Juvenile trabecular ossifying fibroma of the inferior turbinate.

Nasal obstruction is a commonly reported issue in the Otorhinolaryngology Outpatient Department. In this case, an early adolescent boy with a long-standing problem of right-sided nasal obstruction since childhood sought consultation. Diagnostic nasal endoscopy revealed a deviation of the nasal septum to the left, coupled with right inferior turbinate hypertrophy, all overlying healthy mucosa. A CT scan of the nose and paranasal sinuses further identified a bony hyperdense lesion with ground glass attenuation, confined to the right inferior turbinate. Subsequent biopsy confirmed juvenile trabecular ossifying fibroma (JTOF). The patient underwent endoscopic right medial maxillectomy, and the final histology affirmed the diagnosis of JTOF.

Magnetic Resonance Image Findings and Potential Anatomic Risk Factors for Chodromalacia in Children and Adolescents Suffering from Non-Overload Atraumatic Knee Pain in the Ambulant Setting.

PURPOSE: To evaluate magnetic resonance image (MRI) findings in children and adolescents suffering from knee pain without traumatic or physical overload history and to identify potential anatomic risk factors. MATERIAL AND METHODS: A total of 507 MRIs of 6- to 20-year-old patients (251 males; 256 females) were evaluated with regard to detectable pathologies of the knee. The results were compared to a control group without pain (n = 73; 34 males; 39 females). A binary logistic regression model and t-tests for paired and unpaired samples were used to identify possible risk factors and significant anatomic differences of the study population. RESULTS: In 348 patients (68.6%), at least one pathology was detected. The most commonly detected finding was chondromalacia of the patellofemoral (PF) joint (n = 205; 40.4%). Chondral lesions of the PF joint occurred significantly more often in knee pain patients than in the control group (40% vs. 11.0%; p = 0.001), especially in cases of a patella tilt angle > 5° (p ≤ 0.001), a bony sulcus angle > 150° (p = 0.002), a cartilaginous sulcus angle > 150° (p = 0.012), a lateral trochlear inclination < 11° (p ≤ 0.001), a lateralised patella (p = 0.023) and a Wiberg type II or III patella shape (p = 0.019). Moreover, a larger patella tilt angle (p = 0.021), a greater bony sulcus angle (p = 0.042), a larger cartilaginous sulcus angle (p = 0.038) and a lower value of the lateral trochlear inclination (p = 0.014) were detected in knee pain patients compared to the reference group. CONCLUSION: Chondromalacia of the PF joint is frequently observed in children and adolescents suffering from non-overload atraumatic knee pain, whereby a patella tilt angle > 5°, a bony sulcus angle > 150°, a cartilaginous sulcus angle > 150°, a lateral trochlear inclination < 11°, a lateralised patella and a Wiberg type II or III patella shape seem to represent anatomic risk factors.

Viable cartilage allograft outperforms existing treatments for focal knee cartilage defects.

PURPOSE: Viable cartilage allograft (VCA) is a cartilage tissue matrix that contains cryopreserved viable allogeneic cartilage fibres. This study aimed to assess safety and benefits in treating focal knee cartilage defects with VCA. We hypothesized that VCA is a safe single-stage procedure in isolated chondral defects. METHOD: In vitro analysis, in vivo studies and a prospective case series were performed. VCA was evaluated in a goat cartilage repair model. Symptomatic International Cartilage Repair Society grade 3/4A lesions of the femoral condyle or patella were implanted with VCA. International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome (KOOS) subscales, Lysholm, Short Form-12, Visual Analog Scale and pain frequency levels were assessed. Radiographic and magnetic resonance imaging (MRI) was performed at regular intervals postoperatively. Data were analysed by statisticians to determine the power and significance of the results. RESULTS: The goat study confirmed that VCA is effective for cartilage repair. Twenty patients were implanted; the mean age was 28.1 (16-56), the mean body mass index (BMI) was 27.9 ± 5.6 and the mean follow-up was 24.1 months (range = 12.0-36.0 months). Lesions were in either the femoral condyle (7) or patella (13). Lesion sizes ranged from 1.5 to 6.0 cm2 (mean = 4.58 cm2 ). Outcome scores improved from preoperative baseline (POB): IKDC (78.2), Lysholm (89.0), KOOS: Pain (95.8), Symptoms (86.3), ADL (87.8), Sports (85.0) and QOL (75.0). MRI imaging demonstrated excellent osteochondral allograft assimilation. Second-look arthroscopy (two patients) demonstrated complete fill and incorporation (Brittberg scores 11/12). Functional scores were maintained at 24 (M): IKDC (86.24 ± 17.2), Lysholm (87.23 ± 15.0), KOOS: Pain (91.72 ± 17.3), Symptoms (84.92 ± 16.1), ADLs (93.80 ± 16.1), Sports (84.45 ± 27.7), QOL (81.30 ± 20.8). CONCLUSION: VCA is an off-the-shelf, single-stage, conformable allogeneic graft that treats chondral defects with no additional fixation. Preclinical and short-term prospective clinical studies show that VCA can safely treat chondral defects with potential advantages to existing options. LEVEL OF EVIDENCE: Level IV study.

The Combined Intraosseous Administration of Orthobiologics Outperformed Isolated Intra-articular Injections in Alleviating Pain and Cartilage Degeneration in a Rat Model of MIA-Induced Knee Osteoarthritis.

BACKGROUND: Intra-articular (IA) platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) injections have shown efficacy and safety in treating osteoarthritis (OA). However, the effectiveness and mechanisms of combined intraosseous (IO) administration of these orthobiologics have yet to be explored. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the effect on pain, cartilage, synovium/infrapatellar fat pad (IFP), and subchondral bone in rat knee OA, comparing isolated IA with combined IA and IO (IA+IO) injections of PRP or BMAC. It was hypothesized that combined injections would be superior to sole IA injections. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 48 rats were divided into 6 groups: sham (only joint puncture during OA induction with IA+IO saline injection treatment) and 5 groups with OA induction, control (IA+IO saline injection), PRP (IA PRP+IO saline injection), BMAC IA (IA BMAC+IO saline injection), PRP IA+IO (IA+IO PRP injection), and BMAC IA+IO (IA+IO BMAC injection). OA was induced by IA injection of monosodium iodoacetate (MIA). Rats were administered different orthobiologics according to their grouping 3 weeks after the MIA injection. Pain changes were evaluated using the weightbearing ratio assay at weeks 3, 4, 5, 7, and 9 after OA induction. Rats were euthanized at week 9 for gross, radiological, histological, immunohistochemical, and immunofluorescence assessments of cartilage, synovium, and subchondral bone. RESULTS: Compared with the control group, all orthobiologics injection groups had reduced joint pain. Compared with IA injection, IA+IO injections provided superior pain relief by suppressing calcitonin gene-related peptide and substance P in both the synovium/IFP and subchondral bone. IA+IO injections slowed the progression of subchondral bone lesions by inhibiting CD31hiEmcnhi vessel formation and excessive osteoclast and osteoblast turnover while preserving subchondral bone microarchitecture, slowing cartilage degeneration. However, IA+IO injections did not outperform isolated IA injections in reducing synovitis and synovium/IFP fibrosis. Compared with PRP, BMAC exhibited superior inhibition of pain-related mediators, but no significant differences were observed in synovitis suppression, infrapatellar fat pad fibrosis, and subchondral bone protection. CONCLUSION: IA+IO injections of orthobiologics were more effective in relieving pain, slowing cartilage degeneration, and inhibiting abnormal vascularization and remodeling compared with isolated IA injections. BMAC showed superior pain relief in the synovium/IFP and subchondral bone compared with PRP. Further research is needed to optimize PRP and BMAC components for enhanced efficacy in OA management. CLINICAL RELEVANCE: Our findings contribute to advancing the understanding of pain relief mechanisms and support the endorsement of IO injection of orthobiologics for the treatment of OA and joint pain.

TLR4 antagonism provides short-term but not long-term clinical benefit in a full-depth cartilage defect mouse model.

PURPOSE/AIM: Cartilage injury and subsequent osteoarthritis (OA) are debilitating conditions affecting millions worldwide. As there are no cures for these ailments, novel therapies are needed to suppress disease pathogenesis. Given that joint injuries are known to produce damage-associated molecular patterns (DAMPs), our central premise is that the Toll-like receptor 4 (TLR4) pathway is a principal driver in the early response to cartilage damage and subsequent pathology. We postulate that TLR4 activation is initiated/perpetuated by DAMPs released following joint damage. Thus, antagonism of the TLR4 pathway immediately after injury may suppress the development of joint surface defects. MATERIALS AND METHODS: Two groups were utilized: (1) 8-week-old, male C57BL6 mice treated systemically with a known TLR4 antagonist and (2) mice injected with vehicle control. A full-depth cartilage lesion on the midline of the patellofemoral groove was created in the right knee of each mouse. The left knee was used as a sham surgery control. Gait changes were evaluated over 4 weeks using a quantitative gait analysis system. At harvest, knee joints were processed for pathologic assessment, Nanostring® transcript expression, and immunohistochemistry (IHC). RESULTS: Short-term treatment with a TLR4 antagonist at 14-days significantly improved relevant gait parameters; improved cartilage metrics and modified Mankin scores were also seen. Additionally, mRNA expression and IHC showed reduced expression of inflammatory mediators in animals treated with the TLR4 antagonist. CONCLUSIONS: Collectively, this work demonstrates that systemic treatment with a TLR4 antagonist is protective to further cartilage damage 14-days post-injury in a murine model of induced disease.

MRI identification of pseudolesions in the distal tibia articular surface: Frequency and diagnostic criteria.

OBJECTIVE: Pseudolesions of joints are known as focal irregularities of chondral or subchondral bone in typical joint areas and occur frequent but without clinical relevance. This study aims to report the prevalence and describe MRI findings of a previously unreported chondral, mostly posterior located pseudolesion of the distal tibia, and to define criteria to distinguish it from pathologic osteochondral lesions, as well as from another known pseudolesion of this area - the so called "Notch of Harty". MATERIAL AND METHODS: A tri-centric retrospective case-control study included a total of 2,428 patients with ankle MRI examinations performed over a period of 6 years. MRI scans were evaluated by three radiologists in consensus for any cartilage irregularity of the distal tibial articular surface. For this purpose, the tibial articular surface was divided into 9 topographic regions. Proton-density weighted, fat-suppressed sequences in sagittal and coronal acquisition were used to assess the postero-medial articular surface of the tibia. Imaging features such as size and localization of cartilage irregularity and/or a cortical mould as well as presence of associated edema and/or subchondral cysts were reported. Demographic data (sex, age, and weight) was also recorded. Clinical data comprised presence of pain, movement impairment, and concomitant pathologies. RESULTS: A total of 68 patients (34 male, 34 female) with a lesion of the distal tibia were identified that had a new pseudolesion (prevalence of 3%). These lesions occurred most frequently (50 out of 68, 74%) in the postero-medial distal tibia plafond and were more commonly detected in the age group of 9-30 years (47%). In 13 of these 68 cases, the cartilage irregularity was the sole lesion without subchondral abnormalities. By defining these cases as definite pseudolesions, the prevalence was 1% and their age distribution was similar to that of the 55 other lesions with subchondral changes. Here with 11 of the 13 cases the majority (85%) were seen in the posterior part, especially in the postero-medial part (55%) of the distal tibia. The size of the cartilage defect ranged from 1 to 7 mm, and the majority (69%) sized from 2 to 3 mm. In 36 of 68 patients, we have seen subchondral alterations such as edema and/or cysts in addition to cartilage irregularity. 66% (n = 45) of these changes were edema and 37% (n = 25) were cysts. None of these 68 new pseudolesions with or without subchondral changes needed surgical or arthroscopic intervention. In the radiological and orthopaedic reports, clinical symptoms such as pain or instability were never associated with our observed lesions and there was no significant correlation between the presence of motion-related pain and imaging findings of cartilage irregularity, subchondral edema, and subchondral cysts. Thirteen patients had MRI follow-up examinations. Here the lesions did not show any MR morphological changes or clinical deterioration. Besides the new pseudolesion, which occured mainly in the posterior part of the tibia surface, we observed the "Notch of Harty" with a higher prevalence (25%) in our patient cohort. The typical localization was in the antero-medial tibial articular surface, without any edema or cysts. There were no coincidences of patients with both a new pseudolesion and the "Notch of Harty" CONCLUSION: A new pseudolesion is typically seen in the postero-central and postero-medial tibial articular surface with a prevalence of 3% and may be associated with only a small cartilage irregularity. In many cases, however, additional findings such as bone edema and/or an adjacent bone cysts were found, which impairs differentiation of these lesions from pathologic osteochondral lesions. The latter are obviously often associated with a larger cartilage defect and clinical symptoms. Due to the balanced age distribution between those pseudolesions with and without subchondral changes and the lack of clinical symptoms, we conclude that the here reported pseudolesions are not a predilection for a clinically manifest osteochondral lesion (OCL). At the very least, the apparent lack of clinical relevance increases the likelihood that we are dealing with a new true pseudolesion.

Quantification of Synovial Fluid Using Magnetic Resonance Fingerprinting Multicomponent Imaging in the Articular Cartilage of the Knee.

RATIONALE AND OBJECTIVES: The purpose of this study was to verify the feasibility of magnetic resonance fingerprinting (MRF)-derived synovial fluid fraction (SFF) mapping for quantifying subvoxel-sized cartilage defects. MATERIALS AND METHODS: MRF was performed on a 3-Tesla scanner and used to derive T2 and SFF maps. An ex vivo experiment was performed using bovine bone; different numbers of holes (4, 6, 8, 10, and 12) were drilled separately on the articular surface, and SFF values were compared among the drilled areas. In a clinical study, 16 osteoarthritis patients underwent sagittal 3D fast spinecho (FSE) and MRF scanning, and knee cartilage segmentation was performed on each image. For morphologic analysis, fluid-excluded images of the SFF (FEISFF) and T2 maps (FEIT2) were generated using the cartilage segmentations, and the whole-organ magnetic resonance imaging score (WORMS) of each FEI and 3D FSE image were compared using the kappa coefficient. For quantitative analysis, intact cartilage volumes in the SFF (VSFF) and T2 maps (VT2) were calculated, and their correlations with reference to the actual cartilage volume on 3D FSE images (V3D) were evaluated. RESULTS: In the ex vivo experiment, the SFF value increased as the number of holes increased. The kappa coefficients of the WORMS were 0.80 and 0.64 in the SFF and T2 maps, respectively, and substantial to almost perfect agreement was observed in the medial tibiofemoral joint. The V3D-VSFF and V3D-VT2 correlation coefficients differed by 0.03 or more in the medial tibiofemoral joint. CONCLUSION: The MRF-derived SFF map can feasibly evaluate small, invisible cartilage defects and quantify cartilage volumes.

[Current MR imaging of cartilage in the context of knee osteoarthritis (part 1) : Principles and sequences]. / Aktuelle MRT-Bildgebung des Knorpels im Kontext der Gonarthrose (Teil 1) : Grundlagen und Sequenzen.

Magnetic resonance imaging (MRI) is the clinical method of choice for cartilage imaging in the context of degenerative and nondegenerative joint diseases. The MRI-based definitions of osteoarthritis rely on the detection of osteophytes, cartilage pathologies, bone marrow edema and meniscal lesions but currently a scientific consensus is lacking. In the clinical routine proton density-weighted, fat-suppressed 2D turbo spin echo sequences with echo times of 30-40 ms are predominantly used, which are sufficiently sensitive and specific for the assessment of cartilage. The additionally acquired T1-weighted sequences are primarily used for evaluating other intra-articular and periarticular structures. Diagnostically relevant artifacts include magic angle and chemical shift artifacts, which can lead to artificial signal enhancement in cartilage or incorrect representations of the subchondral lamina and its thickness. Although scientifically validated, high-resolution 3D gradient echo sequences (for cartilage segmentation) and compositional MR sequences (for quantification of physical tissue parameters) are currently reserved for scientific research questions. The future integration of artificial intelligence techniques in areas such as image reconstruction (to reduce scan times while maintaining image quality), image analysis (for automated identification of cartilage defects), and image postprocessing (for automated segmentation of cartilage in terms of volume and thickness) will significantly improve the diagnostic workflow and advance the field further.

Cell Therapy Approaches for Articular Cartilage Regeneration.

Articular cartilage is a common cartilage type found in a multitude of joints throughout the human body. However, cartilage is limited in its regenerative capacity. A range of methods have been employed to aid adults under the age of 45 with cartilage defects, but other cartilage pathologies such as osteoarthritis are limited to non-steroidal anti-inflammatory drugs and total joint arthroplasty. Cell therapies and synthetic biology can be utilized to assist not only cartilage defects but have the potential as a therapeutic approach for osteoarthritis as well. In this review, we will cover current cell therapy approaches for cartilage defect regeneration with a focus on autologous chondrocyte implantation and matrix autologous chondrocyte implantation. We will then discuss the potential of stem cells for cartilage repair in osteoarthritis and the use of synthetic biology to genetically engineer cells to promote cartilage regeneration and potentially reverse osteoarthritis.

Evaluation of the relationship between trochlear and patellar morphology and patellar chondromalacia with magnetic resonance imaging.

It was aimed to investigate the relationship between magnetic resonance imaging (MRI) measurements of trochlear and patellar morphology and grade 3-4 patellar chondromalacia. Grade 3-4 patellar chondromalacia group, and an age- and sex-matched control group with normal patellar joint cartilage were comprised. For trochlear morphology evaluation in MRI; sulcus angle, trochlear angle, lateral trochlear inclination angle and medial trochlear inclination angle were measured. For patellar morphology evaluation; patella trochlear ratio, insall-salvati ratio, modified Insall- Salvati ratio and Blackburne-Peel ratio were measured. Obtained measurements were statistically analyzed according to demographic characteristics. One hundred and twenty-five patients with chondromalacia and 125 controls participated. The sulcus angle and the trochlear angle were significantly higher in the patellar chondromalacia group (p<0.05). The lateral trochlear inclination angle was significantly less in the patellar chondromalacia group (p=0.011). There was no significant difference between the groups in terms of medial trochlear inclination angle (p=0.520). There was no significant difference between the groups in terms of patella-trochlear ratio (p=0.617). Insall-Salvati ratio was significantly higher in the patellar chondromalacia group (p=0.003). Modified Insall-Salvati ratio was significantly lower in the patellar chondromalacia group (p=0.001). The rate of Blackburne-Peel was significantly higher in the patellar chondromalacia group (p=0.004). Measurements of sulcus angle, trochlear angle, lateral trochlear inclination angle, Insall-Salvati ratio, modified Insall-Salvati ratio, Blackburne-Peel ratio have diagnostic value for grade 3-4 chondromalacia.

Association between infrapatellar fat pad ultrasound elasticity and anterior knee pain in patients with knee osteoarthritis.

This study investigates whether infrapatellar fat pad (IPFP) elasticity is associated with anterior knee pain in patients with knee osteoarthritis (KOA). The IPFP elasticity of 97 patients with KOA (Kellgren and Lawrence [KL] grades of the femorotibial and patellofemoral joints ≥ 2 and ≤ 2, respectively), aged 46-86 years, was evaluated via shear wave speed using ultrasound elastography. The patients were divided into two groups according to the presence or absence of anterior knee pain. Univariate analyses were used to compare patient age, sex, femorotibial KL grade, magnetic resonance imaging findings (Hoffa, effusion synovitis, bone marrow lesion scores, and IPFP size), and IPFP elasticity between the groups. Multivariate logistic regression analyses were subsequently performed using selected explanatory variables. IPFP elasticity was found to be associated with anterior knee pain in the univariate (p = 0.007) and multivariate (odds ratio: 61.12, 95% CI 1.95-1920.66; p = 0.019) analyses. Anterior knee pain is strongly associated with stiffer IPFPs regardless of the femorotibial KL grade, suggesting that ultrasound elastography is useful for the diagnosis of painful IPFP in patients with KOA.

Morphological analysis of three-dimensional MR images of patellofemoral joints in asymptomatic subjects.

The existing methods for analyzing patellofemoral (PF) osteoarthritis (OA) are limited. Our purpose was to clarify the frequency, localization, and morphological progression of PFOA by observing three-dimensional (3D) magnetic resonance (MR) images from a cohort population. The subjects were 561 patients aged 30-79 years from the Kanagawa Knee Study who had not visited a hospital for more than three consecutive months for knee symptoms. MR images of the PF joints, separated into the medial and lateral types, were presented in order of the highest to lowest patella cartilage area ratios. Cartilage defects in the patella were detected in 37 subjects (6.6%). Medial lesions (4.6%) were significantly more frequent than lateral lesions (2.0%) (p < 0.01). For both medial and lateral lesions, the patellar cartilage defects were divided into confined and unconfined types. The 3D MR images of the PF joint showed that the patellar cartilage defect occurred along each ridge of the femoral trochlea. The 3D MR images revealed a 6.6% prevalence of patellar cartilage defects, higher in the medial than lateral regions. The 3D MR images can easily determine PF morphology and cartilage defect location, making them useful in understanding the pathophysiology and etiology of PFOA.

In situ observation of cartilage matrix based on two-photon fluorescence microscopy.

Articular cartilage lesions remain a major challenge for clinicians and researchers. Several techniques, such as histological scoring, magnetic resonance imaging, and tissue section staining, are available for detecting cartilage degeneration and lesions and evaluating cartilage repairs. Nevertheless, these methods are complex and have numerous influencing factors, which may present obstacles to efficient communication between studies. In this study, we developed a fluorescence observation system that integrated a two-photon laser scanning confocal microscope (TPLSCM) with the second-harmonic generation (SHG) of a cartilage matrix. The observation system enabled the detection of autofluorescence emitted by the cartilage matrix without species specificity, facilitating both qualitative and quantitative analyses of the cartilage matrix. Notably, this observation could be applied three-dimensionally to a fresh specimen in situ up to a depth of 300 µm, obviating the need for traditional histological fixation, slicing, or staining. Furthermore, using this observation system, we reconstructed a three-dimensional (3D) image and a 3D model of the cartilage matrix. The utilization of the 3D fluorescence model may serve as a dependable option for the fabrication of cartilage matrix biomimetic scaffolds in future studies.

Novel Osteochondral Biotemplate Improves Long-term Cartilage Repair Compared With Microfracture in an Ovine Model.

BACKGROUND: Current cartilage repair therapies do not re-create the complex mechanical interface between cartilage and bone, which is critical for long-term repair durability. New biomaterial designs that include hard tissue-soft tissue interface structures offer promise to improve clinical outcomes. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the efficacy and safety of a naturally derived osteochondral biotemplate with a novel contiguous hard tissue-soft tissue interface in an ovine model as a regenerative solution for articular cartilage defects. It was hypothesized that the osteochondral biotemplate would produce structurally superior repair tissue compared with microfracture over a 13-month period. STUDY DESIGN: Controlled laboratory study. METHODS: Osteochondral biotemplates were manufactured from porcine cancellous bone. Skeletally mature sheep (N = 30) were randomly allocated to 3 groups: early healing stage (euthanasia at 4 months), 6-month treatment, and 13-month treatment. In the early healing stage group, an 8 mm-diameter by 5 mm-deep osteochondral defect was created on the medial femoral condyle and treated at the time of iatrogenic injury with an osteochondral biotemplate. The contralateral limb received the same treatment 2 months later. In the 6- and 13-month treatment groups, 1 limb received the same osteochondral procedure as the early healing stage group. In the contralateral limb, an 8 mm-diameter, full-thickness cartilage defect (1-2 mm deep) was created and treated with microfracture. Cartilage repair and integration were quantitatively and qualitatively assessed with gross inspection, histological evaluation, and magnetic resonance imaging (MRI). Wilcoxon signed-rank and McNemar tests were used to compare the treatments. RESULTS: At 6 and 13 months after treatment, the biotemplate was not present histologically. At 13 months, the biotemplate treatment demonstrated statistically higher histological scores than microfracture for integration with surrounding cartilage (biotemplate: 74 ± 31; microfracture: 28 ± 39; P = .03), type 2 collagen (biotemplate: 72 ± 33; microfracture: 40 ± 38; P = .02), total cartilage (biotemplate: 71 ± 9; microfracture: 59 ± 9; P = .01), and total integration (biotemplate: 85 ± 15; microfracture: 66 ± 20; P = .04). The osteochondral biotemplate treatment produced a notable transient nonneutrophilic inflammatory response that appeared to approach resolution at 13 months. MRI results were not statistically different between the 2 treatments. CONCLUSION: Even with the inflammatory response, after 13 months, the osteochondral biotemplate outperformed microfracture in cartilage regeneration and demonstrated superiority in integration between the repair tissue and host tissue as well as integration between the newly formed cartilage and the underlying bone. CLINICAL RELEVANCE: This work has demonstrated the clinical potential of a novel biomaterial template to regenerate the complex mechanical interface between cartilage and the subchondral bone.

Abnormalities of the pericruciate fat pad: Correlations with the location and severity of chondral lesions of the knee.

PURPOSE: The aim of this study was to evaluate the relationship between the grade of signal change of the pericruciate fat pad (PCFP) and the location and severity of cartilage alterations in the knee on magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective study included 234 patients (M:F = 96:138, mean: 51 years) who underwent knee MRI. Two experienced musculoskeletal radiologists assessed any PCFP alterations (as grades 0-3) and chondral lesions using the modified Outerbridge grade (as grades 0-4). Bone marrow lesions (BMLs), meniscal status, anterior cruciate ligament alterations, and effusion-synovitis were also evaluated on the MRI. The relationships between PCFP alteration and MR findings (including the grade of chondral lesion) were evaluated. RESULTS: Signal changes in the PCFP were detected in 150 cases by Reader 1 (grade 0, 67 cases; grade 1, 53 cases; grade 2, 21 cases; grade 3, 9 cases) and in 154 cases by Reader 2 (grade 0, 59 cases; grade 1, 61 cases; grade 2, 24 cases; grade 3, 10 cases). The grade of PCFP signal change was statistically significantly correlated with the grade of the chondral lesion of the medial femoral condyle (MFC) (p = 0.029 and p = 0.003, respectively) and the medial tibial plateau (MTP) (p = 0.045, p = 0.002, Readers 1 and 2, respectively). The grade of PCFP signal change was significantly correlated with the grade of the BMLs of the MFC, MTP, and lateral femoral condyle (p < 0.05) for both readers. PCFP alteration was related to effusion-synovitis and tears of the medial meniscus. CONCLUSIONS: The grade of PCFP signal change was correlated with the severity of the cartilage alteration in the medial compartment of the knee joint and was also correlated with BMLs in the medial compartment, medial meniscal tears, and synovitis. Therefore, signal change in the PFCP seen on MRI can be an additional clue of the presence of osteoarthritis in the knee, particularly in the medial compartment.

Retrograde Drilling and Bone Graft for Hepple Stage V Subchondral Bone Lesion of Talus Using 3D Image-Based Navigation-Assisted Endoscopic Technique.

BACKGROUND: Retrograde drilling remains technically challenging, because of the difficulty of identifying the accurate location of cysts during surgery. This study's aim was to evaluate the 3-dimensional (3D) image-based surgical navigation-assisted endoscopic retrograde drilling technique for subchondral bone lesions of the talus. METHODS: From March 2017 to June 2020, a total of 21 cases with Hepple stage V subchondral bone lesions of the talus were treated with 3D image-based surgical navigation-assisted endoscopic retrograde drilling and bone graft technique. Arthroscopic views were categorized per Pritsch classifications. The correlation between the drilled tunnel with preoperative cystic lesions were assessed under postoperative computer tomographic (CT) scans. The American Orthopaedic Foot & Ankle Society (AOFAS) scores, visual analog scale (VAS) scores, and Foot and Ankle Ability Measure (FAAM) sports scales were evaluated at the preoperative and final consultation. All complications were recorded. RESULTS: On postoperative CT scans, in 20 cases (95.2%), the drilled tunnel was judged to have been in the center of previous cysts. Only 9 cases (42.9%) showed intact normal cartilage (grade 0, group A); 12 cases (57.1%) had intact, but soft, cartilage (grade I, group B). The median follow-up time was 24 (24, 30) months, and at final follow-up, there were no significant differences between the mean AOFAS and VAS scores in both groups (89.0 ± 6.4 vs 88.3 ± 7.0 and 1 vs 0.5) or postoperative FAAM sports scales (28.2 ± 2.2 vs 26.6 ± 4.9, P = .363). Two patients had revision surgery in group B. CONCLUSION: The 3D image-based surgical navigation-assisted endoscopic retrograde drilling and bone graft technique for the subchondral bone lesions of the talus in this small case series showed encouraging results. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Platelet-Derived Exosomes Alleviate Knee Osteoarthritis by Attenuating Cartilage Degeneration and Subchondral Bone Loss.

BACKGROUND: Osteoarthritis (OA) is the most prevalent chronic degenerative joint disease among the aged population. However, current treatments for OA are limited to alleviating symptoms, with no therapies that prevent and regenerate cartilage deterioration. PURPOSE: To assess the effects of platelet-derived exosomes (Plt-exos) on OA and then to explore the potential molecular mechanism. STUDY DESIGN: Controlled laboratory study. METHODS: Exosomes derived from human apheresis platelets were isolated and identified. The effects of Plt-exos in protecting chondrocytes under interleukin 1ß stimulation were evaluated by analyzing the proliferation and migration in human primary chondrocytes. RNA sequencing was later performed in vitro for primary chondrocytes to reveal the underlying mechanisms of Plt-exo treatment. Anterior cruciate ligament transection was used to construct an OA mice model, and intra-articular injection of Plt-exos was given once a week for 6 weeks. Mice were sacrificed 4 weeks after the last injection. Histologic and immunohistochemistry staining and micro-computed tomography analysis were performed to assess alterations of articular cartilage and subchondral bone. RESULTS: Plt-exos significantly promoted proliferation and migration of chondrocytes within a dose-dependent manner, as well as dramatically promoted cartilage regeneration and attenuated abnormal tibial subchondral bone remodeling, thus slowing the progression of OA. After being treated with Plt-exos, 1797 genes were differentially expressed in chondrocytes (923 upregulated and 874 downregulated genes). Functional enrichment results and hub genes were mainly involved in anti-inflammatory effects, mediating cell adhesion, stimulating cartilage repair, promoting anabolism, and inhibiting catabolism. CONCLUSION: Our results demonstrated that Plt-exos promoted chondrocyte proliferation and migration in vitro, as well as attenuated cartilage degeneration, improved the microarchitecture of subchondral bone, and retarded OA progression in vivo. CLINICAL RELEVANCE: Our study illustrated that the administered Plt-exos could alleviate knee OA by attenuating cartilage degeneration and subchondral bone loss, possibly serving as a novel promising treatment for OA in the future.

Therapeutic effect of C-type natriuretic peptide on persistent pain in a rat knee arthritis model.

BACKGROUND: Intra-articular injection of C-type natriuretic peptide (CNP) at the acute inflammatory stage suppressed fibrotic changes in the infrapatellar fat pad (IFP), articular cartilage degeneration, and persistent pain in a monoiodoacetic acid (MIA)-induced rat knee arthritis model. In this study, we administered CNP during the inflammation subsiding period to evaluate CNP effectiveness in knees with osteoarthritis (OA) pathology. METHODS: 20 male Wistar rats were randomly divided into two groups. The rats received an intra-articular injection of MIA solution in the right knee to induce inflammation-induced joint degeneration. One group subsequently received an intra-articular CNP injection for six consecutive days from day 8, whereas another group received vehicle solution. Pain avoidance behavior tests and histological analyses were conducted to examine the therapeutic effects of CNP. RESULTS: The incapacitance test indicated that the percent weight on the ipsilateral limb decreased after MIA injection by day 4 and continued to decrease until the end of the experiment in the vehicle group, suggesting persistent pain in the knee. Intra-articular injection of CNP reversed the weight-bearing ratio on day 19. Histological evaluation showed that the CNP group had more residual fat tissue in the IFP and fewer calcitonin gene-related peptide-positive nerve endings compared to the vehicle group. CNP could not reverse articular cartilage degeneration. CONCLUSIONS: Intra-articular injection of CNP after the IFP fibrosis onset had no significant effect on OA severity and extent. Nevertheless, CNP might be utilized therapeutically for OA treatment since it can alleviate persistent knee pain and inhibit structural changes in residual fat tissue.

The Subchondral Bone Condition During Microfracture Affects the Repair of the Osteochondral Unit in the Cartilage Defect in the Rat Model.

BACKGROUND: Microfracture (MF) is frequently performed as a first-line treatment for articular cartilage defects. Although good clinical outcomes are often obtained in the short term, poor clinical outcomes sometimes occur because of subchondral bone deterioration. The condition of the subchondral bone treated with MF may affect the repair of the osteochondral unit. PURPOSE: To analyze histological findings of the osteochondral unit after performing MF on subchondral bone in different states-normal, absorption, and sclerosis-in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Full-thickness cartilage defects (5.0 × 3.0 mm) were created in the weightbearing area of the medial femoral condyle in both knees of 47 Sprague-Dawley rats. Five MF holes were created within the cartilage defect using a 0.55-mm needle to a depth of 1 mm at 0 weeks (normal group), 2 weeks (absorption group), and 4 weeks (sclerosis group) after the cartilage defect was created. In the left knee, MF holes were filled with ß-tricalcium phosphate (ß-TCP). At 2 and 4 weeks after MF, knee joints were harvested and histologically analyzed. RESULTS: MF holes were enlarged at 2 weeks and further enlarged at 4 weeks in all groups. In the absorption group, osteoclast accumulation around the MF holes and cyst formation were observed. The trabecular bone surrounding the MF holes was thickened in the sclerosis group. The diameter of the MF hole was largest in the absorption group at 2 and 4 weeks after MF compared with the other groups. No subchondral bone cysts were observed after ß-TCP implantation. Pineda scores in all groups were significantly better with ß-TCP implantation than without ß-TCP implantation at 2 and 4 weeks. CONCLUSION: MF for subchondral bone with bone absorption induced enlargement of the MF holes, cyst formation, and delay of cartilage defect coverage. Implantation of ß-TCP into the MF holes enhanced remodeling of the MF holes and improved repair of the osteochondral unit compared with MF only. Therefore, the condition of the subchondral bone treated with MF affects repair of the osteochondral unit in a cartilage defect.