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HEALING OF CARTILAGE

INTRODUCTION, STRUCTURE AND FUNCTION

  • Cartilage is composed of 3 main elements: chondrocytes, matrix and water.
  • The chondrocytes occupy lacunae in the matrix and are arranged in columns along lines of stress.
  • Although the metabolic rate of cartilage is low, the metabolic activity of individual chondrocytes is similar to other body cells.
  • The chondrocytes make the matrix which consists of collagen (type II, found almost exclusively in cartilage), elastin and ground substance (proteoglycans or protein polysaccharides).
  • Cartilage has no blood or lymphatic vessels and relies on diffusion of nutrients through its matrix. Water is essential for diffusion which is facilitated by movement and compression. Immobilisation can impair diffusion resulting in absorption of cartilage.
  • Perichondrium is the vascular fibrous capsule that surrounds the cartilage, some of its fibres being in continuity with the collagen fibres in the matrix.

Classification

  • Cartilage can be classified into 3 types according to the fibrous network:

1. Hyaline: costo-chondral junctions, articular, larynx, trachea and bronchi, nasal alae and septum. Type II cartilage.

2. Elastic: Where flexibility is required: external ear, auditory tube, epiglottis, parts of the larynx. Type II cartilage with elastic fibers

3. Fibrocartilage: Where firm support or tensile strength is required:TMJ, sternoclavicular joint, pubic symphysis, intervertebral discs, volar plate, TFCC and in ligamentous and tendon attachments to bone. Type 1 cartilage orientated along stress lines.

Growth

  • Both appositional and interstitial.
  • Appositional growth
  • new cartilage cells, chondroblasts, arise from inner layer of the surrounding perichondrium and secrete extracellular matrix; forms new cartilage at surface of preexisting cartilage
  • Interstitial growth
  • forms new cartilage within the cartilage mass; chondrocytes divide and secrete matrix from within their lacunae; This cartilage cell division occurs in all types of cartilage.
  • The perichondrial connective tissue cells secrete matrix elements and become incorporated into the cartilage substance as intra-cartilaginous chondrocytes.
  • Cartilage growth ceases with adulthood.
  • Chondrocytes are not replaced during the life of an individual, in fact there is a progressive in the number of chondrocytes during an individuals life.

Healing

  • Unlike osteoblasts, chondrocytes show little reparative ability.
  • Following injury, healing is by formation of undifferentiated fibrous tissue.
  • Continuous passive motion can promote ehaling of articular cartilage
  • mechanisms of repair:
  • when articular cartilage is injured, the type of healing that will take place is influenced by the depth of the injury;
  1. extrinsic healing:
  • Dependent on a synovial reaction or subchondral bone being penetrated at the time of injury;
  • WITH subchondral injury, capillary injury forms a fibrin clot, which is then replaced by granulation tissue and fibrocartilage
  • if defect is limited to cartilage, no blood vessels are disrupted, and inflammatory response is less intense than if injury extends through cartilage into subchondral bone, as occurs in intraarticular fractures;
  1. intrinsic healing (isolated injury):
  • dependent on chondrocytes to synthesize a new matrix;
  • since cartilage is largely avascular, healing is dependent on diffusion of nutrients from synovial fluid;
  • potential for intrinsic healing appears somewhat limited;
  • isolated injuries to cartilage (which do not extend to subchondral bone heal slowly and incompletely;
  • surgical options for articular cartilage repairtypically include
  1. graft implantation
  2. entail theimplantation of autologous osteochondral plugs, allografts,periosteal grafts, and perichondrial grafts
  3. subchondral bone microfractures
  4. includesubchondral drilling, microfracture, and spongialization.
  • clinical outcomes of these treatments often result in the formation of fibrocartilage and are associated with joint pain and stiffness

PROPERTIES OF CARTILAGE

1. Visco-elasticity (memory)

  • Following deformation, cartilage returns to its original position.
  • If the deforming force is continued for several months, cartilage will remodel.
  • The cartilage’s shape is independent of the perichondrium and isdue to balanced forces (interlocking stresses) within the cartilage, especially tension existing in the taut, compact, outer, sub-perichondrial layer.
  • Cartilage has internal swelling pressuredue to interlocking of protein polysaccharide complexes and binding of large amounts of water. Inhibition of protein polysaccharide complexes shown to abolish the interlocking stress within cartilage (Fry).
  • Carving, scoring, trauma, etc, affect the balance of the intrinsic forces in a way that may be unpredictable.
  • Warping can take months or years to develop and can ruin an otherwise good reconstruction, especially of the nose (less so in the ear).

Strategies to avoid warping

  1. banking carved rib cartilage grafts in an abdominal pocket for 3 months before use
  2. balanced cross-sectional carving significantly reduces the incidence of cartilage warping.
  • Involves keeping equal amount of outer cartilage on opposing surfaces
  • However, a curved rib cannot be readily modified into a straight dorsal graft or columellar strut without violating the principles of balanced cross sections.
  1. avoid cartilage carving.
  • Balanced carving restricts warping, ie, keeping an equal amount of outer cartilage on opposing surfaces. Abrahams and Duggan (1965) noted that carved cartilage fully distorts within 30 minutes.

2. Immunological privilege

  • Although chondrocytes exhibit antigenic properties similar to other cells, they are protected by the matrix which lacks vascular channels. The matrix is only weakly antigenic.
  • The cartilage allograft is said, therefore, to enjoy relative immunological privilege. In the clinical setting, however, the allograft has a high tendency to resorb if followed up over long periods of time and it is believed that the immunological privilege merely represents a retardation in the rejection process d/t the mechanical protection of the chondrocytes afforded by the matrix. (See allografts, below).

CARTILAGE TRANSPLANTATION

Autografts

  • Since cartilage normally survives by diffusion, it is the ideal graft material.
  • No metaplastic changes occur following transfer.
  • Fresh autografts exhibit good long term survival maintaining their structure & volume for years. Infection, haematoma, etc, will result in resorption.
  • Less resorption results if the perichondrium is left intact, but the presence or absence of perichondrium does not affect survival.
  • After transfer, it is the perichondrium that becomes vascularised.
  • Growth potential, although shown experimentally, has not been demonstrated clinically.
  • Donor sites: auricular (conchal), nasal (septal, UL), costal
  • Uses: rhinoplasty, otoplasty, eyelid reconstruction, orbital wall reconstruction, nipple, umbilicus, TMJ, etc. Found not to be good for TMJ. Cartilage grafts are best for onlay reconstruction and augmentation. Compared with bone;

1) cartilage is easy to carve and shape

2) does not require functional use to ensure its survival and bulk

3) does not need a vascular supply for survival

4) has a lower resorption rate after implantation

  • On the negative side it cannot provide as much structural support and is prone to warping.
  • Preserved cartilage autografts allow warping to occur prior to transplantation, but chondrocyte survival is ed resulting in resorption. Grafts can be stored in sterile moist air or ringer’s lactate at 4oC for about 2 weeks without problems of later resorption. This may allow, for example, a 2 stage ear reconstruction: costo-chondral harvest, leisurely carving, quick insertion.
  • Auricular cartilage grafts: the ideal source and the most versatile. Easy to attain under LA, conchal cartilage harvest leaves insignificant donor site deformity, easily contoured and very useful, especially for ear and nose reconstructions.

Allografts

  • Fresh allografts are impractical and risk transfer of infection. Preserved therefore used.
  • Because of immunological privilege, allografts survive transplantation for a while, but the absence of chondrocytes in the matrix renders these implants non viable and resorption is invariable after a time. Although some have shown good results with preserved allografts, it is generally believed that resorption rates are too high.
  • Gillies, starting in 1920, used maternal cartilage for microtia reconstruction in 37 children. In 1977, Converse examined 21 of these ear reconstructions and found cartilage persisted in only one (presumably d/t fortuitous close tissue typing between mother and child), whereas in the others, the maternal auricular transplants had undergone shrinkage and resorption.
  • The immunological privilege must therefore be questioned. The rejection response occurs as with other tissue, it is just retarded by the matrix barrier.

Xenografts

  • Immune response to matrix Ag’s resulting in complete resorption.
  • Chondrocytes impregnated in calcium alginate gel templates and implanted will result in the formation of formed cartilaginous shape that can be used for reconstruction.

FIXATION OF GRAFTS

  • Sutures: absorbable or non-absorbable can both be uses.
  • Glues: organic (fibrin glue) or non organic (cyanoacrylate glue) have both been used.

PRESERVATION OF GRAFTS

1.Lyophilisation

2.Freezing

3.Immersing in anti-septic solutions

4.Irradiation (renders the cartilage non viable) - reduces the antigenicity of cartilage, but some forms of freezing also render it non viable.

CARTILAGE TISSUE ENGINEERING

  • Cartilage tissue engineering is a frontier that will greatly advance reconstructive options for treatment of denegerative arthritis, and in ear/nose reconstruction.
  • Seen as achievable - a relatively simple tissue containing a single cell type that relies on diffusion as a source for nourishment.
  • Challenges
  • developing efficient methods to form cartilage with chondrocytes in culture
  • low cell yield from cartilage haervest
  • limited proliferation that these cells will undergo in vitro (BMP-7 most effective)
  • Suitable scaffold to build construct - alginate, agarose, gelatin, or fibrin
  • Formation of stable vascularised constructs