Editing Soft tissue

{{Short description|Tissue in the body that is not hardened by ossification}}
[[Image:Tendon - add - high mag.jpg|thumb|[[Micrograph]] of a [[tendon]]. [[H&E stain|Hematoxylin and eosin stain]].]]
'''Soft tissue''' [[connective tissue|connects]] and surrounds or supports internal organs and bones, and includes [[muscle]], [[tendon]]s, [[ligament]]s, [[Adipose tissue|fat]], [[fibrous tissue]], [[Lymphatic vessel|lymph]] and [[blood vessel]]s, [[fascia]]e, and [[synovial membrane]]s.<ref name="Dict"/><ref "name=Cancer">{{cite web | url = https://www.cancer.gov/publications/dictionaries/cancer-terms/def/soft-tissue | title = Soft Tissue | work =  NCI Dictionaries | publisher = at [[National Cancer Institute]] }}</ref> Soft tissue is [[Tissue (biology)|tissue]] in the body that is not [[hard tissue|hardened]] by the processes of [[ossification]] or [[calcification]] such as [[bone]]s and [[teeth]].<ref name="Dict">{{cite web |title=Soft tissue |url=https://www.merriam-webster.com/medical/soft%20tissue |access-date=13 July 2020}}</ref>

It is sometimes defined by what it is not – such as "nonepithelial, extraskeletal [[mesenchyme]] exclusive of the [[reticuloendothelial]] system and [[glia]]".<ref name="isbn0-07-143833-5">{{cite book | vauthors = Skinner HB |title=Current diagnosis & treatment in orthopedics |publisher=Lange Medical Books/McGraw Hill |location=Stamford, Conn |year=2006 |page=346  |isbn=0-07-143833-5 }}</ref>

== Composition ==
The characteristic substances inside the [[extracellular matrix]] of soft 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.<ref name="Junqueira">{{cite book | vauthors = Junqueira LC, Carneiro J, Gratzl M |title=Histologie|publisher=Springer Medizin Verlag |location=Heidelberg|year=2005|page= 479|isbn=3-540-21965-X}}</ref>

== Mechanical characteristics ==
At small [[Deformation (mechanics)|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 material|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.<ref>{{cite journal | vauthors = Amar M, Alkhaledi K, Cochran D |title=Estimation of mechanical properties of soft tissue subjected to dynamic impact |journal=Journal of Engineering Research |date=2014 |volume=2 |issue=4 |doi=10.7603/s40632-014-0026-8|pages=87–101|doi-access=free }}</ref> When a solid object impacts a human soft tissue, the energy of the impact will be absorbed by the tissues to reduce the effect of the impact or the pain level; subjects with more soft tissue thickness tended to absorb the impacts with less aversion.<ref>{{cite book | vauthors = Alkhaledi K, Cochran D, Riley M, Stentz T, Bashford G, Meyer G | title = Proceedings of the 29th Annual European Conference on Cognitive Ergonomics | chapter = The psycophysical effects of physical impact to human soft tissue | date = August 2011 | pages = 269–270 | doi = 10.1145/2074712.2074774 | isbn = 9781450310291 | s2cid = 34428866 }}</ref>

[[Image:Pseudoelastic response (stress vs stretch ratio).png|300px|right|thumb|Graph of [[Stress (mechanics)#Euler-Cauchy's stress principle|lagrangian stress]] (T) versus [[Strain (materials science)|stretch ratio]] (λ) of a preconditioned soft tissue]]
Soft tissues have the potential to undergo large deformations and still return to the initial configuration when unloaded, i.e. they are [[hyperelastic material]]s, and their [[stress-strain curve]] is [[nonlinear]]. The soft tissues are also [[viscoelastic]], [[Incompressible flow|incompressible]] and usually [[anisotropic]]. Some viscoelastic properties observable in soft tissues are: [[Relaxation (physics)|relaxation]], [[Creep (deformation)|creep]] and [[hysteresis]].<ref name="Humphrey">{{cite journal | vauthors = Humphrey JD |title=Continuum biomechanics of soft biological tissues |journal=Proceedings of the Royal Society of London A |year=2003|volume=459 |pages=3–46|doi=10.1098/rspa.2002.1060|bibcode=2003RSPSA.459....3H|issue=2029|s2cid=108637580 }}</ref><ref name="Fung">{{cite book | vauthors = Fung YC |title=Biomechanics: Mechanical Properties of Living Tissues|publisher=Springer-Verlag |location=New York|year=1993|page= 568|isbn=0-387-97947-6}}</ref> 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.<ref>{{cite journal | vauthors = Sherman VR, Yang W, Meyers MA | title = The materials science of collagen | journal = Journal of the Mechanical Behavior of Biomedical Materials | volume = 52 | pages = 22–50 | date = December 2015 | pmid = 26144973 | doi = 10.1016/j.jmbbm.2015.05.023 | doi-access = free }}</ref>

=== Pseudoelasticity ===
Even though soft tissues have viscoelastic properties, i.e. stress as function of strain rate, it can be approximated by a [[Hyperelastic material|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.
:<math>\mathbf{S}=\mathbf{S}(\mathbf{E},\dot{\mathbf{E}}) \quad\rightarrow\quad \mathbf{S}=\mathbf{S}(\mathbf{E})</math>

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.<ref name="Fung"/>

=== Residual stress ===
In physiological state soft tissues usually present [[residual stress]] that may be released when the tissue is [[Surgery|excised]]. [[Physiologists]] and [[histologists]] must be aware of this fact to avoid mistakes when analyzing excised tissues. This retraction usually causes a [[visual artifact]].<ref name="Fung"/>

=== Fung-elastic material ===
[[Yuan-Cheng Fung|Fung]] developed a [[constitutive equation]] for preconditioned soft tissues which is 
:<math>W = \frac{1}{2}\left[q + c\left( e^Q -1 \right) \right]</math>
with
:<math>q=a_{ijkl}E_{ij}E_{kl} \qquad Q=b_{ijkl}E_{ij}E_{kl}</math>
quadratic forms of [[strain (mechanics)|Green-Lagrange strains]] <math>E_{ij}</math> and <math>a_{ijkl}</math>, <math>b_{ijkl}</math> and <math>c</math> material constants.<ref name="Fung"/> <math>W</math> is the [[Strain energy density function|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 (<math>\lambda_i</math>):
:<math>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]</math> , 
where a, b and c are constants.

==== Simplification for small and big stretches ====
For small strains, the exponential term is very small, thus negligible.
:<math>W = \frac{1}{2}a_{ijkl}E_{ij}E_{kl}</math>

On the other hand, the linear term is negligible when the analysis rely only on big strains.
:<math>W = \frac{1}{2}c\left( e^{b_{ijkl}E_{ij}E_{kl}} -1 \right)</math>

=== Gent-elastic material ===
{{Further|Gent (hyperelastic model)}}
:<math>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)</math>

where <math>\mu > 0</math> is the shear modulus for infinitesimal strains and <math>J_m > 0</math> is a stiffening parameter, associated with limiting chain extensibility.<ref>{{cite journal| vauthors = Gent AN |title=A new constitutive relation for rubber|journal=Rubber Chem. Technol.|year=1996|volume=69|pages=59–61|doi=10.5254/1.3538357}}</ref> This constitutive model cannot be stretched in uni-axial tension beyond a maximal stretch <math>J_m</math>, which is the positive root of

:<math>\lambda_m^2 + 2\lambda_m - J_m - 3 = 1 </math>

== 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 [[collagen#Molecular structure|tropocollagen]] is proportional to these stimuli. Diseases, injuries and changes in the level of mechanical load may induce remodeling.<ref>{{cite journal | vauthors = Saini K, Cho S, Dooling LJ, Discher DE | title = Tension in fibrils suppresses their enzymatic degradation - A molecular mechanism for 'use it or lose it' | journal = Matrix Biology | volume = 85-86 | pages = 34–46 | date = January 2020 | pmid = 31201857 | pmc = 6906264 | doi = 10.1016/j.matbio.2019.06.001 | series = Matrix Biomechanics }}</ref><ref>{{Cite journal | vauthors = Topol H, Demirkoparan H, Pence TJ |date=2021-09-01 |title=Fibrillar Collagen: A Review of the Mechanical Modeling of Strain-Mediated Enzymatic Turnover |url=https://doi.org/10.1115/1.4052752 |journal=Applied Mechanics Reviews |volume=73 |issue=5 |page=050802 |doi=10.1115/1.4052752 |bibcode=2021ApMRv..73e0802T |s2cid=244582251 |issn=0003-6900|url-access=subscription }}</ref> 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.<ref name="Humphrey"/>

Growth and remodeling have a major role in the cause of some common soft tissue diseases, like arterial [[stenosis]] and [[aneurisms]]<ref name="Humphrey2">{{cite journal | vauthors = Humphrey JD | title = Vascular adaptation and mechanical homeostasis at tissue, cellular, and sub-cellular levels | journal = Cell Biochemistry and Biophysics | volume = 50 | issue = 2 | pages = 53–78 | year = 2008 | pmid = 18209957 | doi = 10.1007/s12013-007-9002-3 | publisher = Springer-Verlag | s2cid = 25942366 }}</ref><ref name="Holzapfel_Ogden">{{cite journal | vauthors = Holzapfel GA, Ogden RW |title=Constitutive modelling of arteries |journal=Proceedings of the Royal Society of London A| publisher = The Royal Society|year=2010|volume=466 |pages=1551–1597|doi=10.1098/rspa.2010.0058 |issue=2118|bibcode = 2010RSPSA.466.1551H |doi-access=free }}</ref> 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 [[artery|arterial]] wall.

== Imaging techniques ==
There are certain issues that have to be kept in mind when choosing an imaging technique for visualizing soft tissue [[extracellular matrix]] (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 [[Image segmentation|segmentation]] easier, especially when color information is available. In addition, the need for [[Fixation (histology)|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%), [[ethanol|alcohol]] (10%), [[bouin solution|bouin]] (<5%).<ref name=":0">{{cite journal | vauthors = Elbischger PJ, Bischof H, Holzapfel GA, Regitnig P | title = Computer vision analysis of collagen fiber bundles in the adventitia of human blood vessels | journal = Studies in Health Technology and Informatics | volume = 113 | pages = 97–129 | year = 2005 | pmid = 15923739 }}</ref>

Imaging methods used in [[Extracellular matrix|ECM]] visualization and their properties.<ref name=":0" /><ref>{{cite journal | vauthors = Georgakoudi I, Rice WL, Hronik-Tupaj M, Kaplan DL |author4-link=David L. Kaplan (engineering) | title = Optical spectroscopy and imaging for the noninvasive evaluation of engineered tissues | journal = Tissue Engineering. Part B, Reviews | volume = 14 | issue = 4 | pages = 321–340 | date = December 2008 | pmid = 18844604 | pmc = 2817652 | doi = 10.1089/ten.teb.2008.0248 }}</ref>

{| class="wikitable"
 
  |  
  
  |
'''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&nbsp;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   
 
|}

==Clinical significance==
'''Soft tissue disorders''' are medical conditions affecting soft tissue. [[Soft tissue injuries]] are some of the most chronically painful and difficult conditions to treat because it is very difficult to see what is going on under the skin with the soft connective tissues, fascia, joints, muscles and tendons.{{Citation needed|date=May 2024}}

Musculoskeletal specialists, manual therapists, neuromuscular physiologists and neurologists specialize in treating injuries and ailments in the soft tissue areas of the body. These specialized clinicians often develop innovative ways to manipulate the soft tissue to speed natural healing and relieve the mysterious pain that often accompanies soft tissue injuries. This area of expertise has become known as [[soft tissue therapy]] and is rapidly expanding as technology continues to improve the ability of these specialists to identify problem areas.{{Citation needed|date=May 2024}}

A promising new method of treating wounds and soft tissue injuries is via [[platelet-derived growth factor]].<ref>{{cite journal | vauthors = Rozman P, Bolta Z | title = Use of platelet growth factors in treating wounds and soft-tissue injuries | journal = Acta Dermatovenerologica Alpina, Pannonica, et Adriatica | volume = 16 | issue = 4 | pages = 156–165 | date = December 2007 | pmid = 18204746 }}</ref>

There is a close overlap between the term "soft tissue disorder" and [[rheumatism]]. Sometimes the term "soft tissue rheumatic disorders" is used to describe these conditions.<ref name="urlOverview of soft tissue rheumatic disorders">{{Cite web | vauthors = Meleger AL | date =  June 2022 | veditors = Isaac Z, Case SM |url=http://www.uptodate.com/patients/content/topic.do?topicKey=~ctAVYKgfORUJle |title=Overview of soft tissue rheumatic disorders | work = UpToDate }}</ref>

[[Soft tissue sarcoma]]s are many types of [[cancer]] that can develop in the soft tissues.

== See also ==
* [[Biomaterial]]
* [[Biomechanics]]
* [[Davis's law]]
* [[Rheology]]

== References ==
{{Reflist}}

== External links ==
*{{Commons category-inline}}

{{Connective tissue}}
{{Soft tissue disorders}}
{{Authority control}}

{{DEFAULTSORT:Soft Tissue}}
[[Category:Soft tissue| ]]
[[Category:Biomechanics]]
[[Category:Tissues (biology)]]
[[Category:Continuum mechanics]]