Editing Cartilage (section)

== Function ==
=== Mechanical properties ===
The mechanical properties of articular cartilage in load-bearing joints such as the [[knee]] and [[hip]] have been studied extensively at macro, micro, and nano-scales. These mechanical properties include the response of cartilage in frictional, compressive, shear and tensile loading. Cartilage is resilient and displays [[Viscoelasticity|viscoelastic]] properties.<ref name="pmid5111002">{{cite journal | vauthors = Hayes WC, Mockros LF | title = Viscoelastic properties of human articular cartilage | journal = Journal of Applied Physiology | volume = 31 | issue = 4 | pages = 562–8 | date = October 1971 | pmid = 5111002 | doi = 10.1152/jappl.1971.31.4.562 | url = http://jap.physiology.org/content/31/4/562.full.pdf }}</ref>

Since cartilage has interstitial fluid that is free-moving, it makes the material difficult to test. One of the tests commonly used to overcome this obstacle is a confined compression test, which can be used in either a 'creep' or 'relaxation' mode.<ref name="mansour2013">{{cite book | last=Mansour | first=J. M. | date=2013 | title=Biomechanics of Cartilage | pages=69–83}}</ref><ref name="patel2019">{{cite journal |last1=Patel |first1=J. M. |last2=Wise |first2=B. C. |last3=Bonnevie |first3=E. D. |last4=Mauck |first4=R. L. |date=2019 |title=A Systematic Review and Guide to Mechanical Testing for Articular Cartilage Tissue Engineering |url=https://doi.org/10.1089/ten.tec.2019.0116 |journal=Tissue Eng Part C Methods |volume=25 |issue=10 |pages=593–608|doi=10.1089/ten.tec.2019.0116 |pmid=31288616 |pmc=6791482 }}</ref> In creep mode, the tissue displacement is measured as a function of time under a constant load, and in relaxation mode, the force is measured as a function of time under constant displacement. During this mode, the deformation of the tissue has two main regions. In the first region, the displacement is rapid due to the initial flow of fluid out of the cartilage, and in the second region, the displacement slows down to an eventual constant equilibrium value. Under the commonly used loading conditions, the equilibrium displacement can take hours to reach.

In both the creep mode and the relaxation mode of a confined compression test, a disc of cartilage is placed in an impervious, fluid-filled container and covered with a porous plate that restricts the flow of interstitial fluid to the vertical direction. This test can be used to measure the aggregate modulus of cartilage, which is typically in the range of 0.5 to 0.9 MPa for articular cartilage,<ref name="mansour2013"></ref><ref name="patel2019"></ref><ref name="korhonen2002">{{cite journal |last1=Korhonen |first1=R. K. |last2=Laasanen |first2=M. S. |last3=Töyräs |first3=J. |last4=Rieppo |first4=J. |last5=Hirvonen |first5=J. |last6=Helminen |first6=H. J. |last7=Jurvelin |first7=J. S. |date=2002 |title=Comparison of the Equilibrium Response of Articular Cartilage in Unconfined Compression, Confined Compression and Indentation |url=https://doi.org/10.1016/S0021-9290(02)00052-0 |journal=Journal of Biomechanics |volume=35 |issue=7 |pages=903–909|doi=10.1016/S0021-9290(02)00052-0 |pmid=12052392 |url-access=subscription }}</ref> and the Young’s Modulus, which is typically 0.45 to 0.80 MPa.<ref name="mansour2013"></ref><ref name="korhonen2002"></ref> The aggregate modulus is "a measure of the stiffness of the tissue at equilibrium when all fluid flow has ceased",<ref name="mansour2013"></ref> and Young’s modulus is a measure of how much a material strains (changes length) under a given stress.

The confined compression test can also be used to measure permeability, which is defined as the resistance to fluid flow through a material. Higher permeability allows for fluid to flow out of a material’s matrix more rapidly, while lower permeability leads to an initial rapid fluid flow and a slow decrease to equilibrium. Typically, the permeability of articular cartilage is in the range of 10^-15 to 10^-16 m^4/Ns.<ref name="mansour2013"></ref><ref name="patel2019"></ref> However, permeability is sensitive to loading conditions and testing location. For example, permeability varies throughout articular cartilage and tends to be highest near the joint surface and lowest near the bone (or "deep zone"). Permeability also decreases under increased loading of the tissue.

Indentation testing is an additional type of test commonly used to characterize cartilage.<ref name="mansour2013"></ref><ref name="kabir2021">{{cite journal |last1=Kabir |first1=W. |last2=Di Bella |first2=C. |last3=Choong |first3=P. F. M. |last4=O’Connell |first4=C. D. |date=2021 |title=Assessment of Native Human Articular Cartilage: A Biomechanical Protocol |url=https://doi.org/10.1177/1947603520973240 |journal=Cartilage |volume=13 |issue=2 Suppl |pages=427S–437S|doi=10.1177/1947603520973240 |pmid=33218275 |pmc=8804788 }}</ref> Indentation testing involves using an indentor (usually <0.8 mm) to measure the displacement of the tissue under constant load. Similar to confined compression testing, it may take hours to reach equilibrium displacement. This method of testing can be used to measure the aggregate modulus, Poisson's ratio, and permeability of the tissue. Initially, there was a misconception that due to its predominantly water-based composition, cartilage had a Poisson's ratio of 0.5 and should be modeled as an incompressible material.<ref name="mansour2013"></ref> However, subsequent research has disproven this belief. The Poisson’s ratio of articular cartilage has been measured to be around 0.4 or lower in humans <ref name="mansour2013"></ref><ref name="kabir2021"></ref> and ranges from 0.46–0.5 in bovine subjects.<ref name="jin2004">{{cite journal |last1=Jin |first1=H. |last2=Lewis |first2=J. L. |date=2004 |title=Determination of Poisson's Ratio of Articular Cartilage by Indentation Using Different-Sized Indenters |url=https://doi.org/10.1115/1.1688772 |journal=Journal of Biomechanical Engineering |volume=126 |issue=2 |pages=138–145|doi=10.1115/1.1688772 |pmid=15179843 |url-access=subscription }}</ref> 

The mechanical properties of articular cartilage are largely anisotropic, test-dependent, and can be age-dependent.<ref name="mansour2013"></ref> These properties also depend on collagen-proteoglycan interactions and therefore can increase/decrease depending on the total content of water, collagen, glycoproteins, etc. For example, increased glucosaminoglycan content leads to an increase in compressive stiffness, and increased water content leads to a lower aggregate modulus.

=== Tendon-bone interface ===
In addition to its role in load-bearing joints, cartilage serves a crucial function as a gradient material between softer tissues and bone. Mechanical gradients are crucial for your body’s function, and for complex artificial structures including joint implants. Interfaces with mismatched material properties lead to areas of high [[stress concentration]] which, over the millions of loading cycles experienced by human joins over a lifetime, would eventually lead to failure. For example, the elastic modulus of human bone is roughly 20 GPa while the softer regions of cartilage can be about 0.5 to 0.9 MPa. <ref>{{cite journal |last1=Handorf |first1=Andrew |title=Tissue Stiffness Dictates Development, Homeostasis, and Disease Progression |journal=Organogensis |date=27 April 2015 |volume=11 |issue=1 |pages=1–15 |doi=10.1080/15476278.2015.1019687 |pmid=25915734 |pmc=4594591 }}</ref><ref>{{cite book |last1=Mansour |first1=Joseph |title=Biomechanics of Cartilage |publisher=MDPI |pages=66–79 |url=https://web.mit.edu/cortiz/www/3.052/3.052CourseReader/27_BiomechanicsofCartilage.pdf}}</ref> When there is a smooth gradient of materials properties, however, stresses are distributed evenly across the interface, which puts less wear on each individual part. 

The body solves this problem with stiffer, higher modulus layers near bone, with high concentrations of mineral deposits such as hydroxyapatite. Collagen fibers (which provide mechanical stiffness in cartilage) in this region are anchored directly to bones, reducing the possible deformation. Moving closer to soft tissue into the region known as the tidemark, the density of [[chondrocytes]] increases and collagen fibers are rearranged to optimize for stress dissipation and low friction. The outermost layer near the articular surface is known as the superficial zone, which primarily serves as a lubrication region. Here cartilage is characterized by a dense extracellular matrix and is rich in proteoglycans (which dispel and reabsorb water to soften impacts) and thin collagen oriented parallel to the joint surface which have excellent shear resistant properties. <ref>{{cite journal |last1=Chen |first1=Li |title=Preparation and Characterization of Biomimetic Functional Scaffold with Gradient Structure for Osteochondral Defect Repair |journal=Bioengineering |date=6 February 2023 |volume=10 |issue=2 |page=213 |doi=10.3390/bioengineering10020213 |doi-access=free |pmid=36829707 |pmc=9952804 }}</ref> 

Osteoarthritis and natural aging both have negative effects on cartilage as a whole as well as the proper function of the materials gradient within. The earliest changes are often in the superficial zone, the softest and most lubricating part of the tissue. Degradation of this layer can put additional stresses on deeper layers which are not designed to support the same deformations. Another common effect of aging is increased crosslinking of collagen fibers. This leads to stiffer cartilage as a whole, which again can lead to early failure as stiffer tissue is more susceptible to fatigue based failure. Aging in calcified regions also generally leads to a larger number of mineral deposits, which has a similarly undesired stiffening effect. <ref>{{cite journal |last1=Lotz |first1=Martin |title=Effects of aging on articular cartilage homeostasis |journal=Bone |date=28 March 2012 |volume=51 |issue=2 |pages=241–248 |doi=10.1016/j.bone.2012.03.023 |pmid=22487298 |pmc=3372644 }}</ref> Osteoarthritis has more extreme effects and can entirely wear down cartilage, causing direct bone-to-bone contact.<ref>{{cite web |title=Osteoarthritis |url=https://www.mayoclinic.org/diseases-conditions/osteoarthritis/symptoms-causes/syc-20351925 |website=Mayo Clinic |access-date=13 May 2024}}</ref>

=== Frictional properties ===
[[Lubricin]], a [[glycoprotein]] abundant in cartilage and [[synovial fluid]], plays a major role in bio-lubrication and wear protection of cartilage.<ref name=Rhee2005>{{cite journal | vauthors = Rhee DK, Marcelino J, Baker M, Gong Y, Smits P, Lefebvre V, Jay GD, Stewart M, Wang H, Warman ML, Carpten JD | display-authors = 6 | title = The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth | journal = The Journal of Clinical Investigation | volume = 115 | issue = 3 | pages = 622–31 | date = March 2005 | pmid = 15719068 | pmc = 548698 | doi = 10.1172/JCI22263 }}</ref>

=== Repair ===
Cartilage has limited repair capabilities: Because chondrocytes are bound in [[Lacuna (histology)|lacunae]], they cannot migrate to damaged areas. Therefore, [[cartilage damage]] is difficult to heal. Also, because hyaline cartilage does not have a blood supply, the deposition of new matrix is slow. Over the last years, surgeons and scientists have elaborated a series of [[articular cartilage repair|cartilage repair procedures]] that help to postpone the need for joint replacement. A [[Tear of meniscus|tear of the meniscus]] of the knee cartilage can often be surgically trimmed to reduce problems. Complete healing of cartilage after injury or repair procedures is hindered by cartilage-specific inflammation caused by the involvement of M1/M2 [[Macrophage|macrophages]], [[Mast cell|mast cells]], and their intercellular interactions.<ref>{{Cite journal |last1=Klabukov |first1=I. |last2=Atiakshin |first2=D. |last3=Kogan |first3=E. |last4=Ignatyuk |first4=M. |last5=Krasheninnikov |first5=M. |last6=Zharkov |first6=N. |last7=Yakimova |first7=A. |last8=Grinevich |first8=V. |last9=Pryanikov |first9=P. |last10=Parshin |first10=V. |last11=Sosin |first11=D. |last12=Kostin |first12=A.A. |last13=Shegay |first13=P. |last14=Kaprin |first14=A.D. |last15=Baranovskii |first15=D. |date=2023 |title=Post-Implantation Inflammatory Responses to Xenogeneic Tissue-Engineered Cartilage Implanted in Rabbit Trachea: The Role of Cultured Chondrocytes in the Modification of Inflammation |journal=International Journal of Molecular Sciences |volume=24 |issue=23 |pages=16783 |doi=10.3390/ijms242316783 |doi-access=free |issn=1422-0067 |pmc=10706106 |pmid=38069106}}</ref>

[[Biological engineering]] techniques are being developed to generate new cartilage, using a cellular "scaffolding" material and [[Autologous chondrocyte implantation|cultured cells]] to grow artificial cartilage.<ref>[http://www.cartilage.org International Cartilage Repair Society ICRS]</ref> Extensive researches have been conducted on freeze-thawed [[Polyvinyl alcohol|PVA]] [[hydrogel]]s as a base material for such a purpose.<ref name=":0">{{Cite journal|last1=Adelnia|first1=Hossein|last2=Ensandoost|first2=Reza|last3=Shebbrin Moonshi|first3=Shehzahdi|last4=Gavgani|first4=Jaber Nasrollah|last5=Vasafi|first5=Emad Izadi|last6=Ta|first6=Hang Thu|date=2022-02-05|title=Freeze/thawed polyvinyl alcohol hydrogels: Present, past and future|url=https://www.sciencedirect.com/science/article/pii/S0014305721007084|journal=European Polymer Journal|language=en|volume=164|pages=110974|doi=10.1016/j.eurpolymj.2021.110974|bibcode=2022EurPJ.16410974A |s2cid=245576810|issn=0014-3057|hdl=10072/417476|hdl-access=free}}</ref> These gels have exhibited great promises in terms of biocompatibility, wear resistance, [[shock absorption]], [[friction]] coefficient, [[Stiffness|flexibility]], and lubrication, and thus are considered superior to polyethylene-based cartilages. A two-year implantation of the PVA hydrogels as artificial meniscus in rabbits showed that the gels remain intact without degradation, fracture, or loss of properties.<ref name=":0" />