WOUND HEALING AND

MANAGEMENT OF CHRONIC
WOUNDS

Presenter-Dr Gautam Kalra

Department of Plastic and Reconstructive Surgery
CONTENTS
• DEFINITION OF WOUND
• CLASSIFICATION OF WOUNDS- ACUTE AND CHRONIC
• STAGES OF WOUND HEALING
• FACTORS FACILITATING WOUND HEALING
• FACTORS INHIBITING WOUND HEALING
• CHRONIC WOUNDS AND TYPES OF CHRONIC WOUNDS
• FACTORS TO CONSIDER IN CHRONIC WOUND
• MANAGEMENT OF A CHRONIC WOUNDS
• RECENT ADVANCES IN MANAGEMENT OF CHRONIC WOUND
DEFINTION OF WOUND AND TYPES
• Wound is a physical trauma where by the integrity of skin or any
tissue is compromised.

• It is a separation or discontinuity of skin or mucus membrane or

tissue due to physical, chemical and biological insult.
 ACUTE AND CHRONIC WOUNDS
ACUTE WOUND CHRONIC WOUND

Usually heal in anticipated time frame Wounds fail to heal in anticipated time frame and often
reoccur

Immediate to few weeks duration Duration 4 weeks to 3 months

Eg. Acquired due to trauma or surgical procedure Occur as a result of an underlying condition like extended
pressure on tissues, poor circulation or poor nutrition.

Eg. Pressure ulcers, venous ulcers, diabetic foot ulcer.

STAGES OF WOUND HEALING
1. Stage of Haemostasis

2. Stage of Inflammation

3. Stage of Proliferation

4. Stage of Remodelling
Timeline of wound healing- 4 phases do not follow
linear order but overlap in time
STAGES OF WOUND HEALING
I) HEMOSTASIS
• Injury → lacerated vessel → transient vasoconstriction. (minutes to few hours)
• Thromboplastic tissue products (subendothelium) exposed.

• Platelet aggregation → hemostatic plug.

• Intrinsic + extrinsic coagulation pathway activation
↓
Prothrombin → Thrombin
↓
Fibrinogen → Fibrin → Stable clot

Thrombus formed => haemostasis achieved

STAGES OF WOUND HEALING
II STAGE OF INFLAMMATION (Duration- upto 3days, can extend to 7 days)
• Tissue injury triggers an acute-phase inflammation (Latin, inflammare, to set on
fire).

• Series of responses of vascularized tissues of the body to injury.

• Inflammation give rise to the macroscopic events (Celsus), namely,

• rubor (redness)
• tumor (swelling)
• calor (heat)
• dolor(pain)
• The acute inflammatory process, triggered rapidly after injury
or invasion by foreign microbes.

• characterized by vascular permeability, edema, and a cellular

response dominated by neutrophils.

• Insults that trigger the acute inflammation include

• infections (bacterial, viral, fungal, parasitic),
• Trauma
• tissue necrosis and ischemia
• foreign bodies
• Hypersensitivity reactions.
STAGE OF INFLAMMATION
• Formation of the clot is dependent on platelet activation.
• This platelet-rich blood clot also entraps polymorphonuclear cells (neutrophils).

• In a matter of hours after injury, large numbers of neutrophils extravasate (by

transmigration) to wound site.

• To enable this, local blood vessels are activated by proinflammatory cytokines

such as IL-1β,TNF ⍺ and interferon-Ɣ

• These cytokines induce adhesion molecules such as integrins as well as P-selectin

and E-selectin (on surface of endothelium) enabling diapedesis of neutrophils.
Role Of Neutrophils
• In an infected wound, bacterial products such as lipopolysaccharide and formyl-
methionyl peptides can enhance neutrophil recruitment.

• Neutrophils traverse postcapillary venules at sites of inflammation  degrade

pathogens within phagolysosomes  apoptosis.

• OPSONISATION-Neutrophils coated with opsonins (generally complement and/or

antibody)

• Microorganisms bind to surface of the phagocyte  invagination of the cell

membrane  intracellular phagosome.
What happens when there Is too much Of inflammatory
response?
• There follows a burst of oxygen consumption, convertion to highly reactive
oxygen species. This is called Respiratory Burst.
• Antimicrobial systems formed in the phagosome consists of
• myeloperoxidase (MPO) (Degranulation)
• hydrogen peroxide (H2O2) (respiratory burst)
• a halide(particularly chloride)

• The initial product of the MPO-H2O2-chloride system is hypochlorous acid, and

subsequent formation of chlorine, hydroxyl radicals, singlet oxygen(Super oxide).

• These toxic agents can be released to the outside of the cell (attack normal
tissue).
Inflammatory Phase
• In a healing wound, neutrophil infiltration ceases after a few days of injury.
• Expended neutrophils are Phagocytosed by Macrophages.
• Most macrophages at the wound site are recruited from the peripheral
circulation (Extravasation)
• Factors that guide the extravasated monocyte to the wound site include
• growth factors and chemotactic proteins
• proinflammatory cytokines, and chemokines (macrophage inflammatory protein 1α, MCP-1, and RANTES)
• The source of these chemo-attractants includes
• clot-associated platelets
• wound edge hyperproliferative keratinocytes
• wound tissue fibroblasts
• leukocyte already at the wound site. 
ROLE OF MACROPHAGES
• Mediators in the microenvironment  receptors on the monocyte cell surface, bringing major
changes make of the cell.
• Major examples of such receptors present on the monocyte surface include
• Toll-like receptors (TLRs)
• complement receptors
• Fc receptors.

• At the wound site, macrophages function as antigen-presenting cells and phagocytes.

• In addition, they deliver a wide range of growth factors execute the wound-healing process eg.-
• TGF-β
• TGF-α
• VEGF
• PDGF
• These growth factors enable wound healing 1. cell proliferation 2. synthesis of ECM and 3.
inducing angiogenesis 
ROLE OF MAST CELLS
• At the injury site release proinflammatory mediators (esp. Histamine)
• Mast cells plays a key role in fine tuning immune responses during infection.
(biphasic manner)

• Mast cell activation helps initiate the inflammatory phase of wound healing.
(degranulate within hours)

• Activated mast cell controls the key events of the healing phases:
• triggering and modulation of the inflammatory stage
• proliferation of connective cellular elements
• final remodeling of the newly formed connective tissue matrix.
Role Of Macrophages
• Macrophages represent the predominant cell type in a healing wound 3–5 days
following injury.

• The primary acute function of wound macrophages  Phagocytosis  cleansing

the wound of all matrix and cell debris, including fibrin and apoptotic neutrophils.

• A persistent inflammatory state of diabetic wound macrophages is caused by

impairment in the ability of these cells to phagocytose apoptotic cells at the
wound site.
RESOLUTION OF INFLAMMATION
• Inflammatory responses elicited by injury are helpful, if they are timely and
transient.
• Resolution of inflammation is executed by a number of key factors.

• At the wound site - phagocytosis of dead neutrophils(macrophages).

• Impairment in macrophage function derails the resolution of inflammation.

• Lipid mediators eg.-
• Lipoxins
• Resolvins
• Rotectins
• maresins
have emerged as counter-regulators of excessive acute inflammation.
STAGE OF PROLIFERATION
III) PROLIFERATION
• Begins on the 2/3rd day and lasts for 2–4 weeks.
• It overlaps with the inflammatory phase
• supports re-epithelialization
• the formation of new blood vessels
• the influx of fibroblasts and laying down of the ECM
• Degradation of the fibrin clot by the macrophages has begun and invading
endothelial cells and fibroblast rapidly fill that space.
• Migrating fibroblasts produce the cytokines  keratinocytes to migrate and
proliferate.
• Activated macrophages produce several cytokines (PDGF and TNF)  induce
fibroblasts to produce keratinocyte growth factor (re-epithelialization)
Stage Of Proliferation
Proliferation phase can be divided into-
1. FIBROPLASIA
Fibroblasts synthesize and deposit the replacement ECM at wound site. The initial fibrin matrix is replaced
by provisional matrix of fibronectin and hyaluronan which facilitates fibroblast migration.

2. GRANULATION

3. CONTRACTION

4. EPITHELIALIZATION
FIBROPLASIA
• Fibroblasts are activated and present at the wound by 3 to 5 days after
injury.

• Secrete matrix components and growth factors that continue to stimulate

healing.

• Keratinocyte migration begins over the new matrix.

• Migration starts from the wound edges as well as from epidermal cell nests
(sweat glands and hair follicles)
• Intergrins – transmembrane receptors with extracellular membrane and intracellular protein
domains (composed of alpha and beta subunits) .
• Ligands to integrins include growth factors and ECM components such as collagen, elastin, etc.
• Integrins + ligands→ BINDING→ change in gene expression and new cellular function ensues.

Fibrillar collagen binding to integrin and DDR2 sites on

a fibroblast. Collagen binding stimulates production of
MMP2, ECM remodeling, cellular differentiation, and
migration of fibroblasts through basement
membranes, in addition to exerting control over the
cell cycle.
ECM, extracellular matrix;
MMP, matrix metalloproteases;
DDR, discoidin domain receptor.
• Fibronectin and glycosaminoglycan, hyaluronic acid compose the initial wound
matrix.

• Hyaluronic acid provides matrix (enhances cell migration).

• Adhesion glycoproteins including fibronectin, laminin and tenascin are present in

early matrix and facilitate cell attachment and migration.

• As fibroblasts enter and populate the wound → secrete hyaluronidase→ digest

hyaluronic acid rich matrix  larger sulfated GAGs are deposited.

• New collagen is deposited by fibroblasts onto fibronectin and GAG scaffold in a

disorganized manner, resulting in scar formation.
Collagen

• 30% of total body protein.

• hydroxylation of amino acids lysine and proline by enzymes that
require vitamin C as a cofactor.
• Procollagen is initially formed within the cell.
• Procollagen is transformed into tropocollagen after it is excreted from
the cell.
• Fully formed collagen has a complex structure.
• Consists of three polypeptide chains wound in a left-handed helix.
• These three chains are further wound in a right-handed coil to form the
basic tropocollagen unit.
Thus far, 28 types of collagen have been identified.
Each type shares the same basic structure but differs in the relative composition of hydroxylysine
and hydroxyproline, and in the degree of cross-linking between chains.
Types of Collagen:
∘ Type I: predominant in mature skin, bone and tendon.
∘ Type II: present in hyaline cartilage and cornea.
∘ Type III: present in healing tissue, particularly fetal wounds.
∘ Type IV: predominant constituent of basement membranes.
∘ Type V: similar to type IV. Also found in hair and placenta.

• The ratio of type I collagen to type III collagen in normal skin is 4-5:1.
• Hypertrophic and immature scars contain ratios of 2:1 or less.
Major fibrillar collagens composing ECM in skin and scar are collagen types I and III. Ratio of
collagen I : III is 4:1 in both scar and skin. Although type III collagen is initially deposited in
relatively greater amounts in wound, its amount is always less than type I collagen in mature
scar.
STAGE OF PROLIFERATION - Granulation
• Granulation tissue is dense population of blood vessels, macrophages,
and fibroblasts within a loose provisional matrix of fibronectin,
hyaluronic acid, and collagen.

• Appearance- beefy red “proud flesh” and is present in open wounds.

• It is a consequence of rich bed of new capillary networks

(neoangiogenesis) that form by epithelial cell division and migration.
GRANULATION TISSUE
• Fibrous connective tissue that grows from the base of a wound and is able to
fill wounds of almost any size. 

• During the proliferative phase  granulation tissue is light red or dark pink in
color (perfusion by new capillary loops).

• Initially, it consists of a network of type III collagen(weaker structural protein)

that can be produced rapidly.
•
• This is later replaced by the stronger, long-stranded type I collagen.
Difference between Healthy and Unhealthy
Granulation
HEALTHY GRANULATION UNHEALTHY GRANULATION
Bright Red Dark Red
Moist Dehydrated
Shiny Dull
Does not bleed on touch Bleeds easily on touch
Minimal discharge (serous) Copious Discharge (Purulent/Serosanguinous)
Granular surface with no slough Glazed Slimy looking +/- Slough
No Odour Foul smelling
PHASES OF WOUND HEALING
III)PROLIFERATION – c) contraction
• Process in which the surrounding skin is pulled circumferentially toward an open
wound.

• It does not occur in closed surgical incisions.

• Wound contraction decreases size of wound dramatically without new tissue

formation.

• This repair process speeds wound closure compared with epithelialization and
scar formation alone. Additionally, area of insensate scar is smaller.
• Contractile forces are likely generated by myofibroblasts (fibroblast with alpha
smooth muscle actin and microfilaments in cytoplasm).

• These cells pull surrounding skin towards wound center.

PHASES OF WOUND HEALING
III)PROLIFERATION - EPITHELIALIZATION
• If the epidermal basement membrane is not breached, epithelial cells are
replaced by upward migration of keratinocytes as in uninjured skin.

• If the basement membrane is breached, re-epithelialisation must occur from the

wound margins and from epidermal appendages.
• Re-establishing epithelial continuity consists of these four phases:
1. Mobilisation
2. Migration
3. Mitosis
4. Cellular differentiation
Mobilisation
• Epithelial cells at the wound edges elongate, flatten and form
pseudopodia.
• They detach from neighbouring cells and basement membrane.
Migration
• Decreased contact inhibition promotes cell migration.
• Epithelial cells climb over one another to migrate.
• As cells migrate, epithelial cells at the wound edge proliferate to
replace them.
• Cells migrate until they meet those from the opposite wound edge.
• At this point, contact inhibition is reinstituted and migration ceases.
Mitosis
• Epithelial cells proliferate once they have covered the wound.

• They secrete proteins to form a new basement membrane.

• Desmosomes and hemidesmosomes are re-established to anchor themselves to

the basement membrane and to each other.

• This new epithelial cell layer forms a stratum germinatum and undergoes mitosis
as in normal skin.
Cellular differentitation
• The normal structure of stratified squamous epithelium is re-
established.
• Morphologic changes in keratinocytes at the wound margin are evident within hours
after injury.

• The epidermal cell layer thickens and marginal basal cells migrate over the wound
defect.

• Once these keratinocytes begin migrating, they do not divide until epidermal
continuity is restored.

• New epithelial cells for wound closure are provided by fixed basal cells in a zone near
the edge of the wound.

• Migration of keratinocytes over the wound matrix is guided by cell adhesion

glycoproteins, such as tenascin and fibronectin, which are their "railroad tracks."
• After the re-establishment of the epithelial layer, keratinocytes and
fibroblasts secrete laminin and type IV collagen to form the basement
membrane.

• The keratinocytes become columnar and divide to restore the layering of the
epidermis and re-form a barrier to further contamination and moisture loss.

• Keratinocytes can respond to foreign body stimulation with migration as well.

• Eg. Sutures in skin wounds.

Fibrotic reactions, cysts, and sterile abscesses centered on the suture can occur. These
are treated by removal of the inciting suture and epithelial cell sinus track or cyst.
PHASES OF WOUND HEALING
IV) REMODELLING
• The scaffold that supports cells in both the unwounded and wounded states is
the ECM, which is the structural component of skin that must be repaired after
injury.

• The ECM is dynamic and is constantly undergoing remodelling during repair,

which can be conceptualized as the balance between synthesis, deposition, and
degradation.

• Lysyl oxidase is the major intermolecular collagen cross-linking enzyme. Collagen

cross-linking decreases its degradation and improves wound tensile strength.
• Collagenases and gelatinases are matrix metalloproteinases that degrade ECM
components.
• The balance of collagen deposition and degradation is in part determined by the regulation
of matrix metalloproteinase activity.

• Proteins called tissue inhibitors of matrix metalloproteinase specifically inactivate the matrix
metalloproteinases.

• Scar formation is the ultimate outcome of wound repair.

• Scar has no epidermal appendages (hair follicles and sebaceous glands), and it has a collagen
pattern that is distinctly different from unwounded skin.

• As the collagen matrix forms, densely packed fibers fill the wound site. The ultimate pattern
of collagen in scar is one of densely packed fibers and not the reticular pattern found in
unwounded dermis.
Wound tensile strength as a function of time. Maximal tensile strength is 75%-80% of the
unwounded skin.
• Wound scar remodelling occurs during months to years to form a "mature" scar.

• Early scar appearance is red due to dense capillary network induced at the injury site.
When closure is complete, capillaries regress until relatively few remain.
• As the scar redness dissipates during a period of months, the true scar pigmentation
becomes evident.

• Scars are usually hypo-pigmented after full maturation. Scars can become hyper-
pigmented in darker-pigmented patients and in those lighter-pigmented patients whose
scars receive excess sun exposure.

• Sun protection measures are recommended for patients with early scars on sun exposed
areas such as the scalp, face, and neck.
• During remodelling, wounds gradually become stronger with time but never becomes as strong
as unwounded skin.

• Wound tensile strength increases rapidly from 1 to 8 weeks after wounding and correlates
with collagen cross-linking by lysyl oxidase. Thereafter, tensile strength increases at a slower
pace and increase up to 1 year after wounding.

• Tensile strength of wounded skin at best reaches only approximately 80% that of unwounded
skin.

• Scar is brittle and less elastic than normal skin.

CHRONIC WOUNDS AND
WOUND HEALING IN
CHRONIC WOUNDS
KEY TOPICS

• DEFINE CHRONIC WOUNDS

• TYPES OF CHRONIC WOUNDS
• IMPORTANT ASPECTS TO CONSIDER IN CHRONIC WOUNDS
• HEALING AND MANAGEMENT OF CHRONIC WOUNDS
• RECENT ADVANCES IN THE MANAGEMENT OF CHRONIC WOUND
HEALING
DEFINATION
• IT CAN BE DEFINED AS A LOSS OF CONTINUITY
OF THE SKIN SECONDARY TO INJURY THAT
PERSISTS FOR LONGER THAN 6 WEEKS.
 Local and systemic factors that impede wound healing

Local factors Systemic factors

• Inadequate blood supply • Advancing age and general immobility
• Obesity
• Increased skin tension • Smoking
• Poor surgical apposition • Malnutrition
• Deficiency of vitamins and trace elements
• Wound dehiscence • Systemic malignancy and terminal illness
• Poor venous drainage • Shock of any cause

• Presence of foreign body and foreign body reactions • Chemotheraphy and radiotherapy

• Immunosuppressant drugs, corticosteroids, anticoagulants

• Inherited neutrophil disorders, such as leucocyte adhesion

• Continued presence of microorganisms deficiency
• Infection • Impaired macrophage activity (malacoplakia)
• Excess local mobility, such as over a joint
TYPES

• VASCULAR ULCERS (ARTERIAL/VENOUS)

• DIABETIC ULCERS
• PRESSURE SORES
VASCULAR ULCERS
• THEY INCLUDE VENOUS, ARTERIAL OR MIXED ETIOLOGY.
• VENOUS ULCERS CONSTITUTE 70%, ARTERIAL 10%,MIXED ETIOLOGIES
15%.
• THE REMAINING 5 % FROM LESS PATHOPHYSIOLOGICAL CAUSES.
VENOUS ULCERS
• ITS MORE COMMON AND OCCURS IN 5 %
POPULATION > 65 YEARS.

• CLASSICALLY DISTRIBUTED IN THE GAITER AREA ON

THE MEDIAL ASPECT BETWEEN KNEE AND ANKLE.
• IT OCCURS DUE TO VENOUS INSUFFICIENCY.
PATHOPHYSIOLOGY OF VENOUS
ULCERS

CAPILLARY
DECREASE
LEAKAGE
VALVULAR VENOUS INCREASED IN
BACKFLOW OF PLASMA
INCOMPET INSUFFICIE VENOUS COLLAGEN
OF BLOOD CONSTITUE
ENCE NCY PRESSURE PRODUCTI
NTS LIKE
ON
FIBRIN
PATHOPHYSIOLOGY OF VENOUS
ULCERS

DETECTED BY
ELEVATED SECRETING BEGINS THE
ENDOTHELIAL
VENOUS VASOACTIVE INFLAMMATORY
CELLS(ICAM-
PRESSURE MOLECULES CASCADE
1,CD54)
ARTERIAL ULCERS
•OCCURS DUE TO ARTERIAL INSUFFICIENCY

•MOST COMMON CAUSE NARROWING OF LUMEN DUE TO

ATHEROSCLER0SIS

•OTHER CAUSES WHICH CAUSE ARTERIAL INSUFFICIENCY –

EMBOLISM
DM
VASCULITIS
PYODERMA GANGRENOSUM
SICKLE CELL DISEASE AND THALESSEMIA
DIABETIC FOOT ULCERS
• OCCURS IN ABOUT 15% OF INDIVIDUALS
• FACTORS THAT CONTRIBUTE TO ABERRANT HEALING-
a) Abnormal and chronic inflammatory response
b) Hyperglycemia
c) Microvascular abnormalities
d) Hypoxia
e) Changes of ECM scaffold
PATHWAY OF DIABETIC ULCER

HYPERGLYCAEMI
CELL APOPTOSIS
A LEADS TO NON FORMATION OF
DECREASE & DISRIPTION OF
ENZYMATIC ADVANCED
SOLUBILITY OF NORMAL
BINDING OF GLYCATION END
THE ECM WOUND
SUGAR RESIDUES PRODUCTS
HEALING
TO PROTEINS
PRESSURE INJURIES
• CAUSES INCLUDE- Pressure, friction, shearing forces between tissue
planes and moisture

• PATHWAY -Pressure exceeding arteriolar pressure results in tissue

hypoxia, the creation of free radicals, an ischemic reperfusion injury,
and consequent tissue necrosis.

• FACTORS CONTRIBUTING- Prolonged immobility, patient position,

neuropathy, and existing arterial or venous insufficiency
PRESSURE INJURIES
The National Pressure Ulcer Advisory Panel(NPUAP) staging system
defines four stages of severity to pressure injuries:
• stage 1 pressure injury is nonblanchable erythema of intact skin
• stage 2 pressure injury is a partial-thickness skin loss with exposed
dermis
• stage 3 pressure injury involves full-thickness skin loss
• stage 4 pressure injury involves full-thickness skin and tissue loss
FACTORS THAT AFFECT WOUND
HEALING
• RADIATION THERAPY
• NUTRITION
• MICROORGANISMS
• OBESITY AND METABOLIC SYNDROMES
RADIATION

LATE EFFECT-
IONIZING RADIATION REDUCED PROLONGED
ACUTELY DISRUPTS INCREASED VASCULAR
CAUSES BOTH ACUTE OEDEMA NEOVASCULARIZATION INLAMMATORY PHASE
BASEMENT MEMBRANE PERMEABILITY
AND LATE EFFECTS. OF WOUNDS CAUSES FIBROSIS AND
CONTRACTION
NUTRITION
• CAUSES INCLUDE- General malnutrition state, inadequate caloric
intake, and deficiencies in vitamins, micronutrients, macronutrients.
• MALNUTRITION prolongs the inflammatory phase of wound healing
by reducing the proliferation of fibroblasts and formation of
collagen ,altering the function of immune cells, such as reducing
phagocytosis & decreasing complement levels.
MICRO-ORGANISMS
• Bacteria predominantly exist in biofilms in clinical and natural
settings, as opposed to planktonic states (single organisms/free-
floating).
• Biofilms describe adherent populations of microbes that form
three-dimensional populations and are organized on extracellular
polymers.
• Chronic wounds develop biofilms, as complex interactions
between the host wound microenvironment and heterogeneous
bacterial populations
• They delay and inhibit wound healing by not only producing
toxins and damaging enzymes, but also promoting the complex
chronic inflammatory pathways.
• Proteases released from bacteria impede growth factors and
wound healing proteins. Large levels of microbial exudate have
also been shown to affect cell proliferation and wound healing.
MANAGEMENT OF BIOFILM INFECTED
WOUNDS
• PRESSURE OFF LOADING
• APPROPRIATE DRESSINGS
• SYSTEMIC ANTIBIOTICS
• TISSUE DEBRIDEMENT
• VAC DEVICES
OBESITY AND METABOLIC
SYNDROMES
• CAUSES WOUND INFECTION, IMPAIRED WOUND HEALING, PRESSURE
INJURIES, VENOUS ULCERS, HEMATOMA FORMATION, SEROMA
FORMATION
• OBESITY HAS LOWER LEVELS OF LYMPHOCYTE PROLIFERATION,
ALTERED CYTOKINE LEVELS & PERIPHERAL IMMUNE FUNCTION.
ADVANCED WOUND HEALING
• BIOLOGICAL THERAPIES - GROWTH FACTORS
PDGF & PRP
STEM CELLS
HYPERBARIC OXYGEN
CELL CULTURED PRODUCTS

• SCAFFOLDS
• BIOPHYSICAL FORCES- NEGATIVE PRESSURE WOUND THERAPY
EXTRACORPOREAL SHOCK WAVE THERAPY
ELECTROMAGNETIC THERAPIES
GROWTH FACTORS
• Growth factor–related wound repair has been of immense interest in
wound healing science.
• Commercially marketed growth factors currently available include
recombinant human fibroblast growth factor, recombinant human
platelet-derived growth factor, and recombinant human epidermal
growth factor.
• They can be applied topically or injected
PDGF AND PRP
• Platelet-rich plasma (PRP) and PDGFs obtained from centrifugation of
blood.
• The first commercially available topical PDGF in the United States is
becaplermin gel (Regranex®) & was studied in chronic diabetic foot
ulcers but has increased risk of rate of mortality secondary to
malignancy.
STEM CELLS
• Stem cells are undifferentiated cells that possess the ability to mature
into differentiated cells of either one embryonic germ layer
(multipotent) or all three embryonic germ layers (pluripotent).
• One of the most widely studied multipotent adult stem cells in wound
healing research has been mesenchymal stem cells (MSCs)
HYPERBARIC OXYGEN
• HBOT utilizes compression chambers to deliver high levels of oxygen
concentration at raised atmospheric pressures.
• HBOT aims to promote oxygen-dependent wound healing pathways
and has particularly been a treatment strategy when revascularization
in vascular insufficiency has been unsuccessful.
CELL CULTURED PRODUCTS
• Cell cultured products, also known as tissue-engineered constructs, include
Apligraft, Epicel, and Dermagraft.
• Apligraft utilizes a bovine collagen matrix incorporated with human neonatal
fibroblasts and neonatal keratinocytes to act as a scaffold as well as providing
cells that produce growth factors and ECM components.
• Dermagraft comprises a polyglactin scaffold with dermal neonatal fibroblasts.
• Cultured epithelial autografts using patients’ own keratinocytes, such as Epicel,
have been utilized to treat large burns and take 2 to 3 weeks in culture to grow.
SCAFFOLDS
• Scaffolds act as a platform for cell migration and angiogenesis and are a key
therapeutic modality.
• Scaffolds can be of human origin (donated tissue or cadaveric) and nonhuman
origin (porcine or synthesized through extraction and cross-linking).
• Integra™ is a bilayer matrix of bovine collagen and glycosaminoglycan derived
from shark skin that is lyophilized to form a highly porous scaffold. Integra™
has been used with considerable success in burns, and clinical trial data have
attested its use in the healing of chronic wounds, specifically decreasing time
to wound closure in diabetic foot ulcers.
• Allopatch®, which is a decellularized scaffold derived from human cadaveric
tissue, has demonstrated efficacy in closure of nonhealing diabetic foot ulcers.
BIOPHYSICAL FORCES
• NPWT effectively ensures wound drainage, aids granulation tissue
development, and expedites wound contraction.
• ESWT delivers high-energy acoustic pulses to tissues and is the
standard of care in treating nephrolithiasis and various
musculoskeletal conditions. It has been reported to improve
cutaneous wound healing through increasing cell proliferation and
stimulating angiogenesis.
• Electromagnetic therapies are thought to interact with endogenous
electric fields in the skin to increase expression of growth factors and
nitric oxide and also promote angiogenesis