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AO Foundation
Education
Ahmad Fadzli Sulong, IIUM Kuantan, Malaysia
Bone healing – a response influenced by
biology and mechanics
2
Bone healing
By the end of this talk:
• Reinforce the knowledge of bone healing
• Understand the processes involved in indirect
healing
• Understand the processes in direct healing
• Acknowledge the importance of the various cellular
signaling molecules involved in fracture healing
Bone healing
• Among the few tissue that heals without
formation of scar tissue
• Stages in bone healing resembles embryonic
development
• By its end would form tissue almost exactly the
same as prior to injury
• Therefore is mainly a regenerative process
rather reparative
3
Ferguson et al., 1999
Factors that influence
• Biology – condition of host tissue
• Systemic biological environment
• Local biological environment
• Mechanics – forces and motion at fracture site
4
Bone healing
• Indirect (secondary) bone healing
• Direct (primary) bone healing
5
INDIRECT BONE HEALING
6
Indirect (secondary) bone healing
7
Indirect (secondary) bone healing
8
Inflammation phase
9
Haematoma formation
• Instigates an acute inflammatory response
• Coagulates in between fracture site
• Becomes template for callus formation
10
11
Acute inflammatory response
• Mainly expressed by macrophages
• Tumor necrosis-α (TNF-α)
• Induce osteogenic differentiation of mesenchymal
stem cells (MSCs)
• Inducing secondary inflammatory signals
• Chemotactic agent to recruit necessary cells for
bone healing
12
13
Acute inflammatory response
• Interleukins
• Main types involved in fracture healing – IL-1, IL-6
• Interleukin – 1
• promotes formation of cartilaginous callus
• promotes angiogenesis
• induces production of more IL-6 in osteoblasts
• Interleukin – 6
• Stimulates angiogenesis
• Stimulates vascular endothelial growth factor
(VEGF) production
• Stimulates differentiation of osteoblasts to
osteoclasts
14
15
16
Recruitment of MSC
• Is the main component for bone regeneration
• Need to be recruited, proliferated and
differentiated into osteoprogenitor cells
• Source initially thought to be from bone marrow
only
• Current evidence – from surrounding soft tissue
and systemic circulation
17
Recruitment of MSC
18
Recruitment of MSC
19
Reparative phase – ossification
20
Reparative phase – ossification
• The soft callus and hard callus formation stage
• Formation of cartilaginous callus which later
undergoes
• Mineralization
• Resorption
• Replaced with new bone
• Revascularisation / neoangiogenesis
21
Intramembranous and endochondral
ossification
22
Intramembranous and endochondral
ossification
23
• The cartilage consists of fibrin-rich granulation
tissue
• This cartilaginous callus forms the soft callus
• Soft callus provides some stability to the fracture
site
• Allows intermembranous ossification to start
subperiosteally at the fracture sites
• Hard callus (woven bone) starts to form here
Intramembranous and endochondral
ossification
24
Intramembranous and endochondral
ossification
25
Intramembranous and endochondral
ossification
26
• Intermembranous ossification would progress
until a subperiosteal cuff is formed across the
fracture site
• Through mineralization, resorption of soft callus
and replacement with hard callus
• Gives more stability to the fracture site
• Allowing endochondral ossification to start
• Allows revascularization across the fracture site
Intramembranous and endochondral
ossification
27
Intramembranous and endochondral
ossification
28
• Starts at outer cuff and grows
inward – intramembranous
ossification
• Starts from the inner edges of
the fracture site to its middle
– endochondral ossification
Revascularisation / neoangiogenesis
29
Revascularisation / neoangiogenesis
• Occurs when cuff of hard callus offers stability
• Important for promotion of fracture healing
• Promoted through 2 pathways
• Angiopoietin pathway – vessel in-growth from
surrounding vessels
• VEGF pathway – main vascularization regulator,
forms new vessels that proliferate within the
callus (vasculogenesis) and angiogenesis (vessel
in-growth)
30
Remodelling
31
Remodelling
32
• Hard callus provides biomechanical stability but
does not return normal bone biomechanic
properties
• This is achieved through remodeling
• Is an ongoing process that may take years to
complete
• By the end:
• Woven bone all becomes lamellar bone
• Return of biomechanical property
• Return of normal alignment
• Formation of medullary cavity
Remodelling
33
• Balance of hard callus resorption by osteoclasts
and lamellar bone lay down by osteoblasts
Remodelling
34
• Influenced by Wolff’s law
Remodelling
35
• Influenced by Wolff’s law
Remodelling
36
• Influenced by Wolff’s law
Remodelling
37
DIRECT BONE HEALING
38
Prerequisites
• Anatomical reduction
• Absolute stability
• Rigid fixation
• Almost no gap at fracture site
• Minimal strain across fracture site
39
Direct bone healing
• Attempt to re-establish an anatomically correct
and biomechanically competent lamellar bone
structure
• Has its prerequisites
• Utilizes cutting cones
• Healing process dependent on gap size
• <0.01mm – contact healing
• 0.01mm – 1mm – gap healing
40
Cutting cones
41
Contact healing
42
Gap healing
43
• Gap will initially be filled with perpendicular
aligned lamellar bone
• Will require secondary resorption
Mechanical influence in bone healing
• Concept of ‘relative stability’
• Concept of ‘absolute stability’
44
Conclusions
• Bone healing is an important aspect of trauma
management that need to be understood
• Surgeons must recognize the importance of
preserving the biology of a fracture to ensure
good healing
• Many areas of this process could be utilized in
managing complications of fracture (e.g. non-
union)
45
46

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