Articular Cartilage: What is it? Anatomy, Composition, Structure, Functions and Repair Response

It is a type of   hyaline cartilage that lacks a perichondrium.

Depending on the composition of the matrix, cartilage in the human body is classified into elastic, fibrocartilage , fibroelastic, and hyaline or articular cartilage .

The gliding surfaces of the synovial joint are covered with a specialized type of hyaline cartilage, called “articular cartilage.”

Hyaline cartilage provides a low friction sliding surface with increased resistance to compression and is known to be resistant to wear under normal circumstances.

Cartilage embryology

Cartilage arises from the mesenchyme. Some mesenchymal cells aggregate to form a blastema, at 5 weeks gestational age. The cells of the blastema begin to secrete the cartilage matrix and are later called chondroblasts .

With further development, the extracellular matrix that is produced gradually pushes the cells out. The cells encased in this strong, specialized matrix are called chondrocytes. The mesenchymal tissue that surrounds the blastema gives rise to a membrane called the perichondrium.

Articular (hyaline) cartilage anatomy

Hyaline articular cartilage is an aneural, avascular, and alymphatic structure. Chondrocytes form only 1-5% of the volume of articular cartilage. Chondrocytes receive their nutrition by diffusion through the matrix.

The matrix pH is 7.4, changes in which you can easily alter the highly specialized matrix infrastructure. Chondrocytes are highly specialized cells that are responsible for synthesizing and maintaining the infrastructure of the matrix.

Composition of articular cartilage

Water

From 65% to 80% of the wet weight of cartilage is made up of water, with 80% in the superficial area and 65% in the deep areas. Allows load-dependent deformation of the cartilage.

Provides nutrition and a medium for lubrication, creating a low friction sliding surface. In osteoarthritis, the water content becomes more than 90% due to increased permeability and alteration of the matrix.

This leads to a decreased modulus of elasticity and therefore to a reduction in the load-bearing capacity of the articular cartilage.

collagen

Forms 10-20% of the wet weight of articular cartilage. Type II collagen forms the main component (90-95%) of the macrofibrillar framework and provides a tensile strength for articular cartilage.

Roteoglycans

These polysaccharide protein molecules form 10-20% wet weight and provide compressive strength to articular cartilage.

There are two main classes of proteoglycans found in articular cartilage, large aggregating proteoglycan monomers and small proteoglycans including decorin, biglycan, and fibromodulin. They are produced within chondrocytes and are secreted into the womb.

The subunits of proteoglycans are called glycosaminoglycans (GAGs). These are disaccharide molecules, with two main types, chondroitin sulfate and keratin sulfate. GAGs are attached to the core of the protein through sugar bonds, to form an aggrecan molecule.

The binding protein stabilizes this chain with a central hyaluronic acid chain to form an intricate structure of the GAG ​​molecule.

There are two types of choindroitin sulfate. One type remains constant throughout life, while the other decreases with age. Aggrecan depletion has been found as an early feature in experimental arthritis.

Proteoglycans maintain fluid and electrolyte balance in articular cartilage. These macromolecules have negatively charged sulfate and carboxylate groups, which in turn attract only positively charged molecules and repel negative molecules.

This increases the total concentration of inorganic ions (eg sodium) within the matrix, thus increasing the osmolarity of the articular cartilage, thus creating a Donnan effect.

Chondrocytes

These highly specialized cells, which make up only 1-5% of the volume, are scattered throughout the matrix. Chondrocytes synthesize all the components of the matrix and regulate the metabolism of the matrix.

The characteristics of chondrocytes are:

  1. No cell-to-cell contacts, like osteocytes.
  2. Spheroidal in shape.
  3. Synthesis of type II collagen and large aggregates of proteoglycans and non-collagenous proteins.
  4. Training and maintenance of the specialized matrix.
  5. High individual metabolic activity, but due to the very low overall volume, the total activity is low.
  6. Receive nutrition through double diffusion barrier.
  7. Cells survive with low oxygen concentration and are therefore dependent on anaerobic metabolism.
  8. Produce the enzymes responsible for the degradation of the matrix.
  9. Joint mechanical loading influences chondrocyte functions.

Articular cartilage ultrastructure

Chondrocytes organize collagen, proteoglycans, and non-collagen proteins into a unique and highly specialized tissue, suitable to carry out the functions indicated above.

The composition, structure, and functions of chondrocytes vary according to depth from the surface of the cartilage.

Morphologically there are four named zones:

  1. Surface area.
  2. Transitional zone.
  3. middle (radial) or deep zone.
  4. Calcified area of ​​cartilage.

Surface area

This is the thinnest of all the layers, made up of flattened ellipsoid cells. They lie parallel to the surface of the joint, and are covered by a thin film of synovial fluid, called ‘lamina splendens’ or ‘lubricin’.

This protein is responsible for providing a definitive gliding surface to the articular cartilage. The chondrocytes in this area synthesize a high concentration of collagen and a low concentration of proteoglycans, thus becoming the area with the highest water content.

The parallel arrangement of the fibrils is responsible for providing the highest tensile and shear strength. The alteration of this area alters the mechanical properties of the articular cartilage and thus contributes to the development of osteoarthritis.

This layer also acts as a filter for large macromolecules, thus protecting the cartilage of the immune system from the synovial tissue.

Transitional zone

Cell density in this area is lower, with cells predominantly spheroid-shaped, embedded in abundant extracellular matrix. Large diameter collagen fibers are randomly arranged in this area. The aggrecan concentration of proteoglycans is higher in this area.

Middle zone (radial)

The cells are arranged perpendicular to the surface and are spheroidal in shape. This zone contains the largest diameter of collagen fibrils and the highest concentration of proteoglycans. However, the cell density is lower in this area.

Calcified cartilage area

This mineralized zone contains a small volume of cells embedded in a calcified matrix and therefore shows very low metabolic activity. Chondrocytes in this area express hypertrophic phenotype.

These cells are unique in that they synthesize type X collagen, responsible for providing important structural integrity and providing a buffer in conjunction with the subchondral bone.

The visible border between the third and fourth zones is called the ‘tidemark’, which has a special affinity for basic dyes, such as toluidine blue. This area provides an important transition to the less resistant subchondral bone.

Zone matrix : The matrix is ​​organized into three different zones in the cartilage. The pericellular matrix is ​​a thin matrix border organized in close contact with the cell membrane (2 μm wide).

This region is rich in proteoglycans and non-collagenous proteins, such as the cell membrane-associated molecule anchorin CII, and decorin. The zones are:

  1. Pericellular.
  2. Territorial.
  3. Interterritorial.

The territorial matrix surrounds the pericellular region and is present throughout the cartilage. It envelops individual chondrocytes or a group of chondrocytes, including their pericellular matrix. In the radial zone, it surrounds each column of chondrocytes.

The collagen fibrils in this region are cross-arranged, thus forming a fibrillar basket that surrounds the clustered group of chondrocytes, protecting them from mechanical impacts.

The interterritorial matrix forms most of the volume of all types of matrices, made up of the largest diameter of collagen fibrils.

The fibers are oriented differently in different zones, depending on the requirements, viz. parallel in the superficial zone and perpendicular in the radial zone. This region is distinguished from others by the formation of aggregates of proteoglycan molecules.

Functions of hyaline articular cartilage

The deformation of the matrix produces mechanical, electrical and chemical signals that affect the functions of the chondrocytes. Therefore, the matrix also plays a role in recording an articular cartilage load history.

  1. Provides a low friction sliding surface.
  2. It acts as a shock absorber.
  3. Minimizes peak pressures on the subchondral bone.
  4. Protects chondrocytes from mechanical stress, helping to maintain their phenotype.
  5. Storage of some cytokines and growth factors, necessary for chondrocytes.
  6. Determines the type, concentration, and rate of diffusion of nutrients to chondrocytes.
  7. It acts as a signal transducer for cells.

Repair and regeneration of chondral lesions

Over the past three centuries, doctors and scientists have sought several different ways to repair or regenerate the articular surface of the synovial joint after traumatic damage or cartilage degeneration.

Repair refers to the restoration of a damaged articular surface with a tissue of neo cartilage, which resembles native cartilage, but does not necessarily duplicate its structure, composition, and function.

Regeneration refers to the formation of tissue, indistinguishable from native articular cartilage.

A typical tissue response to injury follows a cascade of scar necrosis, inflammation, repair, and remodeling. The vascular phase of this cascade is the most important determinant of healing. .

Hyaline cartilage, being an avascular structure, lacks the ability to generate this vital response.

Therefore, after any injury or mechanical damage, the intrinsic repair capacity of cartilage is very low. Healing of the cartilage defect means restoring the structural integrity and function of the damaged tissue.

The natural history of cartilage injuries is not well understood, but what we do know can help us identify which patients to treat.

Although isolated cartilage defects were found in the knee in diagnostic arthroscopies of 4%, a considerably higher percentage (40-70%) has been described in knees with menisci and / or ligamentous injuries.

Cartilage injuries can be divided into two broad categories.

  1. Direct mechanical trauma to the matrix, without damaging the cells: in this situation, if the loss of the matrix components does not exceed the ability of the chondrocytes to synthesize new proteoglycan molecules, the cartilage will be restored.
  2. Mechanical destruction of cells and matrix, due to blunt or penetrating trauma: this is the most common situation in clinical practice. The results of the repair depend on several different factors.

Factors associated with the repair response

Depth of defect

Depending on the depth, the articular cartilage defect is classified as chondral or osteochondral. The pure chondral defect is further divided into a full thickness, that is, down to the subchondral bone or a partial thickness or a flap of cartilage.

These defects increase in size and depth and do not repair on their own. The outcome of the repair depends on whether the injury extends to the subchondral vascular bone marrow.

The osteochondral defect consists of a full-thickness cartilage defect that extends into the underlying subchondral bone.

Therefore, the osteochondral defect crosses the tide mark, giving way to the mesenchymal progenitor cells of the bone marrow in the defect.

This leads to the formation of a type of fibrocartilage repair. Therefore, the depth of the defect is crucial to stimulate a repair response.

However, several studies have shown that this repair tissue is biomechanically and structurally inferior to hyaline cartilage, and therefore may not be suitable for a load bearing function.

Default size

The size of the defect is an important factor in the repair response. The study in horses has revealed that defects <3 mm in diameter can lead to a complete repair after 9 months, while larger defects are not completely repaired.

The repair response of the articular cartilage depends on the extent of the injury, as measured by the volume and surface area of ​​the defect. Defects <1 cm in diameter are less likely to affect the distribution of stress in the subchondral bone and are unlikely to progress.

Years

Age is a stronger risk factor for the development of osteoarthritis. Aging reduces the hydration of the cartilage and the chondrocyte population in the cartilage. The mitotic and synthetic activities of chondrocytes decrease with age.

Animal studies in rabbits have shown a better restorative response for chondral defects of 2 mm in younger animals (5 weeks) than in older animals (4 months).

The depth of the injury is related to age. Children and adolescents develop osteochondral lesions, while adults acquire pure chondral lesions, possibly due to the well-developed and mature calcified zone.

Although osteochondrial lesions (osteochondritis dissecantes-OCD) in children with growing bones (open physis) usually heal without any problems; the adult form of OCD rarely cures.

Trauma

Sudden and strong impact on the joint surface or repetitive loading of the articular cartilage can cause microdamage to chondrocytes, leading to cell degeneration and cell death.

This also causes alteration of the collagen matrix leading to increased hydration, cracking in the cartilage and thickening of the subchondral bone.

Trauma also leads to decreased proteoglycan production by chondrocytes. And even though an outer surface of the cartilage appears to be intact, the actual cartilage tends to be softer and puckered at the indentation.

Joint mechanical misalignment

The abnormal loading of the joint in turn leads to excessive focal stresses on the cartilage leading to early degeneration. The location of the defect (whether loaded or unloaded) does influence the cartilage repair response.

This forms the basis for the corrective osteotomy around the knee joint. Cartilage behaves differently in load response. Immobilization or reduced loading leads to a decrease in GAG aggregation and synthesis, which can be reversible up to a certain limit.

Immobilization also leads to a reduction in smaller proteoglycan molecules and irreversible disruption of collagen fibers.

Although the evidence in the available literature varies between patient groups, it is very clear that regenerated tissue does not duplicate the exact composition, structure, and mechanical properties of this highly specialized support surface.

However, it appears that completely normal cartilage regeneration may not be the prerequisite, as most techniques have shown significant improvement in the patient’s symptoms and joint movements, even though the neo-cartilage is not the exact replacement for native articular cartilage.

Surgical treatment of cartilage defects

Bone marrow stimulation

Penetration of the subchondral bone is one of the oldest and most widely used methods to stimulate the regeneration of neo-cartilage. As the name suggests, this method is suitable for a complete chondral defect with an exposed subchondral bone.

Penetration of the subchondral bone plate disrupts the subchondral blood vessels. This leads to the formation of a “super clot” or fibrin clot on the surface of a chondral defect.

If the defect is protected from loading at this stage, then primitive bone marrow mesenchymal stem cells migrate into the super clot, proliferate, and differentiate into cells, morphologically resembling chondrocytes.

Joint drilling and debridement

It was a broad term, including joint trimming, meniscectomy, removal of osteophytes and loose bodies, joint abrasions, and even synovectomy. The combined effect of all these procedures together on the chondral defect outcome was difficult to quantify.

Second, the results of these treatments were influenced by the size, number and degeneration of the chondral defects presented. Pridie described a perforation of the subchondral bone, preceded by careful removal of all loose pieces of cartilage.

In clinical practice, joint debridement is generally combined with other spinal stimulation techniques, such as perforation or microfracture.

Therefore, debridement should be considered as Part I of any spinal cord stimulation technique.

In a randomized, controlled trial described by Hubbard, a simple excision of loose fragments versus simple lavage revealed significantly improved functional results for up to 5 years, with 65% of patients pain-free.

This study included isolated focal chondral defects in the medial femoral condyle, treated with removal of all surrounding unstable cartilage, followed by abrasion of the exposed calcified cartilage layer.

The debridement group had a significant improvement over lavage as measured by the Lysholm score.

Results gradually deteriorated over the 5-year period. Debridement studies in osteoarthritis have conflicting conclusions.

Opinions are divided as to whether arthroscopic debridement has a place in the treatment of established osteoarthritis, but this debate is not relevant to the treatment of localized symptomatic chondral defects.

Spongialization

This method is a modification of debridement and perforation, being a more radical one. Ficat described this term, which implied the removal of the damaged cartilage along with the affected subchondral bone.

Reported 79% good to excellent results in a series of 85 patients with degenerative patellar defects.

Microfracture

Microfracture, a modification of the Pridie perforation method, is a simple and by far the most common arthroscopic method used as a first-line treatment for symptomatic chondral defects.

Rodrigo et al. reported a good improvement in functional outcomes in patients with chondral defect, treated with a combination of debridement and microfracture.

However, the credit for describing microfracture as an isolated treatment for symptomatic chondral defect goes to Steadman et al.

In this procedure, all unstable cartilage is removed to create a stable defect well surrounded by normal cartilage, with full exposure of the subchondral plate. The success of this procedure lies in creating stable perpendicular borders of healthy cartilage around the defect.

An arthroscopic awl is then used to create iatrogenic but controlled fracture holes that penetrate the subchondral plate of the bone, 3-4 mm apart. Importantly, the integrity of the subchondral bone plate must be maintained.

The defect is filled with a so-called “super clot,” an optimal environment for pluripotent marrow cells to differentiate into stable repair tissue. Early mobilization with continuous passive movement, followed by a strictly protected weight-bearing program.

The advantages of microfracture over drilling may be that there is no overheating or burning of subchondral bone and that a rougher surface is produced, facilitating repair of attached tissue. In addition, it is easier to penetrate the defect perpendicular to the surface.

Microfracture, being an arthroscopic procedure, is the most popular treatment among athletes, according to a study in players from the national soccer league, with 76% of players who can return to the game next season.

Although this method is technically easier and less invasive, the surface of the formed neo cartilage has been found to be biomechanically inferior and less durable compared to hyaline cartilage.

Mosaicoplasty

Mosaicplasty was first described in 1993 and has since been widely used to treat chondral and osteochondral defects. In this technique, cylindrical osteochondral plugs are harvested from low weight areas within the knee joint.

The chondral defect is primed, with perpendicular vertical edges of normal cartilage around it. Osteochondral plugs are used to fill the chondral defect to create a “mosaic” pattern, which is called a mosaicplasty.

Various sizes of plugs are used to obtain maximum filling of the defect. The gaps between the plugs are filled with fibrocartilage.

The original technique was an open procedure. Hangody described a mini-open approach to mosaicplasty, especially for larger defects, patellar defects, and defects in the femoral condyle that are difficult to access by arthroscopy.

However, recent developments in surgical instrumentation and techniques have made it possible for this procedure to be performed as an arthroscopic procedure.

Proponents of this technique have an advantage of this technique to provide a stable and firm surface that supports weight.

The gaps between the plugs are generally filled with fibrocartilage derived from the debrided base of the chondral defect, providing secondary stability to the plugs.

However, many authors have described these spaces as ‘dead spaces’, providing less stability to the plugs.

There is always a problem about donor site morbidity, but Hangody recommends avoiding donor site morbidity by limiting the area of ​​the treated defect to be 1-4 cm.

The disadvantages of this procedure are technical difficulty, special equipment, inability to restore congruent surfaces, differences in the heights of the defect cartilage and the surrounding native cartilage.

Carbon fiber implants

Carbon fiber rods and pads were used to treat chondral and osteochondral defects, acting primarily as scaffolds to direct neocartilage regeneration on the joint surface.

Bentley  et al. Carbon fiber implants are commonly used to treat patellar defects, but reported a success rate of only 41%, with low-quality fibrous tissue covering the implant surface.

However, no histological analysis was reported. The introduction of a nonabsorbable material just inside the subchondral bone had been a debatable issue because of its discredit.

Brittberg  et al.  used carbon fiber implants to treat early osteoarthritis, with an 83% success rate in 37 treated patients. Advanced or advanced osteoarthritis may be the only indication these days, with knee replacement being the next option.

Perichondrial grafts

Homminga  et al.  used autologous Perichondrium strips to treat the chondral defect, with fibrin glue that acts as an adhesive.

The long-term results of 88 patients with a mean follow-up of 52 months showed good results in only 38% of the patients (Hospital for Special Surgery Score).

Histological analysis of 22 biopsies revealed satisfactory results in only 6 (27%) biopsies, showing a morphology similar to hyaline.

Periosteal grafts

The periosteum has a potential for both chondrogenesis and osteogenesis, making it an ideal biological membrane for the repair of chondral defects. Alfredson highlighted the importance of continuous passive motion (CPM) in 57 patients treated for patellar defects.

Of the 38 patients who used CPM postoperatively, excellent or good results were seen in 76% of the patients with a mean follow-up of 51 months.

Of the 19 patients who did not use CPM in the immediate postoperative period, 53% were classified as excellent or good at a mean follow-up of 21 months. Graft calcification has been mentioned as a long-term problem.

Osteotomía

Osteotomy is generally reserved for early uni-compartmental osteoarthritis. Osteotomy redistributes joint load and therefore avoids contact pressure loads on the cartilage surface, thus decreasing the rate of cartilage degeneration.

In a prospective series of 95 patients with medial compartment osteoarthritis, Schultz and Gobel compared the effect of isolated osteotomy against debridement or perforation of associated chondral defect in the degenerated compartment.

Follow-up arthroscopy and biopsy revealed better coverage of the degenerated cartilage forming thicker repair tissue when osteotomy was combined with perforation or debridement.

Patients in this series reported an improvement in walking distance and knee extension.

Another study by Kanamiya  et al. revealed a good correlation between the amount of correction achieved and the visible improvement in the articular surface, with almost 60% of the surface of the femorotibial joint covered with new fibrocartilage repair tissue.

One such study that included 146 knees in 115 patients treated with a high tibial osteotomy revealed hyaline or good-quality cartilage formation in 32% of the knees, and 59% showed a partial repair response.

Surprisingly, the study also revealed a greater chance of a good quality repair response in cases treated with overcorrection, possibly leading to increased discharge from the affected compartment.