physiology of wound healing / dental implant courses by Indian dental academy

 A surgeon’s role in wound management is to create an
environment in which the healing process can proceed in
an optimal fashion.
 As noted by John Hunter, “. . . the injury alone has in
all cases a tendency to produce the disposition and the
means of a cure.”
www.indiandentalacademy.com

 The repair of tissue damage broadly separated into two
processes, regeneration and healing .
 Regeneration refers to growth of cells and tissues to replace lost
structures.
 Wound healing is the effort of tissues to restore normal function
and structure after injury
-To reform barriers to fluid loss and infection,
-limit further entry of foreign organisms and material,
-re-establish normal blood and lymphatic flow patterns,
-restore the mechanical integrity of the injured system.

 The earliest accounts of wound healing date back to about 2000 B.C
 Galen of Pergamum emphasized the importance of maintaining a moist
environment to ensure adequate healing.
 Ambriose Paré found that simply dressed gunshot wounds heal faster and
are less painful than when treated with boiling oil, the previously accepted
method.
 Ignaz Philipp Semmelweis advocated need for washing hands
 Joseph Lister began soaking his instruments in phenol and spraying the
operating rooms, reducing the mortality rates from 50 to 15%.

 Wound healing process is orchestrated by the
carefully regulated release of cytokines
 Growth factors bind to specific receptors on cells
which deliver signals which have two general
effects
 1.stimulation of transcription
 2.regulation of cell entry into the cell cycle

 Polypeptides produced in normal and wounded tissue that
stimulate cellular migration, proliferation, and function.
 Often named for the cells from which they were first derived.
 Names are often misleading, because growth factors have
been demonstrated to have multiple functions.
 Most growth factors are extremely potent and produce
significant effects in nanomolar concentrations.

Growth Factor Wound Cell Origin Cellular and Biologic
Effects
PDGF Platelets, macrophages, monocytes,
smooth muscle cells, endothelial cells
Chemotaxis: fibroblasts,
smooth muscle, monocytes,
neutrophils
Mutagenesis: fibroblasts,
smooth muscle cells:
Stimulation of angiogenesis,
collagen synthesis
FGF Fibroblasts, endothelial cells, smooth
muscle cells, chondrocytes
Angiogenesis
Mitogenesis: mesoderm and
neuroectoderm
fibroblasts, keratinocytes,
chondrocytes, myoblasts
Keratinocyte
growth factor
Keratinocytes, fibroblasts Significant homology with
FGF; stimulates keratinocytes
EGF Platelets, macrophages, monocytes
(also identified in salivary glands,
duodenal glands, kidney, and lacrimal
glands)
Stimulates proliferation and
migration of all epithelial cell
types

Growth Factor Wound Cell Origin Cellular and Biologic
Effects
TGF Keratinocytes, platelets, macrophages,
T lymphocytes, neutrophils,
monocytes
Homology with EGF; binds
to EGF receptor , Mitogenic
and chemotactic for
epidermal and endothelial
cells
Stimulates angiogenesis
TGFβ1 stimulates wound
matrix, β3 inhibits scar
formation
Granulocyte-
macrophage
colony-stimulating
factor
Macrophage/monocytes, endothelial
cells, fibroblasts
Stimulates macrophage
differentiation/proliferation
Insulin-like growth
factors (IGF-I,
IGF-II)
Platelets (IGF-I in high concentrations
in liver; IGF-II in high concentrations
in fetal growth); likely the effector of
growth hormone action
Promote protein/extracellular
matrix synthesisIncrease
membrane glucose transport
Vascular
endothelial growth
factor
Macrophages, fibroblasts,
keratinocytes
Similar to PDGF
Mitogen for endothelial cells
(not fibroblasts)www.indiandentalacademy.com

 Small proteins or glycoproteins secreted for the purpose of
altering the function of target cells in an endocrine
(uncommon), paracrine, or autocrine fashion.
 Pleiotropic

TNF α Macrophages PMN margination and
cytotoxicity, ± collagen
synthesis; provides
metabolic substrate
IL 1 Macrophages Fibroblast and keratinocyte
chemotaxis, collagen
synthesisKeratinocytes
IL 2 T Lymphocytes Increases fibroblast
infiltration and metabolism
IL 6 Macrophages Fibroblast proliferation,
hepatic acute-phase
protein synthesis
PMNs
Fibroblasts
IL 8 Macrophages Macrophage and PMN
chemotaxis, keratinocyteFiroblasts
IFN γ T Lymphocytes Macrophage and PMN
activation; retards collagen
synthesis and cross-
linking;stimulates
collagenase activity
Macrophages







IL 4 T Lymphocytes Inhibition of TNF, IL-1, IL-6 production; fibroblast
proliferation, collagen synthesisBasophils
Mast cells
IL 10 T Lymphocytes Inhibition of TNF, IL-1, IL-6 production; inhibits
macrophage and PMN activationMacrocytes
keratinocytes
Anti inflammatory cytokines

Normal wound healing follows a predictable pattern that can
be divided into overlapping phases defined by characteristic
cellular populations and biochemical activities
(a) Hemostasis and Inflammation
(b) Proliferation
(c) Maturation and Remodeling

Phases of wound healing

 Represents the tissue’s attempt to limit damage
 Closely related with healing process
 Healing impossible without inflammation
The events can be divided into:
1. Vascular events
2. Cellular events

 Earliest manifestation is vasodilatation, it follows a transient
constriction of arterioles lasting a few seconds.
 Wounding disrupts tissue integrity and direct exposure of
extracellular matrix to platelets
 Initial contact between platelets and collagen requires the von
Willebrand factor (vWF)
 Binding results in changes in platelet conformation, triggering
intracellular signal transduction pathways that result in platelet
activation and the release of biologically active proteins.

 Platelet α granules are storage organelles that contain
-Platelet-derived growth factor (PDGF),
-Transforming growth factor(TGF)-β,
-Insulin-like growth factor (IGF)-1,
-Fibronectin,
-Fibrinogen,
-Thrombospondin,
-vWF.
 The dense bodies contain the vasoactive amines, such as serotonin, which
cause vasodilation and increased vascular permeability.
 The clotting cascade is initiated through both the intrinsic and the
extrinsic pathways.

 Vasodilation is followed by increased permeability of the microvasculature,
followed by stasis, which leads to accumulation of leucocytes along the
vascular endothelium which then migrate through the vascular wall into the
interstitial tissue.
 Increased permeability is due to
- formation of endothelial gaps in venules,
- direct endothelial injury,
- delayed prolonged leakage,
- leucocyte mediated endothelial injury,
-increased transcytosis and leakage from new vessels
 The combination of intense vasodilation and increased vascular
permeability leads to clinical findings of inflammation,
rubor (redness), tumor (swelling),calor (heat), and dolor (pain).

Cellular infiltration after injury follows a characteristic,
predetermined sequence .

 First infiltrating cells to enter the wound site, peaking at 24 to 48 hours
 Neutrophil migration is stimulated by
- Increased vascular permeability,
- local prostaglandin release, and
- the presence of chemotactic substances, such as
complement factors, interleukin-1 (IL-1), tumor necrosis
factor alpha (TNF-α), TGF β, platelet factor 4, or bacterial
products.
 PMNs are also a major source of cytokines early during inflammation,
especially TNF-α, also release proteases such as collagenases.
 Following functional activation neutrophils scavenge necrotic debris, foreign
material, and bacteria.

 Stimulated neutrophils generate free oxygen radicals with
electrons donated by the reduced form of nicotinamide adenine
dinucleotide phosphate, (NADPH).
 The electrons are transported across the membrane into
lysosomes where superoxide anion (O2-
) is formed.
 This very potent free radical is bactericidal, but it is also toxic
to neutrophils and surrounding viable tissues.
 Migration of PMNs stops when wound contamination has been
controlled, usually within the first few days after injury.

 PMNs do not survive longer than 24 hours
 If wound contamination persists or secondary infection occurs,
continuous activation of the complement system and other
pathways provides a steady supply of chemotactic factors,
resulting in a sustained influx of PMNs into the wound.
 PMNs are not essential to wound healing because their role in
phagocytosis and antimicrobial defense may be taken over by
macrophages.
 Sterile incisions will heal normally without the presence of
PMNs

 Second population of inflammatory cells that invades the wound.
 Macrophage is the one cell that is truly central to wound healing, serving to
orchestrate the release of cytokines and stimulate many of the subsequent
processes of wound healing
 Derived from circulating monocytes, achieve significant numbers in the
wound by 48 to 96 hours post injury and remain present until wound healing
is complete.
 Chemotactic factors specific for monocytes include
-bacterial products, -fibronectin,
-complement degradation products (C5a), -collagen,
-thrombin, -TGF-β

1.Macrophages induce PMN apoptosis
2. Macrophages have specific receptors for IgG (Fc-receptor), C3b (CR1
and CR3), and fibronectin (integrin receptors), which permit surface
recognition of opsonized pathogens and facilitate phagocytosis.
3. Activated wound macrophages also produce nitric oxide which has
antimicrobial properties.
4. Phospholipase is induced, causing enzymatic degradation of the cell
membrane phospholipids, releasing thromboxane A2 and prostaglandin
F2α

5. Releases leukotriene B4 ,a potent neutrophil chemoattractant,
and C4 and 15- and 5-hydroxyeicosatetraenoic acid.
6. Release proteinases, including matrix metalloproteinases (MMP-
1, MMP-2, MMP-3, and MMP-9) which degrade the ECM and
are crucial for removing foreign material, promoting cell
movement through tissue spaces, and regulating ECM turnover.
7. Release growth factors that stimulate fibroblast, endothelial cell,
and keratinocyte proliferation

 Another population of inflammatory/immune cells that routinely
invades the wound.
 Less numerous than macrophages, numbers peak at about 1 week
post injury
 Bridge the transition from the inflammatory to the proliferative
phase of healing
 Depletion of most wound T lymphocytes decreases wound strength
and collagen content
 Also exert a down regulating effect on fibroblast collagen synthesis
by cell-associated interferon-γ, TNF-α, and IL-1.

 Second phase of wound healing and roughly spans days 4
through 12
 It is during this phase that tissue continuity is re-established
 Fibroblasts and endothelial cells are the last cell populations
to infiltrate the healing wound, and the strongest chemotactic
factor for fibroblasts is PDGF.
 Recruited fibroblasts first need to proliferate, and then
become activated, to carry out their primary function of
matrix synthesis remodeling.

Proliferation Phase contd..
The four major events are
1. Fibroplasia
2. Angiogenesis
3. Epithelialization
4. Contraction

 The proliferative phase begins with degradation of the initial
fibrin-platelet provisional matrix.
 During fibroplasia, fibroblasts synthesize and deposit the
replacement ECM at the wound site
 As fibroblasts proliferate, they become predominant cell types
by 3 to 5 days in clean, non infected wounds.
 The initial fibrin matrix is replaced by a provisional matrix of
fibronectin and hyaluron, which facilitates fibroblast migration.

 Specialized cells that differentiate from resting mesenchymal
cells in connective tissue
 They do not arrive in the wound cleft by diapedesis from
circulating cells.
 After injury, the normally quiescent and sparse fibroblasts are
chemoattracted to the inflammatory site, where they divide and
produce the components of the ECM.

 Normally arrested in the G0 phase
 Undergoes replication and proliferation after stimulation by
macrophage and platelet-derived cytokines and growth factors
 Time required for undifferentiated mesenchymal cells to
differentiate into highly specialized fibroblasts accounts for the
delay between injury and the appearance of collagen in a healing
wound.

 Cells grow, move, and differentiate in intimate contact with
macromolecules outside the cells that constitute the ECM.
 Secreted locally and assembles into a network in the spaces
surrounding cells
 Forms a significant proportion of the volume of any tissue.

 Matrix protein sequester water that provide turgor to soft tissue
and minerals that give rigidity to skeletal tissues
 Reservoir for growth factors controlling cell proliferation
 Provide cell to cell interaction and substratum for cells to
adhere, migrate, and proliferate

 1.Fibrous structural proteins such as collagen and
elastins
 2. Adhesive glycoproteins or cell adhesion molecules
 3. Proteoglycans and hyaluronic acid
 4. Basal Lamina

Collagen :
Most common protein in the animal world providing the extracellular
framework for all multicellular organisms
 Its deposition, maturation, and subsequent remodeling are essential
to the functional integrity of the wound.
 At least 27 types of collagen encoded by 41 genes dispersed on
atleast 14 chromosomes,

 Type I collagen is the major component of extracellular matrix in skin.
 Type III, normally present in skin, becomes more prominent and important
during the repair process
 Type IV is non fibrillar, main component of basement membrane together
with laminin.
 Each chain of collagen is composed of a glycine residue in every third
position. The second position in the triplet is made up of proline or lysine

Collagen synthesis, as well as post translational modifications, is
highly dependent on systemic factors such as
1. an adequate oxygen supply
2. the presence of sufficient nutrients (amino acids and
carbohydrates)
3. cofactors (vitamins and trace metals)
4. the local wound environment (vascular supply and lack of
infection).

Provide the resilience to allow for recoil after transient stretch.
 Elastin is composed of hydrophobic and alanine- and lysine-
rich α-helical segments that alternate along the polypeptide
chain
 Elastic fibers consist of an elastin core covered with a sheath of
microfibrils, which are composed of several distinct
glycoproteins, such as fibrillin.
 Microfibrils appear before elastin in developing tissues and
seem to form a scaffold on which the secreted elastin molecules
are deposited.

 Located in the cell membrane where they function as receptors or they are
stored in the cytoplasm.
 Provide interaction between the same cells(homotypic) or different
cells(heterotypic).
 Integrin
Family of cell surface receptors that are closely coupled with the cell’s
cytoskeleton
Serve two major functions:
(1) to interact with components of the ECM, such as fibronectin, and to
provide adhesion and
(2) to provide signal transduction to the cell interior.

 Crucial for cell motility and are required in inflammation and normal
wound healing
 Following extravasation, PMNs, attracted by chemotaxins, migrate
through the ECM by means of transient interactions between integrin
receptors and their ligands.
Four phases of integrin-mediated cell motility have been described
 Adhesion
 Spreading
 Contractility or traction
 Retraction

Spreading is characterized by the development of lamellipodia and filopodia.
Traction at the leading edge of the cell develops through binding of the integrin,
followed by translocation of the cell over the adherent segment of the plasma
membrane.
The integrin is shifted to the rear of the cell and releases its substrate, permitting cell
advancement. Binding sites for integrins have been identified on collagen, laminin,
and fibronectin

 Glycosaminoglycans comprise a large portion of the "ground substance"
that makes up granulation tissue
 The polysaccharide chain is made up of repeating disaccharide units
composed of glucuronic or iduronic acid and a hexosamine, which is
usually sulfated.
Four types of GAGS exist:
(1) hyaluronan
(2) chondroitin sulfate and dermatan sulfate
(3) heparan sulfate
(4) keratan sulphate
 Major glycosaminoglycans present in wounds are dermatan and
chondroitin sulfate
 Fibroblasts synthesize these compounds, increasing their concentration
greatly during the first 3 weeks of healing

 Functions
1. Role in chemical signaling, by binding various secreted
signal molecules, such as growth factors, and modulating
their signaling activity.
2. Also bind other secreted proteins, such as proteases and
protease inhibitors
3. Act as coreceptors that work with other cell surface
receptor proteins, binding cells to the ECM and initiating
the response of cells to extracellular signaling proteins.

 Proteoglycans Contd….
 As scar collagen is deposited, the proteoglycans are incorporated into
the collagen scaffolding.
 With scar maturation and collagen remodeling, the content of
proteoglycans gradually diminishes
 The ECM has other noncollagen proteins, such as the fibronectins,
that have multiple domains and can bind to other matrix
macromolecules and cell surface receptors.
Fibronectin exists as soluble and fibrillar isoforms
Soluble plasma fibronectin circulates in various body fluids,
enhancing blood clotting, wound healing, and phagocytosis
The highly insoluble fibrillar forms assemble on cell surfaces and are
deposited in the ECM.

 Flexible, thin (40- to 120-nm thick) mats of specialized ECM
that separate cells and epithelia from the underlying or
surrounding connective tissue
 In the skin, the basal lamina is tethered to the underlying
connective tissue by specialized anchoring fibrils
 This composite of basal lamina and collagen is the basement
membrane
 Most mature basal laminae contain type IV collagen and the
glycoproteins laminin .

The basal lamina serves numerous functions
1. As a molecular filter, preventing passage of macromolecules
(i.e., in kidney
glomerulus)
2. As a selective barrier to certain cells (i.e., the lamina beneath
the
epithelium prevents fibroblasts from contacting epithelial
cells, but does not stop macrophages or lymphocytes)
3. As a scaffold for regenerating cells to migrate
4. Is important in tissue regeneration where the basal
lamina survives.

Laminins
Consist of three long polypeptide chains (α, β, and γ). Many of
the cell surface receptors for type IV collagen and laminin are
members of the integrin family.

 Fibronectin and the GAG hyaluronic acid compose the initial wound matrix
 Hyaluronic acid provides a matrix that enhances cell migration because of its
large water of hydration
 Adhesion glycoproteins including fibronectin, laminin, and tenascin, are
present throughout the early matrix and facilitate cell attachment and
migration.
 Integrin receptors on cell surfaces bind to the matrix GAGs and
glycoproteins
 As fibroblasts enter and populate the wound, they secrete hyaluronidase to
digest the provisional hyaluronic acid rich matrix, and larger, sulfated GAGs
are subsequently deposited
 Concomitantly, new collagen is deposited by fibroblasts onto the fibronectin
and the GAG scaffold in a disorganized manner, resulting in scar formation.

 Dense population of blood vessels, macrophages and fibroblast
embedded within a loose provisional matrix of fibronectin,
hyaluronic acid and collagen.
 Clinically characterized by its beefy red appearance, proud flesh
and is present in open wounds.
 Consequence of the rich bed of new capillary networks that form
by endothelial cell division.
 The directed growth of vascular endothelium is stimulated by
platelet and activated macrophage and fibroblast products.
 Granulation tissue is a clinical indicator that an open wound is
amenable to skin graft treatment.

 Process of new blood vessel formation
 Macrophage orchestrates angiogenesis during the inflammatory phase.
Angiogenesis is by
1.Degradation of the basement membrane of postcapillary venules
2.Migration of cells through this gap promoted by FGF, PDGF, and TGF-β.
PECAM-1, also found on endothelial cells, modulates their interaction with each
other as they migrate into the wound
3.Tubule or lumen formation involving cell-cell and cell-matrix interactions. New
capillaries differentiate into arterioles and venules, whereas others undergo
involution and apoptosis, with ingestion by macrophages.
4.Deposition of the basement membrane resulting in capillary maturation.

 Process in which the surrounding skin is pulled circumferentially toward an open
wound.
 Does not occur with closed surgical incisions.
 Decrease in the size of the wound dramatically without new tissue formation.
 Speeds wound closure compared to epithelisation and scar formation alone
 The amount of contraction is related to both the size of the wound and the
mobility of the skin.
 In humans contractions is greatest in the trunk and perineum, least on the
extremities, and intermediate on the head and neck.

Cellular mechanisms are not well understood.
1.Contractile forces are likely to be generated by myofibroblasts, which are
fibroblast like cells that contain smooth muscle actin and microfilaments
in their cytoplasm.
2.Membranemetalloproteinases
 Appear to be important for wound contraction. Stromelysin-1 (MMP-3)
strongly affects wound contraction.
 May be necessary to allow cleavage of the attachment between the
fibroblast and the collagen so that the lattice can be made to contract.
Wound contraction must be distinguished from contracture.
 Clinically, contracture is defined as tissue shortening or distortion that
causes decreased joint mobility and function. Scar contracture commonly
refers to decreased function in the area, whereas scar contraction refers to
shortening of the scar length compared with the original.

 New epithelial cells for wound closure are provided by fixed
basal cells in a zone near the edge of the wound
 The epidermal cell layer thickens and the marginal basal cells
migrate over the wound defect. Once these keratinocytes
begin migrating they do not divide until epidermal continuity
is restored.
 Daughter cells flatten and migrate over the wound as a sheet,
moving in a leapfrog and tumbling fashion (epiboly).

 Migration of keratinocytes over the wound is guided by cell
adhesion glycoproteins, such as tenascin and fibronectin,
which are their “railroad tracks”.
 After re-establishment of the epithelial layer, keratinocytes
and fibroblast secrete laminin and type IV collagen to form
basement membrane
 Keratinocytes become columnar and divide to restore the
layering of the epidermis and reform a barrier.

 The migrating cells dissect the wound, separating the
desiccated eschar from the viable tissue
 If the basement membrane zone is intact, epithelialization
proceeds more rapidly. If not intact, it will be repaired first
 After the wound is completely re-epithelialized, the cells
become columnar and stratified again, while firmly attaching
to the re-established basement membrane and underlying
dermis

 The ECM is dynamic and is constantly undergoing remodeling
 Collagen cross linking decreases its degradation and improves
wound tensile strength.
 Lysyl oxidase is the major intermolecular cross linking enzyme.
 Degradation is by collagenases, gelatinases and matrix
metalloproteinases
 Scar formation is the ultimate outcome of wound repair in children
and adults
 The ultimate pattern of collagen in scar is one of densely packed
fibres and not the reticular pattern found in unwounded dermis

 Scar has no epidermal appendages (hair follicles and sebaceous glands)
and it has a collagen pattern that is distinctly different from the
unwounded skin
 Remodeling occurs during months to years to form a mature scar.
 The early scar appearance is red due to its dense capillary network
induced at the injury site
 Scars are usually hypo pigmented after full maturation.
 However can become hyper pigmented in darker pigmented patients and
in those lighter pigmented patients who receive sun exposure.

 During remodeling, wounds gradually become stronger with time.
 Wound tensile strength increases rapidly from 1 to 8 weeks after
wounding and correlates with collagen cross linkage.
 It increases at a slower pace till 1 year.
 Tensile strength of the wound best reaches only 80% that of
unwounded skin.

 Age
 Infections
 Nutrition
 Hypoxia
 Anaemia
 Hypoperfusion
 Metabolic disorders
 Steroids and chemotherapeutic drugs
 Ionising radiation

AGE
 Aging produces intrinsic physiologic changes that result in delayed
or impaired wound healing.
 With aging, collagen undergoes qualitative and quantitative
changes.
 Dermal collagen content decreases with aging and aging collagen
fibers show distorted architecture and organization.
 The increased incidence of cardiovascular disease, metabolic
diseases (diabetes mellitus, malnutrition, and vitamin deficiencies),
cancer all contribute to the higher incidence of wound problems in
the elderly

Infections
Probably the most common cause of healing delays
 If the bacterial count in the wound exceeds 105organisms per
gram of tissue, or if any β-hemolytic streptococci are present, the
wound will not heal by any means.
 Bacteria prolong the inflammatory phase and interfere with
epithelialization, contraction, and collagen deposition.
 Endotoxins stimulate phagocytosis and release of collagenase
 Bacteria may accelerate expression or increase concentrations of
MMPs, growth factors, and cytokines in chronic-type wounds.

Infections
 Inactive precursors of MMPs are activated by bacterial proteinases
of the thermolysin family (Pseudomonas, Vibrio, and Serratia)
 Bacterial phospholipase C can disrupt normal reepithelialization by
decreasing cell-cell contact and increasing cell migration, possibly
by altering integrin expression and by upregulating MMP-9.

Nutrition
Precise calorie requirements for optimal healing has not been determined.
 Malnourished patients have diminished hydroxyproline accumulation
(an index of collagen deposition) into subcutaneously implanted
polytetrafluoroethylene tubes when compared to normally nourished
patients.
 Malnutrition correlates clinically with enhanced rates of wound
complications and increased wound failure after diverse surgical
procedures.

Nutrition - Arginine
 Arginine deficiency results in decreased wound-breaking strength and
wound collagen
 The main effect of arginine on wound healing is to enhance wound
collagen deposition.
 As increases in breaking strength during the first weeks of healing are
directly related to new collagen synthesis
 Arginine supplementation may result in an improvement in wound
strength as a consequence of enhanced collagen deposition

Nutrition - Vitamin A
 Deficiency impairs wound healing, whereas supplemental vitamin A benefits
wound healing in non deficient humans and animals.
 Vitamin A increases the inflammatory response in wound healing, probably by
increasing the lability of lysosomal membranes.
 There is an increased influx of macrophages, with an increase in their activation
and increased collagen synthesis.
 Directly increases collagen production and epidermal growth factor receptors
when it is added in vitro to cultured fibroblasts.
 Supplemental vitamin A can reverse the inhibitory effects of corticosteroids on
wound healing.

Nutrition - Scurvy, or vitamin C deficiency
 Leads to a defect in wound healing, particularly via a failure in collagen
synthesis and cross-linking.
 Vitamin C is required for the conversion of proline and lysine to
hydroxyproline and hydroxylysine, respectively.
 Vitamin C deficiency has also been associated with an increased incidence of
wound infection
Zinc
 In deficiency states there is decreased fibroblast proliferation, decreased
collagen synthesis, impaired overall wound strength, and delayed
epithelialization.

Hypoxia, Anemia, and Hypoperfusion
Low oxygen tension has a profoundly deleterious effect on all aspects
of wound healing.
 Fibroplasia is significantly impaired by local hypoxia.
 Optimal collagen synthesis requires oxygen as a cofactor
 Factors affecting local oxygen delivery
-systemic reasons (low volume or cardiac failure)
-local causes (arterial insufficiency, local vasoconstriction, or
excessive tension on tissues).
 The level of vasoconstriction of the subcutaneous capillary bed is
exquisitely responsive to fluid status, temperature, and hyperactive
sympathetic tone as is often induced by postoperative pain.

Steroids and Chemotherapeutic Drugs
 Large doses or chronic usage of glucocorticoids reduce collagen
synthesis and wound strength.
 Major effect is to inhibit the inflammatory phase of wound healing
and the release of lysosomal enzymes
 Steroids also inhibit epithelialization and contraction and contribute
to increased rates of wound infection, regardless of the time of
administration
 All chemotherapeutic antimetabolite drugs adversely affect wound
healing by inhibiting early cell proliferation and wound DNA and
protein synthesis

Metabolic Disorders
1. Diabetes Mellitus
 Uncontrolled Diabetes results in reduced inflammation,
angiogenesis, and collagen synthesis.
 The accompanying large and small vessel disease contributes to
local hypoxemia.
 Defects in granulocyte function, capillary ingrowth, and fibroblast
proliferation all have been described in Diabetes.

Metabolic Disorders - Diabetes Mellitus contd..
 Obesity, insulin resistance, hyperglycemia, and diabetic renal failure
contribute significantly and independently to the impaired wound
healing observed in diabetics.
 Reduced expression of growth factors like VEGF, IGF 1 FGF 1
KGF and PDGF
 Diabetic fibroblasts and keratinocytes have reduced proliferation
rates and collagen production.

Metabolic Disorders
2. Uremia
 Associated with disordered wound healing.
 Experimentally, uremic animals demonstrate decreased wound
collagen synthesis and breaking strength

Ionizing Radiation
 Causes endothelial cell injury with endarteritis resulting in atrophy,
fibrosis, and delayed tissue repair
 Angiogenesis is not initiated
 Rapidly dividing cell populations like keratinocytes and fibroblasts
are most sensitive to radiation.

Type of wound Features
Clean 1. No hollow viscus entered
2. Primary wound closure
3. No inflammation
4. No breaks in septic technique
5. Elective procedure
Clean contaminated 1. Hollow viscus entered but controlled
2. No inflammation
3. Primary wound closure
4. Minor break in aseptic technique
5. Mechanical drain used
6. Bowel preparation preop
Contaminated 1. Uncontrolled spillage from viscus
2. Inflammation apparent
3. Major break in aseptic technique
Dirty 1. Untreated, uncontrolled spillage from viscus
2.Pus in operative wound
3.Open suppurative wound, severe inflammation

 Healing in surgical wounds

 The smallest suture required to hold the various layers of the wound in
approximation should be selected in order to minimize suture-related
inflammation.
 Nonabsorbable or slowly absorbing monofilament sutures are most suitable for
approximating deep fascial layers, particularly in the abdominal wall.
 Subcutaneous tissues should be closed with braided absorbable sutures, with
care to avoid placement of sutures in fat.
 Drains may be placed in areas at risk of forming fluid collections. In areas of
significant tissue loss, rotation of adjacent musculocutaneous flaps may be
required to provide sufficient tissue mass for closure.
 In areas with significant superficial tissue loss, split-thickness skin grafting
(placed in a delayed manner to assure an adequate tissue bed) may be required

 Antibiotics
Should be used only when there is an obvious wound infection.
• Signs of infection to look for include erythema, cellulitis, swelling,
and purulent discharge.
• Indiscriminate use of antibiotics should be avoided to prevent
emergence of multidrug resistant bacteria.
• Antibiotic treatment of acute wounds must be based on organisms
suspected to be found within the infected wound and the patient's
overall immune status.
• Antibiotics can also be delivered topically as part of irrigations or
dressings, although their efficacy is questionable.

 Dressings
• The main purpose of wound dressings is to provide the ideal environment for
wound healing.
• The dressing should facilitate the major changes taking place during healing to
produce an optimally healed wound.
• Desired Characteristics of Wound Dressings to
-Promote wound healing (maintain moist environment)
-Conformability
-Pain control
-Odor control
-Nonallergenic and nonirritating
-Permeability to gas Safety
-Nontraumatic removal
-Cost-effectiveness
-Convenience

Dressings
 Covering a wound with a dressing mimics the barrier role of epithelium
and prevents further damage.
 Application of compression provides hemostasis and limits edema.
 Occlusion of a wound with dressing material helps healing by controlling
the level of hydration and oxygen tension within the wound.
 It also allows transfer of gases and water vapor from the wound surface to
the atmosphere.
 Occlusion affects both the dermis and epidermis, and it has been shown
that exposed wounds are more inflamed and develop more necrosis than
covered wounds.

 Occlusion also helps in dermal collagen synthesis and epithelial cell
migration and limits tissue desiccation. As it may enhance bacterial
growth, occlusion is contraindicated in infected and highly exudative
wounds.
Dressings can be classified as primary or secondary.
A primary dressing is placed directly on the wound and may provide
absorption of fluids and prevent desiccation, infection, and adhesion of a
secondary dressing.
A secondary dressing is one that is placed on the primary dressing for further
protection, absorption, compression and occlusion

For incisional wounds, dressings optimally include several layers with
different functions.
 1. The layer immediately adjacent to the wound must be sterile and
non adhering and should not be occlusive. A fine meshed gauze
impregnated with a hydrophilic substance meets these demands.
 2. The layer over the contact layer should be absorptive and should
wick exudates or transudate away from the wound surface. Wide
meshed gauze facilitates this capillary action and drainage. Such
absorptive layers must not become saturated which will then collect
on the wound surface and cause maceration.
 3. The outermost layer of the dressing is the binding layer that fixes
the dressing in place. Tape is commonly used, though wraps are
used in extremities.

Dressings
 The type of dressing to be used depends on the amount of wound
drainage.
 A nondraining wound can be covered with a semiocclusive dressing.
-Drainage of less than 1 to 2 mL/d may require a semiocclusive or
absorbent nonadherent dressing.
-Moderately draining wounds (3 to 5 mL/d) can be dressed with a
nonadherent primary layer plus an absorbent secondary layer plus
an occlusive dressing to protect normal tissue.
-Heavily draining wounds (>5 mL/d) require a similar dressing to
moderately draining wounds, but with the addition of a highly
absorbent secondary layer

Absorbent Dressings
 Accumulation of wound fluid can lead to maceration and
bacterial overgrowth.
 The Dressing should absorb without getting soaked through, as
this would permit bacteria from the outside to enter the wound.
 The dressing must be designed to match the exudative properties
of the wound and may include cotton, wool, and sponge.

Nonadherent Dressings
 Nonadherent dressings are impregnated with paraffin, petroleum jelly, or
water-soluble jelly for use as nonadherent coverage.
 A secondary dressing must be placed on top to seal the edges and prevent
desiccation and infection.
Occlusive and Semiocclusive Dressings
 Occlusive and semiocclusive dressings provide a good environment for
clean, minimally exudative wounds.
 These film dressings are waterproof and impervious to microbes, but
permeable to water vapor and oxygen.

Hydrophilic and Hydrophobic Dressings
 Hydrophilic and hydrophobic dressings are components of a
composite dressing.
 Hydrophilic dressing aids in absorption, whereas a hydrophobic dressing
is waterproof and prevents absorption.
Hydrocolloid and Hydrogel Dressings
 Attempt to combine the benefits of occlusion and absorbency.
 Form complex structures with water, and fluid absorption occurs with
particle swelling, which aids in atraumatic removal of the dressing.
 Absorption of exudates by the hydrocolloid dressing leaves a yellowish-
brown gelatinous mass after dressing removal that can be washed off.
 Hydrogel is a cross-linked polymer that has high water content.
 Hydrogels allow a high rate of evaporation without compromising wound
hydration, which makes them useful in burn treatment.

 Absorbable Materials
Are mainly used within wounds as hemostats and include collagen,
gelatin, oxidized cellulose, and oxidized regenerated cellulose
 Medicated Dressings
 Used as a drug-delivery system.
 Agents include benzoyl peroxide, zinc oxide, neomycin, and
bacitracin-zinc.
 These agents have been shown to increase epithelialization by
28%.

 Mechanical Devices
 Augments and improves on certain functions of dressings, in particular
the absorption of exudates and control of odor.
 The vacuum-assisted closure system assists in wound closure by
applying localized negative pressure to the surface and margins of the
wound.
 The negative pressure therapy is applied to a special foam dressing cut
to the dimensions of the wound and positioned in the wound cavity or
over a flap or graft.
 This form of therapy has been found to be effective for chronic open
wounds (diabetic ulcers and stages 3 and 4 pressure ulcers), acute and
traumatic wounds, flaps and grafts.

Skin Replacements
Conventional Skin Grafts:
 Skin grafts have long been used to treat both acute and chronic
wounds.
 Split- or partial-thickness grafts consist of the epidermis plus part of
the dermis, whereas full-thickness grafts retain the entire epidermis and
dermis.
 Split-thickness grafts require less blood supply to restore skin
function.
 The dermal component of full-thickness grafts lends mechanical
strength and resists wound contraction better, resulting in improved
cosmesis

Skin Replacements
Skin Substitutes
 Manufactured by tissue engineering, they combine novel materials with living
cells to provide functional skin substitutes, providing a bridge between dressings
and skin grafts.
 Have advantages of being readily available, not requiring painful harvest, and they
may be applied freely or with surgical suturing.
 They promote healing, either by stimulating host cytokine generation or by
providing cells that may also produce growth factors locally.
 Disadvantages include limited survival, high cost, and the need for multiple
applications .
 Allografting, albeit with a very thin graft, may at times be required to accomplish
complete coverage.

Skin Replacements
 Skin Substitutes
 The acellular (e.g., native collagen or synthetic material) component acts as a
scaffold, promotes cell migration and growth, and activates tissue
regeneration and remodeling.
 The cellular elements re-establish lost tissue and associated function,
synthesize extracellular matrix components, produce essential mediators such
as cytokines and growth factors, and promote proliferation and migration.
 Bioengineered skin substitutes have evolved from keratinocyte monolayers to
dermal equivalents to split-thickness products with a pseudoepidermis and,
most recently, to products containing both epidermal and dermal components
that resemble the three-dimensional structure and function of normal skin .

Growth Factor Therapy
 Growth factors for clinical use may be either recombinant or
homologous/autologous.
 Autologous growth factors are harvested from the patient's own platelets,
yielding an unpredictable combination and concentration of factors, which are
then applied to the wound.
 Recombinant molecular biologic means permit the purification of high
concentrations of individual growth factors.
 At present, only platelet-derived growth factor BB (PDGF-BB) is currently
approved by the Food and Drug Administration for treatment of diabetic foot
ulcers.
 A great deal more needs to be discovered about the concentration, temporal
release, and receptor cell population before growth factor therapy is to make a
consistent impact on wound healing.

Remember
Treat the WHOLE patient
and not just the HOLE
in the patient

physiology of wound healing / dental implant courses by Indian dental academy

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