Soft tissue

Micrograph of a piece of soft tissue (tendon). H&E stain.

In anatomy, soft tissue includes the tissues that connect, support, or surround other structures and organs of the body, not being hard tissue such as bone. Soft tissue includes tendons, ligaments, fascia, skin, fibrous tissues, fat, and synovial membranes (which are connective tissue), and muscles, nerves and blood vessels (which are not connective tissue).^[1]

It is sometimes defined by what it is not. Soft tissue has been defined as "nonepithelial, extraskeletal mesenchyme exclusive of the reticuloendothelial system and glia".^[2]

Composition

The characteristic substances inside the extracellular matrix of this kind of tissue are the collagen, elastin and ground substance. Normally the soft tissue is very hydrated because of the ground substance. The fibroblasts are the most common cell responsible for the production of soft tissues' fibers and ground substance. Variations of fibroblasts, like chondroblasts, may also produce these substances.^[3]

Mechanical characteristics

At small strains, elastin confers stiffness to the tissue and stores most of the strain energy. The collagen fibers are comparatively inextensible and are usually loose (wavy, crimped). With increasing tissue deformation the collagen is gradually stretched in the direction of deformation. When taut, these fibers produce a strong growth in tissue stiffness. The composite behavior is analogous to a nylon stocking, whose rubber band does the role of elastin as the nylon does the role of collagen. In soft tissues the collagen limits the deformation and protects the tissues from injury.

Human soft tissue is highly deformable, and its mechanical properties vary significantly from one person to another. Impact testing results showed that the stiffness and the damping resistance of a test subject’s tissue are correlated with the mass, velocity, and size of the striking object. Such properties may be useful for forensics investigation when contusions were induced.^[4] When solid object impact a human soft tissues, the energy of the impact will be absorbed by the tissues to reducing effect of the impact or the pain level, therefore; subjects with more soft tissue thickness tended to absorb the impacts with less aversion.^[5]

Graph of lagrangian stress (T) versus stretch ratio (λ) of a preconditioned soft tissue.

Soft tissues have the potential to undergo big deformations and still come back to the initial configuration when unloaded, i.e. their stress-strain curve is nonlinear. The soft tissues are also viscoelastic, incompressible and usually anisotropic. Some viscoelastic properties observable in soft tissues are: relaxation, creep and hysteresis.^[6]^[7] In order to describe the mechanical response of soft tissues, several methods have been used. These methods include: hyperelastic macroscopic models based on strain energy, mathematical fits where nonlinear constitutive equations are used, and structurally based models where the response of a linear elastic material is modified by its geometric characteristics.^[8]

Pseudoelasticity

Even though soft tissues have viscoelastic properties, i.e. stress as function of strain rate, it can be approximated by a hyperelastic model after precondition to a load pattern. After some cycles of loading and unloading the material, the mechanical response becomes independent of strain rate.

{\mathbf {S}}={\mathbf {S}}({\mathbf {E}},{\dot {{\mathbf {E}}}})\quad \rightarrow \quad {\mathbf {S}}={\mathbf {S}}({\mathbf {E}})

Despite the independence of strain rate, preconditioned soft tissues still present hysteresis, so the mechanical response can be modeled as hyperelastic with different material constants at loading and unloading. By this method the elasticity theory is used to model an inelastic material. Fung has called this model as pseudoelastic to point out that the material is not truly elastic.^[7]

Residual stress

In physiological state soft tissues usually present residual stress that may be released when the tissue is excised. Physiologists and histologists must be aware of this fact to avoid mistakes when analyzing excised tissues. This retraction usually causes a visual artifact.^[7]

Fung-elastic material

Fung developed a constitutive equation for preconditioned soft tissues which is

W={\frac {1}{2}}\left[q+c\left(e^{Q}-1\right)\right]

with

q=a_{{ijkl}}E_{{ij}}E_{{kl}}\qquad Q=b_{{ijkl}}E_{{ij}}E_{{kl}}

quadratic forms of Green-Lagrange strains $E_{{ij}}$ and $a_{{ijkl}}$ , $b_{{ijkl}}$ and $c$ material constants.^[7] $W$ is the strain energy function per volume unit, which is the mechanical strain energy for a given temperature.

Isotropic simplification

The Fung-model, simplified with isotropic hypothesis (same mechanical properties in all directions). This written in respect of the principal stretches ( $\lambda _{i}$ ):

W={\frac {1}{2}}\left[a(\lambda _{1}^{2}+\lambda _{2}^{2}+\lambda _{3}^{2}-3)+b\left(e^{{c(\lambda _{1}^{2}+\lambda _{2}^{2}+\lambda _{3}^{2}-3)}}-1\right)\right]

where a, b and c are constants.

Simplification for small and big stretches

For small strains, the exponential term is very small, thus negligible.

W={\frac {1}{2}}a_{{ijkl}}E_{{ij}}E_{{kl}}

On the other hand, the linear term is negligible when the analysis rely only on big strains.

W={\frac {1}{2}}c\left(e^{{b_{{ijkl}}E_{{ij}}E_{{kl}}}}-1\right)

Gent-elastic material

W=-{\frac {\mu J_{m}}{2}}\ln \left(1-\left({\frac {\lambda _{1}^{2}+\lambda _{2}^{2}+\lambda _{3}^{2}-3}{J_{m}}}\right)\right)

where $\mu >0$ is the shear modulus for infinitesimal strains and $J_{m}>0$ is a stiffening parameter, associated with limiting chain extensibility.^[9] This constitutive model cannot be stretched in uni-axial tension beyond a maximal stretch $J_{m}$ , which is the positive root of

\lambda _{m}^{2}+2\lambda _{m}-J_{m}-3=0

Remodeling and growth

Soft tissues have the potential to grow and remodel reacting to chemical and mechanical long term changes. The rate the fibroblasts produce tropocollagen is proportional to these stimuli. Diseases, injuries and changes in the level of mechanical load may induce remodeling. An example of this phenomenon is the thickening of farmer's hands. The remodeling of connective tissues is well known in bones by the Wolff's law (bone remodeling). Mechanobiology is the science that study the relation between stress and growth at cellular level.^[6]

Growth and remodeling have a major role in the cause of some common soft tissue diseases, like arterial stenosis and aneurisms ^[10]^[11] and any soft tissue fibrosis. Other instance of tissue remodeling is the thickening of the cardiac muscle in response to the growth of blood pressure detected by the arterial wall.

Imaging techniques

There are certain issues that have to be kept in mind when choosing an imaging technique for visualizing soft tissue ECM components. The accuracy of the image analysis relies on the properties and the quality of the raw data and, therefore, the choice of the imaging technique must be based upon issues such as:

Having an optimal resolution for the components of interest;
Achieving high contrast of those components;
Keeping the artifact count low;
Having the option of volume data acquisition;
Keeping the data volume low;
Establishing an easy and reproducible setup for tissue analysis.

The collagen fibers are approximately 1-2 μm thick. Thus, the resolution of the imaging technique needs to be approximately 0.5 μm. Some techniques allow the direct acquisition of volume data while other need the slicing of the specimen. In both cases, the volume that is extracted must be able to follow the fiber bundles across the volume. High contrast makes segmentation easier, especially when color information is available. In addition, the need for fixation must also be addressed. It has been shown that soft tissue fixation in formalin causes shrinkage, altering the structure of the original tissue. Some typical values of contraction for different fixation are: formalin (5% - 10%), alcohol (10%), bouin (<5%).^[12]

Imaging methods used in ECM visualization and their properties.^[12]^[13]

	Transmission Light	Confocal	Multi-Photon Excitation Fluorescence	Second Harmonic Generation	Optical Coherence Tomography
Resolution	0.25 μm	Axial: 0.25-0.5 μm Lateral: 1 μm	Axial: 0.5 μm Lateral: 1 μm	Axial: 0.5 μm Lateral: 1 μm	Axial: 3-15 μm Lateral: 1-15 μm
Contrast	Very High	Low	High	High	Moderate
Penetration	N/A	10 μm-300 μm	100-1000 μm	100-1000 μm	Up to 2–3 mm
Image stack cost	High	Low	Low	Low	Low
Fixation	Required	Required	Not required	Not required	Not required
Embedding	Required	Required	Not required	Not required	Not required
Staining	Required	Not required	Not required	Not required	Not required
Cost	Low	Moderate to high	High	High	Moderate

References

↑ Definition at National Cancer Institute
↑ Skinner, Harry B. (2006). Current diagnosis & treatment in orthopedics. Stamford, Conn: Lange Medical Books/McGraw Hill. p. 346. ISBN 0-07-143833-5.
↑ Junqueira, L.C.U.; Carneiro, J.; Gratzl, M. (2005). Histologie. Heidelberg: Springer Medizin Verlag. p. 479. ISBN 3-540-21965-X.
↑ Amar, M., Alkhaledi, K., and Cochran, D., (2014). Estimation of mechanical properties of soft tissue subjected to dynamic impact. Journal of Eng. Research Vol. 2 (4), pp. 87-101
↑ Alkhaledi, K., Cochran, D., Riley, M., Bashford, G., and Meyer, G. (2011). The psycophysical effects of physical impact to human soft tissue. ECCE '11 Proceedings of the 29th Annual European Conference on Cognitive Ergonomics Pages 269-270
1 2 Humphrey, Jay D. (2003). The Royal Society, ed. "Continuum biomechanics of soft biological tissues" (PDF). Proceedings of the Royal Society of London A. 459 (2029): 3–46. Bibcode:2003RSPSA.459....3H. doi:10.1098/rspa.2002.1060.
1 2 3 4 Fung, Y.-C. (1993). Biomechanics: Mechanical Properties of Living Tissues. New York: Springer-Verlag. p. 568. ISBN 0-387-97947-6.
↑ Sherman, Vincent R. (2015). "The materials science of collagen". Journal of the Mechanical Behavior of Biomedical Materials. 52: 22–50. PMID 26144973. doi:10.1016/j.jmbbm.2015.05.023.
↑ Gent, A. N. (1996). "A new constitutive relation for rubber". Rub. Chem. Tech. 69: 59–61. doi:10.5254/1.3538357.
↑ Humphrey, Jay D. (2008). Springer-Verlag, ed. "Vascular adaptation and mechanical homeostasis at tissue, cellular, and sub-cellular levels". Cell Biochemistry and Biophysics. 50 (2): 53–78. PMID 18209957. doi:10.1007/s12013-007-9002-3.
↑ Holzapfel, G.A.; Ogden, R.W. (2010). The Royal Society, ed. "Constitutive modelling of arteries". Proceedings of the Royal Society of London A. 466 (2118): 1551–1597. Bibcode:2010RSPSA.466.1551H. doi:10.1098/rspa.2010.0058.
1 2 Elbischger Pierre J; Bischof Horst; Holzapfel Gerhard A; Regitnig Peter (2005). "Computer vision analysis of collagen fiber bundles in the adventitia of human blood vessels". Studies in health technology and informatics. 113: 97–129. PMID 15923739. Missing |last3= in Authors list (help); Missing |last5= in Authors list (help)
↑ Georgakoudi Irene; Rice William L; Hronik-Tupaj Marie; Kaplan David L (2008). "Optical Spectroscopy and Imaging for the Noninvasive Evaluation of Engineered Tissues". Tissue Engineering Part B: Reviews.

Connective tissue

Physiology

Composition

Cells

Resident	Fibroblast Fibrocyte Reticular cell Tendon cell Adipocyte Melanocyte
Wandering cells	Mast cell Macrophage

Extracellular
matrix

Ground substance	Tissue fluid
Fibers	Collagen fibers Reticular fibers: COL3A1 Elastic fibers: Elastin Fibrillin FBN1 FBN2 FBN3 EMILIN1 Elaunin

Classification

Proper

Loose	Reticular Adipose Brown White
Dense	Dense irregular connective tissue Submucosa Dermis Dense regular connective tissue Ligament Tendon Aponeurosis

Embryonic

Specialized

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Soft tissue

Composition

Mechanical characteristics

Pseudoelasticity

Residual stress

Fung-elastic material

Isotropic simplification

Simplification for small and big stretches

Gent-elastic material

Remodeling and growth

Imaging techniques

See also

References