Evaluation of the relationship between Knee Osteoarthritis and Meniscus Pathologies.

Background: Knee osteoarthritis is a common, degenerative joint disease that causes chronic pain that affects daily life. Our study aims to evaluate geriatric patients aged 65 and over with knee pain in terms of osteoarthritis with radiography and magnetic resonance imaging and to investigate its relationship with meniscal pathologies. Methods: Radiography and magnetic resonance imaging of patients aged 65-88 years with knee pain were evaluated in terms of knee osteoarthritis and staging was performed. Meniscal pathologies were evaluated in magnetic resonance imaging, and the prevalence of different meniscal lesion types was calculated. In addition, the relationship between knee osteoarthritis and meniscal pathologies was analyzed. Results: Radiographic evidence of knee osteoarthritis was found in 182 (84.2%) of the 216 cases in our study group. A strong correlation was found between the degrees of knee osteoarthritis on magnetic resonance imaging and radiography. At least one meniscus pathology was observed in all 182 radiography cases with knee osteoarthritis findings. At least one meniscus pathology was observed in 29 (85.3%) of those without osteoarthritis signs. It was determined that meniscus degeneration, tear, and extrusion were observed more frequently in patients with knee osteoarthritis than in patients without osteoarthritis. Meniscal extrusion and complex and horizontaltype tears were the most common lesions. Conclusions: Osteoarthritis was found to be common in geriatric patients with knee pain. A correlation was found between radiography and magnetic resonance imaging regarding knee osteoarthritis. It was observed that meniscal pathologies were detected more frequently in patients with knee osteoarthritis.

An experimental study of the heterogeneity and anisotropy of porcine meniscal ultimate tensile strength.

Characterizing the ultimate tensile strength (UTS) of the meniscus is critical in studying knee damage and pathology. This study aims to determine the UTS of the meniscus with an emphasis on its heterogeneity and anisotropy. We performed tensile tests to failure on the menisci of six month old Yorkshire pigs at a low strain rate. Specimens from the anterior, middle and posterior regions of the meniscus were tested in the radial and circumferential directions. Then the UTS was obtained for each specimen and the data were analyzed statistically, leading to a comprehensive view of the variations in porcine meniscal strength. The middle region has the highest average strength in the circumferential (43.3 ± 4.7 MPa) and radial (12.6 ± 2.2 MPa) directions. This is followed by the anterior and posterior regions, which present similar average values (about 34.0MPa) in circumferential direction. The average strength of each region in the radial direction is approximately one-fourth to one-third of the value in the circumferential direction. This study is novel as it is the first work to focus on the experimental methods to investigate the heterogeneity and anisotropy only for porcine meniscus.

Meniscal Allograft versus Synthetic Graft in Treatment Outcomes of Meniscus Repair: A Mini-review and Meta-analysis.

Meniscal injuries are highly correlated with osteoarthritis (OA) onset and progression. Although meniscal allograft transplantation (MAT) is a therapeutic option to restore meniscal anatomy, a shortage of donor material and the donor-derived infectious risk may be concerns in clinics. This review summarizes the literature reporting meniscus repair status in preclinical models and clinical practice using allografts or synthetic grafts. The advantages and limitations of biodegradable polymer-based meniscal scaffolds, applied in preclinical studies, are discussed. Then, the long-term treatment outcomes of patients with allografts or commercial synthetic scaffolds are compared. A total of 47 studies are included in our network meta-analysis. Compared with the meniscal allografts, the commercial synthetic products significantly improved clinical treatment outcomes in terms of the Knee Injury and Osteoarthritis Outcome Score (KOOS), Visual Analog Scale (VAS) scores, and Lysholm scores. In addition, development strategies for the next generation of novel synthetic scaffolds are proposed through optimization of structural design and fabrication, and selection of cell sources, external stimuli, and active ingredients. This review may inspire researchers and surgeons to design and fabricate clinic-orientated grafts with improved treatment outcomes.

Biodegradable Tyramine Functional Gelatin/6 Arms-PLA Inks Compatible with 3D Two Photon-Polymerization Printing and Meniscus Tissue Regeneration.

The meniscus regeneration can present major challenges such as mimicking tissue microstructuration or triggering cell regeneration. In the case of lesions that require a personalized approach, photoprinting offers the possibility of designing resolutive biomaterial structures. The photo-cross-linkable ink composition determines the process ease and the final network properties. In this study, we designed a range of hybrid inks composed of gelatin(G) and 6-PLA arms(P) that were photo-cross-linked using tyramine groups. The photo-cross-linking efficiency, mechanical properties, degradation, and biological interactions of inks with different G/P mass ratios were studied. The G50P50 network properties were suitable for meniscus regeneration, with Young's modulus of 6.5 MPa, degradation in 2 months, and good cell proliferation. We then confirmed the potential of these inks to produce high-resolution microstructures by printing well-defined microstructures using two-photon polymerization. These hybrid inks offer new perspectives for biocompatible, degradable, and microstructured tissue engineering scaffold creation.

Short-term response of primary human meniscus cells to simulated microgravity.

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.

[Construction of a novel tissue engineered meniscus scaffold based on low temperature deposition three-dimenisonal printing technology].

Objective: To investigate the construction of a novel tissue engineered meniscus scaffold based on low temperature deposition three-dimenisonal (3D) printing technology and evaluate its biocompatibility. Methods: The fresh pig meniscus was decellularized by improved physicochemical method to obtain decellularized meniscus matrix homogenate. Gross observation, HE staining, and DAPI staining were used to observe the decellularization effect. Toluidine blue staining, safranin O staining, and sirius red staining were used to evaluate the retention of mucopolysaccharide and collagen. Then, the decellularized meniscus matrix bioink was prepared, and the new tissue engineered meniscus scaffold was prepared by low temperature deposition 3D printing technology. Scanning electron microscopy was used to observe the microstructure. After co-culture with adipose-derived stem cells, the cell compatibility of the scaffolds was observed by cell counting kit 8 (CCK-8), and the cell activity and morphology were observed by dead/live cell staining and cytoskeleton staining. The inflammatory cell infiltration and degradation of the scaffolds were evaluated by subcutaneous experiment in rats. Results: The decellularized meniscus matrix homogenate appeared as a transparent gel. DAPI and histological staining showed that the immunogenic nucleic acids were effectively removed and the active components of mucopolysaccharide and collagen were remained. The new tissue engineered meniscus scaffolds was constructed by low temperature deposition 3D printing technology and it had macroporous-microporous microstructures under scanning electron microscopy. CCK-8 test showed that the scaffolds had good cell compatibility. Dead/live cell staining showed that the scaffold could effectively maintain cell viability (>90%). Cytoskeleton staining showed that the scaffolds were benefit for cell adhesion and spreading. After 1 week of subcutaneous implantation of the scaffolds in rats, there was a mild inflammatory response, but no significant inflammatory response was observed after 3 weeks, and the scaffolds gradually degraded. Conclusion: The novel tissue engineered meniscus scaffold constructed by low temperature deposition 3D printing technology has a graded macroporous-microporous microstructure and good cytocompatibility, which is conducive to cell adhesion and growth, laying the foundation for the in vivo research of tissue engineered meniscus scaffolds in the next step.

Degradation of Proteoglycans and Collagen in Equine Meniscal Tissues.

Investigate meniscal extracellular matrix degradation. Equine menisci (n = 34 from 17 horses) were studied. Site-matched sections were cut and scored from three regions (ROIs; n = 102) and stained for histology, proteoglycan (safranin O and fast green), aggrecan, and collagen cleavage (NITEGE, DIPEN, and C1,2C antibodies, respectively). Picrosirius red and second harmonic generation microscopy were performed to investigate collagen ultrastructure. A total of 42 ROIs met the inclusion criteria and were included in the final analysis. The median (range) ROI histological score was 3 (0-9), providing a large spectrum of pathology. The median (range) proteoglycan score was 1 (0-3), representing superficial and central meniscal loss. The median (range) of DIPEN, NITEGE, and C1,2C scores was 1 (0-3), revealing immunostaining of the femoral and tibial surfaces. The proteoglycan scores exhibited significant positive associations with both histologic evaluation (p = 0.03) and DIPEN scores (p = 0.02). Additionally, a robust positive association (p = 0.007) was observed between the two aggrecanolysis indicators, NITEGE and DIPEN scores. A negative association (p = 0.008) was identified between NITEGE and histological scores. The C1,2C scores were not associated with any other scores. Picrosirius red and second harmonic generation microscopy (SHGM) illustrated the loss of the collagen matrix and structure centrally. Proteoglycan and collagen degradation commonly occur superficially in menisci and less frequently centrally. The identification of central meniscal proteoglycan and collagen degradation provides novel insight into central meniscal degeneration. However, further research is needed to elucidate the etiology and sequence of degradative events.

Intraoperative identification of patient-specific elastic modulus of the meniscus during arthroscopy.

BACKGROUND AND OBJECTIVE: Degenerative meniscus tissue has been associated with a lower elastic modulus and can lead to the development of arthrosis. Safe intraoperative measurement of in vivo elastic modulus of the human meniscus could contribute to a better understanding of meniscus health, and for developing surgical simulators where novice surgeons can learn to distinguish healthy from degenerative meniscus tissue. Such measurement can also support intraoperative decision-making by providing a quantitative measure of the meniscus health condition. The objective of this study is to demonstrate a method for intraoperative identification of meniscus elastic modulus during arthroscopic probing using an adaptive observer method. METHODS: Ex vivo arthroscopic examinations were performed on five cadaveric knees to estimate the elastic modulus of the anterior, mid-body, and posterior regions of lateral and medial menisci. Real-time intraoperative force-displacement data was obtained and utilized for modulus estimation through an adaptive observer method. For the validation of arthroscopic elastic moduli, an inverse parameter identification approach using optimization, based on biomechanical indentation tests and finite element analyses, was employed. Experimental force-displacement data in various anatomical locations were measured through indentation. An iterative optimization algorithm was employed to optimize elastic moduli and Poisson's ratios by comparing experimental force values at maximum displacement with the corresponding force values from linear elastic region-specific finite element models. Finally, the estimated elastic modulus values obtained from ex vivo arthroscopy were compared against optimized values using a paired t-test. RESULTS: The elastic moduli obtained from ex vivo arthroscopy and optimization showcased subject specificity in material properties. Additionally, the results emphasized anatomical and regional specificity within the menisci. The anterior region of the medial menisci exhibited the highest elastic modulus among the anatomical locations studied (9.97±3.20MPa from arthroscopy and 5.05±1.97MPa from finite element-based inverse parameter identification). The paired t-test results indicated no statistically significant difference between the elastic moduli obtained from arthroscopy and inverse parameter identification, suggesting the feasibility of stiffness estimation using arthroscopic examination. CONCLUSIONS: This study has demonstrated the feasibility of intraoperative identification of patient-specific elastic modulus for meniscus tissue during arthroscopy.

Finite element analysis of meniscus contact mechanical behavior based on kinematic simulation of abnormal gait.

The meniscus plays a crucial role in the proper functioning of the knee joint, and when it becomes damaged, partial removal or replacement is necessary to restore proper function. Understanding the stress and deformation of the meniscus during various movements is essential for developing effective materials for meniscus repair. However, accurately estimating the contact mechanics of the knee joint can be challenging due to its complex shape and the dynamic changes it undergoes during movement. To address this issue, the open-source software SCONE can be used to establish a kinematics model that monitors the different states of the knee joint during human motion and obtains relevant gait kinematics data. To evaluate the stress and deformation of the meniscus during normal human movement, values of different states in the movement gait can be selected for finite element analysis (FEA) of the knee joint. This analysis enables researchers to assess changes in the meniscus. To evaluate meniscus damage, it is necessary to obtain changes in its mechanical behavior during abnormal movements. This information can serve as a reference for designing and optimizing the mechanical performance of materials used in meniscus repair and replacement.

The mediating role of synovitis in meniscus pathology and knee osteoarthritis radiographic progression.

Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between meniscus pathologies and KOA radiographic progression remains unclear. We conducted an observational study in the Osteoarthritis Initiative (OAI) cohort, with a 48-month follow-up. Meniscus pathology and synovitis were measured by MRI osteoarthritis knee score (MOAKS) at baseline and 24 months, and a comprehensive synovitis score was calculated using effusion and Hoffa synovitis scores. The knee osteoarthritis radiographic progression was considered that Kellgren-Lawrence (KL) grade and joint space narrowing (JSN) grade at 48 months were increased compared to those at baseline. This study included a total of 589 participants, with KL grades mainly being KL1 (26.5%), KL2 (34.1%), and KL3 (30.2%) at baseline, while JSN grades were mostly 0 at baseline. A logistic regression model was used to analyze the relationship between meniscus pathology, synovitis, and KOA progression. Mediation analysis was used to evaluate the mediation effect of synovitis. The average age of the participants was 61 years old, 62% of which were female. The medial meniscus extrusion was longitudinally correlated with the progression of KL (odds ratio [OR]: 2.271, 95% confidence interval [CI]: 1.412-3.694) and medial JSN (OR: 3.211, 95% CI: 2.040-5.054). Additionally, the longitudinal correlation between medial meniscus damage and progression of KOA (OR: 1.853, 95% CI: 1.177-2.941) and medial JSN (OR: 1.655, 95% CI: 1.053-2.602) was significant. Synovitis was found to mediate the relationship between medial meniscus extrusion and KL and medial JSN progression at baseline (ß: 0.029, 95% CI: 0.010-0.053; ß: 0.022, 95% CI: 0.005-0.046) and beyond 24 months (ß: 0.039, 95% CI: 0.016-0.068; ß: 0.047, 95% CI: 0.020-0.078). However, we did not find evidence of synovitis mediating the relationship between meniscal damage and KOA progression. Synovitis mediates the relationship between medial meniscus extrusion (rather than meniscus damage) and KOA progression.

Injectable ChitHCl-DDA tissue adhesive with high adhesive strength and biocompatibility for torn meniscus repair and regeneration.

Suture pull-through is a clinical problem in meniscus repair surgery due to the sharp leading edge of sutures. Several tissue adhesives have been developed as an alternative to traditional suturing; however, there is still no suitable tissue adhesive specific for meniscus repair treatment due to unsatisfactory biosafety, biodegradable, sterilizable, and tissue-bonding characteristics. In this study, we used a tissue adhesive composed of chitosan hydrochloride reacted with oxidative periodate-oxidized dextran (ChitHCl-DDA) combined with a chitosan-based hydrogel and oxidative dextran to attach to the meniscus. We conducted viscoelastic tests, viscosity tests, lap shear stress tests, Fourier transform infrared (FTIR) spectroscopy, swelling ratio tests, and degradation behavior tests to characterize these materials. An MTT assay, alcian blue staining, migration assay, cell behavior observations, and protein expression tests were used to understand cell viability and responses. Moreover, ex vivo and in vivo tests were used to analyze tissue regeneration and biocompatibility of the ChitHCl-DDA tissue adhesive. Our results revealed that the ChitHCl-DDA tissue adhesive provided excellent tissue adhesive strength, cell viability, and cell responses. This tissue adhesive has great potential for torn meniscus tissue repair and regeneration.

Revealing the complexity of meniscus microvasculature through 3D visualization and analysis.

Three-dimensional information is essential for a proper understanding of the healing potential of the menisci and their overall role in the knee joint. However, to date, the study of meniscal vascularity has relied primarily on two-dimensional imaging techniques. Here we present a method to elucidate the intricate 3D meniscal vascular network, revealing its spatial arrangement, connectivity and density. A polymerizing contrast agent was injected into the femoral artery of human cadaver legs, and the meniscal microvasculature was examined using micro-computed tomography at different levels of detail and resolution. The 3D vascular network was quantitatively assessed in a zone-base analysis using parameters such as diameter, length, tortuosity, and branching patterns. The results of this study revealed distinct vascular patterns within the meniscus, with the highest vascular volume found in the outer perimeniscal zone. Variations in vascular parameters were found between the different circumferential and radial meniscal zones. Moreover, through state-of-the-art 3D visualization using micro-CT, this study highlighted the importance of spatial resolution in accurately characterizing the vascular network. These findings, both from this study and from future research using this technique, improve our understanding of microvascular distribution, which may lead to improved therapeutic strategies.

Shedding light on the effects of blood on meniscus tissue: the role of mononuclear leukocytes in mediating meniscus catabolism.

OBJECTIVE: Traumatic meniscal injuries can cause acute pain, hemarthrosis (bleeding into the joint), joint immobility, and post-traumatic osteoarthritis (PTOA). However, the exact mechanism(s) by which PTOA develops following meniscal injuries is unknown. Since meniscus tears commonly coincide with hemarthrosis, investigating the direct effects of blood and its constituents on meniscus tissue is warranted. The goal of this study was to determine the direct effects of blood and blood components on meniscus tissue catabolism. METHODS: Porcine meniscus explants or primary meniscus cells were exposed to whole blood or various fractions of blood for 3 days to simulate blood exposure following injury. Explants were then washed and cultured for an additional 3 days prior to collection for biochemical analyses. RESULTS: Whole blood increased matrix metalloproteinase (MMP) activity. Fractionation experiments revealed blood-derived red blood cells did not affect meniscus catabolism. Conversely, viable mononuclear leukocytes induced MMP activity, nitric oxide (NO) production, and loss of tissue sulfated glycosaminoglycan (sGAG) content, suggesting that these cells are mediating meniscus catabolism. CONCLUSIONS: These findings highlight the potential challenges of meniscus healing in the presence of hemarthrosis and the need for further research to elucidate the in vivo effects of blood and blood-derived mononuclear leukocytes due to both hemarthrosis and blood-derived therapeutics.

DLL1/NOTCH1 signaling pathway maintain angiogenesis in meniscus development and degeneration.

OBJECTIVES: The decline in vascular capacity within the meniscus is a well-documented phenomenon during both development and degeneration. Maintaining vascular integrity has been proposed as a potential therapeutic strategy for osteoarthritis. Therefore, our study aims to investigate the characteristics of endothelial cells and blood vessels in embryonic and degenerated meniscus tissues. METHODS: Human embryonic and mature menisci were used for histological analyses. Single-cell RNA sequencing was used to identify cell clusters and their significant genes in embryo meniscus to uncover characteristic of endothelial cells. Computer analysis and various staining techniques were used to characterize vessels in development and osteoarthritis meniscus. RESULTS: Vessels structure first observed in E12w and increasing in E14w. Vessels were veins majorly and arteries growth in E35w. Endothelial cells located not only perivascular but also in the surface of meniscus. The expression of DLL1 was observed to be significantly altered in endothelial cells within the vascular network that failed to form. Meniscus tissues affected by osteoarthritis, characterized by diminished vascular capacity, displayed reduced levels of DLL1 expression. Experiment in vitro confirmed DLL1/NOTCH1 be vital to angiogenesis. CONCLUSION: Lack of DLL1/NOTCH1 signaling pathway was mechanism of vascular declination in development and degenerated meniscus.

Meniscal repair with additive manufacture of bioresorbable polymer: From physicochemical characterization to implantation of 3D printed poly (L-co-D, L lactide-co-trimethylene carbonate) with autologous stem cells in rabbits.

Three-dimensional (3D) structures are actually the state-of-the-art technique to create porous scaffolds for tissue engineering. Since regeneration in cartilage tissue is limited due to intrinsic cellular properties this study aims to develop and characterize three-dimensional porous scaffolds of poly (L-co-D, L lactide-co-trimethylene carbonate), PLDLA-TMC, obtained by 3D fiber deposition technique. The PLDLA-TMC terpolymer scaffolds (70:30), were obtained and characterized by scanning electron microscopy, gel permeation chromatography, differential scanning calorimetry, thermal gravimetric analysis, compression mechanical testing and study on in vitro degradation, which showed its amorphous characteristics, cylindrical geometry, and interconnected pores. The in vitro degradation study showed significant loss of mechanical properties compatible with a decrease in molar mass, accompanied by changes in morphology. The histocompatibility association of mesenchymal stem cells from rabbit's bone marrow, and PLDLA-TMC scaffolds, were evaluated in the meniscus regeneration, proving the potential of cell culture at in vivo tissue regeneration. Nine New Zealand rabbits underwent total medial meniscectomy, yielding three treatments: implantation of the seeded PLDLA-TMC scaffold, implantation of the unseeded PLDLA-TMC and negative control (defect without any implant). After 24 weeks, the results revealed the presence of fibrocartilage in the animals treated with polymer. However, the regeneration obtained with the seeded PLDLA-TMC scaffolds with mesenchymal stem cells had become intimal to mature fibrocartilaginous tissue of normal meniscus both macroscopically and histologically. This study demonstrated the effectiveness of the PLDLA-TMC scaffold in meniscus regeneration and the potential of mesenchymal stem cells in tissue engineering, without the use of growth factors. It is concluded that bioresorbable polymers represent a promising alternative for tissue regeneration.

Reconstruction of medial meniscus posterior portion deficiency in pigs with an autologous patellar tendon graft: an experimental study.

OBJECTIVE: This study was performed to investigate the effectiveness of two surgical procedures, autologous patellar tendon graft reconstruction and trans-tibial plateau pull-out repair, using a pig model. The primary focus was to assess the repair capability of medial meniscus posterior portion (MMPP) deficiency, the overall structural integrity of the meniscus, and protection of the femoral and tibial cartilage between the two surgical groups. The overall aim was to provide experimental guidelines for clinical research using these findings. METHODS: Twelve pigs were selected to establish a model of injury to the MMPP 10 mm from the insertion point of the tibial plateau. They were randomly divided into three groups of four animals each: reconstruction (autologous tendon graft reconstruction of the MMPP), pull-out repair (suture repair of the MMPP via a trans-tibial plateau bone tunnel), and control (use of a normal medial meniscus as the negative control). The animals were euthanized 12 weeks postoperatively for evaluation of the meniscus, assessment of tendon bone healing, and gross observation of knee joint cartilage. The tibial and femoral cartilage injuries were evaluated using the International Society for Cartilage Repair (ICRS) grade and Mankin score. Histological and immunohistochemical staining was conducted on the meniscus-tendon junction area, primary meniscus, and tendons. The Ishida score was used to evaluate the regenerated meniscus in the reconstruction group. Magnetic resonance imaging (MRI) was used to evaluate meniscal healing. RESULTS: All 12 pigs recovered well after surgery; all incisions healed without infection, and no obvious complications occurred. Gross observation revealed superior results in the reconstruction and pull-out repair groups compared with the control group. In the tibial cartilage, the reconstruction group had ICRS grade I injury whereas the pull-out repair and control groups had ICRS grade II and III injury, respectively. The Mankin score was significantly different between the reconstruction and control groups; histological staining showed that the structure of the regenerated meniscus in the reconstruction group was similar to that of the original meniscus. Immunohistochemical staining showed that the degree of type I and II collagen staining was similar between the regenerated meniscus and the original meniscus in the reconstruction group. The Ishida score was not significantly different between the regenerated meniscus and the normal primary meniscus in the reconstruction group. MRI showed that the MMPP in the reconstruction and pull-out repair groups had fully healed, whereas that in the control group had not healed. CONCLUSION: Autologous patellar tendon graft reconstruction of the MMPP can generate a fibrocartilage-like regenerative meniscus. Both reconstruction and pull-out repair can preserve the structural integrity of the meniscus, promote healing of the MMPP, delay meniscal degeneration, and protect the knee cartilage.

Collagen/polyester-polyurethane porous scaffolds for use in meniscal repair.

Focusing on the regeneration of damaged knee meniscus, we propose a hybrid scaffold made of poly(ester-urethane) (PEU) and collagen that combines suitable mechanical properties with enhanced biological integration. To ensure biocompatibility and degradability, the degradable PEU was prepared from a poly(ε-caprolactone), L-lysine diisocyanate prepolymer (PCL di-NCO) and poly(lactic-co-glycolic acid) diol (PLGA). The resulting PEU (Mn = 52 000 g mol-1) was used to prepare porous scaffolds using the solvent casting (SC)/particle leaching (PL) method at an optimized salt/PEU weight ratio of 5 : 1. The morphology, pore size and porosity of the scaffolds were evaluated by SEM showing interconnected pores with a uniform size of around 170 µm. Mechanical properties were found to be close to those of the human meniscus (Ey ∼ 0.6 MPa at 37 °C). To enhance the biological properties, incorporation of collagen type 1 (Col) was then performed via soaking, injection or forced infiltration. The latter yielded the best results as shown by SEM-EDX and X-ray tomography analyses that confirmed the morphology and highlighted the efficient pore Col-coating with an average of 0.3 wt% Col in the scaffolds. Finally, in vitro L929 cell assays confirmed higher cell proliferation and an improved cellular affinity towards the proposed scaffolds compared to culture plates and a gold standard commercial meniscal implant.

Assessing the role of surface layer and molecular probe size in diffusion within meniscus tissue.

Diffusion within extracellular matrix is essential to deliver nutrients and larger metabolites to the avascular region of the meniscus. It is well known that both structure and composition of the meniscus vary across its regions; therefore, it is crucial to fully understand how the heterogenous meniscal architecture affects its diffusive properties. The objective of this study was to investigate the effect of meniscal region (core tissue, femoral, and tibial surface layers) and molecular weight on the diffusivity of several molecules in porcine meniscus. Tissue samples were harvested from the central area of porcine lateral menisci. Diffusivity of fluorescein (MW 332 Da) and three fluorescence-labeled dextrans (MW 3k, 40k, and 150k Da) was measured via fluorescence recovery after photobleaching. Diffusivity was affected by molecular size, decreasing as the Stokes' radius of the solute increased. There was no significant effect of meniscal region on diffusivity for fluorescein, 3k and 40k dextrans (p>0.05). However, region did significantly affect the diffusivity of 150k Dextran, with that in the tibial surface layer being larger than in the core region (p = 0.001). Our findings contribute novel knowledge concerning the transport properties of the meniscus fibrocartilage. This data can be used to advance the understanding of tissue pathophysiology and explore effective approaches for tissue restoration.

Quantitative evaluation of meniscus injury using synthetic magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging (MRI) can diagnose meniscal lesions anatomically, while quantitative MRI can reflect the changes of meniscal histology and biochemical structure. Our study aims to explore the association between the measurement values obtained from synthetic magnetic resonance imaging (SyMRI) and Stoller grades. Additionally, we aim to assess the diagnostic accuracy of SyMRI in determining the extent of meniscus injury. This potential accuracy could contribute to minimizing unnecessary invasive examinations and providing guidance for clinical treatment. METHODS: Total of 60 (n=60) patients requiring knee arthroscopic surgery and 20 (n=20) healthy subjects were collected from July 2022 to November 2022. All subjects underwent conventional MRI and SyMRI. Manual measurements of the T1, T2 and proton density (PD) values were conducted for both normal menisci and the most severely affected position of injured menisci. These measurements corresponded to the Stoller grade of meniscus injuries observed in the conventional MRI. All patients and healthy subjects were divided into normal group, degeneration group and torn group according to the Stoller grade on conventional MRI. One-way analysis of variance (ANOVA) was employed to compare the T1, T2 and PD values of the meniscus among 3 groups. The accuracy of SyMRI in diagnosing meniscus injury was assessed by comparing the findings with arthroscopic observations. The diagnostic efficiency of meniscus degeneration and tear between conventional MRI and SyMRI were analyzed using McNemar test. Furthermore, a receiver operating characteristic curve (ROC curve) was constructed and the area under the curve (AUC) was utilized for evaluation. RESULTS: According to the measurements of SyMRI, there was no statistical difference of T1 value or PD value measured by SyMRI among the normal group, degeneration group and torn group, while the difference of T2 value was statistically significant among 3 groups (P=0.001). The arthroscopic findings showed that 11 patients were meniscal degeneration and 49 patients were meniscal tears. The arthroscopic findings were used as the gold standard, and the difference of T1 and PD values among the 3 groups was not statistically significant, while the difference of T2 values (32.81±2.51 of normal group, 44.85±3.98 of degeneration group and 54.42±3.82 of torn group) was statistically significant (P=0.001). When the threshold of T2 value was 51.67 (ms), the maximum Yoden index was 0.787 and the AUC value was 0.934. CONCLUSIONS: The measurement values derived from SyMRI could reflect the Stoller grade, illustrating that SyMRI has good consistency with conventional MRI. Moreover, the notable consistency observed between SyMRI and arthroscopy suggests a potential role for SyMRI in guiding clinical diagnoses.

In Situ Loading and Time-Resolved Synchrotron-Based Phase Contrast Tomography for the Mechanical Investigation of Connective Knee Tissues: A Proof-of-Concept Study.

Articular cartilage and meniscus transfer and distribute mechanical loads in the knee joint. Degeneration of these connective tissues occurs during the progression of knee osteoarthritis, which affects their composition, microstructure, and mechanical properties. A deeper understanding of disease progression can be obtained by studying them simultaneously. Time-resolved synchrotron-based X-ray phase-contrast tomography (SR-PhC-µCT) allows to capture the tissue dynamics. This proof-of-concept study presents a rheometer setup for simultaneous in situ unconfined compression and SR-PhC-µCT of connective knee tissues. The microstructural response of bovine cartilage (n = 16) and meniscus (n = 4) samples under axial continuously increased strain, or two steps of 15% strain (stress-relaxation) is studied. The chondrocyte distribution in cartilage and the collagen fiber orientation in the meniscus are assessed. Variations in chondrocyte density reveal an increase in the top 40% of the sample during loading, compared to the lower half. Meniscus collagen fibers reorient perpendicular to the loading direction during compression and partially redisperse during relaxation. Radiation damage, image repeatability, and image quality assessments show little to no effects on the results. In conclusion, this approach is highly promising for future studies of human knee tissues to understand their microstructure, mechanical response, and progression in degenerative diseases.