Tissues under load Flashcards
Types of mechanical loads
Unloaded
Tension (up + down away force)
Compression (up + down in force)
Bending (tension + compression)
Shear (opposite forces on opposite sides)
Torsion (twisting)
Combined loading (torsion and compression)
Type 1 collagen
90% of all collagen - bone/ligaments/skin
Structural collagen against tension
Type II collagen
Collagen - fibre - structural
Cornea
Type III collagen
Reticular fibres
Muscle, arteries, skin
fibre - thin
Type IV collagen
Basement membrane of epithelia
mesh
Structural levels of collagen type I: collagen synthesis
Synthesis of pro-alpha chain containing Gly-X-Y repeats.
Self-assembly of three pro-alpha chains.
Procollagen triple helix formation followed by secretion into the ECM.
Cleavage of propeptide
Self-assembly into FIBRIL (see banding pattern in the EM)
Aggregation of collagen fibrils to form a collagen FIBRE
What is x and y in Gly-X-Y repeats?
gly- glycine
x- proline
y - hydroxyproline
Scurvy
Vit C deficiency
Essential for production of lysyl hydroxylase, the enzyme that catalyses the hydroxylation of proline and lysine. Absence of Vit C - collagen doesn’t formed its coiled structure. Most prominent in areas with high collagen turnover (periodontal ligament)
Symptoms include rotten teeth, bleeding from all mucous membranes and bowed legs
Vit C role in collagen synthesis
Helps with cleaving using enzymes and golgi modification
Osteogenesis Imperfecta
Genetic disease - mutation int two genes that encode collagen type I.
Symptoms include brittle bones, weak tendons (tendinosis), abnormal skin, teeth and healing
Stickler syndrome
Type I - autosomal dominant inherited mutations in the COL2A1 gene
Type II defective formation of collagen type II
Flattened facial appearance, nearsightedness, varying hearing loss, osteoarthritis, joint pain
Proteoglycans
a core protein + one or more covalently attached glycosaminoglycan (GAG) chain
Long linear polysaccharides
Negatively charged due to sulphate and uronic acid groups. Repeating disaccharide units including glucosamine
Multiple GAG chains
Aggrecan, versican, perlecan
Biglycan
Two chains
Decorin
One chain
- decorates collagen fibres - limiting fibre size
Hyaluronan
Only GAG that is not sulphated
Binds large amounts of water - important for tissue hydration, joint lubrication and diffusion of molecules
Aggrecan
Larger aggregating protein rich in chondroitin sulphate. It forms large aggregates by binding to HA via link protein. Highly negatively charged and is ‘water loving’ forming a stiff gel within cartilage and the intervertebral disc. Loss of aggrecan in the intervertebral disc with age results in less shock-absorbing capacity
ECM turnover
Replaced by enzymes/protease (collagenases). Some are broken by metalloproteases. Secreted in development
Types of Collagenases
MMP1 and MMP13
Types of Aggrecanases
ADAMTS-4 and ADAMTS -5
Bone composition
Water 25%
Mineral composition 60-70%
Collagen 5-10%
Resist compression
Compact bone
dense and solid
Same cells but organised in concentric lamellae around blood vessels = osteons
Spongy bone
Network of struts and plates - same cells, parallel lamellae
Micro-organization of bone
Lamellae are cylindrical and aligned parallel to the long axis of bone.
Collagen (type I) spiral along lamella providing resistance to tensile forces.
Crystalline structure provides resistance to compression.
Macro-organisation of bone
Distribution of forces
Strength of bone is dependent on:
Quality and amount of collagen (mainly type I)
Mineral content (hydroxyapatite)
Overall density
Where is compact bone found
Regions of high loads in the cortex and in the diaphysis
Spongy/ trabecular location
Region of low loads or where stresses come from several angles. Spongy bone helps distribute loads, making bone light and protects the marrow within. Strength is gain from the organisation of trabeculae
Effect of gravity
Bone loss in lower extremities and lumbar spine
Aging and osteoporosis
Lose mineral and bones become less dense. Bone resorption outpaces bone formation resulting in decreased bone mass. Density and quality of bone is reduced.
Increased osteoclast activity and reduced osteoblast activity. Loss of calcium from the body and hormonal changes post menopause
Preventing osteoporosis
Weight-bearing activity - subject bones to stress. Bone cells lay down more collagen and mineral salts in bone matrix. Makes bones stronger
Articular cartilage resist load
Experiences compression with low amounts of tension & shear at articular surface.
Articular cartilage is a specialised form of hyaline cartilage, found at end of bones within synovial joints
Transition from a gel-like pliable tissue into the hard, ossified bone, with an intermediate of calcified cartilage acting as a protective cushion
What happens to the cartilage ECM when a load is removed?
The ECM begins to reabsorb water and return to its original shape and thickness.
How does water reabsorption occur in the cartilage ECM during unloading?
Proteoglycans, such as aggrecan, attract water back into the ECM due to their high negative charge density.
What is the role of the collagen network during the unloading of cartilage?
The collagen fibers help to restore the ECM’s original structure by providing tensile strength and preventing excessive deformation.
How does the viscoelastic nature of cartilage affect the unloading process?
Due to its viscoelastic properties, cartilage gradually returns to its original shape and thickness over time after the removal of the load.
Describe the recovery phase of cartilage ECM during unloading.
During the recovery phase, the interstitial fluid flows back into the cartilage, rehydrating the ECM and restoring its biomechanical properties.
What changes occur in the proteoglycan network during unloading?
The proteoglycan network re-expands as water is reabsorbed, helping to restore the cartilage’s ability to resist compressive forces.
How does unloading affect nutrient and waste transport in cartilage?
Unloading allows for the diffusion of nutrients and waste products through the rehydrated ECM, supporting chondrocyte metabolism and health.
Exercise and Aging
Cartilage remodels itself following mechanical stimulation however, both too little and too much mechanical stimulation can have deleterious effects on the tissue health.
Age - cartilage becomes stiffer, collagen has slow turnover and new collaged is rarely replaced. We lose water and cartilage thins
Under use/Immobilisation
Muscle wasting, bone thinning and loss of cartilage matrix due to lack of loading stimuli.
Patients put on continuous passive motion (CPM) machines to maintain joint function
Excessive use
Site specific reduction in proteoglycan content in articular cartilage which can lead to early onset of osteoarthritis.
Osteoarthritis
Affects all tissues of the joint. Presents as degeneration of articular cartilage. Low grade inflammation which is thought to contribute to ECM breakdown and viscous cycle begins.
Stiffness, joint swelling, reduced mobility. Joint replacement surgery or exercise needed
Articular cartilage composition
70-85% water
10-20% collagen - Type II
5-10% proteoglycans
5% chondrocytes
Aneural and avascular
Zones within articular cartilage
Superficial (Tangential) Zone:
Location: The outermost layer, closest to the joint cavity.
Characteristics: Contains flattened chondrocytes and a high concentration of collagen fibers arranged parallel to the surface.
Function: Provides a smooth, low-friction surface and resists shear forces.
Middle (Transitional) Zone:
Location: Below the superficial zone.
Characteristics: Contains round chondrocytes and collagen fibers arranged obliquely.
Function: Acts as a transition between the superficial and deeper zones, absorbing compressive forces.
Deep (Radial) Zone:
Location: Beneath the middle zone.
Characteristics: Contains larger, columnar chondrocytes aligned perpendicular to the surface, and collagen fibers are arranged in a radial orientation.
Function: Provides the greatest resistance to compressive forces and contributes to the overall thickness of the cartilage.
Calcified Zone:
Location: The deepest layer, adjacent to the subchondral bone.
Characteristics: Contains hypertrophic chondrocytes and is characterized by the presence of calcified cartilage matrix.
Function: Anchors the articular cartilage to the subchondral bone, providing stability and distributing loads to the underlying bone.
How OA progresses
Fibrillations - fraying of collagen
Collagen beneath SZ start to breakdown -> Free PG bring in H2O by bringing in more cations, increasing art cart height
Fissures develop - chondrocytes divide for futile repair and increase matrix prodution
Inflammation occurs - increased collagenase 1 and aggreanase which breaks down matrix
Bone is stiff, has pain and effusion with swelling
Do supplements work
No, not really
Why do we need tissue engineering
For articular cartilage and non-union fracture where gap between the two ends doesn’t bone
Type of engineered tissues
Mechanical replacement
Cartilage
Blood vessels
Bone
Bladder
Skin
Biochemical replacement
Liver cells
Pancreas cells
Stem cells
Making tissue in 3D
TE technique = cells + biocompatible scaffold
Sources of cells
Autologous - from the person who is having the replacement
Allogenic - donor from the same species
Xenogenic - From a different species
Scaffolds
Cells are placed in an artificial matrix forming a 3D structure
1. Allow cells to attach
2. Allow nutrient/waste delivery
3. Can apply mechanical loads
Types of scaffolds
Collagens
Alginate gels
Scaffold must be..
Biodegradable or biocompatible
Provide support for the initial growth phase
Moulded into any shape
Autologous Chondrocyte Implant
- Biopsy
- Culturing of chondrocytes
- Inject of cultured chondrocytes and periosteal graft sutured over lesion
- The cells are implanted under the graft
Produces fibrocartilage NOT articular cartilage
Complex synovial joint - the knee
Intra-articulating disc or meniscus
Bones of the knee joint
Femur , tibia and patella. The fibula is not considered part of the knee joint.
3 articulating surfaces within the knee joint
Between condyles of tibia and femur (later and medial tibio-femoral joints) Third is between the paella and the femur (patellar-femoral joint) on the anterior aspect of the joint.
Knee flexion and extension
Movement in the sagittal plane
Adaptation of the lower limbs bones permit 140* of flexion.
What restricts sliding of the knee
Intercondylar fossa & eminence restrict sliding
Knee abduction and adduction
Not permitted by collateral ligaments
Supporting ligaments
Connect bones and supporting viscera. Distribute tensile loads and control limit of joint motion.
Extracapsular ligament
Ligaments that occur outside the articular capsule
Capsular ligaments
Form part of the outer fibrous layer of the articular capsule
Tibial (or Medial) collateral ligament
Reinforces medial surface of knee joint by joining the femur to the tibia
Fibular (or Lateral) Collateral ligament
Reinforces the lateral surface of the knee by joining the femur to the fibula/tibia
Intracapsular ligaments
Found inside the articular capsule (intercondylar fossa). Covered with synovial membrane that is continuous from lining of the articular capsule. Are the CRUCIATE ligaments
ACL
Prevents forward gliding of the tibia in relation to the femur. Role in preventing knee from hyperextending
Past 30% hyperextension = rupture ACL
PCL
Ligament prevents backward gliding of the tibia in relation to the femur
Tendons of the knee
Are attached to muscle, placed under tension. Active stabilisation of the knee by the muscles and their tendons can help protect the knee when the ligaments are loose.
Extensor muscles of the knee
Quadriceps femoris: consists of 4 muscles sharing insertion into tibial tuberosity via patella and retinaculae.
Most superficial is rectus femoris with 3 vastus muscles below
Flexor muscles of the knee
Hamstring muscles: Three muscles with the semimembranosus and semitendinosus inserting inserting into the medial side of the tibia, while bicep femoris inserts on the lateral side of the tibia and head of fibula
