Recent Advances in Burns Management

Dr. Sunil Keswani
National Burns Centre

Dr.Sunil Keswani, National Burns Centre,
www...
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 di...
AGE
•Aging produces intrinsic physiologic changes that result in delayed or
impaired wound healing.
•Dermal collagen conte...
HYPOXIA, ANEMIA, AND HYPOPERFUSION

•Low oxygen tension has a profoundly deleterious effect on all aspects of
wound healin...
STEROIDS
•Large doses or chronic usage of glucocorticoids reduce collagen
synthesis and wound strength.
•Inhibit the infla...
METABOLIC DISORDERS
•Uncontrolled diabetes results in reduced inflammation, angiogenesis,
and collagen synthesis.
•Defects...
NUTRITION
•Not fully understood
•Efforts

are

being

made

to

develop

wound-specific

nutritional

interventions and th...
•

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

•

Arginine deficiency results i...
•

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

•

Vitamin A increa...
ZINC
•In deficiency states there is decreased fibroblast proliferation,
decreased collagen synthesis, impaired overall wou...
INFECTION
•If the wound is contaminated with >105 microorganisms, the risk of
wound infection is markedly increased, but t...
DRESSING
•The main purpose of wound dressings is to provide the ideal
environment for wound healing.
•Ideal dressing – not...
•

Occlusion also helps in dermal collagen synthesis and epithelial cell
migration and limits tissue desiccation.

•

As i...
Absorbent Dressings
•Absorb without getting soaked through, as this would permit bacteria
from the outside to enter the wo...
Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Occlusive and Semiocclusive Dressings

•Good environment for clean & minimally exudative wounds.
•Waterproof and imperviou...
Alginates
•Brown algae and contain long chains of polysaccharides containing
mannuronic and glucuronic acid.
•Processed as...
Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
•

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

•

Nondraining Wound - with a semiocclusive dressi...
•

Vacuum-assisted closure system assists in wound closure by applying
localized negative pressure to the surface and marg...
Hyperbaric oxygen
•As adjunct in the management of nonhealing wounds.
•Most non-healing tissues are hypoxic
Mechanism of a...
Skin Replacements
•All wounds require coverage in order to prevent evaporative losses and
infection and to provide an envi...
Current Skin Engineering
• Tissue-engineered skin exists
as cells grown in vitro and
subsequently seeded onto a
scaffold o...
NEED FOR ARTIFICIAL SKIN
 Drawbacks of conventional treatment
 In severe burns like 3rd degree burns, normal wound
heali...
EVOLUTION OF BURN WOUND CARE
Burn wounds were occluded with dressings
Animal and reptile skin used as a "skin substitute"
...
Contn…
First Cultivation of Human Epidermal Cells (1960’s)
(autologous keratinocytes)

Use of allogenic keratinocyte graft...
Process

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
COMMERCIALLY AVAILABLE SKIN SUBSTITUTES
With advancing technology, a host of both permanent and temporary
biologically act...
III. Collagen based dermal analogs
- De-epithelized allograft
- Alloderm
IV. Cell Culture -derived
- Keratinocyte Cells Sp...
Application of cells spray along with autograft for extensive burns

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

...
Preliminary Safety-Study on application of
autologous keratinocytes cell spray

Before Cell Spray

During Cell Spray
No si...
GMP cell culture facility @ NBC
GMP cell culture facility @ NBC

Change Room

Clean room 3 class 1000 HEPA

Class 1lakh HE...
Cell Spray making process

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

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Secondary Culture of keratinocytes

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
PREPARATION OF SKIN COMPOSITE

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

FUNCTIONA...
BIOBRANE
 Biobrane is a bilayer synthetic skin substitute
 Outer epidermal analog constructed of a thin silicone film wi...
BIOBRANE

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
BIOBRANE APPLIED TO WOUNDS

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

A superficial partial thickness burn
The zone of necrosis isDr.Sunil Keswani, the upper dermis & is us...
Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com

Viable wound bed showing fibrin and coll...
Dr.Sunil Keswani, National
Bilayer BIOBRANE placed on clean wound
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Biobrane adhered to surface by nylon-collagen mesh.
Dr.Sunil Keswani, National
Preservation of thin Burns Centre, www.burn...
Dr.Sunil Keswani, National
Biobrane peeled back from surface to demonstrate rapid
Burns Centre, www.burnsmigration of new ...
Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com

Biobrane removed with re-epithelializati...
APPLICATION OF BIOBRANE

BIOBRANE REMOVAL

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.co...
TRANSCYTE
 Trancyte is a bilayer skin substitute
 Outer epidermal analog is a thin nonporous silicone film with
barrier ...
TRANSCYTE

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

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

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
ALLODERM
 AlloDerm is an acellular dermal matrix designed to serve as a
biologic scaffold for normal tissue remodeling
 ...
NORMAL DERMIS

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

ALLODERM
Day 1: Biologic Scaffold

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 7-10
• Host fibroblast cells and blood vessels respond to the
transplantation of the AlloDerm matrix
• Initiation of t...
Day 45
Replacement and revascularization of the transplant
continues as normal connective tissue

Dr.Sunil Keswani, Nation...
Day 90
AlloDerm repopulated with the patient's own cells
Fibroblasts continue to lay down autologous collagen

Dr.Sunil Ke...
INTEGRA
 INTEGRA is a bilayer membrane system for skin replacement
 The dermal replacement layer - porous matrix of fibe...
Contn…
 Upon adequate vascularization of the dermal layer and
availability of donor autograft tissue, the temporary silic...
HEALING WITH INTEGRA

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

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

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

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

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

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
MATERIALS & METHODS
Surplus cutting

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
MATERIALS & METHODS
Positioning on plate.

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.co...
MATERIALS & METHODS
Dermatome cut through

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.co...
MATERIALS & METHODS
Adhesive Spraying

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
MATERIALS & METHODS
Cork removing.

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
MATERIALS & METHODS
Gauze expansion

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
MATERIALS & METHODS
Gauze expanded.

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
MATERIALS & METHODS
Micrograft positioning

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.c...
MATERIALS & METHODS
After gauze removal. 7th day.

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@...
MATERIALS & METHODS
10th day wound care.

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
MATERIALS & METHODS
Long term control.

POST-PHYSICAL REHABILITATION OUTCOME
Dr.Sunil Keswani, National
Burns Centre, www....
Case 1- day of admission

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 3-Preop

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 3-Early excison and homografting-postop

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail....
Day 5

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 7

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 9

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 15

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Case 2- day of admission

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 3
Postop

Preop

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 7

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 12

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 21

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

Discharge

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Case 3- day of admission

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Early excison and grafting

Pre-Op wound

Application of Homograft
Day 3

Complete healing
Day 21

Dr.Sunil Keswani, Natio...
Case 4- day of admission

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Pre-Op Wound

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Progressive healing of Wound

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

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

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Case 5- day of Admission

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Before and After Homografting

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

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

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Case 6- day of admission

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Progressive healing of RIGHT HAND

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Progressive Healing of LEFT HAND

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Day 15
Homograft Application

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

post op
Case 7-Chemical Burns on admission

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
Progressive healing-Autografting

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
End Result-Autografting

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
DERMAGRAFT
 is an example of a synthetic matrix combined with allogenic
fibroblasts and has good resistance to tearing (B...
DERMAGRAFT

Dermagraft cassettes ready for patient use

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcai...
APLIGRAF
 is supplied as a living, bi-layered skin substitute
 The lower dermal layer combines bovine type 1 collagen an...
Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
SOME CASE STUDIES FOR APLIGRAF APPLICATION

1

2

3

4

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcai...
Traditional Skin Graft

Artificial skin

• Skin graft from the patient • Two-layer template composed
of a porous matrix in...
Current Research and Challenges



•

Role of Stem cells in wound healing (e.g- MSCs)
Role of Gene Therapy to stimulate...
Future Directions
 More effective cell preservation techniques could
enhance shelf life and minimize issues related to st...
Contn…
 Efforts by manufacturers to further reduce the cost of
cellular skin substitute wound therapy could change the
ro...
Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
THANK YOU
BURNS Helpline:
022 2779 3333

Dr.Sunil Keswani, National
Burns Centre, www.burnsindia.com,
nbcairoli@gmail.com
...
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Recent advances in burns management by Dr. Sunil Keswani, National Burns Centre, Airoli

  1. 1. Recent Advances in Burns Management Dr. Sunil Keswani National Burns Centre Dr.Sunil Keswani, National Burns Centre, www.burns-india.com, nbcairoli@gmail.com
  2. 2. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  3. 3. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  4. 4. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  5. 5. 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. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  6. 6. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  7. 7. 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. Dr.Sunil Keswani, National •Uremia also hasBurns Centre, www.burnsbeen associated with disordered wound healing. india.com, nbcairoli@gmail.com
  8. 8. 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. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  9. 9. • 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  10. 10. • 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. • Dr.Sunil Keswani, National Doses rangingBurns Centre, www.burns- IU per day from 25,000 to 100,000 india.com, nbcairoli@gmail.com
  11. 11. ZINC •In deficiency states there is decreased fibroblast proliferation, decreased collagen synthesis, impaired overall wound strength, and delayed epithelialization. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  12. 12. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  13. 13. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsConvenience india.com, nbcairoli@gmail.com
  14. 14. • 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. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  15. 15. 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 Dr.Sunil Keswani, National seal the edges and prevent desiccation and infection. Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  16. 16. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  17. 17. Occlusive and Semiocclusive Dressings •Good environment for clean & minimally exudative wounds. •Waterproof and impervious to microbes, •Permeable to water vapour and oxygen. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  18. 18. 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. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  19. 19. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  20. 20. • 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. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  21. 21. • 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 Dr.Sunil Keswani, National with neoplasms forming part of the wound floor. Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  22. 22. 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 Dr.Sunil Keswani, National Aminoglycosides and Quinolones. Thus it is life saving in gas gangrene and Burns Centre, www.burnssevere necrotising infections. india.com, nbcairoli@gmail.com
  23. 23. 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). Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  24. 24. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  25. 25. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  26. 26. 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) Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  27. 27. Contn… First Cultivation of Human Epidermal Cells (1960’s) (autologous keratinocytes) Use of allogenic keratinocyte grafts Bilayered Artificial Skin Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  28. 28. Process Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  29. 29. 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 Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  30. 30. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  31. 31. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  32. 32. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  33. 33. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  34. 34. Cell Spray making process Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  35. 35. Primary cell culture Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  36. 36. Secondary Culture of keratinocytes Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  37. 37. PREPARATION OF SKIN COMPOSITE Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com FUNCTIONAL EPIDERMIS
  38. 38. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  39. 39. BIOBRANE Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  40. 40. BIOBRANE APPLIED TO WOUNDS Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  41. 41. 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, nbcairoli@gmail.com
  42. 42. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com Viable wound bed showing fibrin and collagen
  43. 43. Dr.Sunil Keswani, National Bilayer BIOBRANE placed on clean wound Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  44. 44. Biobrane adhered to surface by nylon-collagen mesh. Dr.Sunil Keswani, National Preservation of thin Burns Centre, www.burnswater layer on surface to allow epithelial india.com, migration along innernbcairoli@gmail.com layer
  45. 45. Dr.Sunil Keswani, National Biobrane peeled back from surface to demonstrate rapid Burns Centre, www.burnsmigration of new epithelium along nylon-collagen mesh india.com, nbcairoli@gmail.com
  46. 46. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com Biobrane removed with re-epithelialization
  47. 47. APPLICATION OF BIOBRANE BIOBRANE REMOVAL Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  48. 48. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  49. 49. TRANSCYTE Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  50. 50. TRANCYTE IN PLACE Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  51. 51. TRANSCYTE Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  52. 52. 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, Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  53. 53. NORMAL DERMIS Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com ALLODERM
  54. 54. Day 1: Biologic Scaffold Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  55. 55. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  56. 56. Day 45 Replacement and revascularization of the transplant continues as normal connective tissue Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  57. 57. Day 90 AlloDerm repopulated with the patient's own cells Fibroblasts continue to lay down autologous collagen Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  58. 58. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  59. 59. 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) Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  60. 60. HEALING WITH INTEGRA Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  61. 61. Integra Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  62. 62. Acticoat Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  63. 63. Fascial Excision Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  64. 64. Integra applied Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  65. 65. Covered with Acticoat Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  66. 66. MATERIALS & METHODS Surplus cutting Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  67. 67. MATERIALS & METHODS Positioning on plate. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  68. 68. MATERIALS & METHODS Dermatome cut through Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  69. 69. MATERIALS & METHODS Adhesive Spraying Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  70. 70. MATERIALS & METHODS Cork removing. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  71. 71. MATERIALS & METHODS Gauze expansion Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  72. 72. MATERIALS & METHODS Gauze expanded. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  73. 73. MATERIALS & METHODS Micrograft positioning Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  74. 74. MATERIALS & METHODS After gauze removal. 7th day. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  75. 75. MATERIALS & METHODS 10th day wound care. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  76. 76. MATERIALS & METHODS Long term control. POST-PHYSICAL REHABILITATION OUTCOME Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  77. 77. Case 1- day of admission Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  78. 78. Day 3-Preop Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  79. 79. Day 3-Early excison and homografting-postop Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  80. 80. Day 5 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  81. 81. Day 7 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  82. 82. Day 9 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  83. 83. Day 15 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  84. 84. Case 2- day of admission Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  85. 85. Day 3 Postop Preop Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  86. 86. Day 7 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  87. 87. Day 12 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  88. 88. Day 21 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  89. 89. Admission Discharge Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  90. 90. Case 3- day of admission Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  91. 91. Early excison and grafting Pre-Op wound Application of Homograft Day 3 Complete healing Day 21 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  92. 92. Case 4- day of admission Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  93. 93. Pre-Op Wound Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  94. 94. Progressive healing of Wound Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  95. 95. On Discharge Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  96. 96. On Discharge Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  97. 97. Case 5- day of Admission Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  98. 98. Before and After Homografting Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  99. 99. Progressive healing Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  100. 100. Progressive Healing Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  101. 101. Case 6- day of admission Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  102. 102. Progressive healing of RIGHT HAND Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  103. 103. Progressive Healing of LEFT HAND Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  104. 104. Day 15 Homograft Application Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com post op
  105. 105. Case 7-Chemical Burns on admission Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  106. 106. Progressive healing-Autografting Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  107. 107. End Result-Autografting Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  108. 108. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  109. 109. DERMAGRAFT Dermagraft cassettes ready for patient use Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  110. 110. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  111. 111. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  112. 112. SOME CASE STUDIES FOR APLIGRAF APPLICATION 1 2 3 4 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  113. 113. 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 Dr.Sunil Keswani, National • Stiffness of graft area Burns Centre, www.burns- skin • Pliable india.com, nbcairoli@gmail.com
  114. 114. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  115. 115. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  116. 116. 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 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  117. 117. Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com
  118. 118. THANK YOU BURNS Helpline: 022 2779 3333 Dr.Sunil Keswani, National Burns Centre, www.burnsindia.com, nbcairoli@gmail.com www.burns-india.com

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