Rat Tail Tendon Research Articles

Aggregation and self assembly of non-enzymatic glycation of collagen in the presence of amino guanidine and aspirin: An in vitro study

Non-enzymatic glycation of collagen has been used in modern biomaterials science. This paper deals with in vitro studies on the effects of amino guanidine (AG) and aspirin in the non-enzymatic glycation (NEG) of collagen using thermal, conformational, fluorescence, turbidity and powder XRD measurements. There is no significant change in the fluorescence emission spectra for different concentrations of AG treated NEG of collagen whereas the emission intensity decreases as the concentration of aspirin increases. Circular dichroism (CD) revealed the disappearance of the positive peak at 220 nm for glycated collagen in the presence of amino guanidine and aspirin suggesting the collapse of triple helical configuration. Nearly 15 °C decrease is observed in shrinkage temperature of glycated rat tail tendon (RTT) collagen fibres in the presence of aspirin. Powder XRD of glycated collagen nano-fibrils in the presence of amino guanidine reveals high crystalline nature and the enhancement of self assembly processes when compared to aspirin. To the best of our knowledge, this is the first report of powder XRD of the self assembly of collagen nano-fibrils without mineralization. Our experimental results suggest that in the non-enzymatic glycation of collagen both AG and aspirin play a pivotal role in the aggregation and self assembly processes. From the present study, it is possible to conclude that while AG significantly influences the self assembly processes, aspirin facilitates the aggregation processes.

Functional analysis of tenocytes gene expression in tendon fascicles subjected to cyclic tensile strain

Tenocytes are known to be mechanoresponsive and the present study tests the hypothesis that distinct mechanical stimulation regimes, associated with the short-term and extended application of cyclic tensile strain, alters the balance between anabolic and catabolic processes. Microarray technology has been used to provide a comprehensive analysis of alterations in gene expression within isolated tendon fascicles in response to cyclic tensile strain using a well-established model system. Isolated rat tail tendon fascicles were subjected to cyclic tensile strain (3% amplitude superimposed on a 2% static strain) for 1 or 24 hr. Messenger RNA expression level was assessed using Illumina microarray. The number of genes significantly altered in strained fascicles from the level of unstrained control fascicles was greater at 24 hr than 1 hr. The expression levels of many extracellular matrix components remained unchanged at both time points; however, a number of members of the matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with a thrombospondin (ADAMTS) families were significantly downregulated at 24 hr. Functional annotation revealed that upregulated genes were significantly associated with the regulation of transcription at 1 hr and translation at 24 hr. Downregulated genes were associated with inflammatory responses at 1 hr, and genes inhibited at 24 hr were significantly associated with cell apoptosis and a variety of metabolic functions. The present results suggest that the metabolic balance was shifted in favor of catabolism by the application of a small number of tensile strain cycles, whereas an extended number stimulates strong anti-catabolic effects.

Antihyperglycemic activity and inhibition of advanced glycation end product formation by Cuminum cyminum in streptozotocin induced diabetic rats

Cuminum cyminum is widely used as a spice in many countries. The aim of the present study was to investigate the effect of methanolic extract of seeds of C. cyminum (CC) on diabetes, oxidative stress and formation of advanced glycated end products (AGE) and obtain comparison with glibenclamide. In vitro studies indicated that CC inhibited free radicals and AGE formation. Treatment of streptozotocin-diabetic rats with CC and glibenclamide for 28 days caused a reduction in blood glucose, glycosylated hemoglobin, creatinine, blood urea nitrogen and improved serum insulin and glycogen (liver and skeletal muscle) content when compared to diabetic control rats. Significant reduction in renal oxidative stress and AGE was observed with CC when compared to diabetic control and glibenclamide. CC and glibenclamide improved antioxidant status in kidney and pancreas of diabetic rats. Diabetic rats showed increase in rat tail tendon collagen, glycated collagen, collagen linked fluorescence and reduction in pepsin digestion. Treatment with CC significantly improved these parameters when compared to diabetic control and glibenclamide group. Though the antidiabetic effect of CC was comparable to glibenclamide it had better effect in controlling oxidative stress and inhibiting the AGE formation, which are implicated in the pathogenesis of diabetic microvascular complications.

Effects of probe pollutants on morphological and mechanical measurements of muscle and collagen fibers using atomic force microscopy

Because of the interaction between probes and samples, pollutants in buffer solution or in the air would easily bind to probes and make the probe polluted, which might influence the morphological and mechanical measurements with atomic force microscopy. The polluted probes might transfer the pollutants onto the samples and thus change the surface ultrastructure of samples, or collect the deviated feedback signals to make the phantasm images. The former process is irreversible even if a new probe is employed, and the latter one is a reversible process as long as changing the used/polluted probe. Effects of polluted probes on morphological and mechanical characteristics of insect flight muscle and rat tail tendon collagen I fibers had been discussed in this study, in which, we constructed a series of methods to avoid/reduce the collecting of phantasm images and deviated mechanical information, such as changing the scanning direction and scanning force, replacing the new probes, or cleaning the polluted probes.

Abstract 521: Impaired migration of human fibrosarcoma cells HT1080 on glycated collagen type I

Abstract Although a strict link does exist between cancer and aging, elderly patients present less invasive tumors than their younger counterparts. During aging, the fibrillar collagen type I, which is an abundant component of the extracellular matrix, becomes a prominent target of post-translational modifications such as glycation. Our present study is mainly designed to investigate the effect of non-enzymatic glycation of this long-lived protein on the proliferation and migration of human fibrosarcoma cells HT1080. For this purpose, collagen type I extracted from rat tail tendons was used for in vitro glycoxydation with ribose. Tumor cell behaviour was then evaluated on 2-dimensional plastic surfaces coated with native or glycated collagen type I. Results showed that the proliferation rate of HT1080 cells on glycated collagen type I did not differ from that on native collagen I after 1, 2 and 3 days of culture. Furthermore, the migration ability of HT1080 cells was studied by quantifying cell speed and trajectories via time-lapse videomicroscopy. At day 1, glycated collagen type I distinctly slowed down the cell locomotion by decreasing the mean cell speed by 47% (20.2 μm/h for glycated versus 38.3 μm/h for its native form). Continuous single cell tracking also permitted the investigation of cell trajectories. Cells grown on glycated collagen exhibited shorter or circular trajectories around their starting point in accordance with the cell speed inhibition. Because actin and vinculin appeared as key proteins involved in cell locomotion, we next investigated the effect of glycated collagen on the organization of these proteins in individual cells in motion. Cells exhibited a dramatic disorganization of F-actin cytoskeleton with loss of stress fibers as compared to native collagen. Actin was principally localized at the rim of the cell. Disturbance of actin integrity was accompanied with a disorganization of vinculin that also localized at the cell periphery. The impact of glycated collagen on the non-receptor protein tyrosine kinase FAK, which plays a crucial role in focal adhesion formation and cell locomotion, was also evaluated. We found that at day 1, glycated collagen significantly inhibits FAK expression by 39% but did not affect their phosphorylation state. These data clearly suggest that age-related changes of extracellular matrix proteins may contribute to a less invasive behaviour of tumor cells. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 521.

High-speed spectral domain polarization- sensitive optical coherence tomography using a single camera and an optical switch at 1.3 µm

We propose high-speed spectral domain polarization-sensitive optical coherence tomography (SD-PS-OCT) using a single camera and a 1x2 optical switch at the 1.3-microm region. The PS-low coherence interferometer used in the system is constructed using free-space optics. The reflected horizontal and vertical polarization light rays are delivered via an optical switch to a single spectrometer by turns. Therefore, our system costs less to build than those that use dual spectrometers, and the processes of timing and triggering are simpler from the viewpoints of both hardware and software. Our SD-PS-OCT has a sensitivity of 101.5 dB, an axial resolution of 8.2 microm, and an acquisition speed of 23,496 A-scans per second. We obtain the intensity, phase retardation, and fast axis orientation images of a rat tail tendon ex vivo.

Molecular Architecture of the Collagen Based Extra-Cellular Matrix

The fibrous collagens are the fundamental constituents of the Extracellular Matrix (ECM) of animals, forming the structural basis of all known mammalian connective tissues and organ systems (1). Yet, despite the fundamental biological importance of collagen, many of us are perplexed by the complexity of the assemblies that the collagens form. This is particularly true at what may be the most significant aspect of collagen structure from a cellular point of view, at the intermediate sub-fibrillar and at fibril surface levels (i.e. collagens molecular packing) where many important biological processes occur in growth, development and disease (1, 2). These include but are not limited to: fibrillogenesis, tissue remolding and in forming the scaffolding upon which organ systems, bones, cartilage, etc., i.e. the animal body, are built upon. Clearly, obtaining an unambiguous and contextualized visualization of collagen molecules would be of significant value to the scientific community. We have recently determined the structure of the type I collagen microfibril (3) and fibril (2) at the molecular level from whole intact rat-tail tendons and produced an initial one dimensional structure for type II collagen from lamprey notochord. Using these data, it is possible to map the amino acid chemistry, ligand binding data and other observations onto the defining shape modality of the fibrillar collagen ECM. In so doing, we have been able to propose the first fibrillar based mechanism of collagenolysis and provide a number of illuminating observations regarding other collagen fibril - ligand interactions involving cell adhesion and matrix organization.1. Sweeney S et al. (2008) “Candidate cell and matrix interaction domains…” J Biol Chem 283:21187-97.2. Perumal et al., (2008) “Collagen fibril architecture,… govern its proteolysis.” PNAS 105:2824-9.3. Orgel J et al (2006) Microfibrillar structure of type I collagen in situ. PNAS 103:9001-5.

Corticosteroid administration alters the mechanical properties of isolated collagen fascicles in rat‐tail tendon

Overload tendon injuries are frequent in recreational and elite sports. The optimal treatment strategy remains unknown, but local administration of corticosteroids is one common treatment option. The direct effects of the corticosteroid administration on the tissue are not fully understood. The present study examined the biomechanical effects of intratendinous corticosteroid injections on healthy rat-tail tendon collagen fascicles. A total of 24 Wistar male rats were divided into (A) a corticosteroid group where the animals were injected in the tail tendon with methylprednisolone acetate, 1.0 mL of 40 mg/mL mixed with 1.0 mL 9% saline (n=12), and (B) a control group that was injected with 9% saline (n=12). Three days after the injections, the animals were sacrificed and single individual collagen fascicles were collected and underwent displacement to failure. Corticosteroid administration significantly reduced tensile fascicle yield strength by 16% and Young's modulus by 14% compared with sham treatment (10.5+/-0.8 vs 12.4+/-0.5 MPa, P< or =0.05, and 537+/-27 vs 641+/-30 MPa, P<0.05, respectively), while the strain properties were unaffected. Peak stress was similar between the two groups. There was no difference in fascicle diameter between the two groups.

Relative contributions of mechanical degradation, enzymatic degradation, and repair of the extracellular matrix on the response of tendons when subjected to under‐ and over‐ mechanical stimulations in vitro

Tendon response to mechanical loading results in either homeostasis, improvement, or degeneration of tissue condition. In an effort to better understand the development of tendinopathies, this study investigated the mechanical and structural responses of tendons subjected to under- and over-stimulations (1.2% and 1.8% strain respectively, 1 Hz). The objective was to examine three sub-processes of tendon response: mechanical degradation, enzymatic degradation, and repair of the extracellular matrix. We subjected rat tail tendons to a 10-day stimulation protocol with four periods of 6 h each day: 30 min of stimulation and 5 h 30 min of rest. To investigate the contribution of the three sub-processes, we controlled the contribution of the cells through variations in the nutrient and protease inhibitor content in the in vitro solutions. Using nondestructive cyclic tests, we evaluated the daily changes in the peak stress. To assess structural changes, we carried out microscopic analyses at the end of the study period. We observed that the relative contributions of the sub-processes differed according to the stimulation amplitude. With over-stimulation of tendons immersed in DMEM, we succeeded in reducing enzymatic degradation and increasing peak stress. In under-stimulation, the addition of protease inhibitors was required to obtain the same result.

Evidence against proteoglycan mediated collagen fibril load transmission and dynamic viscoelasticity in tendon

The glycosaminoglycan (GAG) dermatan sulfate and chondroitin sulfate side-chains of small leucine-rich proteoglycans have been increasingly posited to act as molecular cross links between adjacent collagen fibrils and to directly contribute to tendon elasticity. GAGs have also been implicated in tendon viscoelasticity, supposedly affecting frictional loss during elongation or fluid flow through the extra cellular matrix. The current study sought to systematically test these theories of tendon structure–function by investigating the mechanical repercussions of enzymatic depletion of GAG complexes by chondroitinase ABC in a reproducible tendon structure–function model (rat tail tendon fascicles). The extent of GAG removal (at least 93%) was verified by relevant spectrophotometric assays and transmission electron microscopy. Dynamic viscoelastic tensile tests on GAG depleted rat tail tendon fascicle were not mechanically different from controls in storage modulus (elastic behavior) over a wide range of strain-rates (0.05, 0.5, and 5% change in length per second) in either the linear or nonlinear regions of the material curve. Loss modulus (viscoelastic behavior) was only affected in the nonlinear region at the highest strain-rate, and even this effect was marginal (19% increased loss modulus, p = 0.035). Thus glycosaminoglycan chains of small leucine-rich proteoglycans do not appear to mediate dynamic elastic behavior nor do they appear to regulate the dynamic viscoelastic properties in rat tail tendon fascicles.

Rotational multiphoton endoscopy with a 1 μm fiber laser system

We present multiphoton microendoscopy with a rotational probe and a 1 microm fiber-based femtosecond laser. The rotational probe is based on a double-clad photonic crystal fiber, a gradient index lens, a microprism, and a rotational microelectronicmechanical system (MEMS) motor. The MEMS motor has a diameter of 2.2 mm and can provide 360 degrees full-view rotation. The fiber laser provides ultrashort pulses with a central wavelength at 1.034 microm and a repetition rate of 50 MHz. Second-harmonic-generation images of rat-tail tendon and fish scale are demonstrated with the rotational probe-based multiphoton system.

Structural Insights into the Interactions between Platelet Receptors and Fibrillar Collagen

Collagen peptides have been used to identify binding sites for several important collagen receptors, including integrin alpha(2)beta(1), glycoprotein VI, and von Willebrand factor. In parallel, the structures of these collagen receptors have been reported, and their interactions with collagen peptides have been studied. Recently, the three-dimensional structure of the intact type I collagen fiber from rat tail tendon has been resolved by fiber diffraction. It is now possible to map the binding sites of platelet collagen receptors onto the intact collagen fiber in three dimensions. This minireview will discuss these recent findings and their implications for platelet activation by collagen.

A new procedure for rapid, high yield purification of Type I collagen for tissue engineering

Collagen, which is one of the most abundant proteins in mammalian proteomes, is of significant medical and also biotechnological importance. In tissue engineering, collagen is used as natural matrix to facilitate growth of mammalian cells in 3D-structures. Here, large amounts of highly purified Type I collagen have been obtained from rat tail tendon by a two-step purification, suitable for industrial up-scaling, involving extraction with 9 M urea followed by Superose 12 chromatography. Mass spectrometry identified only collagen Type I peptides indicating that the extracted collagen was homogeneous. Furthermore, a substantial amount of post-translational modifications were identified, including the presence of hydroxylated proline at the X-position in the G-X-Y repeats, which give new insight into collagen structure in vivo. The purified collagen was renatured quantitatively to form triple-helices by dialysis against water, as judged by UV-circular dichroism. This urea-extracted collagen (UC) was tested for its suitability as a matrix for growth of mammalian cells in tissue engineering. Cultures of a fibroblast cell line grown on urea-extracted collagen showed a higher motility and reduced stress levels than those grown on acetic acid-extracted collagen as determined by morphological studies and transcriptional analysis of selected marker genes using real time-PCR. These results indicate the suitability of the urea-extracted collagen obtained for biotechnological applications and tissue engineering.

Scanning all-fiber-optic endomicroscopy system for 3D nonlinear optical imaging of biological tissues

An extremely compact all-fiber-optic scanning endomicroscopy system was developed for two-photon fluorescence (TPF) and second harmonic generation (SHG) imaging of biological samples. A conventional double-clad fiber (DCF) was employed in the endomicroscope for single-mode femtosecond pulse delivery, multimode nonlinear optical signals collection and fast two-dimensional scanning. A single photonic bandgap fiber (PBF) with negative group velocity dispersion at two-photon excitation wavelength (i.e. approximately 810 nm) was used for pulse prechirping in replacement of a bulky grating/lens-based pulse stretcher. The combined use of DCF and PBF in the endomicroscopy system made the endomicroscope basically a plug-and-play unit. The excellent imaging ability of the extremely compact all-fiber-optic nonlinear optical endomicroscopy system was demonstrated by SHG imaging of rat tail tendon and depth-resolved TPF imaging of epithelial tissues stained with acridine orange. The preliminary results suggested the promising potential of this extremely compact all-fiber-optic endomicroscopy system for real-time assessment of both epithelial and stromal structures in luminal organs.

Stabilization of type I collagen using dialdehyde cellulose

Type I collagen from rat tail tendon (RTT) fibres was crosslinked with dialdehyde cellulose to bring about stabilization of the matrix. Dialdehyde cellulose (DAC) was prepared by periodate oxidation of hydrolyzed cellulose. Autoclaving of DAC resulted in hydrolysis and lower molecular weight oligomeric species. The formation of the crosslinked network between DAC and the collagen fibres has brought about significant thermal and enzymatic stability to collagen. DAC crosslinked collagen fibres exhibited an increase in hydrothermal stability by 20 °C with autoclaved DAC at pH 8. The collagen matrix resulted in an increase in denaturation peak temperature ( T D) and an increase in phase change of activation energy ( E a) and enthalpy change (Δ H) for the shinking process indicating intermolecular crosslinking arising from covalent interactions. Thermal stability and crosslinking efficiency was found to increase with pH and concentration of DAC. DAC treated collagen exhibited 93% resistance to collagenolytic hydrolysis.

Deformation-Dependent Enzyme Mechanokinetic Cleavage of Type I Collagen

Collagen is a key structural protein in the extracellular matrix of many tissues. It provides biological tissues with tensile mechanical strength and is enzymatically cleaved by a class of matrix metalloproteinases known as collagenases. Collagen enzymatic kinetics has been well characterized in solubilized, gel, and reconstituted forms. However, limited information exists on enzyme degradation of structurally intact collagen fibers and, more importantly, on the effect of mechanical deformation on collagen cleavage. We studied the degradation of native rat tail tendon fibers by collagenase after the fibers were mechanically elongated to strains of epsilon=1-10%. After the fibers were elongated and the stress was allowed to relax, the fiber was immersed in Clostridium histolyticum collagenase and the decrease in stress (sigma) was monitored as a means of calculating the rate of enzyme cleavage of the fiber. An enzyme mechanokinetic (EMK) relaxation function T(E)(epsilon) in s(-1) was calculated from the linear stress-time response during fiber cleavage, where T(E)(epsilon) corresponds to the zero order Michaelis-Menten enzyme-substrate kinetic response. The EMK relaxation function T(E)(epsilon) was found to decrease with applied strain at a rate of approximately 9% per percent strain, with complete inhibition of collagen cleavage predicted to occur at a strain of approximately 11%. However, comparison of the EMK response (T(E) versus epsilon) to collagen's stress-strain response (sigma versus epsilon) suggested the possibility of three different EMK responses: (1) constant T(E)(epsilon) within the toe region (epsilon<3%), (2) a rapid decrease ( approximately 50%) in the transition of the toe-to-heel region (epsilon congruent with3%) followed by (3) a constant value throughout the heel (epsilon=3-5%) and linear (epsilon=5-10%) regions. This observation suggests that the mechanism for the strain-dependent inhibition of enzyme cleavage of the collagen triple helix may be by a conformational change in the triple helix since the decrease in T(E)(epsilon) appeared concomitant with stretching of the collagen molecule.

Scanning fiber-optic nonlinear endomicroscopy with miniature aspherical compound lens and multimode fiber collector

A flexible scanning fiber-optic endomicroscope using a miniature compound lens and a multimode-fiber (MMF) collector was developed for two-photon fluorescence (TPF) and second-harmonic generation (SHG) imaging. The compound lens consisted of a pair of aspherical lenses and exhibited reduced chromatic aberration compared with gradient-index lenses, thus increasing the TPF/SHG collection efficiency. The introduction of a short MMF collector at the distal end of the double-clad fiber of the endomicroscope further mitigated the adverse influence of chromatic aberration of the lens and enhanced the TPF/SHG collection efficiency. Both ray-tracing simulations and experiments on TPF imaging of fluorescent beads and SHG imaging of rattail tendon demonstrated approximately nine (approximately four) times improved collection efficiency for TPF (SHG) with the new endomicroscope design that utilized a compound lens and an MMF collector.

Robust Pore Size Analysis of Filamentous Networks from 3D Confocal Microscopy

We describe a robust method for determining morphological properties of filamentous biopolymer networks, such as collagen or other connective tissue matrices, from confocal microscopy image stacks. Morphological properties including pore size distributions and percolation thresholds are important for transport processes, e.g. particle diffusion or cell migration through the extracellular matrix. The method is applied to fluorescently labeled fiber networks prepared from rat tail tendon and calf skin collagen, at concentrations of 1.2, 1.6 and 2.4 mg/ml. The collagen fibers form an entangled and branched network. The medial axes, or skeletons, representing the collagen fibers are extracted from the image stack by threshold intensity segmentation and distance-ordered homotopic thinning. The size of the fluid pores as defined by the radii of largest spheres that fit into the cavities between the collagen fibers is derived from Euclidean distance daps and maximal covering radius transforms of the fluid phase. The size of the largest sphere that can traverse the fluid phase between the collagen fibers across the entire probe, called the percolation threshold, was computed for both horizontal and vertical directions. We demonstrate that by representing the fibers as the medial axis the derived morphological network properties are both robust against changes of the value of the segmentation threshold intensity and robust to problems associated with the point-spread function of the imaging system. We also provide empirical support for a recent claim that the percolation threshold of a fiber network equals the fiber diameter for which the Euler index of the networks becomes zero.

An engineering, multiscale constitutive model for fiber‐forming collagen in tension

This work proposes a nonlinear constitutive model for a single collagen fiber. Fiber-forming collagen can exhibit different hierarchies of basic units, called fascicles, bundles, fibrils, microfibrils, and so forth, down to the molecular (tropocollagen) level. Exploiting the fact that at each hierarchy level the microstructure can be seen, at least approximately, as that of a wavy, or crimped, extensible cable, the proposed stress-strain model considers a given number of levels, each of which contributes to the overall mechanical behavior according to its own geometrical features (crimp, or waviness), as well as to the basic mechanical properties of the tropocollagen. The crimp features at all levels are assumed to be random variables, whose statistical integration furnishes a stress-strain curve for a collagen fiber. The soundness of this model-the first, to the Authors' knowledge, to treat a single collagen fiber as a microstructured nonlinear structural element-is checked by its application to collagen fibers for which experimental results are available: rat tail tendon, periodontal ligament, and engineered ones. Here, no attempt is made to obtain a stress-strain law for generic collagenous tissues, which exhibit specific features, often much more complex than those of a single fiber. However, it is trivial to observe that the availability of a sound, microstructurally based constitutive law for a single collagen fiber (but applicable at any sub-level, or to any other material with a similar microstructure) is essential for assembling complex constitutive models for any collagenous fibrous tissue.

Constitutive modeling of crimped collagen fibrils in soft tissues

A microstructurally oriented constitutive formulation for the hyperelastic response of crimped collagen fibrils existing in soft connective tissues is proposed. The model is based on observations that collagen fibrils embedded in a soft matrix crimp into a smooth three-dimensional pattern when unloaded. Following ideas presented by Beskos and Jenkins [Beskos, D., Jenkins, J., 1975. A mechanical model for mammalian tendon. ASME Journal of Applied Mechanics 42, 755–758] and Freed and Doehring [Freed, A., Doehring, T., 2005. Elastic model for crimped collagen fibrils. Journal of Biomechanical Engineering 127, 587–593] the collagen fibril crimp is approximated by a cylindrical helix to represent the constitutive behavior of the hierarchical organized substructure of biological tissues at the fibrillar level. The model is derived from the nonlinear axial force–stretch relationship of an extensible helical spring, including the full extension of the spring as a limit case. The geometrically nonlinear solution of the extensible helical spring is carried out by an iterative procedure. The model only requires one material parameter and two geometrical parameters to be determined from experiments. The ability of the proposed model to reproduce the biomechanical response of fibrous tissues is demonstrated for fascicles from rat tail tendons, for porcine cornea strips, and for bovine Achilles tendons.