Recent advances in burns management by Dr. Sunil Keswani, National Burns Centre, Airoli

Recent Advances in Burns Management

Dr. Sunil Keswani
National Burns Centre

Dr.Sunil Keswani, National Burns Centre,
www.burns-india.com, nbcairoli@gmail.com

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com

Factors Affecting Wound Healing
Systemic

Local

Age

Mechanical injury

Nutrition

Infection

Trauma

Edema

Metabolic diseases

Ischemia/necrotic tissue

Immunosuppression

Topical agents

Connective tissue disorders

Ionizing radiation

Smoking

Low oxygen tension
Foreign bodies
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AGE
•Aging produces intrinsic physiologic changes that result in delayed or
impaired wound healing.
•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
•Non collagenous protein accumulation at wounded sites is decreased
with aging, which may impair the mechanical properties of scarring in
elderly patients
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HYPOXIA, ANEMIA, AND HYPOPERFUSION

•Low oxygen tension has a profoundly deleterious effect on all aspects of
wound healing.
•Fibroplasia,

although

stimulated

initially

by

the

hypoxic

wound

environment, is significantly impaired by local hypoxia.
•Optimal collagen synthesis requires oxygen as a cofactor, for the
hydroxylation steps.
•Increasing subcutaneous oxygen tension levels for brief periods during
and immediately after surgery results in enhanced collagen deposition and
in decreased rates of wound infection after elective surgery.
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STEROIDS
•Large doses or chronic usage of glucocorticoids reduce collagen
synthesis and wound strength.
•Inhibit the inflammatory phase of wound healing (angiogenesis,
neutrophil and macrophage migration, and fibroblast proliferation) and
the release of lysosomal enzymes.
•Steroids used after the first 3 to 4 days postinjury do not affect wound
healing as severely as when they are used in the immediate
postoperative period.
•Steroid-delayed healing of cutaneous wounds can be stimulated to
epithelialize by topical application of vitamin A
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METABOLIC DISORDERS
•Uncontrolled diabetes results in reduced inflammation, angiogenesis,
and collagen synthesis.
•Defects in granulocyte function, capillary ingrowth, and fibroblast
proliferation all have been described in diabetes
•Obesity, insulin resistance, hyperglycemia, and diabetic renal failure
contribute significantly and independently to the impaired wound healing
observed in diabetics.
•Diabetic wound appears to be lacking in sufficient growth factor levels,
which signal normal healing.
•Uremia also hasBurns Centre, www.burnsbeen associated with disordered wound healing.
india.com,
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NUTRITION
•Not fully understood
•Efforts

are

being

made

to

develop

wound-specific

nutritional

interventions and the pharmacologic use of individual nutrients as
modulators of wound outcomes.
•Malnourished patients have diminished hydroxyproline accumulation
(an index of collagen deposition)
•It reflects impaired healing response as well as reduced cell-mediated
immunity, phagocytosis, and intracellular killing of bacteria by
macrophages and neutrophils.

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•

The main effect of Arginine on wound healing is to enhance wound
collagen deposition.

•

Arginine deficiency results in decreased wound-breaking strength and
wound collagen accumulation.

•

Vitamins most closely involved with wound healing are vitamin C and
vitamin A.

•

vitamin C deficiency, leads to a defect in wound healing, particularly
via a failure in collagen synthesis and cross-linking.

•

Biochemically, 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
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•

Vitamin A deficiency impairs wound healing, whereas supplemental
vitamin A benefits wound healing.

•

Vitamin A increases the inflammatory response in wound healing,
probably by increasing the lability of lysosomal membranes.

•

Vitamin A 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.

•

Vitamin A also can restore wound healing that has been impaired by
diabetes, tumor formation, cyclophosphamide, and radiation.

•

Doses rangingBurns Centre, www.burns- IU per day
from 25,000 to 100,000
india.com,
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ZINC
•In deficiency states there is decreased fibroblast proliferation,
decreased collagen synthesis, impaired overall wound strength, and
delayed epithelialization.

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INFECTION
•If the wound is contaminated with >105 microorganisms, the risk of
wound infection is markedly increased, but this threshold may be much
lower in the presence of foreign materials.
•The most common organisms responsible for wound infections, in
order of frequency, are Staphylococcus species, coagulase-negative
Streptococcus, enterococci, and Pseudomonas.
•Bacteria

prolong

the

inflammatory

phase

and

interfere

with

epithelialization, contraction, and collagen deposition.
•Bacteria may accelerate expression or increase concentrations of
MMPs, growth factors, and cytokines in chronic-type wounds
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DRESSING
•The main purpose of wound dressings is to provide the ideal
environment for wound healing.
•Ideal dressing – not a clinical reality.
DESIRED CHARACTERISTICS OF WOUND DRESSINGS
Promote wound healing (maintain moist environment)
Conformability
Pain control
Odor control
Nonallergenic and nonirritating
Permeability to gas
Safety
Nontraumatic removal
Cost-effectiveness
Burns Centre, www.burnsConvenience
india.com,
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•

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.

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Absorbent Dressings
•Absorb without getting soaked through, as this would permit bacteria
from the outside to enter the wound.
• sponge.

Non adherent Dressings
•Dressings impregnated with paraffin, petroleum jelly, or water-soluble
jelly for use as non adherent coverage.
•A secondary dressing must be placed on top to
seal the edges and prevent desiccation and infection.
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Occlusive and Semiocclusive Dressings

•Good environment for clean & minimally exudative wounds.
•Waterproof and impervious to microbes,
•Permeable to water vapour and oxygen.

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Alginates
•Brown algae and contain long chains of polysaccharides containing
mannuronic and glucuronic acid.
•Processed as the calcium form, alginates turn into soluble sodium
alginate through ion exchange in the presence of wound exudates.
•The polymers gel, swell, and absorb a great deal of fluid.
•Used when there is skin loss, in open surgical wounds with medium
exudation, and on full-thickness chronic wounds.

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•

Type of dressing to be used depends on the amount of wound drainage

•

Nondraining Wound - with a semiocclusive dressing.

•

Mild Drainage (1 to 2 mL/d) - semiocclusive or absorbent nonadherent
dressing.

•

Moderately draining wounds (3 to 5 mL/d) - 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.
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•

Vacuum-assisted closure system assists in wound closure by applying
localized negative pressure to the surface and margins of the wound.

•

Found to be effective for chronic open wounds (diabetic ulcers and stages 3
and 4 pressure ulcers), acute and traumatic wounds, flaps and grafts,

dehisced incisions.
Mechanism of action

Problems – Pain, fluid loss, especially in large wounds, and risk of bleeding. It is
contraindicated in patients with frail, thin or easily bruised skin, and in those
with neoplasms forming part of the wound floor.
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Hyperbaric oxygen
•As adjunct in the management of nonhealing wounds.
•Most non-healing tissues are hypoxic
Mechanism of action of hyperbaric oxygen
•Hyperoxygenation causes
1.

Immune stimulation by restoring WBC function and enhancing their
phagocytic capabilities and

2.

Neo-vascularization in hypoxic areas by augmenting fibroblastic
activity and capillary growth.

•Vasoconstriction reduces edema and tissue swelling while ensuring
adequate Oxygen delivery.
•Bactericidal for anaerobic organisms & inhibits growth of aerobic bacteria.
It Inhibits production of alpha-toxin by C Welchii and is synergistic with
Aminoglycosides and Quinolones. Thus it is life saving in gas gangrene and
Burns Centre, www.burnssevere necrotising infections.
india.com,
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Skin Replacements
•All wounds require coverage in order to prevent evaporative losses and
infection and to provide an environment that promotes healing.

Conventional Skin Grafts
•Split thickness grafts
•Full-thickness grafts
•Autologous grafts
•Allogeneic grafts
•Xenogeneic grafts (e.g., porcine).

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Current Skin Engineering
• Tissue-engineered skin exists
as cells grown in vitro and
subsequently seeded onto a
scaffold or some porous
material which is then placed
in vivo at the site of injury.
• Three categories of skin
substitutes:
– Epidermal Substitutes
– Dermal Substitutes
– Dermo-epidermal Substitutes
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NEED FOR ARTIFICIAL SKIN
 Drawbacks of conventional treatment
 In severe burns like 3rd degree burns, normal wound
healing is slow and larger area is involved
 Natural skin has limited options to recover, hence need for
synthetic skin
 Use of patient’s own skin - costly, hospitalization,
anesthesia, pain, immobilization etc.
 Solution to skin grafting is artificial skin transplants

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EVOLUTION OF BURN WOUND CARE
Burn wounds were occluded with dressings
Animal and reptile skin used as a "skin substitute"

Pig skin became popularized in the 1960’s

Human tissue used as a skin substitute
(cadaver skin & human amnion)
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Contn…
First Cultivation of Human Epidermal Cells (1960’s)
(autologous keratinocytes)

Use of allogenic keratinocyte grafts

Bilayered Artificial Skin

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Process

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COMMERCIALLY AVAILABLE SKIN SUBSTITUTES
With advancing technology, a host of both permanent and temporary
biologically active skin substitutes are available to replace allograft
and xenografts.I. Naturally occurring tissues
- Cutaneous allografts
- Cutaneous xenografts
- Amniotic membranes
II. Skin substitutes
- Synthetic bilaminate
- Collagen based composites
Biobrane
TransCyte
Integra Dr.Sunil Keswani, National
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III. Collagen based dermal analogs
- De-epithelized allograft
- Alloderm
IV. Cell Culture -derived
- Keratinocyte Cells Sprays
-Bilayer human tissue (Apligraf)
- Cultured autologous keratinocytes
- Fibroblast seeded dermal analogs
- Collagen-glycosaminoglycan matrix
- Polyglycolic or acid mesh (Dermagraft)
- Epithelial seeded dermal analog
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Application of cells spray along with autograft for extensive burns

Case Study
Queen Victoria hospital, UK- 90%
TBSA FT

Successful Treatment with
meek micro graft+ cell spray

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Preliminary Safety-Study on application of
autologous keratinocytes cell spray

Before Cell Spray

During Cell Spray
No sign of any
adverse reaction on
day 4 after surgery

Control arm
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GMP cell culture facility @ NBC
GMP cell culture facility @ NBC

Change Room

Clean room 3 class 1000 HEPA

Class 1lakh HEPA

Clean room 2 Class 10 000 HEPA

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Cell Spray making process

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Primary cell culture

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Secondary Culture of keratinocytes

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PREPARATION OF SKIN COMPOSITE

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FUNCTIONAL
EPIDERMIS

BIOBRANE
 Biobrane is a bilayer synthetic skin substitute
 Outer epidermal analog constructed of a thin silicone film with
barrier functions
 Small pores present in silicone to allow for exudates removal
and permeability to topical antibiotics
 Inner dermal analog composed of nylon filament weave upon
which is bonded type I collagen peptides

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BIOBRANE

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BIOBRANE APPLIED TO WOUNDS

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PROCESS OF HEALING

A superficial partial thickness burn
The zone of necrosis isDr.Sunil Keswani, the upper dermis & is usually
confined to National
separated by a layer ofBurns Centre, www.burnsedema from the viable wound surface
india.com,
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Viable wound bed showing fibrin and collagen

Bilayer BIOBRANE placed on clean wound
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Biobrane adhered to surface by nylon-collagen mesh.
Preservation of thin Burns Centre, www.burnswater layer on surface to allow epithelial
india.com,
migration along innernbcairoli@gmail.com
layer

Biobrane peeled back from surface to demonstrate rapid
Burns Centre, www.burnsmigration of new epithelium along nylon-collagen mesh
india.com,
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Biobrane removed with re-epithelialization

APPLICATION OF BIOBRANE

BIOBRANE REMOVAL

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TRANSCYTE
 Trancyte is a bilayer skin substitute
 Outer epidermal analog is a thin nonporous silicone film with
barrier functions
 Inner dermal analog is layered with human fibroblast products
mainly collagen type 1, fibronectin and Glycosaminoglycan
 Subsequent cryo-preservation destroys fibroblasts but preserves
activity of fibroblast-derived products
 Thin water layer at surface is maintained for epidermal cell
migration
 It is removed after re-epithelialization
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TRANSCYTE

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TRANCYTE IN PLACE

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ALLODERM
 AlloDerm is an acellular dermal matrix designed to serve as a
biologic scaffold for normal tissue remodeling
 It is a donated human tissue processed to remove all epidermal and
dermal cells while preserving the remaining biological dermal matrix
 It directs normal revascularization and cell repopulation as blood
vessels, collagens, proteoglycans and elastin are preserved
 This extracelullar matrix contains the blood vessel channels which
serve as conduits for revascularization
 Collagens, proteoglycans and elastin provide structure and
information for cell repopulation
 The preserved proteoglycans and proteins direct the patient's own
cells to initiate revascularization andNational
cell repopulation
Dr.Sunil Keswani,
nbcairoli@gmail.com

NORMAL DERMIS

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ALLODERM

Day 1: Biologic Scaffold

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Day 7-10
• Host fibroblast cells and blood vessels respond to the
transplantation of the AlloDerm matrix
• Initiation of the revascularization and normal tissue
remodeling process

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Day 45
Replacement and revascularization of the transplant
continues as normal connective tissue

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Day 90
AlloDerm repopulated with the patient's own cells
Fibroblasts continue to lay down autologous collagen

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INTEGRA
 INTEGRA is a bilayer membrane system for skin replacement
 The dermal replacement layer - porous matrix of fibers of
cross-linked bovine tendon collagen and a glycosaminoglycan
(chondroitin-6-sulfate)
 The temporary epidermal substitute layer - synthetic
polysiloxane polymer (silicone) and functions to control moisture
loss from the wound
 The collagen dermal replacement layer serves as a matrix for
the infiltration of fibroblasts, macrophages, lymphocytes, and
capillaries derived from the wound bed
 As healing progresses an endogenous collagen matrix is
deposited by fibroblasts
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Contn…
 Upon adequate vascularization of the dermal layer and
availability of donor autograft tissue, the temporary silicone layer
is removed
 A thin, meshed layer of epidermal autograft is placed over the
"neodermis"(usually 14-21 days after application)
 Cells from the epidermal autograft grow and form a confluent
stratum corneum, thereby closing the wound reconstituting a
functional dermis and epidermis
 After final healing of the wound, the neodermis tissue
histologically and functionally is similar to normal dermis
 used for child limb injuries (Violas et al., 2005)
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HEALING WITH INTEGRA

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Integra

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Acticoat

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Fascial Excision

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Integra applied

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Covered with Acticoat

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MATERIALS & METHODS
Surplus cutting

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MATERIALS & METHODS
Positioning on plate.

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MATERIALS & METHODS
Dermatome cut through

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MATERIALS & METHODS
Adhesive Spraying

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MATERIALS & METHODS
Cork removing.

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MATERIALS & METHODS
Gauze expansion

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MATERIALS & METHODS
Gauze expanded.

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MATERIALS & METHODS
Micrograft positioning

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MATERIALS & METHODS
After gauze removal. 7th day.

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MATERIALS & METHODS
10th day wound care.

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MATERIALS & METHODS
Long term control.

POST-PHYSICAL REHABILITATION OUTCOME
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Case 1- day of admission

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Day 3-Preop

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Day 3-Early excison and homografting-postop

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Day 5

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Day 7

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Day 9

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Day 15

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Day 3
Postop

Preop

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Day 12

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Day 21

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Admission

Discharge

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Early excison and grafting

Pre-Op wound

Application of Homograft
Day 3

Complete healing
Day 21

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Pre-Op Wound

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Progressive healing of Wound

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On Discharge

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Case 5- day of Admission

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Before and After Homografting

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Progressive healing

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Progressive Healing

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Progressive healing of RIGHT HAND

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Progressive Healing of LEFT HAND

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Day 15
Homograft Application

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post op

Case 7-Chemical Burns on admission

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Progressive healing-Autografting

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End Result-Autografting

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DERMAGRAFT
 is an example of a synthetic matrix combined with allogenic
fibroblasts and has good resistance to tearing (Bello et al., 2001)
 Dermal fibroblasts are seeded onto biocompatible Vicryl
scaffold to form a living tissue
 The scaffold Vicryl is a blend of polylactic and polyglycolic
acids (synthetic absorbable surgical sutures)
 Vicryl is inert, non-antigenic, non-pyrogenic and elicit only a
mild tissue reaction during absorption
 Dermagraft is a total skin replacement for
• full thickness burns and
• chronic wounds like diabetic foot ulcers
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DERMAGRAFT

Dermagraft cassettes ready for patient use

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APLIGRAF
 is supplied as a living, bi-layered skin substitute
 The lower dermal layer combines bovine type 1 collagen and
human fibroblasts (dermal cells), which produce additional matrix
proteins
 The upper epidermal layer is formed by promoting human
keratinocytes (epidermal cells) first to multiply and then to
differentiate to replicate the architecture of the human epidermis
 APLIGRAF does not contain melanocytes, Langerhans' cells,
macrophages, and lymphocytes, or other structures such as blood
vessels, hair follicles or sweat glands
 approved by the FDA to treat patients exhibiting venous leg ulcers
& for diabetic foot ulcer treatment
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SOME CASE STUDIES FOR APLIGRAF APPLICATION

1

2

3

4

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Traditional Skin Graft

Artificial skin

• Skin graft from the patient • Two-layer template composed
of a porous matrix inner layer
applied to wound
and a silicone outer layer
applied to the wound
• Grafted dermis does not
• Dermis is regenerated and
regenerate, resulting in
grows
scars that contract
Regenerated dermis maintains
• Larger donor sites are
shape and strength
needed to compensate for
graft shrinkage
• Harvested donor sites are Thin epidermal graft does not
painful, itchy and red
create lasting donor site wound
• Stiffness of graft area
Burns Centre, www.burns- skin
• Pliable
india.com,
nbcairoli@gmail.com

Current Research and Challenges



•

Role of Stem cells in wound healing (e.g- MSCs)
Role of Gene Therapy to stimulate wound healing
Development of autologous cell based skin substitutes
Methods to evaluate safety and efficacy of the products
in vivo.

• Challenges:
Cost related concerns
• Variable clinical study data
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Future Directions
 More effective cell preservation techniques could
enhance shelf life and minimize issues related to storage
 Simplified thawing and rinsing of cryopreserved
products would make such products more user-friendly
 A more complete understanding of the mechanism of
therapeutic action of bioengineered skin could lead to even
more efficacious products
eg) genetic modification of the cells to overproduce
specific cytokines like growth factors might be
feasible and productive
nbcairoli@gmail.com

Contn…
 Efforts by manufacturers to further reduce the cost of
cellular skin substitute wound therapy could change the
role of this approach dramatically
 Lower cost could also allow for multiple applications
and possibly increase the efficacy of the course of
treatment

nbcairoli@gmail.com

THANK YOU
BURNS Helpline:
022 2779 3333

nbcairoli@gmail.com

www.burns-india.com

Recent advances in burns management by Dr. Sunil Keswani, National Burns Centre, Airoli

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Recent advances in burns management by Dr. Sunil Keswani, National Burns Centre, Airoli