An in vitro investigation to understand the synergistic role of MMPs-1 and 9 on articular cartilage biomechanical properties

AbstractMatrix metalloproteinases (MMPs) play a crucial role in enzymatically digesting cartilage extracellular matrix (ECM) components, resulting in degraded cartilage with altered mechanical loading capacity. Overexpression of MMPs is often caused by trauma, physiologic conditions and by disease. To understand the synergistic impact MMPs have on cartilage biomechanical properties, MMPs from two subfamilies: collagenase (MMP-1) and gelatinase (MMP-9) were investigated in this study. Three different ratios of MMP-1 (c) and MMP-9 (g), c1:g1, c3:g1 and c1:g3 were considered to develop a degradation model. Thirty samples, harvested from bovine femoral condyles, were treated in groups of 10 with one concentration of enzyme mixture. Each sample was tested in a healthy state prior to introducing degradative enzymes to establish a baseline. Samples were subjected to indentation loading up to 20% bulk strain. Both control and treated samples were mechanically and histologically assessed to determine the impact of degradation. Young’s modulus and peak load of the tissue under indentation were compared between the control and degraded cartilage explants. Cartilage degraded with the c3:g1 enzyme concentration resulted in maximum 33% reduction in stiffness and peak load compared to the other two concentrations. The abundance of collagenase is more responsible for cartilage degradation and reduced mechanical integrity.

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Effect of Biomechanical Environment on Degeneration of Meckel’s Cartilage

Journal of Dental Research ◽

10.1177/0022034520960118 ◽

2020 ◽

pp. 002203452096011

Author(s):

M. Farahat ◽

G.A.S. Kazi ◽

E.S. Hara ◽

T. Matsumoto

Keyword(s):

Endochondral Ossification ◽

Biomechanical Properties ◽

Cartilage Degradation ◽

Middle Region ◽

Meckel's Cartilage ◽

3 Dimensional ◽

Meckel’S Cartilage ◽

Surrounding Environment ◽

Rigid Environment

During orofacial tissue development, the anterior and posterior regions of the Meckel’s cartilage undergo mineralization, while the middle region undergoes degeneration. Despite the interesting and particular phenomena, the mechanisms that regulate the different fates of Meckel’s cartilage, including the effects of biomechanical cues, are still unclear. Therefore, the purpose of this study was to systematically investigate the course of Meckel’s cartilage during embryonic development from a biomechanical perspective. Histomorphological and biomechanical (stiffness) changes in the Meckel’s cartilage were analyzed from embryonic day 12 to postnatal day 0. The results revealed remarkable changes in the morphology and size of chondrocytes, as well as the occurrence of chondrocyte burst in the vicinity of the mineralization site, an often-seen phenomenon preceding endochondral ossification. To understand the effect of biomechanical cues on Meckel’s cartilage fate, a mechanically tuned 3-dimensional hydrogel culture system was used. At the anterior region, a moderately soft environment (10-kPa hydrogel) promoted chondrocyte burst and ossification. On the contrary, at the middle region, a more rigid environment (40-kPa hydrogel) enhanced cartilage degradation by inducing a higher expression of MMP-1 and MMP-13. These results indicate that differences in the biomechanical properties of the surrounding environment are essential factors that distinctly guide the mineralization and degradation of Meckel’s cartilage and would be valuable tools for modulating in vitro cartilage and bone tissue engineering.

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EZH2 inhibition reduces cartilage loss and functional impairment related to osteoarthritis

Scientific Reports ◽

10.1038/s41598-020-76724-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Lyess Allas ◽

Sybille Brochard ◽

Quitterie Rochoux ◽

Jules Ribet ◽

Cleo Dujarrier ◽

...

Keyword(s):

Functional Disability ◽

Ex Vivo ◽

Cartilage Degradation ◽

Motor Functions ◽

Methyl Transferase ◽

Expression Of Genes ◽

Medial Meniscectomy ◽

The Impact

Abstract Histone methyltransferase EZH2 is upregulated during osteoarthritis (OA), which is the most widespread rheumatic disease worldwide, and a leading cause of disability. This study aimed to assess the impact of EZH2 inhibition on cartilage degradation, inflammation and functional disability. In vitro, gain and loss of EZH2 function were performed in human articular OA chondrocytes stimulated with IL-1β. In vivo, the effects of EZH2 inhibition were investigated on medial meniscectomy (MMX) OA mouse model. The tissue alterations were assayed by histology and the functional disabilities of the mice by actimetry and running wheel. In vitro, EZH2 overexpression exacerbated the action of IL-1β in chondrocytes increasing the expression of genes involved in inflammation, pain (NO, PGE2, IL6, NGF) and catabolism (MMPs), whereas EZH2 inhibition by a pharmacological inhibitor, EPZ-6438, reduced IL-1β effects. Ex vivo, EZH2 inhibition decreased IL-1β-induced degradation of cartilage. In vivo, intra-articular injections of the EZH2 inhibitor reduced cartilage degradation and improved motor functions of OA mice. This study demonstrates that the pharmacological inhibition of the histone methyl-transferase EZH2 slows the progression of osteoarthritis and improves motor functions in an experimental OA model, suggesting that EZH2 could be an effective target for the treatment of OA by reducing catabolism, inflammation and pain.

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Divalent magnesium restores cytoskeletal storage lesions in cold-stored platelet concentrates

10.21203/rs.3.rs-667016/v2 ◽

2021 ◽

Author(s):

Konstanze Aurich ◽

Jan Wesche ◽

Martin Ulbricht ◽

Oliver Otto ◽

Andreas Greinacher ◽

...

Keyword(s):

Biomechanical Properties ◽

Platelet Concentrates ◽

Bacterial Proliferation ◽

Cytoskeletal Structure ◽

C Storage ◽

Additive Solution ◽

The Impact ◽

Deformability Cytometry

Abstract Cold storage of platelet concentrates (PC) has become attractive due to the reduced risk of bacterial proliferation, but in vivo circulation time of cold-stored platelets is reduced. Ca2+ release from storage organelles and higher activity of Ca2+ pumps at temperatures < 15°C triggers cytoskeleton changes. This is suppressed by Mg2+ addition, avoiding a shift in Ca2+ hemostasis and cytoskeletal alterations. We report on the impact of 2–10 mM Mg2+ addition on cytoskeleton alterations of platelets from PC stored at room temperature (RT) or 4°C in additive solution (PAS), 30% plasma. Deformation of platelets was assessed by real-time deformability cytometry (RT-DC), a method for biomechanical cell characterization. Deformation was strongly affected by storage at 4°C and preserved by Mg2+ addition ≥ 4 mM Mg2+ (mean ± SD of median deformation 4°C vs. 4°C + 10mM Mg2+ 0.073 ± 0.021 vs. 0.118 ± 0.023, p < 0.01; n = 6, day 7). These results were confirmed by immunofluorescence microscopy, showing that Mg2+ ≥ 4mM prevents 4°C storage induced cytoskeletal structure lesion. Standard in vitro platelet function tests showed minor differences between RT and cold-stored platelets. Hypotonic shock response was reduced in cold-stored platelets (45.65 ± 11.59% vs. RT stored platelets 56.38 ± 29.36; p = 0.042) but normal at 4°C + 10 mM Mg2+ (55.22 ± 11.16%, all n = 6, day 1). CD62P expression and platelet aggregation response were similar between RT and 4°C stored platelets, with minor changes in the presence of higher Mg2+ concentrations. In conclusion, increasing Mg2+ up to 10 mM in PAS counteracts 4°C storage lesions in platelets, maintains platelet cytoskeletal integrity and biomechanical properties comparable to RT stored platelets.

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In vitro investigation of the impact of remaining tooth structure on the tensile failure loads of overdenture copings

Journal of Clinical and Experimental Dentistry ◽

10.4317/jced.56228 ◽

2019 ◽

pp. 0-0

Author(s):

A Fotiou ◽

SN Kamalakidis ◽

AL Pissiotis ◽

K Michalakis

Keyword(s):

Tensile Failure ◽

Tooth Structure ◽

In Vitro Investigation ◽

Failure Loads ◽

The Impact

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In vitro Biomechanical Study of Pulvertaft Tendon Weaving Technique

Journal of Orthopaedics Trauma and Rehabilitation ◽

10.1016/j.jotr.2011.04.005 ◽

2011 ◽

Vol 15 (2) ◽

pp. 62-64 ◽

Cited By ~ 1

Author(s):

Yuen Chi-Pan ◽

Yen Chi-Hung ◽

Leung Hon-Bong ◽

Tse Wing-Lim ◽

Ho Pak-Cheong ◽

...

Keyword(s):

Peak Load ◽

Tendon Repair ◽

Early Mobilization ◽

Biomechanical Properties ◽

Biomechanical Study ◽

Load To Failure ◽

Active Mobilization ◽

Passive Mobilization ◽

Single Suture

Background/Purposes The outcome of tendon repair depends on the strength, which allows early active mobilization to achieve better function without rupture. The aims of this study are to assess quantitatively the biomechanical properties and relationship between the number of tendon weaving and suture method using Pulvertaft technique. Results We found that the load to failure was increased with increasing number of weaves and sutures. From 1-weave to 4-weave single suture samples, the peak load to failure was 9.5 N, 19.7 N, 37.5 N, and 42.6 N, respectively. Based on previous studies, wrist and finger tendons should withstand 1–8N on passive mobilization. Conclusion On active mobilization, finger tendon repair need to provide 34 N for immediate mobilization. Therefore, irrespective of number of sutures, both 3- and 4-weave repairs could allow early mobilization biomechanically.

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In vitro investigation on the impact of airway mucus on drug dissolution and absorption at the air-epithelium interface in the lungs

European Journal of Pharmaceutics and Biopharmaceutics ◽

10.1016/j.ejpb.2019.05.022 ◽

2019 ◽

Vol 141 ◽

pp. 210-220 ◽

Cited By ~ 8

Author(s):

Emanuela Cingolani ◽

Safar Alqahtani ◽

Robyn C Sadler ◽

David Prime ◽

Snjezana Stolnik ◽

...

Keyword(s):

Drug Dissolution ◽

In Vitro Investigation ◽

Airway Mucus ◽

The Impact

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In vitro investigation on the impact of the surface-active excipients Cremophor EL, Tween 80 and Solutol HS 15 on the metabolism of midazolam

Biopharmaceutics & Drug Disposition ◽

10.1002/bdd.383 ◽

2004 ◽

Vol 25 (1) ◽

pp. 37-49 ◽

Cited By ~ 61

Author(s):

Roberto C. Bravo González ◽

Jörg Huwyler ◽

Franziska Boess ◽

Isabelle Walter ◽

Beate Bittner

Keyword(s):

Tween 80 ◽

Cremophor El ◽

In Vitro Investigation ◽

Surface Active ◽

Solutol Hs 15 ◽

The Impact

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In vitro investigation of the impact of pulsatile blood flow on the vascular architecture of decellularized porcine kidneys

Scientific Reports ◽

10.1038/s41598-021-95924-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Peter R. Corridon

Keyword(s):

Blood Flow ◽

Blood Perfusion ◽

Pulsatile Blood Flow ◽

Venous Outflow ◽

Venous Flow ◽

Vascular Architecture ◽

Arterial Perfusion ◽

In Vitro Investigation ◽

The Impact

AbstractA method was established using a scaffold-bioreactor system to examine the impact pulsatile blood flow has on the decellularized porcine kidney vascular architecture and functionality. These scaffolds were subjected to continuous arterial perfusion of whole blood at normal physiological (650 ml/min and 500 ml/min) and pathophysiological (200 ml/min) rates to examine dynamic changes in venous outflow and micro-/macrovascular structure and patency. Scaffolds subjected to normal arterial perfusion rates observed drops in venous outflow over 24 h. These reductions rose from roughly 40% after 12 h to 60% after 24 h. There were no apparent signs of clotting at the renal artery, renal vein, and ureter. In comparison, venous flow rates decreased by 80% to 100% across the 24 h in acellular scaffolds hypoperfused at a rate of 200 ml/min. These kidneys also appeared intact on the surface after perfusion. However, they presented several arterial, venous, and ureteral clots. Fluoroscopic angiography confirmed substantial alterations to normal arterial branching patterns and patency, as well as parenchymal damage. Scanning electron microscopy revealed that pulsatile blood perfusion significantly disrupted glomerular microarchitecture. This study provides new insight into circumstances that limit scaffold viability and a simplified model to analyze conditions needed to prepare more durable scaffolds for long-term transplantation.

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Impact of Horse Hoof Wall with Different Solid Surfaces

Applied Sciences ◽

10.3390/app10238743 ◽

2020 ◽

Vol 10 (23) ◽

pp. 8743

Author(s):

Jing Zhao ◽

Dan B. Marghitu ◽

John Schumacher ◽

Wenzhong Wang

Keyword(s):

Contact Force ◽

Coefficient Of Friction ◽

Coefficient Of Restitution ◽

Solid Surfaces ◽

Effective Coefficient ◽

In Vitro Investigation ◽

Equine Hoof ◽

Impact Angles ◽

The Impact

This study aimed to investigate the impact of a horse hoof wall on three solid surfaces: steel, concrete and asphalt. Impact experiments were conducted for different impact angles and different initial impact velocities. The effect of impact surfaces, impact angles and initial impact velocities on the coefficient of restitution and the effective coefficient of friction were tested using one-way ANOVA. Analytical and numerical modeling of the impact were developed. The impact interval was divided into two phases: compression and restitution. For compression, a contact force with a damping term was used. The restitution was characterized by an elastic contact force. The stiffness and damping coefficients of the contact force were estimated from the normal impacts. The simulated velocities after the oblique impacts were compared to the velocities in the in vitro investigation. The coefficient of restitution varied significantly on different surfaces. The effective coefficient of friction was lower on steel compared to concrete and asphalt. The model presented in this study can be applied to refine the impact simulation of the equine hoof during locomotion.

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