Altered Mechanical Properties and Fiber Re-Alignment in Diabetic Mouse Supraspinatus and Achilles Tendons

Author(s):  
Brianne K. Connizzo ◽  
Kenneth W. Liechty ◽  
Louis J. Soslowsky

Tendons function to transfer load, maintain alignment and permit motion in joints. To perform these functions, tendons have complex mechanical behavior which is modulated by the tissue’s structure and composition, such as the collagen fibers and surrounding extracellular matrix. When these matrix proteins are altered, the mechanical properties are also altered, which could potentially lead to reduced loading and healing capacity. Diabetes is a metabolic disease which, among other co-morbidities, has been associated with Achilles tendon disorganization and tendinopathy, as well as increased overall joint stiffness in humans [1]. We have recently reported that the skin from the Db/Db diabetic mouse, a model of Type II Diabetes, as well as the skin from human diabetics, have impaired biomechanical properties compared to non-diabetic skin as the result of altered extracellular matrix composition. [2]. However, the mechanical properties of tendons from these animals have never been studied and could serve as a unique model of altered collagen structure as well as provide further understanding to the cause of tendinous injuries in the diabetic population. Therefore, the objective of this study is to measure the tensile mechanical properties and collagen fiber re-alignment in the db/db mouse model compared to non-diabetic controls. We hypothesize that tendon stiffness and modulus will be increased in the db/db group in the insertion site and midsubstance, and that db/db tendons will re-align earlier and faster during the testing protocol.

2019 ◽  
Author(s):  
Charis R Saville ◽  
Venkatesh Mallikarjun ◽  
David F Holmes ◽  
Elaine Emmerson ◽  
Brian Derby ◽  
...  

ABSTRACTHormone deficiency has been widely linked to accelerated tissue ageing, and increased incidence of chronic degenerative disease. Furthermore, age-associated hormonal dysregulation is thought to be a major contributing factor to the increased fragility of aged skin. The ageing process is driven by an aggregation of damage to cells and extracellular matrix, which can directly influence the mechanical properties of the tissue. Here we report on the correlation between mechanical properties and composition of skin from ovariectomised and aged mice, to assess the extent to which estrogen deprivation drives dermal ageing. We found that age and estrogen abrogation affected skin mechanical properties in contrasting ways: ageing led to increased tensile strength and stiffness while estrogen deprivation had the opposite effect. Mass spectrometry proteomics showed that the quantity of extractable fibrillar collagen-I decreased with ageing, but no change was observed in ovariectomised mice. This observation, in combination with measurements of tensile strength, was interpreted to reflect changes to the extent of extracellular matrix crosslinking, supported by a significant increase in the staining of advanced glycation endpoints in aged skin. Loss of mechanical strength in the skin following ovariectomy was consistent with a loss of elastic fibres. Other changes in extracellular matrix composition broadly correlated between aged and ovariectomised mice, confirming the important role of estrogen-related pathways in ageing. This study offers new insight into the relationship between tissue composition and mechanics, and suggests that the deleterious effects of intrinsic skin ageing are compounded by factors beyond hormonal dysregulation.


2021 ◽  
Vol 17 (2) ◽  
pp. e1008764
Author(s):  
Inês G. Gonçalves ◽  
Jose Manuel Garcia-Aznar

In this work, we show how the mechanical properties of the cellular microenvironment modulate the growth of tumour spheroids. Based on the composition of the extracellular matrix, its stiffness and architecture can significantly vary, subsequently influencing cell movement and tumour growth. However, it is still unclear exactly how both of these processes are regulated by the matrix composition. Here, we present a centre-based computational model that describes how collagen density, which modulates the steric hindrance properties of the matrix, governs individual cell migration and, consequently, leads to the formation of multicellular clusters of varying size. The model was calibrated using previously published experimental data, replicating a set of experiments in which cells were seeded in collagen matrices of different collagen densities, hence producing distinct mechanical properties. At an initial stage, we tracked individual cell trajectories and speeds. Subsequently, the formation of multicellular clusters was also analysed by quantifying their size. Overall, the results showed that our model could accurately replicate what was previously seen experimentally. Specifically, we showed that cells seeded in matrices with low collagen density tended to migrate more. Accordingly, cells strayed away from their original cluster and thus promoted the formation of small structures. In contrast, we also showed that high collagen densities hindered cell migration and produced multicellular clusters with increased volume. In conclusion, this model not only establishes a relation between matrix density and individual cell migration but also showcases how migration, or its inhibition, modulates tumour growth.


Author(s):  
Flavia Carneiro ◽  
Boudewijn PT Kruithof ◽  
Kanthesh Balani ◽  
Arvind Agarwal ◽  
Vinciane Gaussin ◽  
...  

2007 ◽  
Vol 88 ◽  
pp. S218-S219
Author(s):  
J. Norian ◽  
G. Christman ◽  
C. Korecki ◽  
J. Iatridis ◽  
F. Chen ◽  
...  

2001 ◽  
Vol 90 (4) ◽  
pp. 1400-1406 ◽  
Author(s):  
Débora S. Faffe ◽  
Gabriela H. Silva ◽  
Pedro M. P. Kurtz ◽  
Elnara M. Negri ◽  
Vera L. Capelozzi ◽  
...  

The dynamic mechanical properties of lung tissue and its contents of collagen and elastic fibers were studied in strips prepared from mice instilled intratracheally with saline (C) or silica [15 (S15) and 30 days (S30) after instillation]. Resistance, elastance, and hysteresivity were studied during oscillations at different frequencies on S15 and S30. Elastance increased from C to silica groups but was similar between S15 and S30. Resistance was augmented from C to S15 and S30 and was greater in S30 than in S15 at higher frequencies. Hysteresivity was higher in S30 than in C and S15. Silica groups presented a greater amount of collagen than did C. Elastic fiber content increased progressively along time. This increment was related to the higher amount of oxytalan fibers at 15 and 30 days, whereas elaunin and fully developed elastic fibers were augmented only at 30 days. Silicosis led not only to pulmonary fibrosis but also to fibroelastosis, thus assigning a major role to the elastic system in the silicotic lung.


2013 ◽  
Vol 135 (2) ◽  
Author(s):  
Brianne K. Connizzo ◽  
Joseph J. Sarver ◽  
Renato V. Iozzo ◽  
David E. Birk ◽  
Louis J. Soslowsky

Collagen fiber realignment is one mechanism by which tendon responds to load. Re-alignment is altered when the structure of tendon is altered, such as in the natural process of aging or with alterations of matrix proteins, such as proteoglycan expression. While changes in re-alignment and mechanical properties have been investigated recently during development, they have not been studied in (1) aged tendons, or (2) in the absence of key proteoglycans. Collagen fiber re-alignment and the corresponding mechanical properties are quantified throughout tensile mechanical testing in both the insertion site and the midsubstance of mouse supraspinatus tendons in wild type (WT), decorin-null (Dcn-/-), and biglycan-null (Bgn-/-) mice at three different ages (90 days, 300 days, and 570 days). Percent relaxation was significantly decreased with age in the WT and Dcn-/- tendons, but not in the Bgn-/- tendons. Changes with age were found in the linear modulus at the insertion site where the 300 day group was greater than the 90 day and 570 day group in the Bgn-/- tendons and the 90 day group was smaller than the 300 day and 570 day groups in the Dcn-/- tendons. However, no changes in modulus were found across age in WT tendons were found. The midsubstance fibers of the WT and Bgn-/- tendons were initially less aligned with increasing age. The re-alignment was significantly altered with age in the WT tendons, with older groups responding to load later in the mechanical test. This was also seen in the Dcn-/- midsubstance and the Bgn-/- insertion, but not in the other locations. Although some studies have found changes in the WT mechanical properties with age, this study did not support those findings. However, it did show fiber re-alignment changes at both locations with age, suggesting a breakdown of tendon's ability to respond to load in later ages. In the proteoglycan-null tendons however, there were changes in the mechanical properties, accompanied only by location-dependent re-alignment changes, suggesting a site-specific role for these molecules in loading. Finally, changes in the mechanical properties did not occur in concert with changes in re-alignment, suggesting that typical mechanical property measurements alone are insufficient to describe how structural alterations affect tendon's response to load.


2021 ◽  
Vol 64 (6) ◽  
pp. 41-48
Author(s):  
Olga Ignatov ◽  
◽  
Adrian Melnic ◽  
Vitalie Procopciuc ◽  
Viorica Mihaluta ◽  
...  

Background: Peripheral neuropathy usually leads to a major cause of motor disability, but the functional restoration after treatment continues to show modest results. Acupoint thread-embedding therapy is a subtype of acupuncture treatment in which biodegradable threads are inserted into skin, subcutaneous tissue or muscles at specific points for long stimulation. Different biodegradable materials have been developed and widely used. Human amniotic membrane is rich in collagen, extracellular matrix proteins and growth factors. The avascular, low immunogenic, anti-inflammatory, antibacterial, anti-fibrotic and non-tumorigenic properties of amniotic membrane make it valuable in medical applications and its use has no ethical problems. Elasticity, stiffness and other biomechanical properties also make it possible to use the amniotic membrane for various medical purposes. AM is almost always considered as discarded substance, it satisfies most of the criteria of an ideal biological tissue and shows almost zero rejection phenomenon. Conclusions: The human amniotic membrane, the cellular compounds and extracellular matrix have a lot of benefic proprieties that are or could be used in treatment of many human diseases. Its biological and biomechanical properties are promising in the manufacture and use of filaments in acupoint thread embedding therapy.


1997 ◽  
Vol 10 (01) ◽  
pp. 6-11 ◽  
Author(s):  
R. F. Rosenbusch ◽  
L. C. Booth ◽  
L. A. Dahlgren

SummaryEquine tendon fibroblasts were isolated from explants of superficial digital flexor tendon, subcultured and maintained in monolayers. The cells were characterized by light microscopy, electron microscopy and radiolabel studies for proteoglycan production. Two predominant cell morphologies were identified. The cells dedifferentiated toward a more spindle shape with repeated subcultures. Equine tendon fibroblasts were successfully cryopreserved and subsequently subcultured. The ability to produce proteoglycan was preserved.The isolated cells were identified as fibroblasts, based on their characteristic shape by light microscopy and ultrastructure and the active production of extracellular matrix proteins. Abundant rough endoplasmic reticulum and the production of extracellular matrix products demonstrated active protein production and export. Proteoglycans were measurable via liquid scintillation counting in both the cell-associated fraction and free in the supernatant. This model is currently being utilized to study the effects of polysulfated glycosaminoglycan on tendon healing. Future uses include studying the effects of other pharmaceuticals, such as hyaluronic acid, on tendon healing.A model was developed for in vitro investigations into tendon healing. Fibroblasts were isolated from equine superficial digital flexor tendons and maintained in monolayer culture. The tenocytes were characterized via light and electron microscopy. Proteoglycan production was measured, using radio-label techniques. The fibroblasts were cryopreserved and subsequently subcultured. The cells maintained their capacity for proteoglycan production, following repeated subculturing and cryopreservation.


1992 ◽  
Vol 05 (04) ◽  
pp. 158-162 ◽  
Author(s):  
D. Blackketter ◽  
J Harari ◽  
J. Dupuis

Bone/lateral collateral ligament/bone preparations were tested and structural mechanical properties compared to properties of cranial cruciate ligament in 15 dogs. The lateral collateral ligament has sufficient stiffness to provide stifle joint stability and strength to resist acute overload following fibular head transposition.


2004 ◽  
Vol 216 (03) ◽  
Author(s):  
U Schüller ◽  
W Hartmann ◽  
A Koch ◽  
K Schilling ◽  
OD Wiestler ◽  
...  

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