Articular cartilage has a limited capacity to self-heal once damaged. Tissue-specific stem cells are a solution for cartilage regeneration; however, ex vivo expansion resulting in cell senescence remains a challenge as a large quantity of high-quality tissue-specific stem cells are needed for cartilage regeneration. Our previous report demonstrated that decellularized extracellular matrix (dECM) deposited by human synovium-derived stem cells (SDSCs), adipose-derived stem cells (ADSCs), urine-derived stem cells (UDSCs), or dermal fibroblasts (DFs) provided an ex vivo solution to rejuvenate human SDSCs in proliferation and chondrogenic potential, particularly for dECM deposited by UDSCs. To make the cell-derived dECM (C-dECM) approach applicable clinically, in this study, we evaluated ex vivo rejuvenation of rabbit infrapatellar fat pad-derived stem cells (IPFSCs), an easily accessible alternative for SDSCs, by the abovementioned C-dECMs, in vivo application for functional cartilage repair in a rabbit osteochondral defect model, and potential cellular and molecular mechanisms underlying this rejuvenation. We found that C-dECM rejuvenation promoted rabbit IPFSCs' cartilage engineering and functional regeneration in both ex vivo and in vivo models, particularly for the dECM deposited by UDSCs, which was further confirmed by proteomics data. RNA-Seq analysis indicated that both mesenchymal-epithelial transition (MET) and inflammation-mediated macrophage activation and polarization are potentially involved in the C-dECM-mediated promotion of IPFSCs’ chondrogenic capacity, which needs further investigation.
The massive usage of electronic and telecommunication devices have led to serious concerns regarding undesired electromagnetic pollution. While metals such as silver, aluminum and copper are the mostly used materials...
To assess articular cartilage in vivo, a noninvasive measurement is proposed to evaluate damage of the cartilage. It is hypothesized that glycosaminoglycan chemical exchange saturation transfer (gagCEST) can be applied as a noninvasive imaging technique as it would relate to electromechanical indentation and GAG content as measured with biochemical assays. This pilot study applies gagCEST MRI in total knee arthroplasty (TKA) patients to assess substantially damaged articular cartilage. The outcome was verified against electromechanical indentation and biochemical assays to assess the potential of gagCEST MRI. Five TKA patients were scanned on a 7.0 T MRI with a gagCEST sequence. Articular resurfacing cuts after TKA were obtained for electromechanical and biochemical analyses. The gagCEST MRI measurements on the medial condyle showed a moderate correlation with the GAG content, although sensitivity on the lateral condyle was lacking. Additionally, a strong negative correlation of gagCEST MRI with the electromechanical measurements was observed in the regression analysis. Correlation of gagCEST MRI with electromechanical measurements was shown, but the correlation of gagCEST MRI with GAG content was not convincing. In conclusion, gagCEST could be a useful tool to assess the GAG content in articular cartilage noninvasively, although the mismatch in heterogeneity requires further investigation.
Objective We aimed to demonstrate that electroarthrography (EAG) measures streaming potentials originating in the cartilage extracellular matrix during load bearing through electrodes adhered to skin surrounding an articular joint. Design Equine metacarpophalangeal joints were subjected to simulated physiological loads while (1) replacing synovial fluid with immersion buffers of different electrolyte concentrations and (2) directly degrading cartilage with trypsin. Results An inverse relationship between ionic strength and EAG coefficient was detected. Compared to native synovial fluid, EAG coefficients increased ( P < 0.05) for 5 of 6 electrodes immersed in 0.1X phosphate-buffered saline (PBS) (0.014 M NaCl), decreased ( P < 0.05) for 4 of 6 electrodes in 1X PBS (0.14 M NaCl), and decreased ( P < 0.05) for all 6 electrodes in 10X PBS (1.4 M NaCl). This relationship corresponds to similar studies where streaming potentials were directly measured on cartilage. EAG coefficients, obtained after trypsin degradation, were reduced ( P < 0.05) in 6 of 8, and 7 of 8 electrodes, during simulated standing and walking, respectively. Trypsin degradation was confirmed by direct cartilage assessments. Streaming potentials, measured by directly contacting cartilage, indicated lower cartilage stiffness ( P < 10 ⁻⁵ ). Unconfined compression data revealed reduced Em, representing proteoglycan matrix stiffness ( P = 0.005), no change in Ef, representing collagen network stiffness ( P = 0.15), and no change in permeability ( P = 0.24). Trypsin depleted proteoglycan as observed by both dimethylmethylene blue assay ( P = 0.0005) and safranin-O stained histological sections. Conclusion These data show that non-invasive EAG detects streaming potentials produced by cartilage during joint compression and has potential to become a diagnostic tool capable of detecting early cartilage degeneration.
A novel approach for stimulating articular cartilage repair was developed and evaluated in skeletally aged Arcott sheep with signs of early osteoarthritis. Freeze-dried (FD) chitosan formulations were optimized to produce ultraporous cylinders that slowly rehydrate and disperse into bioactive chitosan microparticles in coagulating blood plasma. FD-chitosan implants (80% Degree of Deacetylation, 85 kDa) were produced at 3 doses (initial concentrations of 5, 10, 20 mg/mL, pH 2.5). Full-thickness cartilage defects were created bilaterally in medial femoral condyles of 8–9 year-old sheep (N = 12), microdrilled with 11 holes, then in one knee per sheep, one implant cylinder was inserted into each bleeding drill hole. At 1 day (N = 2), 3 months (N = 5) and 9 months (N = 5) post-operative, repair tissues were analyzed macroscopically and by micro-computed tomography, histology, biochemistry, and mechanics. Chitosan microparticles were detected in day 1 subchondral blood clots and mostly cleared at 3 months. At 3 months, microdrill holes were 2-fold larger, filled with angiogenic granulation tissue, callus, and woven bone, with more chondroinduction in treated versus control drill holes (p = 0.021). At 9 months, biomaterial treatment enhanced bone plate repair and stimulated 68% cartilage resurfacing vs 53% for drill-only controls (p = 0.047). Both treated and control cartilage repair tissues had lower glycosaminoglycan content than intact cartilage and were thinner, stiffer, and more permeable. Upon indentation, hyaline-like repair cartilage showed poroelastic behavior. This study showed that FD-chitosan can be locally delivered to incorporate chitosan microparticles into subchondral bone blood clots and exert anabolic therapeutic effects on articular cartilage resurfacing in aged sheep knees.
Objectives/Hypothesis Various animal models have been employed to investigate vocal fold (VF) and phonatory function. However, biomechanical testing techniques to characterize vocal fold structural properties vary and have not compared critical properties across species. We adapted a nondestructive, automated indentation mapping technique to simultaneously quantify VF structural properties (VF cover layer and intact VF) in commonly used species based on the hypothesis that VF biomechanical properties are largely preserved across species. Study Design Ex vivo animal model. Methods Canine, leporine, and swine larynges (n = 4 each) were sagittally bisected, measured, and subjected to normal indentation mapping (indentation at 0.3 mm; 1.2 mm/s) with a 2‐mm spherical indenter to quantify normal force along the VF cover layer, structural stiffness, and displacement at 0.8 mN; two‐dimensional maps of the free VF edge through the conus elasticus were created for these characterizations. Results Structural stiffness was 7.79 gf/mm (0.15–74.55) for leporine, 2.48 gf/mm (0.20–41.75) for canine, and 1.45 gf (0.56–4.56) for swine. For each species, the lowest values were along the free VF edge (mean ± standard deviation; leporine: 0.40 ± 0.21 gf/mm, canine: 1.14 ± 0.49 gf/mm, swine: 0.89 ± 0.28 gf/mm). Similar results were obtained for the cover layer normal force at 0.3 mm. On the free VF edge, mean (standard deviation) displacement at 0.08 gf was 0.14 mm (0.05) in leporine, 0.11 mm (0.03) in canine, and 0.10 mm (0.02) in swine. Conclusions Automated indentation mapping yielded reproducible biomechanical property measurement of the VF cover and intact VF. Divergent VF structural properties across canine, swine, and leporine species were observed. Level of Evidence NA. Laryngoscope, 2018
Quantitative assessments of articular cartilage function are needed to aid clinical decision making. Our objectives were to develop a new electromechanical grade to assess quantitatively cartilage quality and test its reliability. Electromechanical properties were measured using a hand-held electromechanical probe on 200 human articular surfaces from cadaveric donors and osteoarthritic patients. These data were used to create a reference electromechanical property database and to compare with visual arthroscopic International Cartilage Repair Society (ICRS) grading of cartilage degradation. The effect of patient-specific and location-specific characteristics on electromechanical properties was investigated to construct a continuous and quantitative electromechanical grade analogous to ICRS grade. The reliability of this novel grade was assessed by comparing it with ICRS grades on 37 human articular surfaces. Electromechanical properties were not affected by patient-specific characteristics for each ICRS grade, but were significantly different across the articular surface. Electromechanical properties varied linearly with ICRS grade, leading to a simple linear transformation from one scale to the other. The electromechanical grade correlated strongly with ICRS grade (r = 0.92, p < 0.0001). Additionally, the electromechanical grade detected lesions that were not found visually. This novel grade can assist the surgeon in assessing human knee cartilage by providing a quantitative and reliable grading system.
Objective This study tested the hypothesis that presolidified chitosan-blood implants are retained in subchondral bone channels perforated in critical-size sheep cartilage defects, and promote bone repair and hyaline-like cartilage resurfacing versus blood implant. Design Cartilage defects (10 × 10 mm) with 3 bone channels (1 drill, 2 Jamshidi biopsy, 2 mm diameter), and 6 small microfracture holes were created bilaterally in n = 11 sheep knee medial condyles. In one knee, 10 kDa chitosan–NaCl/blood implant (presolidified using recombinant factor VIIa or tissue factor), was inserted into each drill and Jamshidi hole. Contralateral knee defects received presolidified whole blood clot. Repair tissues were assessed histologically, biochemically, biomechanically, and by micro–computed tomography after 1 day ( n = 1) and 6 months ( n = 10). Results Day 1 defects showed a 60% loss of subchondral bone plate volume fraction along with extensive subchondral hematoma. Chitosan implant was resident at day 1, but had no effect on any subsequent repair parameter compared with blood implant controls. At 6 months, bone defects exhibited remodeling and hypomineralized bone repair and were partly resurfaced with tissues containing collagen type II and scant collagen type I, 2-fold lower glycosaminoglycan and fibril modulus, and 4.5-fold higher permeability compared with intact cartilage. Microdrill holes elicited higher histological ICRS-II overall assessment scores than Jamshidi holes (50% vs. 30%, P = 0.041). Jamshidi biopsy holes provoked sporadic osteonecrosis in n = 3 debrided condyles. Conclusions Ten kilodalton chitosan was insufficient to improve repair. Microdrilling is a feasible subchondral marrow stimulation surgical approach with the potential to elicit poroelastic tissues with at least half the compressive modulus as intact articular cartilage.
Electroarthrography (EAG) is a novel technique for recording potentials on the knee surface that are generated by the compression of articular cartilage and that reflect both compression force and cartilage quality. The mechanical loading of the knee is achieved by transferring the subject’s body weight from a bipedal stance to a unipedal stance. We hypothesized that EAG potentials change with postural sway. The study was performed on 20 normal subjects (10 male, 10 female; age 29 ± 10.5 yrs.; mass 68.8 ± 14.2 kg; height 172.6 ± 11.4 cm). Data was recorded during 10 successive loading cycles repeated on two different days. During loading, EAG potentials were recorded with 4 electrodes placed on both sides of the knee and the ground reaction force (GRF) and the antero-posterior and medial-lateral displacements of the center of pressure (COP) were measured with a force plate. Two electromechanical models predicting the EAG signal from the GRF alone or from the GRF plus the COP displacements were computed by linear regression. The mean relative error between the four EAG signals and the predicted signals ranged from 24% to 49% for the GRF model, and from 15% to 35% for the GRF + COP model, this reduction was statistically significant at 3 electrode sites (p < 0.05). The GRF + COP model also improved the repeatability of the parameters estimated on the first and second days when compared to the GRF model. In conclusion, EAG signals can be predicted by GRF and COP displacements and may reflect changes in the knee contact force due to postural sway.
Electroarthrography (EAG) is a new technique for measuring electrical potentials appearing on the knee surface during loading that reflects cartilage quality and joint contact force. Our objective was to investigate the evolution of EAG signals during successive loading cycles. The study was conducted on 20 standing subjects who shifted their body weight to achieve knee loading. Their EAG signals were recorded during 10 successive loading cycles, and during a subsequent sequence of 10 cycles recorded after a 15 min exercise period. Multiple linear regression models estimated the electro-mechanical ratio (EMR) interpreting the ability of cartilage to generate a certain potential for a given ground reaction force by taking into account this force and the center of pressure displacements during unipedal stance. The results showed that the EMR values slowly decreased with successive cycles: during the initial sequence, the correlation coefficients between EMR values and sequence numbers were significant at 3 of the 4 electrode sites (p<0.05); for the post-exercise sequence, the EMR values still decreased and were significantly lower than during the initial sequence (p<0.001). The reduction of EMR values could arise from muscle activity and habituation of the stretch reflex, and also from the time dependent electromechanical properties of cartilage. In conclusion, refraining from physical activity before the EAG measurements is important to improve measurement repeatability because of the EMR decrease. The electromechanical model confirmed the role of EAG as a natural sensor of the changes in the knee contact force and also improved EAG measurement accuracy.
Recent advances in the development of new drugs to halt or even reverse the progression of Osteoarthritis at an early-stage requires new tools to detect early degeneration of articular cartilage. We investigated the ability of an electromechanical probe and an automated indentation technique to characterize entire human articular surfaces for rapid non-destructive discrimination between early degenerated and healthy articular cartilage. Human cadaveric asymptomatic articular surfaces (4 pairs of distal femurs and 4 pairs of tibial plateaus) were used. They were assessed ex vivo: macroscopically, electromechanically (maps of the electromechanical quantitative parameter, QP, reflecting streaming potentials), mechanically (maps of the instantaneous modulus, IM) and through cartilage thickness. Osteochondral cores were also harvested from healthy and degenerated regions for histological assessment, biochemical analyses and unconfined compression tests. The macroscopic visual assessment delimited three distinct regions on each articular surface: region I was macroscopically degenerated, region II was macroscopically normal but adjacent to region I and region III was the remaining normal articular surface. Thus, each extracted core was assigned to one of the three regions. A mixed effect model revealed that only the QP (p < 0.0001) and IM (p < 0.0001) were able to statistically discriminate the three regions. Effect size was higher for QP and IM than other assessments, indicating greater sensitivity to distinguish early degeneration of cartilage. When considering the mapping feature of the QP and IM techniques, it also revealed bilateral symmetry in a moderately similar distribution pattern between bilateral joints. This article is protected by copyright. All rights reserved.
Objective: To compare the regenerative capacity of 2 distinct bilayer implants for the restoration of osteochondral defects in a preliminary sheep model. Methods: Critical sized osteochondral defects were treated with a novel biomimetic poly-ε-caprolactone (PCL) implant (Treatment No. 2; n = 6) or a combination of Chondro-Gide and Orthoss (Treatment No. 1; n = 6). At 19 months postoperation, repair tissue (n = 5 each) was analyzed for histology and biochemistry. Electromechanical mappings (Arthro-BST) were performed ex vivo. Results: Histological scores, electromechanical quantitative parameter values, dsDNA and sGAG contents measured at the repair sites were statistically lower than those obtained from the contralateral surfaces. Electromechanical mappings and higher dsDNA and sGAG/weight levels indicated better regeneration for Treatment No. 1. However, these differences were not significant. For both treatments, Arthro-BST revealed early signs of degeneration of the cartilage surrounding the repair site. The International Cartilage Repair Society II histological scores of the repair tissue were significantly higher for Treatment No. 1 (10.3 ± 0.38 SE) compared to Treatment No. 2 (8.7 ± 0.45 SE). The parameters cell morphology and vascularization scored highest whereas tidemark formation scored the lowest. Conclusion: There was cell infiltration and regeneration of bone and cartilage. However, repair was incomplete and fibrocartilaginous. There were no significant differences in the quality of regeneration between the treatments except in some histological scoring categories. The results from Arthro-BST measurements were comparable to traditional invasive/destructive methods of measuring quality of cartilage repair.
In order to figure out the mechanical properties of freeform bio-medical parts made by Additive Manufacturing (AM), Instrumented Indentation Testing (IIT) is introduced to measure the Young's modulus from the free surface of the parts. The research also conducted several other different methodologies alongside the IIT in measuring the effective Young's modulus as a comparison. A special designed testing machine Mach-1TM is used conducting the IIT, 3-point bending and compression test. The traditional compression test on standard cylinder parts made from the same binder jetting machine are used as a benchmark of the test material. Three different unit structures with different relative densities are considered, the solid part, the part with 1.0mm size of grid lattice and the part with 1.5mm size of grid lattice. Compared with the benchmark results obtained from traditional testing machines and the 3-point bending, the IIT bears a 15% error measuring solid and lattice freeform samples. Through the primary results, the porosity of the material as well as the stylus size and the lattice size contribute largely to the error.
This study mainly evaluates the elastic modulusof 316stainless steel atticestructuresfabricatedvia binder jetting process. In this present research, both solid and lattice samples are designed and fabricated by binder jetting process for two different types of mechanical tests. Besides experimental study, a numerical model based on energy approach has been proposed to predict the effective elastic modulus of fabricated lattice samples. By comparing the calculated results of the proposed numerical model with the experimental results, the established model is proved to be validated. This numerical model can be used to determine the parameters of lattice structures fabricated by binder jetting process for desired mechanical properties. At the end, both advantages and disadvantages of the lattice structures fabricated by binder jetting process are analysed. Based on this analysis, the potential application and future research work are pointed out.
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