and this number is estimated to increase drastically. Current clinical methods to diagnose or predict joint health status relies on symptoms and tissue failures obtained from clinical imaging. In a joint with no detectable injuries, the diagnosis of the future health of the knee can be assumed to be very subjective. Quantitative approaches are therefore needed to assess the personalized risk for the onset and development of knee OA. FE analysis utilizing an atlas-based modeling approach has shown a preliminary capability for simulating subject-specific cartilage mechanical responses. However, it has been verified with a very limited subject number. Thus, the aim of this study is to verify the real capability of the atlas-based approach to simulate cartilage degeneration utilizing different material descriptions for cartilage. A fibril reinforced poroviscoelastic (FRPVE) material formulation was considered as state-of-the-art material behavior, since it has been preliminary validated against real clinical follow-up data. Simulated mechanical tissue responses and predicted cartilage degenerations within knee joint with FRPVE material were compared against simpler constitutive models for cartilage. The capability of the atlas-based modeling to offer a feasible approach with quantitative evaluation for the risk for the OA development (healthy vs osteoarthritic knee, p < 0.01, AUC ~ 0.7) was verified with 214 knees. Furthermore, the results suggest that accuracy for simulation of cartilage degeneration with simpler material models is similar to models using FPRVE materials if the material parameters are chosen properly.

3D T1rho sequences with FASE, UTE, and MAPSS acquisitions for knee evaluation.

For biochemical evaluation of soft tissues of the knee, T1rho magnetic resonance imaging (MRI) has been proposed. Purpose of this study was to compare three T1rho sequences based on fast advanced spin echo (FASE), ultrashort echo time (UTE), and magnetization-prepared angle-modulated partitioned k-space spoiled gradient echo snapshots (MAPSS) acquisitions for the knee evaluation. We developed two T1rho sequences using 3D FASE or 3D radial UTE acquisitions. 3D MAPSS T1rho was provided by the manufacturer. Agarose phantoms with varying concentrations were imaged. Additionally, bilateral knees of asymptomatic subjects were imaged sagittally. T1rho values of the phantoms and 4 regions of interest (ROI) of the knees (i.e., anterior and posterior meniscus, femoral and tibial cartilage) were determined. In phantoms, all T1rho values monotonically decreased with increasing agarose concentration. 3D MAPSS T1rho values of 51, 34, and 38ms were found for 2, 3, and 4% agarose, respectively, similar to published values on another platform. In the knee, the raw images were detailed with good contrast. Cartilage and meniscus T1rho values varied with the pulse sequence, being the lowest in the 3D UTE T1rho sequence. Comparing different ROIs, menisci generally had lower T1rho values compared to cartilage, as expected in healthy knees. We have successfully developed and implemented the new T1rho sequences and validated them using agarose phantoms and volunteer knees. All sequences were optimized to be clinically feasible (~ 5min or less) and yielded satisfactory image quality and T1rho values consistent with the literature.

The role of genetic polymorphisms of interleukin-1 (IL-1R1 and IL-1RN) in primary knee osteoarthritis in Indonesia

This study aimed to evaluate the association of SNPs of the IL-1 family with the clinical severity of knee OA. This case‒control study was performed among 100 healthy knees and 130 osteoarthritis (OA) knees of people aged ≥ 50 years with a BMI ≥ 25 kg/m2. The possible correlations among clinical findings, radiographic evaluations, serum levels of IL-1R1 and IL-1Ra, and genotype analyses were evaluated. Three SNPs of IL-1R1, rs871659, rs3771202, and rs3917238, were associated with primary knee OA. Females with IL-1R1 SNP rs871659 allele A had a higher prevalence of primary knee OA. No correlation was found between SNPs of IL-1R1 and IL-1RN and clinical or radiologic severity or serum concentrations of IL-1R1 and IL-1Ra (p > 0.05). BMI and IL-1R1 rs3917238 genotype C/C were correlated with moderate-severe VAS scores. A correlation was also found between the EQ-5D-3L self-care dimension and obesity and between the EQ-5D-3L pain and usual activity dimensions and age ≥ 60 and obesity (p < 0.05). Radiologic severity was only associated with age ≥ 60 years (p < 0.05). We found the IL-1R1 SNPs rs871659, rs3771202, and rs3917238 to be predisposing factors for primary knee osteoarthritis. The clinical findings, radiographic severity, and serum concentrations of IL-1R1 and IL-1Ra were not correlated with these gene polymorphisms.

The effect of bisphosphonate and platelet-rich plasma in anterior cruciate ligament reconstruction: an article review

Link of Video Abstract: https://youtu.be/fn9kA601YVo ACL rupture is a common injury often resulting from previously healthy individuals' non-contact knee injuries. ACL rupture in young adults and teenagers are becoming more common, contrary to earlier theories that suggested ACL damage was uncommon in skeletally immature people. This risk is significantly raised by concomitant meniscal injury whether or not an ACL reconstruction is undertaken. Although surgical management with allograft or autograft reconstruction can be achieved successfully, there are some serious complications following ACL reconstruction. The supply of autografts is limited, especially in situations with numerous ligament injuries or re-ruptures, which might result in morbidity at the donor site. Allografts can increase the spread of illness and trigger an inflammatory response, which is a drawback. There has been much interest in a tissue-engineered ACL graft because of these issues and current developments in bioengineering and regenerative medicine. According to recent research, following an ACL repair, the bone marrow density surrounding the knee area diminishes. Platelet Rich Plasma (PRP) and Bisphosphonate are the substrates that could ameliorate this phenomenon. Therefore, this review aims to compile evidence of PRP and bisphosphonate and its effect on the tendon-bone interface in ACL reconstruction.

Targeting damaged collagen for intra-articular delivery of therapeutics using collagen hybridizing peptides.

The objective of this study was to investigate the potential of collagen hybridizing peptides (CHPs), which bind to denatured collagen, to extend the retention time of near-infrared fluorophores (NIRF) following intra-articular (IA) injection in rat knee joints. CHPs were synthesized with a NIRF conjugated to the N-terminus. Male Sprague-Dawley rats were assigned to one of four experimental groups: healthy, CHP; osteoarthritis (OA), CHP; healthy, scrambled-sequence CHP (sCHP), which has no collagen binding affinity; or OA, sCHP. Animals in the OA groups received an IA injection of monosodium iodoacetate to induce OA. All animals then received the corresponding CHP injection. Animals were imaged repeatedly over 2 weeks using an in vivo fluorescence imaging system. Joint components were isolated and imaged to determine CHP binding distribution. Safranin-O and Fast Green histological staining was performed to confirm the development of OA. CHPs were found to be retained within the joint following IA injection in both healthy and OA animals for the full study period. In contrast, sCHP signal was negligible by 24-48 h. CHP signal was significantly greater (p < 0.05) in OA joints when compared to healthy joints. At the 2-week end point, multiple joint components retained CHPs, including cartilage, meniscus, and synovium. CHPs dramatically extended the retention time of NIRFs following IA injection in healthy and OA knee joints by binding to multiple collagenous tissues in the joint. These results support the pursuit of further research to develop CHP based therapeutics for IA treatment of OA.

Influence of Medial Patellofemoral Ligament Reconstruction on Patellofemoral Contact in Patients With Low-Flexion Patellar Instability: An MRI Study.

Medial patellofemoral ligament (MPFL) reconstruction is a well-established procedure for the treatment of patients with patellofemoral instability (PFI) at low flexion angles (0°-30°). Little is known about the effect of MPFL surgery on patellofemoral cartilage contact area (CCA) during the first 30° of knee flexion. The purpose of this study was to investigate the effect of MPFL reconstruction on CCA using magnetic resonance imaging (MRI). We hypothesized that patients with PFI would have a lower CCA than patients with healthy knees and that CCA would increase after MPFL reconstruction over the course of low knee flexion. Cohort study; Level of evidence, 2. In a prospective matched-paired cohort study, the CCA of 13 patients with low-flexion PFI was determined before and after MPFL reconstruction, and the data were compared with those of 13 healthy volunteers (controls). MRI was performed with the knee at 0°, 15°, and 30° of flexion in a custom-designed knee-positioning device. To suppress motion artifacts, motion correction was performed using a Moiré Phase Tracking system via a tracking marker attached to the patella. The CCA was calculated on the basis of semiautomatic cartilage and bone segmentation and registration. The CCA (mean ± SD) at 0°, 15°, and 30° of flexion for the control participants was 1.38 ± 0.62, 1.91 ± 0.98, and 3.68 ± 0.92 cm2, respectively. In patients with PFI, the CCA at 0°, 15°, and 30° of flexion was 0.77 ± 0.49, 1.26 ± 0.60, and 2.89 ± 0.89 cm2 preoperatively and 1.65 ± 0.55, 1.97 ± 0.68, and 3.52 ± 0.57 cm2 postoperatively. Patients with PFI exhibited a significantly reduced preoperative CCA at all 3 flexion angles when compared with controls (P ≤ .045 for all). Postoperatively, there was a significant increase in CCA at 0° of flexion (P = .001), 15° of flexion (P = .019) and 30° of flexion (P = .026). There were no significant postoperative differences in CCA between patients with PFI and controls at any flexion angle. Patients with low-flexion patellar instability showed a significant reduction in patellofemoral CCA at 0°, 15°, and 30° of flexion. MPFL reconstruction increased the contact area significantly at all angles.

Recovery of leg strength based on isokinetic testing after tumor resection and reconstruction with a modular rotating hinge knee system: Prospective cross-sectional study with a minimum follow-up of 24 months

BackgroundWhile modular reconstruction implants can be used to replace the bone lost after bone tumor resection, tumor excision from the neighboring soft tissues can lead to loss of strength and joint range of motion (ROM), which results in worse knee function. Functional recovery after total knee arthroplasty for osteoarthritis has been extensively documented. But few studies have evaluated the recovery after total knee reconstruction following tumor excision despite the fact that most of these patients are young and have high functional demands. We did a prospective cross-sectional study to: 1) compare muscle strength recovery around the knee with an isokinetic dynamometer after tumor excision and reconstruction with a modular implant to the healthy contralateral knee; 2) determine if the differences in peak torque (PT) in the knee extensors and flexors had a clinical impact. HypothesisResection of soft tissues during tumor excision around the knee causes strength loss that cannot be fully recovered. MethodsThe 36 patients who underwent extra- or intra-articular resection of a primary or secondary bone tumor in the knee area followed by reconstruction with a rotating hinge knee system between 2009 and 2021 were eligible for this study. The primary outcome was the ability to actively lock the operated knee. The secondary outcomes were the concentric PT during isokinetic testing at slow (90°/sec) and fast (180°/sec) speeds, flexion-extension ROM, Musculoskeletal Tumor Society (MSTS) score, the IKS, Oxford Knee Score (OKS) and KOOS. ResultsNine patients agreed to participate in the study, all of whom had regained the ability to lock their knee postoperatively. PT in flexion and extension on the operated knee was less than the healthy knee. The PT ratio for the operated/healthy knee at 60°/sec and 180°/sec in flexion was 56.3%±16.2 [23.2–80.1] and 57.8%±12.3 [37.7–77.4], respectively, which corresponded to a slow-speed strength deficit of 43.7% in the knee flexors. The PT ratio for the operated/healthy knee at 60°/sec and 180°/sec in extension was 34.3%±24.6 [8.6–76.5] and 43%±27.2 [13.1–93.4], respectively, which corresponded to a slow-speed strength deficit of 65.7% in the knee extensors. The mean MSTS was 70%±20 [63–86]. The OKS was 29.9/48±11 [15–45], the mean IKS knee was 149.6±36 [80–178] and the mean KOOS was 67.43±18.5 [35-88.7]. DiscussionDespite all patients having the ability to lock out their knee, there was an imbalance in the strength between opposite muscle groups: 43.7% strength deficit at slow-speed and 42.2% at fast speed for the hamstring muscles, and 65.7% at slow-speed and 57% at fast speed for the quadriceps muscles. This difference is considered pathological with an increased risk of knee injury. Despite this strength deficit, this joint replacement technique, which is free of complications, can preserve good knee function with acceptable knee joint ROM and satisfactory quality of life. Level of evidenceIII; prospective cross-sectional case-control study.

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

Finite element analysis of a healthy knee joint at deep squatting for the study of tibiofemoral and patellofemoral contact

BackgroundIn non-western countries, deep squatting is a daily activity, and prolonged deep squatting is common among occupational squatters. Household tasks, taking a bath, socializing, using toilets, and performing religious acts are among the activities frequently carried out while squatting by the Asian population. High knee loading is responsible for a knee injury and osteoarthritis. Finite element analysis is an effective tool to determine stresses on the knee joint. MethodsMagnetic Resonance Imaging (MRI) and Computed Tomographic (CT) images were acquired of one adult without knee injuries. The CT images were acquired at the fully extended knee and one more set of images was acquired with the knee at a deeply flexed knee position. The MRI was acquired with the fully extended knee. 3-Dimensional models of bones were created using CT and soft tissue using MRI with the help of 3D Slicer software. Kinematics and finite element analysis of the knee was performed for standing and deep squatting posture using Ansys Workbench 2022. ResultsHigh peak stresses were observed at deep squatting compared to standing along with the reduction in the contact area. Peak von Mises stresses on femoral cartilage, tibial cartilage, patellar cartilage, and meniscus were increased from 3.3 MPa to 19.9 MPa, 2.9 MPa to 12.4 MPa, 1.5 MPa to 16.7 MPa and 15.8 MPa to 32.8 MPa respectively during deep squatting. Posterior translation of 7.01 mm, and 12.58 mm was observed for medial and lateral femoral condyle respectively from full extension to 153° knee flexion. ConclusionsIncreased stresses in the knee joint at deep squat posture may cause cartilage damage. A sustained deep squat posture should be avoided for healthy knee joints. More posterior translations of the medial femoral condyle at higher knee flexion angle warrant further investigation.

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

Hemophilic arthropathy can cause recurrent hemarthroses and severe damage to the synovium and articular cartilage. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an essential role in neoangiogenesis. Bevacizumab, a monoclonal VEGF inhibitor, is used clinically to prevent angiogenesis. However, its effects on hemophilic arthropathy are unknown. Using a hemophilic arthropathy rabbit model, we asked: Does an intra-articular injection of bevacizumab (1) inhibit VEGF, (2) decrease signal intensity in dynamic contrast-enhanced MRI (DCE-MRI) as an assessment of capillary permeability and neoangiogenesis, (3) reduce cartilage damage, (4) reduce synovial changes, and (5) affect macroscopic changes during the development of hemophilic arthropathy? Twenty-five male New Zealand rabbits were divided into four groups. Eight knees from four rabbits were used as the control group. We used an established animal model for hemophilic arthropathy in the remaining 21 rabbits. Animals were assigned randomly to three groups with seven rabbits in each group. One group was used to establish mild arthropathy, and the other two were used to establish severe arthropathy. Autologous blood from the rabbits' ears was injected into the right and left knees twice per week for 8 weeks to represent mild arthropathy and for 16 weeks to represent severe arthropathy. In the mild arthropathy group, bevacizumab was injected into the right knee once every 2 weeks. Bevacizumab was injected into the right knee of rabbits in one of the severe arthropathy groups once every 2 weeks for 16 weeks, and intra-articular bevacizumab injections were administered to the right knees of rabbits in the other severe arthropathy group once every 2 weeks after the eighth week. An equal volume of 0.9% saline was injected into the left knee of rabbits in all arthropathy groups. To explore the efficacy of bevacizumab, joint diameters were quantitatively measured, and cartilage and synovial changes were examined. Degeneration of articular cartilage was evaluated with the semiquantitative Osteoarthritis Research Society International grading system. Synovial damage was analyzed with a semiquantitative microscopic scoring system. In addition, we evaluated perfusion and angiogenesis using DCE-MRI (quantitative signal intensity changes). Immunohistochemical testing was used to measure VEGF levels (analyzed by Western blotting). Intra-articular bevacizumab treatment inhibited VEGF in our rabbit model of hemophilic arthropathy. VEGF protein expression levels were lower in the mild arthropathy group that received intra-articular bevacizumab (0.89 ± 0.45) than the mild arthropathy control group (1.41 ± 0.61) (mean difference -0.52 [95% CI -0.898 to -0.143]; p = 0.02). VEGF levels were lower in the severe arthropathy group that received treatment for 16 weeks (0.94 ± 0.27) than in the control knees (1.49 ± 0.36) (mean difference -0.55 [95% CI -0.935 to -0.161]; p = 0.01). In the severe arthropathy group, the Osteoarthritis Research Society International score indicating cartilage damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than in the control group (median 17 [range 13 to 18] versus 18 [range 17 to 20]; difference of medians 1; p = 0.02). Additionally, the scores indicated synovial damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than the control group (median 5 [range 4 to 9] versus 9 [range 8 to 12]; difference of medians 4; p = 0.02). The mean of mean values for signal intensity changes was higher in the nontreated severe groups than in the group of healthy knees. The signal intensity changes were higher in the severe arthropathy control groups (Groups BC and CC) (median 311.6 [range 301.4 to 361.2] and 315.1 [range 269.7 to 460.4]) than in the mild arthropathy control group (Group AC) (median 234.1 [range 212.5 to 304.2]; difference of medians 77.5 and 81, respectively; p = 0.02 and p = 0.04, respectively). In the severe arthropathy group, discoloration caused by hemosiderin deposition in the cartilage and synovium was more pronounced than in the mild arthropathy group. In the severe arthropathy group treated with intra-articular bevacizumab, joint diameters were smaller than in the control group (Group BT median 12.7 mm [range 12.3 to 14.0] versus Group BC median 14.0 mm [range 13.1 to 14.5]; difference of medians 1.3 mm; p = 0.02). Hemarthrosis damages the synovial tissues and cartilage in the knees of rabbits, regardless of whether they are treated with intra-articular bevacizumab. However, intra-articular injection of bevacizumab may reduce cartilage and synovial damage in rabbits when treatment is initiated early during the development of hemophilic arthropathy. If the findings in this study are replicated in larger-animal models that consider the limitations of our work, then a trial in humans might be appropriate to ascertain whether intra-articular injection of bevacizumab could reduce cartilage damage and synovial changes in patients with hemophilia whose hemarthroses cannot otherwise be controlled.

MARGIN OF STABILITY INCREASES IN THE SURGICAL LIMB OF ARTHRITIS PATIENTS DEPENDING ON THE AFFLICTED JOINT

Arthritis is a common and debilitating disease and is associated with an increased fall risk. The purpose of this study was to examine the effect of impacted joint and limb on fall risk as measured by the margin of stability (MOS).There were 110 participants, including healthy controls (HC; n=30), ankle arthritis (AA; n=30), knee arthritis (KA; n=20) and hip arthritis (HA; n=30) patients. All protocols were Institutional Review Board approved and all participants signed informed consent. Participants walked approximately 6 meters at a self-selected pace. MOS was calculated in the foot coordinate system in the anterior/posterior (AP) and medial/lateral (ML) directions at heel strike. A one-way ANOVA was used to examine group effects (HC, AA, KA, HA) on gait speed. A two-way repeated measures ANOVA was used to examine the effects of limb (Non-Surgical, Surgical) and group on AP and ML MOS.HC had the fastest gait speed (1.40±0.24 m/s; p&lt;0.001) when compared to AA (0.85±0.24 m/s), KA (0.94±0.22 m/s) and HA (1.05±0.22 m/s). HA participants had a greater gait speed compared to AA (p=0.004). AP MOS was greater in the surgical limb compared to the non-surgical limb for AA (p&lt;0.001) and HA (p&lt;0.001). AP MOS was smaller in HC compared to AA, KA, and HA, regardless of limb (p&lt;0.030). AP MOS was similar between AA, KA, and HA for the non-surgical limb (p&gt;0.194) and the surgical limb (p&gt;0.096). ML MOS was greater in the surgical compared to non-surgical limb (p=0.003). ML MOS was smaller in KA participants compared to all other groups (p&lt;0.001).Our results demonstrate stability during gait varies between limbs in arthritis patients, with a more conservative pattern for the surgical limb and suggest KA may be at an increased risk of falls with a smaller ML MOS.

Analysis of RNA Polyadenylation in Healthy and Osteoarthritic Human Articular Cartilage.

Polyadenylation (polyA) defines the 3' boundary of a transcript's genetic information. Its position can vary and alternative polyadenylation (APA) transcripts can exist for a gene. This causes variance in 3' regulatory domains and can affect coding sequence if intronic events occur. The distribution of polyA sites on articular chondrocyte transcripts has not been studied so we aimed to define their transcriptome-wide location in age-matched healthy and osteoarthritic knee articular cartilage. Total RNA was isolated from frozen tissue samples and analysed using the QuantSeq-Reverse 3' RNA sequencing approach, where each read runs 3' to 5' from within the polyA tail into the transcript and contains a distinct polyA site. Differential expression of transcripts was significant altered between healthy and osteoarthritic samples with enrichment for functionalities that were strongly associated with joint pathology. Subsequent examination of polyA site data allowed us to define the extent of site usage across all the samples. When comparing healthy and osteoarthritic samples, we found that differential use of polyadenylation sites was modest. However, in the genes affected, there was potential for the APA to have functional relevance. We have characterised the polyadenylation landscape of human knee articular chondrocytes and conclude that osteoarthritis does not elicit a widespread change in their polyadenylation site usage. This finding differentiates knee osteoarthritis from pathologies such as cancer where APA is more commonly observed.

Multileveled Hierarchical Hydrogel with Continuous Biophysical and Biochemical Gradients for Enhanced Repair of Full-Thickness Osteochondral Defect.

The repair of hierarchical osteochondral defect requires sophisticated gradient reestablishment; however, few strategies for continuous gradient casting consider the relevance to clinical practice regarding cell adaptability, multiple gradient elements, and precise gradient mirroring native tissue. Here, a hydrogel with continuous gradients in nano-hydroxyapatite (HA) content, mechanical, and magnetism is developed using synthesized superparamagnetic HA nanorods (MagHA) that easily respond to a brief magnetic field. To precisely reconstruct osteochondral tissue, the optimized gradient mode is calculated according to magnetic resonance imaging (MRI) of healthy rabbit knees. Then, MagHA are patterned to form continuous biophysical and biochemical gradients, consequently generating incremental HA, mechanical, and electromagnetic cues under an external magnetic stimulus. To make such depth-dependent biocues work, an adaptable hydrogel is developed to facilitate cell infiltration. Furthermore, this approach is applied in rabbit full-thickness osteochondral defects equipped with a local magnetic field. Surprisingly, this multileveled gradient composite hydrogel repairs osteochondral unit in a perfect heterogeneous feature, which mimics the gradual cartilage-to-subchondral transition. Collectively, this is the first study that combines an adaptable hydrogel with magneto-driven MagHA gradients to achieve promising outcomes in osteochondral regeneration.

Geographic Variation in Knee Phenotypes Based on the Coronal Plane Alignment of the Knee Classification: A Systematic Review

BackgroundThe extent of geographic variation in knee phenotypes remains unclear. The Coronal Plane Alignment of the Knee (CPAK) Classification proposes 9 coronal plane phenotypes based on constitutional limb alignment and joint line obliquity. This systematic review aims to examine differences in the distributions of CPAK types across geographic regions. MethodsA systematic review of the literature was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting distributions of knee phenotypes according to the CPAK classification for healthy and/or arthritic knees were included. ResultsThere were 7 studies included, accounting for 5,964 knees in 3,917 subjects. Among healthy knees (n = 1,214), CPAK type II was the most common type in Belgium (39.2%), Taiwan (39.3%), and India (25.6%). Among arthritic knees (n = 2,804), CPAK type I was the most common in France (33.4%), India (58.8%), and Japan (53.8%), whereas CPAK type II was the most common in Australia (32.8%). The proportion of CPAK type I and II knees varied significantly across geographic regions among healthy (P < .01) and arthritic knees (P < .01). ConclusionSignificant variation in CPAK distributions exists between countries. Further work is needed to delineate racial and sexual differences in CPAK types, which were not explored in this article. A better understanding of population-level variability in knee phenotypes may enable orthopaedic surgeons to offer a more personalized approach to knee arthroplasty.

Long-term effects of retrograde approach on the knee after motorized femoral limb lengthening.

The retrograde femoral approach is an established technique for implantation of nails for leg lengthening and correction and in cases of distal femoral fractures. The purpose of this study was to determine the 10-year outcome of this technique by analyzing the clinical long-term effects and radiological status of the knee after leg lengthening via a retrograde femoral approach. This retrospective single-center study included 13 patients (median age at surgery 17 [range 15-20] years) who underwent unilateral, retrograde, femoral lengthening with a motorized nail. Outcome measurements were graded variables of the SF-36, ISKD score, and Lysholm score. MRI of both knees was performed in all patients. MRI was evaluated for the presence of degenerative changes and compared with the healthy contralateral knee. Cartilage condition was graded according to the International Cartilage Repair Society (ICRS) scoring system. All patients were pain-free and had a full range of motion 10 (range 10.0-12.2) years after surgery. All postoperative knees showed fibrosis of Hoffa's fat pad and moderate to severe cartilage defects (ICRS Grade 2-4) of the trochlear groove (nail entry site). 6 out of 13 operated knees exhibited retropatellar cartilage defects. Our study showed that patients were pain-free, but cartilage defects at the entry point and arthrofibrosis at Hoffa's fat pad were observed without causing clinical impairment.

Impaired Efferocytosis by Synovial Macrophages in Patients With Knee Osteoarthritis.

Osteoarthritis (OA) exposes all joint tissues to physiologic stresses, increasing the need to clear apoptotic cells from tissues, including the synovium. We undertook this study to assess the burden of apoptotic cells in synovial tissue in patients with late-stage knee OA and to investigate whether OA impairs the macrophage-mediated clearance of apoptotic cells via efferocytosis. Synovial tissue was collected from individuals with healthy knees and patients with late-stage knee OA during arthroplasty. Synovial apoptotic cell burden was assessed by immunofluorescence for cleaved caspase 3. Efferocytosis of apoptotic Jurkat cells by CD14+ synovial tissue macrophages and peripheral blood-derived macrophages was quantified using immunofluorescence microscopy. Effects of OA on macrophage-mediated efferocytosis were modeled by stimulating blood-derived macrophages with synovial fluid collected from individuals with healthy knees and patients with early- or late-stage knee OA. Patients with late-stage knee OA had more apoptotic synovial cells compared to healthy individuals. There was a marked reduction in the fraction of synovial tissue macrophages engaging in efferocytosis and the quantity of material efferocytosed by individual macrophages in OA patients. Blood-derived macrophages exposed to synovial fluid from patients with knee OA recapitulated the defective efferocytosis, with the greatest effect from patients with early-stage knee OA and higher disease activity (pain and inflammation). Apoptotic cells accumulate in the synovium of patients with late-stage knee OA. Our results suggest that OA impairs critical homeostatic functions of synovial macrophages, leading to accumulation of apoptotic cells.

Change in Descriptive Kinematic Parameters of Patients with Patellofemoral Instability When Compared to Individuals with Healthy Knees—A 3D MRI In Vivo Analysis

Patellofemoral instability (PFI) leads to chronic knee pain, reduced performance and chondromalacia patellae with consecutive osteoarthritis. Therefore, determining the exact patellofemoral contact mechanism, as well as the factors leading to PFI, is of great importance. The present study compares in vivo patellofemoral kinematic parameters and the contact mechanism of volunteers with healthy knees and patients with low flexion patellofemoral instability (PFI). The study was performed with a high-resolution dynamic MRI. In a prospective cohort study, the patellar shift, patella rotation and the patellofemoral cartilage contact areas (CCA) of 17 patients with low flexion PFI were analyzed and compared with 17 healthy volunteers, matched via the TEA distance and sex, in unloaded and loaded conditions. MRI scans were carried out for 0°, 15° and 30° knee flexion in a custom-designed knee loading device. To suppress motion artifacts, motion correction was performed using a moiré phase tracking system with a tracking marker attached to the patella. The patellofemoral kinematic parameters and the CCA was calculated on the basis of semi-automated cartilage and bone segmentation and registrations. Patients with low flexion PFI showed a significant reduction in patellofemoral CCA for 0° (unloaded: p = 0.002, loaded: p = 0.004), 15° (unloaded: p = 0.014, loaded: p = 0.001) and 30° (unloaded: p = 0.008; loaded: p = 0.001) flexion compared to healthy subjects. Additionally, patients with PFI revealed a significantly increased patellar shift when compared to volunteers with healthy knees at 0° (unloaded: p = 0.033; loaded: p = 0.031), 15° (unloaded: p = 0.025; loaded: p = 0.014) and 30° flexion (unloaded: p = 0.030; loaded: p = 0.034) There were no significant differences for patella rotation between patients with PFI and the volunteers, except when, under load at 0° flexion, PFI patients showed increased patellar rotation (p = 0.005. The influence of quadriceps activation on the patellofemoral CCA is reduced in patients with low flexion PFI. Patients with PFI showed different patellofemoral kinematics at low flexion angles in both unloaded and loaded conditions compared to volunteers with healthy knees. Increased patellar shifts and decreased patellofemoral CCAs were observed in low flexion angles. The influence of the quadriceps muscle is diminished in patients with low flexion PFI. Therefore, the goal of patellofemoral stabilizing therapy should be to restore a physiologic contact mechanism and improve patellofemoral congruity for low flexion angles.

Inverse kinematic alignment accommodates native coronal knee alignment better in comparison to adjusted mechanical alignment and restricted kinematic alignment.

The purpose was to determine the proportion of native non-arthritic knees that fit within the target zones of adjusted mechanical alignment (aMA), restricted kinematic alignment (rKA), and inverse kinematic alignment (iKA), and to estimate adjustments in native coronal alignment to bring outlier knees within the respective target zones. The hypothesis was that the target zone of iKA, compared to the target zones of aMA and rKA, accommodates a higher proportion of native non-arthritic knees. The study used measurements obtained from a computed tomography (CT) scan database (SOMA, Stryker) of 972 healthy knees (Caucasian, 586; Asian, 386). Hip knee ankle (HKA) angle, medial proximal tibial angle (MPTA) and lateral distal femoral angle (LDFA) were used to estimate the proportions of knees within the patient-specific alignment target zones; and to estimate theoretical adjustments of MPTA, LDFA and soft tissue balance (HKA) to bring outlier knees within target zones. Theoretical adjustments to bring outlier knees within the alignment target zones of aMA, rKA and iKA were calculated by subtracting the native coronal alignment angles (MPTAnative, LDFAnative and HKAnative) from angles on the nearest target zone border (MPTAtarget, LDFAtarget and HKAtarget). Patients were aged 59.8 ± 15.8years with a BMI of 25.0 ± 4.4kg/m2. The HKA angles were between 168° and 186°, MPTA between 78° and 98° and LDFA between 79° and 93°. Of the 972 knees, 81 (8%) were in the aMA target zone, 530 (55%) were in the rKA target zone, and 721 (74%) were in the iKA target zone. Adjustments of MPTA, LDFA and HKA angle to bring outlier knees within the target zones, were, respectively, 90, 91 and 28% for aMA, 45, 28 and 25% for rKA, and 25, 23 and 7% for iKA. There is considerable variability in native knee coronal alignment that corresponds to different proportions of the restricted patient-specific alignment target zones for TKA. Although extension of the MPTA and LDFA target zones with rKA accommodate native knee alignment better than aMA, up to 25% would require adjustment of native HKA angle. By also extending the HKA angle target zone into varus, iKA accommodates a greater proportion (93%) of native limb alignment. IV.

Inertial Sensor Location for Ground Reaction Force and Gait Event Detection Using Reservoir Computing in Gait.

Inertial measurement units (IMUs) have shown promising outcomes for estimating gait event detection (GED) and ground reaction force (GRF). This study aims to determine the best sensor location for GED and GRF prediction in gait using data from IMUs for healthy and medial knee osteoarthritis (MKOA) individuals. In this study, 27 healthy and 18 MKOA individuals participated. Participants walked at different speeds on an instrumented treadmill. Five synchronized IMUs (Physilog®, 200 Hz) were placed on the lower limb (top of the shoe, heel, above medial malleolus, middle and front of tibia, and on medial of shank close to knee joint). To predict GRF and GED, an artificial neural network known as reservoir computing was trained using combinations of acceleration signals retrieved from each IMU. For GRF prediction, the best sensor location was top of the shoe for 72.2% and 41.7% of individuals in the healthy and MKOA populations, respectively, based on the minimum value of the mean absolute error (MAE). For GED, the minimum MAE value for both groups was for middle and front of tibia, then top of the shoe. This study demonstrates that top of the shoe is the best sensor location for GED and GRF prediction.