CF basics: bone/cartilage, distraction osteogenesis Flashcards

1
Q

What are the components of bone?

A
  • Cellular components
    • osteoblasts: mature metabolically active bone forming cells - secrete osteoid (non-mineral matrix)
    • osteoclasts: multi-nucleated cells controlled by humoral and cellular mechanisms - bone resorption (and release or inorganic matrix)
    • osteocytes: mature osteoblasts trapped in bone matrix, control extracellular Ca, P
  • Matrix
    • Organic
      • Collagen - tensile stregth
      • Proteoglycans - compressive strength
      • Non-collagenous proteins - promotes mineralization & bone formation
      • GFs and cytokins - promotes bone homeostasis: TGF-B, IL-1, IL-6, IGF
    • Inorganic
      • Ca Hydroxyapatite - compressive strength
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2
Q

Describe the types of bone

A
  • two types of bone: Woven (immature) and lamellar (mature) bone
  • Woven bone
    • immature or pathologic bone; random organization of collagen
  • Lamellar bone, mature bone: Cortical vs. cancellous
    • Cortical bone = compact bone, 80%
      • structural unit is osteon - dense compact bone forming surface of bone
      • Osteons are based around Haversian canels, in which travel vessels, nerves, lymph channels
    • Cancellous bone = trabecullar / spongey bone
      • internal core / medulla of bone
      • more elastic and vascularized
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3
Q

Describe different types of bone formation.

A
  1. Endochondral ossification
    1. from a cartilage precursor, where bone replaces cartilage
    2. undifferentiated cells differentiate into chondrocytes and secrete cartilaginous matrix
    3. osteoclasts resorb and debride calcified cartilage, osteoblasts then lay down osteon
  2. Intramembranous ossification
    1. direct bone formation, no cartilage template
    2. undifferentiated mesenchymal stem cells differentiate directly into osteoblasts and aggregate into layers (membrane)
    3. begin to lay down organic matrix that mineralizes to form bone
  3. Appositional ossification
    1. osteoblasts align on existing bone and lay down new bone
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4
Q

Describe the different types of bone healing

A
  1. Direct bone healing
    1. Bone that heals via intramembranous ossification, where mesenchyme cells differentiate directly into osteoblasts to lay down new bone, without a cartilage framework or intermediate
    2. Requires no motion at fracture site
  2. Indirect bone healing
    1. Bone that heals via endochondral ossificaiton (and intramembranous ossification remote to the fracture), wehreby the majority of the bone heals via an intermediate cartilage framework, which calcifies and then is replaced by bone
    2. Occurs when there is motion
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5
Q

What are the prerequisites for direct bone healing?

A
  1. No motion at fracture site (< 2%), no shear
  2. Stable fixation
  3. Anatomic reduction
  4. Interfragmentary compression

SCAM = stable, compression, anatomic, motion

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6
Q

What is the difference between contact healing and gap healing in direct bone healing?

A

o Contact healing – stimulated by destruction of osteons =>formation cutting cones (mainly active osteoclasts), allowing ingrowth of vessels and undifferentiated MSC (MSC differentiate into osteoblasts). Woven bone produced, remodels to lamellar bone (weeks - months)

o Gap Healing – Interfragmenatry gaps remain (even in anatomic reductions) => heal by ingrowth of blood vessels, mesenchymal cell differentiation into osteoblasts which begin to lay down osteoid on exposed surfaces

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7
Q

What are the phases of direct bone healing when there is contact between bone ends?

A
  1. MSCs are released from injured periosteum
  2. Fracture site is resorbed by osteoclasts via cutting cone mechanism, new haversian systems developed
  3. allows ingrowth of MSCs and vessels and Osteoblast differentiation
  4. Intramembranous ossification - laying down of immature woven bone
  5. Remodels to lamellar bone
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8
Q

What are the phases of indirect bone healing?

A
  • Hematoma & inflammation
    • hematoma formation
    • GF and cytokine release
  • Reparative
    • MSCs differentiate into chondrocytes, form fibrocartilage intermediate = soft callous
    • Soft callous calcifies to form hard callous, immature woven bone via endochondral ossification; remote to fracture IMO occurs for direct new bone formation
  • Remodelling
    • replacement of woven bone with lamellar bone
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9
Q

List and describe 5 systemic factors that influence bone healing

A
  • oxygen - chronic hypoxia delays healing; however in bone, acute local hypoxia (at fracture site) induces bone healing
  • nutrients - insufficient Vit C and vit D impair bone healing, whereas excess Vit A impairs helaing
  • diabetes - affects collagen cross linking and impairs osteoblast function
  • nicotine - vasoconstrictive to chronic decrease O2 and decrease osteoblast actrivity
  • chemotherapy - broadly impairs wound healing, fibroblast function, collagen depostion
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10
Q

What hormone are involved in bone hemeostasis?

A
  • Vit D
  • Parathyroid hormone
  • Calcitonin
  • Growth hormone
  • indirectly, cortisol - which inhibits inflammatory response and callous formation
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11
Q

What growth factors are involved in bone homeostasis?

A
  • TGF-B - regulates cartilage and bone formation in callous
  • IGF - stimulates collagen
  • BMP - osteoinductive
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12
Q

List factors that affect bone healing

A
  • Systemic
    • Hormonal: cortisone, PTH, calcitriol, GH
    • Oxygen perfusion - local acute and systemic chronic
    • Malnutrition - vit D, vit C, vit A, deficient [Ca]
    • DM
    • Smoking/nicotine
    • Genetic
  • Local
    • GFs: TGF-B, IGF, PDGF, BMP, EGF
    • Injury mechanism
    • Plate porosis
    • High strain
    • Infection
    • Radiation
    • Tumour
  • Other adjuncts
    • electromagnetic field
    • low intensity ultrasound
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13
Q

Define distraction osteogenesis

A
  • Osteogenesis and lengthening of bone via surgical corticotomy and controlled distraction
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14
Q

What model explains the physiology of distraction osteogenesis

A
  • Tension stress model
  • applicaiton of slow, steady traction to tissues causes them to become metabolically active, inducing proliferative and biosynthetic functions
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15
Q

During distraction osteogenesis, by what mechanism does new bone form?

A
  • intramembranous ossificaiton
  • undifferentiated MSCs migrate to the site, differentiate into osteoblasts and lay down new bone
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16
Q

What are the clinical phases of distraction osteogenesis?

A
  1. Corticotomy and application of the device
  2. Latency - period of time between corticotomy and distraction, to allow fibrin scaffold
  3. Distraction - period of slow steady bone lengthening, ~ 0.5 - 3mm / day, if slower can consolidate too quickly
  4. Consolidation - after distraction to desired length, formation of new bone via IMO - woven then lamellar bone; generally 2-3 times the distraction period
17
Q

what are the histologic stages of distraction osteogenesis?

A
  • Stage 1: central fibrous zone - intervening gap filled by fibrous tissue
  • Stage 2: transistion zone - bone trabeculae extend from osteotomized edges
  • Stage 3: Bone remodelling zone - resoprtion and remodelling of immature bone
  • Stage 4: Mature bone zone - early lamellar/compact bone froms; normal architecture
18
Q

List and define the three ideal properties of a bone graft

A
  1. Osteoconduction - physical scaffold property, on which new bone forms via creeping substitution
  2. Osteoinduction - induction of differentiation of osteoprogenitor cells into osteoblast by local growth factors, cytokines and cells; does not require viable bone cells upon transfer (main are BMP and demineralized bone matrix)
  3. Osteogenesis - ability of graft to produce new bone
19
Q

How do you classify bone graft?

A
  • Vascularity: non-vascularized vs. vascularized (technically a flap)
  • Origin: autograft, allograft, xenograft
  • Recipient: orthotopic, heterotopic, onlay, inlay
  • Preservation: fresh, frozen, freeze-dried, other
20
Q

List the overall stages of vascularized bone graft healing & compare to non-vascularized bone healing.

A
  • Same stages as non-vascularized (hemorrhage / inflammation; revasc/resoprtion; osteoinduction; osteogenesis; remodelling)
  • but also more closely mimics traditional bone healing (MSC influx, osteoclast cutting cones, osteoblast differentiation – osteogensis (IMO) woven à lamellar bone)
  • ie there is osteogenesis / new bone formation much more than creeping substitution, more rapid healing
  • No necrosis, minimal resportion; doesn’t rely on recipient bed for blood supply; more graft elements remain viable; more osteogenic cellular activity; biomechanically superior; stress important for strength (Wolf’s Law)
21
Q

List 5 indications for vascularized bone grafts

A
  • Segmental loss > 6cm (in mandible)
  • XRT to region, scarred or poorly vascularized
  • Children - permits bone growth
  • Rapid healing required (vs. creeping substitution)
  • Composite defects
22
Q

In table format, list and compare differences in cancellous vs cortical bone grafts in terms of healing

A

Cortical

Cancellous

Revascularization

  • starts immediately in cancellous vs cortical and is complete earlier (2wks vs 2months)

Mechanism

  • Cortical graft heal by haversian canal ingrowth
  • Cancellous heal by end-end anastomosis

Bone Deposition

  • earlier for cancellous

Bone Resorption

  • later for cancellous

Repair

  • at final repair in cortical bone, there is incomplete resorption– final mix of living/dead bone

Strength

  • Cortical: initially stronger, then weakens to 60% for 1st 6wks-6mo post-grafting. Strength equal to normal bone @ 1-2y
  • Cancellous: initially weaker, then strengthens with deposition of new bone – as necrotic cores removed, strength normalizes
23
Q

describe healing of allogeneic bone grafts

A
  • very few if any donor cells survive - most are resorbed
  • those that do survive initiate an immune response that may make host susceptible to rejection (bone marrow highest risk)
  • therefore role of allograft is as a osteoconductive scaffold; bone will grow via creeping substitution from periphery
  • slow union requires long term fixation
24
Q

Compare non-vascularized bone graft, vascularized bone graft, allograft and xenograft on their properties, immunologic response, indications, advantages and disadvantages

A

Non-vascularized autograft and Vascularized autograft

Allograft

Xenograft

Properties:

Osteo-conduction, Osteo-induction, Osteogenic cell activity

Others; Osteo-conduction

Immunologic response

None

None

Increases with genetic disparity and depends on processing

Intense cell mediated and humoral response

Clinical result

Small defects, well vascularized bed, skeletally mature pt, no adjuvant tx

Large defects, poor vasc bed & XRT, growing pt, require rapid healing, composite defect

Small defect, well vascularized bed, benign disease (-), no donor available or desired

Poor incorporation and high resorption

Advantages

Also strong & good incorporation

Defects < 6cm, no XRT

Disease free, no immunogenicity

Least cost (?)

Best incorporation, strength

Defects > 6cm, XRT

Disease free, no immunogenicity

Less cost (?)

Variable strength & incorportion

No donor site morbidity

Readily available

Sufficient quantity

Disadvantages

Donor site morbidity

Increased OR time

Limited availability/finite

Donor site morbidity

Microvascular anastomosis

Increased OR time

Limited availability/finite

Delayed vascular penetration

Slow bone formation; delayed/incomplete incorporation

Less strong

Higher delayed / non-union

25
Q

What is the difference between a bone graft substitute, enhancer and extender?

A
  • substitute is an alternate or to use instead of autologous bone graft, with at least equivalent properties for strength & fusion
  • extender is a volume expander w/ autologous bone graft
  • enhancer induces / increases osteoinduction of autologous graft with/without expansion property
26
Q

List and describe examples of bone graft substitutes, by class

A

Allograft based

  • DBM, Allogro®, Othroblast®, Opteform®, Grafton®

Factor based

  • natural & recombinant growth factors used alone or in combination with other materials :TGF-b, PDGF, FGF, BMP

Cell based

  • cells used to generate new tissue alone or seeded onto a support matrix: Mesenchymal stem cells

Ceramic based

  • includes calcium phosphate, calcium sulfate, and bioglass used alone or in combination:
  • Osteograf®, Norian SRS®, ProOsteon®, Osteoset®
  • CaPO4 – integrates, osteoconductive, +/- osteoinductive
  • Often combine w/ other materials

Polymer based

  • both degradable/nondegradable polymers used alone and in combination with other materials: Cortoss®, OPLA®, Immix®
27
Q

List types and location of cartilage

A

o Hyaline - type II collagen: costal, nasal septum, alar, articular, tracheobronchial

o Elastic - suited for deformation; pinna and canal, nasal tip, eustacian tube, epiglottis

o Fibrocartilage - suited for support, tensile strength, compressive forces; vertebral disc, symphysis pubis, TMJ, TFCC

28
Q

How does cartilage receive its nutrition?

A
  • cartilage is avascular
  • cartilage receives nutrition via diffusion from subchondral bone
  • also superficial cartilage will receive some nutrition from perichondrium
29
Q

describe cartilage growth

A
  • Type I Defect (superficial laceration) - confined to cartilage, not penetrating subchondral bone
    • necrosis around injury
    • no histological evidence of repair (no blood supply)
  • Type II Defect (penetrating injury) - through cartilage and into subchondral bone
    • elicits repair response: hematoma, inflammation, influx of progenitor cells, formation of granulation tissue
    • healing is via diffusion from subchrondral bone and still incomplete – defect initially filled with fibrocartilage that over time fails
30
Q

List factors that influence cartilage repair

A

o Depth on cartilage surface / wound bed / maturity of cartilage / position / movement

31
Q

List mechanisms to prevent warping in use of cartilage grafts

A
  • avoid carving
  • carve concentric
  • carve central core (larger better than smaller)
32
Q

List advantages and disadvantages of use of cartilage grafts

A

Advantages

Disadvantages

  • provides form/bulk like bone but doesn’t require functional stress to retain bulk
  • readily obtainable
  • easily carved
  • doesn’t require vascular supply for survival
  • low resorption/remodeling (fresh autografts)
  • will survive under thin cover
  • growth potential (graft grows with age)
  • can be used as osteochondral graft
  • warping – wait 30 minutes
  • resorption
  • freezing results in nonviable chondrocytes
33
Q
A