Knee Cartilage Regeneration

Courtesy: Prof Paul Lee FRCSOrth, London

What is Articular Cartilage?

• It is the smooth, white tissue that covers the ends of bones where they come together to form joints
• It is a hyaline cartilage and is almost 1- 5mm thick
• Ability to withstand good amount of pressure
• It is composed of chondrocytes
• It derives its nutrition from Synovial fluid
• Healthy cartilage allows the joints to move freely without any friction.
• It has no Intrinsic repair capability

Articular Cartilage Components

• It is composed of chondrocytes that produce a large amount of ECM(Extra Cellular Matrix) which consist of collagen fibers, ProteoGlycans(PGs), Elastic fibres.
• ECM contains Type II collagen (10- 30%), Proteoglycans(3-10%) & water (most abundant),inorganic salts ,glycoproteins and lipids.

Structure and Function Articular Cartilage

• Collagen type II and IX provides tensile strength assist chondrocytes attach to ECM (type VI), contribute to structural support & aid carriage mineralization
• Once cartilage is damaged ,it is replaced by fibrocartilage, with Type I collagen
• When left untreated, articular cartilage lesions can lead to early osteoarthritis

How Articular cartilage gets Damaged?
• Damaged by mechanical Trauma
• Chronic Degeneration(OsteoArthritis)
• Free movement of Osteochondral Fragments in joint
• Tumor- Chondroma | Chondrosarcoma
• Arthroscopic knee procedures
• Osteochondritis Dessicans, Blood deprivation of subchondral bone, AVN,Bone resporption

Does Articular Cartilage Heal?

• Articular cartilage is devoid of blood vessels, lymphatics, and nerves and is subject to a harsh biomechanical environment
• Damaged articular cartilage has poor healing response and defects larger than 2-4 mm rarely heal.
• Injury to articular cartilage is recognized as a cause of significant musculoskeletal morbidity

Layers of Articular Cartilage
• Superficial Zone
• Middle Zone
• Deep Zone
• Calcified Cartilage
• Tide Mark
• Subchondral bone
• Cancellous bone

Layers of Articular Cartilage

Superficial Zone(10-15%)

• Also Called Tangential Layer
• Highest Conc. of collagen
• Highest Tensile strength
• Highest conc. Of Water and Lowest conc.of Proteoglycans ( swelling)
• Chondrocytes and collagens arranged horizontally

Middle Zone(40-60%)

• Also Called Transition Zone
• Chondrocytes and collagens oriented randomly
• Collagen in oblique orientation

Deep Zone (30%)
• Collagen in perpendicular orientation
• Highest conc. Proteoglycans and Lowest conc.water
• Fourth Layer (Calcified Cartilage and Cancellous bone)
• Calcified cartilage starts at tidemark and has type X collagen
• Its the transition zone between subchondral bone and cartilage

Tidemark-

• Boundary between calcified and uncalcified layers
• Tidemark seen only in mature articular cartilage

Chondrocytes

• They are highly specialized, metabolically active cells that play a unique role in the development, maintenance, and repair of the ECM.
• It derives from chondroblasts that are trapped in lacunae and become chondrocytes
• It originate from mesenchymal stem cells and constitute about 2% of the total volume of articular cartilage
• Chondrocyte survival depends on an optimal chemical and mechanical environment.

Extra Cellular Matrix
• ECM fluid represents between 65% and 80% of the total weight.
• Collagens and proteoglycans account for the remaining dry weight.
• Other molecules include lipids, phospholipids, noncollagenous proteins,and glycoproteins.
• Extra Cellular Matrix can be divided based on Proximity to Chondrocytes into:
• Pericellular region
• Territorial region
• Interterritorial region

Classification based on Proximity to chondrocytes

Pericellular region
• It is a thin layer adjacent to the cell membrane, and it completely surrounds the chondrocyte
• It contains mainly proteoglycans, as well as glycoproteins and other noncollagenous proteins
• This matrix region may play a functional role to initiate signal transduction within cartilage with load bearing

Territorial region
• It surrounds the pericellular matrix
• It is composed mostly of fine collagen fibrils, forming a basket like network around the cells
• This region is thicker than the pericellularmatrix
• It has been proposed that the territorial matrix protect the cartilage cells against mechanical stresses and contribute to the resiliency of the articular cartilage structure and its ability to withstand substantial loads

• Interterritorial region
• It is the largest of the 3 matrix regions
• It contributes most to the biomechanical properties of articular cartilage
• It is characterized by the randomly oriented bundles of large collagen fibrils, arranged parallel to the surface of the superficial zone,
• Then obliquely in the middle zone, and perpendicular to the joint surface in the deep zone.
• Proteoglycans are abundant in the interterritorial zone

Collagens
• It is the most abundant structural macromolecule in ECM makes up about 60% of the dry weight of cartilage.
• Type II collagen represents 90% to 95% of the collagen in ECM and forms fibrils and fibers
• Collagen types I, IV, V, VI, IX, and XI are also present but contribute only a minor proportion.

Healing Process of Articular Cartilage

• The self repair depends on the size, depth and location of the defect, apart from the age of the patient
• Cartilage defects are classified in to two types according to the depth of the lesion in to Partial (Chondral) or Full Thickness (Osteochondral).
• In full thickness (osteochondral) defects are lesions that penetrate the subchondral bone, and in such cases, the bone marrow provides vascularisation and Mesenchymal Stem Cells to promote the better repair
• Articular cartilage lesions, when left untreated, forms fibrocartilage, leading to the very early onset of degenerative osteoarthritis

Outerbridge classification

Healing Process of Articular Cartilage

• If injury is at Chondral region there is activation of chondrocytes which modulates gene expression, protein synthesis, fibroblast differentiation, hypertrophy or regeneration of mature cartilage.
• The repair mostly relies on the limited mitotic activities of resident chondrocytes which are rarely effective
• Injured cartilage heals slowly by scar tissue formation mainly composed of fibrocartilage
• If the injury extends down to the Subchondral bone, self-healing processes are initiated by the release of mesenchymal progenitor cells from bone marrow (BM) and periosteum into the defect
• Cartilage healing can be accelerated by surgical intervention particularly marrow stimulation techniques

 

Management of Articular Cartilage Damage

Conservative

Continuous Passive Motion (CPM)

• It enhances cartilage healing after surgical techniques

Electrical Stimulation

• Less effective than CPM

Laser Therapy

Pharmacological agents (Hyaluronic Acid)

Before Operating the patient: Patient Eligibility
• Preferred for younger age groups
• Mostly with a single injury or a lesion
• Older patients with many lesions in a single joint is less likely to be benifited
• Knee is the most common area for cartilage restoration.
• Ankle, shoulder, and elbow problems may also be treated.

Management of Articular Cartilage Damage

Surgical method: Operative Strategies
• Palliative
• Reparative
• Restorative

Management of Articular Carriage Damage: Surgical methods

Palliative (Debridement and Lavage)
• Articular Trimming
• Removal of loose bodies
• Synovectomy
• Reparative
• Subchondral Drilling
• Multiple holes drilled with surgical drill or wire in subchondral bone
• Poor access, less precise, risk of thermal necrosis and long term efficacy is questionable
• Like microfracture, drilling yields fibrocartilage, not hyaline cartilage.

 

Microfracture
• Unstable cartilage removed and small holes are made and distributed across the entire articular cartilage lesion site
• Done at a distance of 3–4 mm apart and down to a depth of 4 mm, thus yielding about 3–4 holes per cm
• Subchondral plate completely exposed
• Goal is to stimulate the growth of new articular cartilage by creating a new blood supply
• Best candidates are lower demand (less active) patients with single and smaller lesions and healthy subchondral bone

Abrasion Chondroplasty
• It is similar to drilling, instead of drills or wires, high-speed burrs are used
• This creates a bleeding surface and later formation scar tissue that replaces the original articular cartilage
• It also produces fibrocartilage, not hyaline cartilage
• Its beneficial for treating smaller lesions in lower

Matrix-induced Autologous Chondrocyte Implantation (MACI)
• Its a two-step procedure in which new cartilage cells are grown and then implanted in the cartilage defect.
• First, healthy cartilage tissue is removed from a Non Weight Bearing area of the bone.
• The cells are cultured on a collagen matrix (a biologic scaffold) in lab and increase in number over a period of 1month.
• An open surgical procedure, or arthrotomy, is then done to implant the newly grown cells onto another collagen matrix, which is secured within the defect using fibrin glue
• Its useful for younger patients who have single defects larger than 2 cm in diameter.
• It provides more durable hyaline cartilage. No chances of rejection
• It is a two-stage procedure that takes several weeks to complete. And need to open knee

Restorative(Osteochondral Autograft Transplantation ,Osteochondral Allograft Transplantation)

Osteochondral Autograft Transplantation (OATS)
• Here, cartilage is transferred from one part of the joint to another.
• It provides more durable hyaline cartilage to the defect area
• A cylinder-shaped graft of healthy cartilage tissue and subchondral bone is taken from a NWB area
• If surgeon perform procedure using multiple plugs, its called Mosaicplasty.
• It is typically used for patients aged<50 and with minimal cartilage damage, and available healthy cartilage for transfer

Osteochondral Allograft Transplantation
• If a cartilage defect is too large for an allograft may be considered
• Its taken from a cadaver donor, tissue is sterilized, prepared, and tested for any possible diseases
• Allograft is typically larger than an autograft, it also provide hyaline cartilage to the defect
• It can be shaped to fit the exact contour of the defect and then press fit into place.
• It is typically done through an open incision

Stem Cells and Tissue Engineering
• Current research is focused on new ways to make the body grow healthy cartilage tissue from Mesenchymal cells
• Mesenchymal stem cells are basic human cells obtained from living human tissue, such as bone marrow
• When stem cells are placed in a specific environment, they can give rise to cells that are similar to the host tissue
• Tissue engineering procedures are still at an experimental stage. Most tissue engineering is performed at research centers as part of clinical trials.

Rehabilitation
• After surgery, the joint surface must be protected while the cartilage heals
• Continuous Passive Motion therapy
• Restricted Weight bearing
• Physiotherapy

Take Home Message
• Only injury beyond tidemark will initiate healing process
• Articular cartilage is hyaline cartilage but healed with fibrocartilage.
• CPM and early controlled weight bearing are mandatory for post op rehabilitation
• Reparative/Restoration surgeries are recommended for young individuals with articular damage to prevent early OA.