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Arthroscopy : the Journal of... Jun 2024Articular cartilage defects in the knee are common and possess limited ability to inherently heal. Many of the surgical management options for cartilage repair that...
Articular cartilage defects in the knee are common and possess limited ability to inherently heal. Many of the surgical management options for cartilage repair that result in a hyaline or hyaline-like chondral surface have donor site morbidity, are resource intensive, are costly, and may require multiple surgeries. Autologous minced cartilage implantation is an encouraging, single-stage technique that can be safely and efficiently performed arthroscopically to address focal chondral defects in the knee. The limited morbidity and cost-effective nature of using autograft tissue has clear advantages, including an ability to treat patients at the time a clinically relevant defect is identified, increased availability of tissue, reduced patient morbidity with the use of an arthroscopic harvest technique, and the production of a hyaline cartilage repair product with active chondrocytes. Clinically, it has been demonstrated to be superior to microfracture. However, mincing technique may compromise cell viability. A recent porcine model investigation demonstrated that arthroscopic cartilage harvest using a shaver, contains a significantly lower median number of viable chondrocytes compared to open scalpel harvest, resulting in reduced proteoglycans, glycosaminoglycans, aggrecan, and COL2A1 expression, a result of fewer viable chondrocytes. The authors suggest that traditional open scalpel harvest results in a superior single-stage autologous minced cartilage transplantation product with more hyaline-like tissue compared to arthroscopic mincing techniques. However, the findings of the study regarding cell viability after arthroscopic harvest are in stark contrast to previous findings, including our prior work. Pending future research, it is our view that an arthroscopic single-stage autologous cartilage transplant is more reproducible, efficient, and of lower morbidity than open harvest, and we and others have shown the arthroscopic technique to be both safe and effective.
PubMed: 38908489
DOI: 10.1016/j.arthro.2024.06.025 -
Methods in Molecular Biology (Clifton,... 2024Polymeric delivery systems could enable the fast- and low-side-effect transport of various RNA classes. Previously, we demonstrated that polyvinylamine (PVAm), a...
Polymeric delivery systems could enable the fast- and low-side-effect transport of various RNA classes. Previously, we demonstrated that polyvinylamine (PVAm), a cationic polymer, transfects many kinds of RNAs with high efficiency and low toxicity both in vitro and in vivo. The modification of poly lactic-co-glycolic acid (PLGA) with cartilage-targeting peptide (CAP) enhances its stiffness and tissue-specific delivery of RNA to overcome the avascular nature of articular cartilage. Here we describe the protocol to use PVAm as an RNA carrier, and further, by modifying PVAm with PLGA and CAP, the corresponding co-polymer could be applied for functional RNA delivery for osteoarthritis treatment.
Topics: Polyvinyls; Animals; Polylactic Acid-Polyglycolic Acid Copolymer; Humans; Lactic Acid; Transfection; Gene Transfer Techniques; Polyglycolic Acid; Drug Carriers; RNA, Small Interfering; Osteoarthritis
PubMed: 38907928
DOI: 10.1007/978-1-0716-3918-4_22 -
Cell Communication and Signaling : CCS Jun 2024Mechanical unloading of the knee articular cartilage results in cartilage matrix atrophy, signifying the osteoarthritic-inductive potential of mechanical unloading. In...
BACKGROUND
Mechanical unloading of the knee articular cartilage results in cartilage matrix atrophy, signifying the osteoarthritic-inductive potential of mechanical unloading. In contrast, mechanical loading stimulates cartilage matrix production. However, little is known about the response of meniscal fibrocartilage, a major mechanical load-bearing tissue of the knee joint, and its functional matrix-forming fibrochondrocytes to mechanical unloading events.
METHODS
In this study, primary meniscus fibrochondrocytes isolated from the inner avascular region of human menisci from both male and female donors were seeded into porous collagen scaffolds to generate 3D meniscus models. These models were subjected to both normal gravity and mechanical unloading via simulated microgravity (SMG) for 7 days, with samples collected at various time points during the culture.
RESULTS
RNA sequencing unveiled significant transcriptome changes during the 7-day SMG culture, including the notable upregulation of key osteoarthritis markers such as COL10A1, MMP13, and SPP1, along with pathways related to inflammation and calcification. Crucially, sex-specific variations in transcriptional responses were observed. Meniscus models derived from female donors exhibited heightened cell proliferation activities, with the JUN protein involved in several potentially osteoarthritis-related signaling pathways. In contrast, meniscus models from male donors primarily regulated extracellular matrix components and matrix remodeling enzymes.
CONCLUSION
These findings advance our understanding of sex disparities in knee osteoarthritis by developing a novel in vitro model using cell-seeded meniscus constructs and simulated microgravity, revealing significant sex-specific molecular mechanisms and therapeutic targets.
Topics: Humans; Meniscus; Male; Female; Weightlessness Simulation; Cells, Cultured; Middle Aged; Cell Proliferation; Chondrocytes; Adult; Transcriptome
PubMed: 38907358
DOI: 10.1186/s12964-024-01684-w -
Medical Engineering & Physics Jul 2024The aim of this work is to investigate in-silico the biomechanical effects of a proximal fibular osteotomy (PFO) on a knee joint with different varus/valgus deformities...
The aim of this work is to investigate in-silico the biomechanical effects of a proximal fibular osteotomy (PFO) on a knee joint with different varus/valgus deformities on the progression of knee osteoarthritis (KOA). A finite element analysis (FEA) of a human lower extremity consisting of the femoral, tibial and fibular bones and the cartilage connecting them was designed. The FEA was performed in a static standing primitive position to determine the contact pressure (CP) distribution and the location of the center of pressure (CoP). The analysis examined the relationship between these factors and the degree of deformation of the hip-knee angle in the baseline condition. The results suggested that PFO could be a simple and effective surgical treatment for patients with associated genu varum. This work also reported that a possible CP homogenization and a CoP correction can be achieved for medial varus deformities after PFO. However, it reduced its effectiveness for tibial origin valgus misalignment and worsened in cases of femoral valgus misalignment.
Topics: Osteotomy; Humans; Biomechanical Phenomena; Knee Joint; Pressure; Finite Element Analysis; Computer Simulation; Fibula
PubMed: 38906579
DOI: 10.1016/j.medengphy.2024.104185 -
Magma (New York, N.Y.) Jun 2024Osteoarthritis (OA) is a disabling chronic disease involving the gradual degradation of joint structures causing pain and dysfunction. Magnetic resonance imaging (MRI)... (Review)
Review
Osteoarthritis (OA) is a disabling chronic disease involving the gradual degradation of joint structures causing pain and dysfunction. Magnetic resonance imaging (MRI) has been widely used as a non-invasive tool for assessing OA-related changes. While anatomical MRI is limited to the morphological assessment of the joint structures, quantitative MRI (qMRI) allows for the measurement of biophysical properties of the tissues at the molecular level. Quantitative MRI techniques have been employed to characterize tissues' structural integrity, biochemical content, and mechanical properties. Their applications extend to studying degenerative alterations, early OA detection, and evaluating therapeutic intervention. This article is a review of qMRI techniques for musculoskeletal tissue evaluation, with a particular emphasis on articular cartilage. The goal is to describe the underlying mechanism and primary limitations of the qMRI parameters, their association with the tissue physiological properties and their potential in detecting tissue degeneration leading to the development of OA with a primary focus on basic and preclinical research studies. Additionally, the review highlights some clinical applications of qMRI, discussing the role of texture-based radiomics and machine learning in advancing OA research.
PubMed: 38904746
DOI: 10.1007/s10334-024-01174-7 -
International Journal of Biological... 2024Osteoarthritis (OA) is a challenging degenerative joint disease to manage. Previous research has indicated that cell-free fat extract (CEFFE) may hold potential for OA...
Osteoarthritis (OA) is a challenging degenerative joint disease to manage. Previous research has indicated that cell-free fat extract (CEFFE) may hold potential for OA treatment. This study investigated the role of Annexin A5 (AnxA5) within CEFFE in regulating macrophage polarization and protecting chondrocytes. experiments demonstrated that AnxA5 effectively inhibited M1 macrophage polarization by facilitating toll-like receptor (TLR) 4 internalization and lysosomal degradation through calcium-dependent endocytosis. This process decreased TLR4 expression, suppressed pro-inflammatory mediator release, and reduced the production of reactive oxygen species. Furthermore, AnxA5 displayed protective effects against chondrocyte necrosis and apoptosis. studies revealed that intra-articular administration of AnxA5 ameliorated pain symptoms in a monosodium iodoacetate-induced osteoarthritis rat model. Histological analyses indicated a decrease in synovial inflammation and mitigation of cartilage damage following AnxA5 treatment. These results underscored the potential of AnxA5 as a therapeutic option for OA due to its capacity to regulate macrophage polarization and maintain chondrocyte viability. Further investigation into the specific mechanisms and clinical applications of AnxA5 may help improve the management of OA.
Topics: Animals; Osteoarthritis; Rats; Macrophages; Annexin A5; Chondrocytes; Rats, Sprague-Dawley; Male; Toll-Like Receptor 4; Mice; RAW 264.7 Cells; Reactive Oxygen Species; Apoptosis
PubMed: 38904008
DOI: 10.7150/ijbs.92802 -
Regenerative Biomaterials 2024Cartilage tissues possess an extremely limited capacity for self-repair, and current clinical surgical approaches for treating articular cartilage defects can only...
Cartilage tissues possess an extremely limited capacity for self-repair, and current clinical surgical approaches for treating articular cartilage defects can only provide short-term relief. Despite significant advances in the field of cartilage tissue engineering, avoiding secondary damage caused by invasive surgical procedures remains a challenge. In this study, injectable cartilage microtissues were developed through 3D culture of rat bone marrow mesenchymal stem cells (BMSCs) within porous gelatin microcarriers (GMs) and induced differentiation. These microtissues were then injected for the purpose of treating cartilage defects , via a minimally invasive approach. GMs were found to be noncytotoxic and favorable for cell attachment, proliferation and migration evaluated with BMSCs. Moreover, cartilage microtissues with a considerable number of cells and abundant extracellular matrix components were obtained from BMSC-laden GMs after induction differentiation culture for 28 days. Notably, ATDC5 cells were complementally tested to verify that the GMs were conducive to cell attachment, proliferation, migration and chondrogenic differentiation. The microtissues obtained from BMSC-laden GMs were then injected into articular cartilage defect areas in rats and achieved superior performance in alleviating inflammation and repairing cartilage. These findings suggest that the use of injectable cartilage microtissues in this study may hold promise for enhancing the long-term outcomes of cartilage defect treatments while minimizing the risk of secondary damage associated with traditional surgical techniques.
PubMed: 38903559
DOI: 10.1093/rb/rbae064 -
Annals of Biomedical Engineering Jun 2024In order to improve the ability of clinical diagnosis to differentiate articular cartilage (AC) injury of different origins, this study explores the sensitivity of...
In order to improve the ability of clinical diagnosis to differentiate articular cartilage (AC) injury of different origins, this study explores the sensitivity of mid-infrared (MIR) spectroscopy for detecting structural, compositional, and functional changes in AC resulting from two injury types. Three grooves (two in parallel in the palmar-dorsal direction and one in the mediolateral direction) were made via arthrotomy in the AC of the radial facet of the third carpal bone (middle carpal joint) and of the intermediate carpal bone (the radiocarpal joint) of nine healthy adult female Shetland ponies (age = 6.8 ± 2.6 years; range 4-13 years) using blunt and sharp tools. The defects were randomly assigned to each of the two joints. Ponies underwent a 3-week box rest followed by 8 weeks of treadmill training and 26 weeks of free pasture exercise before being euthanized for osteochondral sample collection. The osteochondral samples underwent biomechanical indentation testing, followed by MIR spectroscopic assessment. Digital densitometry was conducted afterward to estimate the tissue's proteoglycan (PG) content. Subsequently, machine learning models were developed to classify the samples to estimate their biomechanical properties and PG content based on the MIR spectra according to injury type. Results show that MIR is able to discriminate healthy from injured AC (91%) and between injury types (88%). The method can also estimate AC properties with relatively low error (thickness = 12.7% mm, equilibrium modulus = 10.7% MPa, instantaneous modulus = 11.8% MPa). These findings demonstrate the potential of MIR spectroscopy as a tool for assessment of AC integrity changes that result from injury.
PubMed: 38902468
DOI: 10.1007/s10439-024-03540-x -
Biomacromolecules Jun 2024Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage,...
Rheumatoid arthritis (RA) is a complicated chronic disorder of the immune system, featured with severe inflammatory joints, synovium hyperplasia, articular cartilage, and bone damage. In the RA microenvironment, RA-involved cells, overproduced nitric oxide (NO), and pro-inflammatory cytokines are highly interplayed and mutually reinforced, which form a vicious circle and play crucial roles in the formation and progression of RA. To comprehensively break the vicious circle and obtain the maximum benefits, we have developed neutrophil membrane-camouflaged NO scavenging nanoparticles based on an NO-responsive hyaluronic acid derivative for delivery of MTX. These multifunctional nanoparticles (NNO-NPs/MTX), by inheriting the membrane functions of the source cells, possess prolonged circulation and specific localization at the inflamed sites when administrated in the body. Remarkably, NNO-NPs/MTX can neutralize the pro-inflammatory cytokines via the outer membrane receptors, scavenge NO, and be responsively disassociated to release MTX for RA-involved cell regulation and HA for lubrication in the RA sites. In a collagen-induced arthritis mouse model, NNO-NPs/MTX exhibits a significant anti-inflammation effect and effectively alleviates the characteristic RA symptoms such as synovial hyperplasia and cartilage destruction, realizing the synergistic and boosted therapeutic outcome against intractable RA. Thus, NNO-NPs/MTX provides a promising and potent platform to integrately treat RA.
PubMed: 38899740
DOI: 10.1021/acs.biomac.4c00556 -
Journal of ISAKOS : Joint Disorders &... Jun 2024Patellofemoral osteoarthritis (PFOA) is the result of degeneration and loss of articular cartilage of the patella and trochlea, and is a common cause of anterior knee...
Patellofemoral osteoarthritis (PFOA) is the result of degeneration and loss of articular cartilage of the patella and trochlea, and is a common cause of anterior knee pain. PFOA is triggered by insufficient adaptation to overload of the articular cartilage of the PF joint created by abnormal biomechanics. It is important to understand the pathophysiology and natural history to make the diagnosis and to plan treatment. Innate factors including malalignment, patellar instability, kinematic disorders, and acquired factors like trauma, obesity, and endocrine diseases have been found to be causes of PFOA. Genetic predisposition is also described as a contributing cause but without much scientific evidence. The diagnosis will be based on clinical manifestations, such as anterior knee pain aggravated by overloading activities, identification of risk factors, exclusion of referred pain from other pathologies, followed by a systematic and structured physical examination. Imaging will be useful for assessing the presence of early osteoarthritis in the other compartments, for classification of the PFOA, and to identify features to establish an adequate treatment. This paper discusses varying management options for different causes of patellofemoral disease and explains the complexity of the PF joint and its often poorly understood biomechanics.
PubMed: 38897413
DOI: 10.1016/j.jisako.2024.06.004