Test 3 Flashcards
Functions of the Skeletal System
1) Support
2) Mineral storage (Ca2+) and homeostasis
3) Storage of lipids (yellow marrow)
4) Blood cell production (red marrow)
5) Protection of internal organs
6) Leverage & muscle attachment site
Matrix Minerals
2/3 of bone matrix is calcium phosphate, which reacts with calcium hydroxide to form crystals of hydroxyapatite
Matrix Proteins
1/3 of bone matrix is collagen, giving bone great tensile strength
Osteogenic (Osteoprogenitor)
Undifferentiated cells that divide % develop into osteoblasts, found in the inner layer of periosteum & endosteum
Osteoblasts
Bone-building cells, form matrix & collagen fibers but do not divide
Osteocytes
Mature bone cells, main cells of bone tissue that no longer secrete matrix
Osteoclasts
Huge cells originating from fused monocytes, resorb bone tissue
Spongy Bone
- Found in short, flat, irregular bones and epiphyses of long bones
- Does not have osteons
- matrix forms an open network of trabeculae that is filled with red marrow
Intramembranous Ossification
- Occurs in dermis, produces dermal bones
- Connective tissue are replaced by bone
1) Development of ossification center
2) Calcification
3) Formation of trabeculae
4) Development of periosteum
Flat bones
Example: parietal bone of the skull
Endochondral Ossification
Ossifies bones that originate as hyaline cartilage (most bones), comes in 6 steps.
6 Steps of Endochondral Ossification
1) Development of cartilage model
2) Growth of Cartilage Model (interstitial growth: lengths, appositional growth: in width)
3) Development of Primary Ossification Center (nutrient artery penetrates into center of model)
4) Development of Medullary Cavity
5) Development of Secondary Ossification center
6) Formation of articular cartilage & epiphyseal plate
4 Zones of Epiphyseal Plate
1) Zone of Resting Cartilage
2) Zone of Proliferating Cartilage
3) Zone of hypertrophic cartillage
4) Zone of calcified cartilage
Calcitriol
- Synthesis requires Vitamin D
- Promotes calcium absorption
Vitamin C
Required for collagen synthesis, and stimulates osteoblast differentiation
Vitamin A
Stimulates osteoblast activity
Vitamins K and B
Help synthesize collagen
4 steps of fracture repair
1) Blood clot
2) Fibrocartilaginous callus formation
3) Bony callus formation
4) Bone remodeling
Rickets
- Vitamin D deficiency
- Ca2+ not deposited correctly
- Softens bones of growing children
- Results in bowed legs, skull, rib cage and pelvic deformities
Osteomalacia
- New adult bone produced during remodeling fails to ossify
- Hip fractures are common
Scurvy
Vitamin C defeciency
Osteogenesis Imperfecta
- Brittle bone disease
- Born with defective connective tissue / lack of ability to make Type I collagen
- Prone to fracture
Osteopenia
General term for reduced bone mass, bones become thinner and weaker with age
Cancer and Bone Loss
Cancerous tissues release osteoclast activating factor, that stimulates osteoclasts to break down bone
Bone Grafting
- 2n most common graft, after skin graft
- to fill cavities, segmental defects, spinal fusions, bridge joints, non-union fractures, etc.
Effective Bone Grafts
Osteoconductive matrix, osteogenic cells, osteoinductive proteins
Osteoconduction
Grafting material serves as porous scaffold for new bone growth, allowing osteoblasts to spread and generate new tissue. Provides matrix for bone growth.
Osteoinduction
Stimulation of mesenchymal stem cells/osteoprogenitor cells to differentiate into osteo
Osteogenesis
Occurs when transplated osteoblasts/periosteal cells directly product bone
Autografts Advantages
- Contains all properties naturally
- No immune reaction, hosts rejection, disease transmission
Autografts Disadvantages
- Requires additional surgery to acquire grafting material
- very limited quantity
- Chronic pain
- Cosmetic
- Quality not constant
Autogenous Bone Grafts: Cancellous
Osteoconductive: 3D scaffold
Osteogenic: osteocytes and stem cells
Osteoinductive: small quantity of growth factors
Autogenous Bone Grafts: Cancellous Uses and Location
Uses: Bone loss, fractures, hip/knee arthroplasty
Location: Iliac crest
Autogenous Bone Grafts: Cortical
Less biologically active than cancellous bone, longer time to heal
Location: iliac crest
Autogenous Bone Grafts: Aspirate
Osteogenic: MSCs (osteoprogenitor cells)
Osteoinduction: growth factors
5 Major Bone graft substitute categories
1) Allograft based
2) Factor based
3 Cell based
4) Ceramic based
5) Polymer based
8 Cell Sources in Bone Tissue Engineering
1) Bone marrow stem cells
2) Trabecular bone
3) Amniotic Fluid
4) Umbilical cord stem cells
5) Periosteal cells
6) Dental pulp
7) Periodontal ligament cells
8) Adipose derived stemm cells
Factor-based
-Factors responsible for differentiation of progenitor cells and regulation of activities
IGF and TGF-B: modulate synthesis of cartilage matrix
bFGF: stimulates differentiation of chondrocytes
BMP: involved in bone and cartilage development
Allograft advantages
- Increased donor screening, tissue processing, safety
- Eliminates the morbidity of patient’s donor site
- Helps solve supply issues
Allograft disadvantages
- Inferior to autograftt
- Immune reactions
- Greater risk of infection
- Disease transmission
- Reduced mechanical property
- Cost
- Reduction in osteogenic and osteoinductive properties
Fresh Bone Allograft
- Antigenic
- limited time to test for immunogenicity or diseases
- Use limited to joint replacement using shape matched osteochondral allografts
Fresh Frozen Bone Allograft
- Less antigenic
- Time to test for diseases
- FDA regulated
- retain BMP, strong, better incorporation
Freeze Dried Bone Allograft
- Even less antigenic
- Time to test for disease
- FDA regulated
- can be stored for long time
- no BMP, bad osteoconductive
Advantages of Demineralized bone Matrix
- Osteoinductive
- Revascularizes quickly
Disadvantages of Demineralized bone Matrix
- More as bone graft extender, not substitute
- Difficult in handling
- Tendency to migrate from graft site
- Transmit disease
- Donor variability
Xenograft
- Impractical for clinical use on a wide scale
- Removal of protein and fat - processing
- Removes osteoinductive proteins
Polymer Classsification
Can either be Natural/Synthetic, or Biodegradable/Non-Biodegradable
PGA/PLA Collagen
- Animal-derived
- Putty-like consistency
- Used w/ MSCs and HA
- function as Bone graft extenders
Calcium Phosphate
- injectable ceramic paste
- very high compressive strength once hardens
- Uses: middle ear implant, dental implants, bioactive ceramic composite
Advantages of Injectable Calcium Phosphate Cement
- Biodegradable/Biocompatible
- Non-immunogenic
- Limitless supply
- Can be used to fill large fractures
Disadvantages of Injectable Calcium Phosphate Cement
Not much osteogenic or osteoinductive property without added growth factors
How does Injectable Calcium Phosphate Cement work?
- Paste dries and provides mechanical strength comparable to normal bone grafting
- Provides a porous scaffold that resorbs overtime
- Osteoclasts begin recycling the material at the junction between bone and cement almost immediately
Calcium Sulfate
- Osteoconductive void filler
- No structural strength
- Rapidly resorbs
- May be used as an autogenous graft extender
Hydroxyapatite
- Synthetic or Animal
- Produced from marine coral exoskeleton
- Interconnected porous structure closely resembles the porosity of human cancellous bone
- ProOsteon 500/R
TCP
- Tricalcium Phosphate
- Wet compressive strength slightly less than cancellous bone
- Porous nature
- Partial resorption
Composite Grafts
Any combination of materials that include both an osteoconductive matrix and an osteogenic or osteoinductive material.
Functional Classification of Joints
1) Synarthrosis - immovable
2) Amphiarthrosis - slightly movable
3) Diarthrosis - freely movable
Syndesmosis
-Fibrous Joint
- bound by interosseous membrane/ligament
- ampiarthrotic
- ex: between tibia &fibula, tibiofibular articulation
Suture
-Fibrous Joint
- flat bones united by sutural ligament
- synarthrotic
- ex: between skull plates
Gomphosis
-Fibrous Joint
- cone-shaped process surrounded by periodontal ligament
- synarthrotic
- ex: root of tooth
Synchondrosis
-Cartilaginous Joint
- bones united by bands of hyaline cartilage
- synarthrotic
- ex: between the first rib & manubrium
Symphysis
-Cartilaginous Joint
- articular surfaces covered by hyaline cartilage and bones connected by pad of fibrocartilage
- amphiarthrotic
- ex: joints between bodies of vertebrae, pubic symphysis
Fibrous Joints
- Lack cartilage and synovial cavity
- Bones held together closely together by short dense irregular CT
Cartilaginous joints
- No joint cavity
- Provide little to no movement
Synovial joints
- More complex, often diarthrotic
- Ligaments hold bones together to form synovial cavity
- A two layered capsule encloses the synovial cavity
Joint capsule
- Dense Irregular CT
- Lined by synovial membrane
- Encompass joint cavity and synovial fluid
Synovial Fluid
- Synovial membrane secretes synovial fluid
- Contains slippery proteoglycans secreted by fibroblasts
- Functions: lubrication, shock absorption, nutrient distribution, supplies O2 and nutrients to cartilage
Ligaments
Bands of dense regular CT that join one bone to another bone
Bursae
- Flattened fibrous sacs line with synovial membranes and fluid
- Strategically placed to minimize friction in joints
Tendon sheath
Elongated bursa that wraps completely around a tendon
Menisci
Pads of dense fibrocartilage that provide superior strength and allows bones of different shapes to fit together more tightly
Ball-and-socket
-Synovial Joint
- ball-shape head articulates with cup-shaped socket
- multiaxial (including rotation)
- ex: shoulder, hip
Condylar
-Synovial Joint
- oval-shape condyle articulates with elliptical cavity
- biaxial (no rotation)
- ex: joints between metacarpals and phalanges
Plane
-Synovial Joint
- nearly flat or slightly curved articulating surfaces
- nonaxial (sliding/twisting only)
- ex: joints between various bones of wrist and ankle
Hinge
-Synovial Joint
- convex surface articulates with concave surface
- uniaxial (flexion/extension)
- ex: elbow and joints of phalanges
Pivot
-Synovial Joint
- cylindrical surface articulates with ring of bone and ligament
- uniaxial (only rotation)
- ex: joint between proximal ends of radius and ulna
Saddle
-Synovial Joint
- both concave and convex regions fits complementary surface of other bone
- biaxial
- ex: joint between carpal and metacarpal of thumb
Current Engineered Joints
Replacement of whole degenerated joint with inert implants, excellent outcome
Engineered Joints: Cells
- Chondrocytes from hyaline cartilage
- MSCs
- ASCs
Engineered Joints: Biomaterials
Hydrogels as cell carriers for minimal invasive surgeries
- Natural: collagen
- Synthetic: PEG
Solid polymers designed for optimal mechanical stability
-PLA, PGA, PLGA
Engineered Joints: Factors
TGF-beta
Engineered Joints: Biomechanical
Mechanical loading may increase extracellular matrix synthesis during cartilage engineering
