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Process of wound healing
Stages of wound healing
Types of tissue injury
Treatment of wound healing

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  The Wound Healing Society defines healing as complete closing of the
integument.  Skin wounds that heal by primary intention are similar to 
incisions that are created by a scalpel blade and then heal rapidly and 
without complication.  More complicated are the wounds that heal by 
secondary intention.  Secondary intention wounds are large tissue 
defects that fill by granulation followed by epitheliazation.  Wound 
closure occurs to some extent because of wound contraction.

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Process of Normal Healing

  There are four major phases of wound healing; inflammation,
repair, and remodeling. The sequence begins with wound formation. 
After wound formation, hemostasis is achieved as a plug of fibrin 
and cellular debris fills the defect. Platelets release growth 
substances and cytokines, which are chemotactic for neutrophils 
and monocytes, and yield a nonspecific inflammatory response. 
This response is enhanced by monocyte release of cytokines 
interleukin-1 (IL-1) and tumor necrosis factor (TNF), which in turn 
induce complement factors by fibroblasts. As the general inflammatory 
response subsides, polypeptide growth factors platelets derived 
growth factor (PDGF), epidermal growth factor (EGF), and basic 
fibroblast growth factor (b-FGF) gradually replace cytokines in the 
wound fluid. These growth substances down-regulate inflammatory
protein production and upregulate fibroblast collagenase to degrade 
the existing extracellular matrix. A provisional matrix of fibronectin 
and glycosaminoglycans is synthesized by fibroblasts, partially in 
response to PDGF in wound fluid.

After provisional matrix formation, transforming growth factor-beta 
(TGF-beta) peaks between day 7 and day 14 and partially directs
the repair phase, wherein wound fibroblasts synthesize and secrete 
type I collagen. The secreted collagen fibrils self-assemble into 
fibers that form (in a vitamin C-dependent process) cross-links 
between lysine residues and collagen fibrils. These are randomly laid 
down during the repair phase of wound healing within granulation 
Also within granulation tissue, b-FGF induces neo-angiogenesis.  Later,
during the remodeling phase, the dermis becomes stronger, turning 
over collagen fibers so they are retained preferentially along lines of
stress. Simultaneously with early dermal healing, wounds 
re-epithelialize.  Fibroblast-secreted keratinocyte growth factor (KGF)
and IL-6 help cause keratinocytes to proliferate and then differentiate 
into the epidermis. Epidermis at the wound edge, from which nascent 
keratinocytes arise, also directs keratinocytes to cover the opening. 
This is done by way of the skin battery. The skin battery, which is
contained within the stratum spinosum, is an amiloride-blocked 
sodium pump that induces electrical currents at the wound edge 
sufficient to cause keratinocytes to migrate purposefully in the 
direction of wound closure.  Water-loss and bacterial contamination
cease with the closure of the epidermal layer. Normal healing of a 
wound by primary intention takes 3 to 14 days to complete. The 
14-day interval is for deeper, sutured surgical incisions. The process
takes longer for secondary intention wounds. These wounds from 
granulation tissue consisting of a loose connective tissue framework 
with fibroblasts actively synthesizing and secreting extracellular 
matrix, and there is a high density of immature neo-vessels engorging 
the repairing region with oxygen and nutrients.

Process of Healing

1° intention 
- least complicated
- basically a clean incision, deeper damage to skin
Scab – temporary covering
2° intention
- granulation tissue

3° intention
- not being discussed anymore
- leave wound open for several days; if clean, suture
- “ delayed primary healing “

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1. inflammation 
	- initiates healing process
	- release of chemotactic factors (attract other substances)
                  a.k.a growth factors
	- mitosis, cells at edge of wound thicken

2. proliferation of stratum basale
	- re-epithelialization
	- occur almost simultaneously with inflammatory phase

	- inflammation substances are being produced
	- prostaglandin, serotonin, bradykinin, tumor – growth 
                  factor Beta
	- “ granulation tissue formation “

4 Effects of Tumor Growth Factor Beta (TGF ß)
a. stimulate fibroblast migration
b. stimulate fibroblast proliferation
c. stimulate fibroblast synthesis of collagen
d. stimulate angiogenesis – “neovascularization”
                           - new blood vessels are formed

	- also secrete ground substance (bed)
	- substance is responsible in fibroplasias

Capillary Sprouting
	- new vessels are formed

Granulation Tissue – loose framework of capillary sprouting +  
                   - pink under microscope
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1. Partial Thickness Injury - limited to the epidermis and superficial 
               dermis with no damage to the dermal blood vessals. 
               Healing occurs by regeneration of epithelial tissue.

2. Full Thickness Injury - injury involves loss of the dermis and 
              extendes to deeper tissue layers and disruptes dermal 
              blood vessals. Wound healing involves the synthesis of 
              several types of tissue and scar formation.
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wound coverage
       A.Topical antibacterial agents
          - Materide
          - Silver nitrate
          - Gentamicin
          - Povidine iodine
          - Silver sulfadiazine
       B. Biological Dressings
           - skin substitute used for temporary coverage of the burn 
           - skin grafts from cadaver, human fetal membranes, and pigs
           - recommended usage of these dressings:
                i. for immediate coverage of a superficial partial 
                   thickness burn
                ii. wound debridement
                iii. test dressing
                iv. for wound coverage after excision of burn eschar
           - it prevents fluid loss
           - it decrease pain
           - it inhibits bacterial growth on clean wounds
           - it encourages growth of granulation tissue
           - should be change every several days because it may 
             incorporated to the burn wound

      C. Synthetic dressings
          - develop to cover open wounds until the wound healed or 
            until it could be autografted
          - used in place of xenografts and homografts
          - criteria to be effective:
                i. a product was needed must be readily available
                ii. non-allergenic
                iii. relatively expensive
                iv. easily removable had permeable membrane
                v. it comes in large sheets
          - ex. Biobrane ( has a bilaminar structure with silicone on the 
            outside and nylon bonded to the bottom, which is covered 
            with collagen)
          - ex. Opsite ( composed of thin, transparent, elastic, 
            adhesive-coated polyurethane film that is permeable to
            water vapor)

      D. Artificial skin
         - has dermal and epidermal layer
         - dermal layer is porous collagen fibrous matrix on which the 
           patient’s own fibroblasts and epidermal cells are seeded and 
           grow into an epidermal replacement
         - employed in cases of very large, full thickness or deep 
           partial thickness injuries with minimal donor sites for 


1. Debridement 
    - removal of devitalized tissue down to a viable tissue level to 
      prepare the wound bed for definitive coverage
    - removal of eschar aids in healing by preventing bacterial 
         A.Mechanical Debridement
            - best accomplished either during hydrotherapy or 
              immediately following
            - removal of dressings when they are dry is effective in 
              debridement of dead tissue because it adheres to the 

         B.Enzymatic Debridement
            - ex. Sutilains 
            - there is increased fluid drainage through the wound with 
              enzymatic debridement
            - side effects: bleeding, body temperature elevation, pain
            - not used in conjunction with hexachloropene or iodine

         C.Surgical Debridement
            - Fascial Excision (removes nonviable burn tissue and  a 
              variable amount of viable tissue and is reserved for 
              patient with very deep buns;skin grafts adhere much 
              better to fascia than to fat; side effects: fat does not 
              regenerate, can cause severe cosmetic deformities)
            - Tangential Excision (performed at 1- 10 days post-burn; 
              shave thin layers of eschar sequentially until viable 
              tissue is apparent:used to control bleeding, micro-
              crystalline collagen, thrombin, epinephrine, electro-
              cautery; ex. Tourniquets)

2. Skin Grafting
      a. Autograft – removal of skin from one part of the body 
	            and its transfer to another part
      b. Full thickness graft – for reconstructive procedure
      c. Split-thickness graft – used primarily
      d. tanner mesh graft – expandable skin that can be used 
	                     to cover large wounds
      e. postage stamp graft – application of squares/ rectangles 
	                      of various dimensions spread evenly over 
                              the wound
      f. sheet graft – involves using a piece of split-thickness skin
	               without meshing or cutting it into small squares; 
                       used in smaller burn wounds and on the face, neck, 

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