Tissue engineering of cartilage

Transcription

1 Tissue engineering of cartilage Cartilage responds to mechanical forces and is able to remodel in response to the prevailing stress Cartilage, like bone, may respond to mechanical stimulation by increasing production of extracellular matrix components 1

2 Cartilage Osteoarthritis Traumatic diseases Congenital diseases Small capacity for self-repair One cell type: chondrocytes Low oxygen requirements 2

3 Cartilage: is a type of dense connective tissue is composed of cells called chondrocytes which are dispersed in a firm gel-like ground substance, called the matrix is avascular (contains no blood vessels) and nutrients are diffused through the matrix is found in the joints, the rib cage, the ear, the nose, in the throat three main types of cartilage: hyaline, elastic and fibrocartilage 3

4 Types of cartilage (1) Hyaline cartilage is the most abundant type of cartilage and has a translucent matrix or ground substance. Hyaline cartilage is found lining bones in joints (articular cartilage). It is also present inside bones, serving as a center of ossification or bone growth. Elastic cartilage (also called yellow cartilage) is found in the pinna of the ear and several tubes, such as the walls of the auditory, eustachian canals and larynx. Cartilage is present to keep the tubes permanently open. Elastic cartilage is similar to hyaline cartilage but contains elastic bundles (elastin) scattered throughout the matrix. This provides a tissue which is stiff yet 4

5 Types of cartilage (2) Fibrocartilage (also called white cartilage) is a specialised type of cartilage found in areas requiring tough support or great tensile strength, such as between intervertebral disks, the public and other symphyses, and at sites connecting tendons or ligaments to bones. There is rarely any clear line of demarcation between fibrocartilage and the neighboring hyaline cartilage or connective tissue. The fibrocartilage found in intervertebral disks contains more collagen compared to hyaline. Fibrocartilage lacks a perichondrium 5

6 Cartilage injury Articular cartilage injuries can occur as a result of either traumatic mechanical destruction, or progressive mechanical degeneration (wear and tear.) Depending on the extent of the damage, and the location of the injury, it is sometimes possible for the articular cartilage cells to heal. Articular cartilage has no direct blood supply, thus it has little or no capacity to repair itself.. Occasionally an articular cartilage fragment completely breaks loose from the underlying bone. 6

7 Mechanical degeneration (wear and tear) of articular cartilage occurs with the progressive loss of the normal cartilage structure and function. This initial loss begins with cartilage softening fragmentation. As the loss of the articular cartilage lining continues, the underlying bone has no protection from the normal wear and tear of daily living and begins to breakdown, leading to osteoarthritis. 7

8 degenerative joint disease (osteoarthritis) is characterized by three processes: progressive loss of cartilage the body s attempted to repair the cartilage destruction of the bone 8

9 Cartilage defect 9

10 After Brittberg et al 1994 Chondrocyte Implantation 10

11 In vivo studies he static petri dish (petri dishes are made from clear olystyrene and are sterilized) culture system: dry PGA affolds (PGA = polyglycolic acid) seeded with isolated cells he mixed petri dish system: in contrast to the static petri dish ulture. PGA scaffolds prewetted for 12 h in culture medium rior to seeding he spinner flask culture system: prewetted PGA scaffolds readed into 4-in long needles. To seed polymer scaffolds, edium and chondrocytes were added. Medium completely placed every other day 11

12 In vivo studies Athymic mouse model system: cell-polymer constructs based on bovine or human chondrocytes cultivated in static petri dishes for 2-3 dishes in vitro and then implanted in nude mice Explants removed after in vivo intervals of 1-6 months Rabbit model system: cell-polymer based on allograft chondrocytes cultivated in static petri dishes for 3-4 weeks in vitro and then implanted intra-articulary in rabbits. Explants removed after in vivo intervals of 1-6 months 12

13 PGA fibers to form a porous, mechanically stabilized mesh 13

14 Current research needs (1) 1. Establishment of design criteria for tissue-engineered cartilage constructs. The required dimensions, structure, composition, and biomedical properties of the construct at the time of implantation will necessarily depend on the specific clinical application 2. Development of reliable methods to source, amplify human chondrocytes. Chondrocytes can be isolated by needle biopsy and amplified in presence of growth factors 14

15 Current research needs (2) 3. Optimization of in vitro culture conditions to customengineer clinically useful cartilage. The structure and function of cartilage tissue constructs depend on hydrodynamic forces in the vitro culture environment. 4. Matching the strength of the graft with the biomechanical requirements in vivo. The mechanical properties of tissue-engineered cartilage depends on its composition and structure 15