Wound Care: The practice and science of wound healing: history and physiology of wound healing
The practice and science of wound healing: history and
physiology of wound healing
Naude L, BCur, MCur (UP), Certificate in Wound Care (UFS), Certificate in Wound Care (Hertfordshire)
Abstract
This is the first in a series of articles focusing on wound management. In this article, I will discuss the history and physiology of
wound healing, utilising a comparison of wound healing to a building site.
Introduction
Wound healing is a complex process influenced by various
factors such as the host (the patient), the environment, and
the multi-disciplinary team.1 Wound care practitioners can no
longer make use of a single modality for the progressive care
of a wound. They must critically select wound healing therapy
according to the phase of healing of each wound.
The first documentation of wound care can be found in the
ancient Egyptian Edwin Smith Papyrus of 1600 BC, with a
description of the removal of devitalised skin and pus following
war injuries.2 The Hippocratic Collection of 400 BC provides us
with some insight into the Greek practice of using drains to
evacuate pus from abscesses.
Joseph Lister introduced the modern “germ theory” by
demonstrating the beneficial effects of carbolic acid in the
dressings of infected wounds at the turn of the century.3
Debridement, skin cleansing and the use of antiseptics became
common practice thereafter. During the same period gloves,
gowns, and masks were introduced by William Halsted, and
silver foil was revived as an antiseptic in dressings.3 Modern
wound care really took off when, in 1908, Elie Metchnikoff
identified and characterised phagocytosis as it applied to
inflammation and wound debridement.4
DP Kane describes the wound environment as part of a
larger human ecosystem, 1 and I couldn’t agree more. No
wound should be treated as an isolated phenomenon. If
each wound is treated as part of a macroenvironment,
this will result in sustainable wound repair. Comorbidities
and other factors that can potentially affect healing
should always be considered. These factors to be
considered include arterial insufficiency, chronic illness,
diabetes mellitus, cancer, surgery, trauma and venous
insufficiency.
Professional Nursing Today
Correspondence to: Liezl Naude, e-mail: liezl@eloquent.co.za
www.eloquent.co.za
Looking at wound healing like a builder
The process of wound healing is explained by Kane as being
similar to that of rebuilding a house after it has been damaged
for some reason.1
According to this model, the major cells responsible for wound
healing are like the builders who have been hired to repair the
house. The initial phase is characterised by the formation of
a temporary platelet plug to stop the bleeding (haemostasis),
which is like the contractors capping the conduits to prevent
further loss. Within the inflammatory phase, the neutrophils
responsible for phagocytosis are represented by the labourers
who have to clean up the landfill. The proliferation phase
depends on the macrophage in the same way as the rebuilding
process depends on the building supervisor on site.
The macrophage is the key mediator in signalling other
“subcontractors” such as the lymphocytes (specific
site preparers or cleaners), angiocytes (plumbers) and
neurocytes (electricians). The fibroblasts can be seen as
the frame workers or builders of reinforcement structures,
the basic building blocks ensuring a solid appearance. The
keratinocytes are the roofers providing the waterproofing
and an external barrier. Remodelling of scar tissue occurs
over the next two years in the same way we would do
interior decorating of our houses.
Matrix metalloproteinases (MMPs), and their effect on the
extracellular matrix (ECM), are missing from this model.5
According to Gibson and Schultz, MMPs form part of the key
proteins that regulate the actions of the wound cells and they
are essential to remove the denatured ECM and to digest
“holes” in the basement membrane surrounding capillaries
to enable vascular endothelial cells to migrate and form new
capillaries. The ECM can also be compared to the blueprint
prepared by the structural engineer or architect, which
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 Wound Care: The practice and science of wound healing: history and physiology of wound healing

provides the plan for the rebuilding project.7 The ECM is key Figure 2: Schematic representation of haemostasis with vaso-
to ensuring that the final product is delivered according to the constriction and platelet releasing growth factors. (Graphics used
building plan. with permission from Dr G Schultz.) It is important to note that fibrin
clot forms a provisional wound matrix that promotes coagulation
and migration of fibroblasts and vascular endothelial cells, and that
Wound healing from a physiological perspective
platelets release growth factors that initiate healing by stimulating
chemotaxis, proliferation, and matrix synthesis.
For wound healing to take place, both the macro- and
microvascular structures must be intact, with adequate
cardiac output and flow to perfuse the wound environment.
Adequate nutrition and a well-balanced and functioning
immune system are also important. Without these, white cell
debridement, bio-burden control and wound repair cannot
take place, resulting in a non-healing wound.

The stages of the wound healing process

Figure 1: The stages of the wound healing process

Injury PDGF
EGF
VEGF
Haemostasis
Aggregated Platelets
Eary Inflammatory
Inflammation Phase TGFß
Late
FGF
Inflammation

Angiogenesis Fibrin net RBC

Proliferation
Phase
Granulation
Inflammation
As soon as the clot stops the bleeding, neutrophils are attracted
Epithelialisation by the inflammatory messengers within the coagulum.
Maturation
Phase The released endothelial prostaglandins, kinins, and hista-
Remodelling
mines promote vasodilatation and neutrophil leakage into
the ECM, along with inflammatory proteins, causing oedema.
These non-specific white cells produce MMPs and reactive
oxygen species (ROS) in order to combat invading microbes
Injury and begin the phagocytic removal of debris and micro-
Tissue injury is followed by the different phases of wound organisms. The cell signalling attracts monocytes, which will
healing. morph into activated macrophages (“Pac-Man cells”). The
macrophages synthesise nitric oxide, creating more toxic
Haemostasis free radicals, vasodilatation and phagocytosis. The activated
The predominant cells active duriadothelium stimulates macrophages are essential and central to the progress
platelets to release factors essential for vasoconstriction towards the proliferative stage.1
and endothelial and other platelet activation,resulting
in the initiation of the coagulation cascade.1 Thrombin, Proliferation
followed by a temporary fibrin clot, causes the initial matrix The predominant cells during this phase are lymphocytes and
to stop bleeding. Complement prostaglandin, vascular fibroblasts. The activated macrophages release several chemical
endothelial transforming growth factors, nitric oxide and activators and messengers to promote healing. Several released
other cytokines are released at the site of injury, resulting growth factors (see Table I) stimulate vessel development and
in the production and migration and attraction of a host of angiogenesis. Connective tissue formation or fibrogenesis of the
inflammatory cells at the wound site. ECM is generated from some of these growth factors.

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 Wound Care: The practice and science of wound healing: history and physiology of wound healing

Figure 3: The inflammatory phase. The proteases and reactive oxygen
species act like cleaners. The neutrophils and the macrophages act
like debris removers
MMPs continue to break down the debris, creating a
granular foundation for the wound. Angiogenesis provides
the “conduits” for further cell migration towards the centre
of the wound. Peripheral keratinocytes migrate there, and
then the “scaffolding” provided by the connective tissue and
fibroblasts for cover and closure of the wound. Fibroblasts
and endothelial cells are the primary cells in the proliferation
phase, which is under T-cell control.

Figure 4: Schematic representation of controlled inflammation.

(Graphics used with permission from Dr G Schultz.) Inflammatory
cells kill micro-organisms by phagocytosis and with free radicals
(O2-, H2O2, HOCl), and release proteases (MMPs, elastase) that remove
denatured ECM components and permit wound healing to proceed
through the inflammatory phase.

Table I: Growth factors involved in wound healing Maturation and remodelling

The fibroblasts are essential for
Growth Factor Abbreviation Source Activity scar remodelling. The remodelling
of the ECM is a very complex
Transforming TGF platelets  angiogenesis process, since it contains collagen,
growth factor macrophages  fibroblast proliferation proteoglycans, fibronectin and
lymphocytes  collagen synthesis elastin. Fibroblasts produce
fibroblasts cell division proteoglycans, and fibronectin
keratinocytes
consists of protein connections
Platelet-derived PDGF platelets  macrophage, fibroblast necessary for wound healing.
growth factor macrophages and smooth muscle cell
keratinocytes migration The average wound contracts
endothelial cells  collagen synthesis by 0.6-0.75 mm/day towards its
fibroblasts
centre, with this process beginning
Fibroblast FGF macrophages  angiogenesis four to five days post-injury.
growth factor fibroblasts  fibroblast proliferation Myofibroblasts are responsible for
 keratinocyte proliferation wound contraction. Keratinocytes
Epidermal EGF platelets  collagen synthesis are responsible for the re-
growth factor macrophages  epithelialisation epithelialisation from the wound
keratinocytes edges. Wound tensile strength
is dramatically increased by the
Hepatocyte HGF macrophages  angiogenesis
growth factor fibroblasts  fibroblast proliferation
process of scar remodelling.
 keratinocyte proliferation This process of scar remodelling
continues for 6-24 months,
Vascular endothelial VEGF endothelium  angiogenesis depending on the duration of
growth factor
wound healing.

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 Wound Care: The practice and science of wound healing: history and physiology of wound healing

Figure 5: The proliferation phase

Proliferation

Figure 6: The maturation or remodelling phase

Maturation

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 Wound Care: The practice and science of wound healing: history and physiology of wound healing

Figure 7: Sequence of molecular and cellular events in skin wound healing. (Graphics used with permission from Dr G Schultz.)

Conclusion 5. Gibson DJ, Schultz G. Chronic wound diagnostic for matrix

metalloproteinase. Wound Heal Southern Afr. 2002;2(2):58-70.
6. Aronow WS. Management of peripheral arterial disease. Cardiol Rev.
A firm knowledge of the different phases of wound healing 2005;13(2):61-68.
will enable the practitioner to understand advanced wound
management. Multiple factors influence wound healing, and
holistic wound management utilising a multidisciplinary
team is important. Each wound and patient is unique
and should be treated as such. By comparing the wound
healing process to that of building or renovating a house
we are able to form a much better visual understanding
of the complexity of wound healing. Just like a blueprint
is followed for building a house, so the body has a similar
plan for which certain requirements must be met in order
to facilitate wound healing. The concept of matching the
right wound healing phase to the specific wound dressing
will be addressed in future articles in this series.

References

1. Kane DP. Chronic wound healing and chronic wound management. In:
Rodeheaver GT, Sibbald RG, Krasner DL, editors. Chronic wound care: a
clinical source book for healthcare professionals. 4th ed. Wayne: Health
Management Publications Inc, 2007; p. 11-24.
2. Majuno G. The healing hand: man and wound in the ancient world.
Cambridge: Harvard University Press; 1975.
3. Helling T, McNabney WK. The role of amputation in the management
of battlefield casualties: a history of two millennia. J Trauma.
2000;49:930-939.
4. Tauber AI. Metchnikoff and the phagocytosis theory. Nature Rev Mol Cell
Biol. 2003;4:897-901

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