Wound healing

Aetiology of wound – trauma (physical/mechanical), chemical burns, infections, etc.

Wound – is any disruption to tissue caused by injury

Wound healing is achieved in 3 steps:

1. Coagulum formation – blood clot comprised of RBC, WBC, platelets and fibrin; the blood clot
is outside circulation where bleeding has occurred (as opposed to thrombus which is within
blood vessels)
2. Acute inflammation – all the steps of acute inflammation with the exudate and infiltrate
coming in around the wound margin
3. Repair
a. Regeneration
b. Scaring

In some tissue, there is only scaring in others, if the tissue has the potential to regenerate, there is
regeneration and only some scaring.

Types of wounds

1. Contusion – also known “common bruise” or haematoma, whereby blood cells have escaped
the vessels and are now in the tissue; the skin is intact, it is not an open wound
2. Abrasion – also known as “scrape” or “graze”; it is a superficial open wound (within
epidermis), the blood has superficially escaped to the exterior but the margins of the wound
are close together
3. Avulsion – a large opened wound, with the margins wildly apart
4. Puncture – injuries caused by needles where the skin is punctured; deep, penetrating into
underlying tissue, but the margins of the wound are close together
5. Laceration – extensive, deep subcutaneous injured tissue, which is also torn, mangled and
even crushed; if a limb is lacerated it may require amputation
6. Missile – high velocity puncture caused by bullet or arrow, with margins that are close
together but the injury is deep
7. Surgical wound – caused by incisions; there is limited damage and the margins are close
together

Types of healing:

1. Healing by primary intention – in wounds with close together margins e.g. incisions,
abrasions, punctures; there is very limited tissue loss and the healing doesn’t take long
2. Healing by secondary intention – in wounds with margins wild apart e.g. avulsion; there is a
quantitative difference to primary intention with more tissue being lost and longer healing
time, so that more scar tissue is produced; however, the healing process is the same

Wound healing by secondary intension

E.g. skin avulsion wound (big opened wound)

The time line below depends on the size of wound and the patient’s healing capacity.

Day 1 – there is a lot of bleeding, vessels are severed; fibrin escapes into the tissue and forms a fibrin
mesh/coagulum limiting further blood loss; the blood clot or coagulum then starts to dehydrate
forming an eschar, or as commonly known a scab, which protects the underlying tissue from getting
infected; the scab also contracts the wound which minimizes the wound and less scar tissue will
need to form later; also, on day 1, the acute inflammatory process (exudate/infiltrate) starts under
the scab and around the wound margin; so, due to hyperaemia blood rushes to the injury site, the
fluid/exudate with proteins (fibrin) and the infiltrate (WBC, mainly neutrophils) flowing out the
vessels into the area of injury.

Day 2-3 – vascular granulation tissue starts forming (immature scar, pink in colour) which initially is
very vascular because it contains many vascular sprouts – new vessel outgrowths. The granulation
tissue also contains a lot of fibroblasts – collagen deposition and macrophages – phagocytic cells
which act as scavengers of debris from the inflammatory zone. Macrophages also release fibrogenic
and angiogenic factors which promote proliferation of fibroblasts and new blood vessels. This layer
of scar tissue forms underneath the scab and the inflammatory zone with the exudate and infiltrate;
this layer grows inwards and upwards to replace the inflamed and scab tissue.

At the same time re-epithelialisation occurs – which is a regeneration of the epidermis at the
wound margin that migrates towards the injured tissue. And when the margins meet the scab can
be lifted and removed. However, the hair follicles, sebaceous and sweat glands do not regenerate in
the injured area.

Day 3 – 30 - by this time, the fibrous granulation tissue is fully developed. As the granulation tissue
matures, the fibroblast lay more and more collagen and as a result the granulation tissue becomes
more fibrous and less vascular. Collagen becomes denser and denser, compressing on the newly
formed capillaries. During the initial stage of healing the blood vessels are needed to bring in
nutrients to speed up the process of healing, but in later stages these blood vessels are not required
and so they die off as they get compressed by the increasingly more fibrous granulation tissue. At
the same time, some of the fibroblasts start to differentiate and form myofibroblasts which are
specialized fibroblasts that have contractile properties (contain actin and myosin filaments). These
also contribute to wound compression, minimizing the surface area of the wound itself.

At some point within this period the re-epithelialisation is complete and the two sides of the dermis
meet.

Several months – during these period, there is a remodelling of the scar, more and more collagen is
being laid down. Early on, in the healing process the young wound is pink in colour, but later there is
a complete blanching of the scar due to maturing collagen which is an indication of a completely
healed wound.

Summary of Healing by secondary intention

 Blood clot/coagulum with a zone of acute inflammation beneath

 Formation of granulation tissue underneath, which grows into the inflamed tissue to replace
it
 Collagen is synthesized and a collagen scar is formed
 New epithelium – epidermis and dermis regenerates, except specialized structures
 Vessels die off and the scar develops a pale colour (blanching)
Wound healing by primary intention
Same steps as per secondary intention, there is only a quantitative difference to primary intention.

 less tissue is replaced

 no wound contraction is required
 not many myofibroblasts are formed (minimal tissue loss)
 small amount of scar tissue formed (only a small wound)

Debridement = removal of debris; cleaning of a wound is debridement of the wound. Large wounds
e.g. avulsion wounds need to be appropriately cleaned to remove foreign debris, bacteria, necrotic
tissue, excessive blood clot. The infiltrate is part of debridement, nursing a wound is also part of
debridement

Simplification = the closer the wound margins the better; wound margins need to be approximated
e.g. by suture, stitching to diminish time required for healing and minimize scar formation, reduce
the risk of infection

Following debridement and simplification, scaring will be minimized.

Complications of healing
Although scar formation is part of the healing process, excessive scar tissue can interfere with the
normal functioning of tissues.

Cicatrisation – excessive scarring can lead to permanent contracture and deformity of the tissue. It is
important to try to minimize, by surgery or other medical interventions, the granulation tissue
activity - the activity of the myofibroblasts so not a lot of collagen is deposited e.g. 3rd degree burns
that lead to facial or body deformity.

Keloid – for some individuals with a genetic disorder, even a trivial injury e.g. vaccination or insect
bite, could develop masses of collagen – scar tissue, that exceeds the margin of wound area (just
keeps growing). Normal but raised scar tissue is also called keloid but these types of scars do not
grow uncontrollably beyond the wound margins.

Excessive granulation – disruption of tissue due to excessive granulation which impends with wound
closure and healing. The healing process will never reach the stage of blanching of the scar. In this
case, the excessive granulation tissue needs to be removed e.g. ingrown toe nail; the growing nail is
injuring the underlying tissue, then as it grows it disrupts the granulation and inflammation process
causing further injury and the cycle continues, the wound never heals and can lead to infections and
other complications.

Factors that delay wound healing:

Localised
1. Lack of adequate immobilization
Will disrupt the wound; granulation tissue is damaged which will then delay
the healing process
2. Lack of blood supply/O2
Healing is energy dependent, cells need a lot of nutrients to proliferation
3. Previous radiation exposure
Areas of the body that have had radiation would have blood and lymphatic
vessels damage
4. Unsuccessful debridement
Promotes infection and inflammation
5. Infection
The most important factor; there is further tissue damage, more
debridement and in some instances healing cannot occur which leads to
amputation

Generalised

1. Malnutrition
Lack of protein, VitC, Zn which are required for collagen synthesis
2. Age
Slows down of metabolism – slower rate of cell proliferation; higher
incidence of systemic disease e.g. atherosclerosis which slows down blood
flow; malnourishment in older age
3. Hormonal effects
Corticosteroids interfere with the healing tissue, delaying it
4. Low temperature
 Slows the rate of cell proliferation
5. Other systemic diseases
e.g. diabetes – poor blood flow

So far, we’ve been talking about a skin avulsion wound where fibrosis occurs as part of the healing
process. We see fibrosis occurring in most of the solid organs, muscles and cartilage. In some of the
solid organs e.g. liver, some of the cells also regenerate. However, in the brain we don’t see fibrosis;
we see the haematoma (blood clot), the inflammatory process, but we don’t see fibroblasts forming
collagen, but glial cells proliferation which form the scar tissue in the brain; we also see
degranulation tissue, vascular sprouts and microglial cells (macrophage equivalent in the CNS).

In liver cirrhosis we see both fibrosis, scar tissue forming and regeneration of hepatocytes, but if the
insult continues and the liver continues to be injured what we see is more scar tissue deposition and
less regeneration which manifests by the presence of nodules in between scar tissue. If too much
scar tissue accumulates it will impair liver function and the individual will require liver transplant.

Fracture healing
Fracture – loss of continuity and integrity of the structure of the bone (damaged/fractured bone)

Aetiology of fracture – caused by trauma (physical/mechanical damage)

In fractured bone, even if only partial, there is damage and inflammation to the soft tissue
surrounding the bode.

Types of fractures (in broad terms):

1. Partial (simple) or open (compound) fracture - caused by trauma with varying complexities
and healing time
2. Pathological fractures – caused by bone disease e.g. bone cancer, osteoporosis (bone
trabeculae are thinner), osteomalacia (demineralised bones) and are degenerative

Specific types of fractures:

Complete fracture – the whole width of the bone is involved, from one side to the other

Incomplete/partial fracture – only part of the width of the bone is involved

Transverse fracture – the fracture is at a right angle with the axis of the bone and it may be
complete or partial

Oblique fracture – the fracture is at an angle with the axis of the bone
Spiral fracture – the fracture twists apart in a spiral fashion

Avulsion fracture – as small piece of bone breaks off that is attached to another ligament or tendon

Comminuted fracture – the bone is crushed and splinted e.g. trauma from a motor accident

Compound/open fracture – the fractured bone pierces the skin and exposes the wound to the
exterior

Simple fracture – the soft tissue around the fracture are intact, could be complete, transverse or
oblique, etc.

Compression fracture – seen in the vertebrae due to extensive compression on the vertebral column
which results in many little bone fragments; a lot of these fractures are pathological e.g.
osteoporosis when lifting heavy objects

Dislocation fracture – occurs near articulations with the bone dislocating from its join
Double fracture – two breaks in the bone; can be transverse, etc. or complete or incomplete

Greenstick fracture – a partial fracture with a band in the bone; usually occurs in very soft bones in
children, but also in osteomalacia where the bone is pliable

Impacted fracture – part of the bone driven toward or into other part by force

Indirect fracture – the force is applied in one part of the bone but the fracture occurs in another;
usually it occurs where there is disease process

Fracture healing
For the bone to heal correctly the parts that are broken have to be in close apposition and the
fracture should be immobilized. The bone has the capacity to regenerate and therefore the bone
needs to be aligned well to avoid deformities (otherwise it will not set in its anatomically correct
position).

The bone is immobilized with the use of splinters or pins (inlay), in order to keep the bone in close
apposition, plaster casts (outlay) and traction apparatus that can apply traction force which
stimulates healing. At the same time, soft tissue damage needs to be treated to prevent infection
and amputation.

E.g. healing of a complete (whole width), simple (soft tissue is intact) fracture

Day 1 – Haematoma formation (blood clot) due to tearing of blood vessels in the periosteum, cortex
and medullary cavity; blood will pour into the two fractured ends. There is also acute inflammation
in the region of the fracture site with macrophages (v. little neutrophils, unless there is infection)
which phagocytise necrotic debris (including the bony bits which might be necrotic) and haematoma.

Day 1 is similar to any other healing process, but from day 2 something different happens.
Day 2 – Demolition by osteoclast; osteoclasts are activated and they start breaking down (trimming
and decalcifying) the bone at the two ragged ends of the fracture site, clearing and tidying the
fracture site; they also help to remove necrotic bone.

Once the clearing of site is complete the formation of fibrovascular granulation tissue starts.
Granulation tissue forms with fibroblasts and vascular sprouts, ingrowing from surrounding tissue
into the haematoma to try to replace it. However there is not much activity of collagen deposition at
this stage.

Day 2 – 25 – Provisional callus (hard, bony tissue) formation within the margin (internal callus) and
outside the margins (external callus) of a fracture; in the periosteum the mesenchymal precursor
cells differentiate into osteoprogenitor cells, which further differentiate into osteoblasts (make
bone) and chondroblasts (make cartilage). The osteoblasts migrate into the granulation tissue and
deposit osteoid (immature bone) tissue preventing the fibroblasts from depositing collagen; there is
still a bit of collagen made by the fibroblasts, which leaves residual collagen growths after healing.

There is also some cartilage made by the chondroblasts which is seen in the external callus.

This healing stage can be determined by measuring the alkaline phosphatase levels, which are high
during this period of healing, due to high osteoblast activity. With an X-ray bony spicules (minute
sharp-pointed bony bits) can also be seen during this period and are haphazard looking (not orderly).

1 – 3 months – the temporary callus is gradually replaced by definitive callus; osteoclasts break
down the temporary callus, which was laid down in a very irregular pattern by osteoblasts.
Osteoblasts start laying down new bone in a very regular fashion – Haversion system, with the bony
spicules aligned along the line of stress which makes the bone more rigid.

3 – 12 months – remodelling occurs, the surplus bony callus is removed by the activity of
osteoclasts but also by the orderly osteoid synthesis by osteoblasts; the osteoclasts are continually
breaking down the callus and the osteoblasts continually lay down new bone resulting in a near
perfect bone regeneration. It will not be 100% strong, as there is some residual scar tissue both in
the medullary cavity and the soft tissue and muscles surrounding the bone, but the compact lamellar
bone is strong as it regenerates without any scar tissue.
Summary

Aberrations of fracture healing

If too much collagen tissue is laid down at the fracture site there is going to be more collagen tissue
(scar tissue) instead of bone which makes the bone soft and weak at that point. It occurs when
immobilization hasn’t been successful and there is excessive movement, or malalignment – incorrect
fixation whereby the fractured bones are not correctly aligned anatomically when pinned or plaster
casted, or if the soft tissues become interposed between the bony ends. If not corrected by surgery
it can lead to pseudo-arthrosis – false joint. The result is a bone that can have a shorter or longer
length as a result of an aberrant healing process.

There are 3 types of aberrations:

1. Deformity
2. Angulation
3. Displacement

Delaying factors in fracture healing

Localised factors:

1. Movement – very important in fracture

2. Infection – can lead to osteomyelitis – infection of the bone, gangrene
3. Lack of blood supply – can lead to arthroplasty e.g. the femoral head is notorious for poor
blood supply, so if there is a fracture at the neck of the femur we see avascular necrosis of
the femoral head which leads to the requirement of prosthesis – artificial joint implantation
called arthroplasty.
4. Localised bone disease – bone tumours can lead to a delay in healing

Generalised factors:

1. Malnutrition – lack of Ca, proteins, VitD delays regeneration of bone

2. Generalised vascular disease – atherosclerosis will affect blood flow
3. Generalised bone diseases – osteoporosis – weak bones can delay the healing process;
osteomalacia – demineralised bones, soft bones compromise the healing process
4. Other systemic disease - diabetes
5. Increasing age: decrease in the efficiency of bone regeneration

SUMMARY

Soft tissue wound healing involves coagulum formation, acute inflammation, regeneration and
scaring.

The difference between healing by primary intention and secondary intention is quantitative in
relation to scaring and contraction of wound.

Abnormalities of wound healing are cicatrisation, keloid and excessive granulation tissue.

Infection is the most important factor in the delay of healing wound.