1. Principles of Wound Healing

2. WHAT IS A WOUND?

3. Wound(woond): Break in the continuity of soft or hard parts of the body structures caused by violence or trauma to tissues.

4. Common chronic wounds of the skin and soft tissues
Arterial
Venous
Pressure
Diabetes
Collagen Vascular disease
Udder

5. Chronic Versus Acute Wounds
Normal acute wounds caused by surgery or trauma usually heal and close rapidly
A chronic non-healing wound has been defined as a wound that fails to proceed through the orderly and timely series of events required to produce a durable structural, functional, and cosmetically acceptable closure.
A chronic non-healing wound has been defined as a wound that fails to proceed through the orderly and timely series of events required to produce a durable structural, functional, and cosmetically acceptable closure.
Wound specialists generally define a chronic wound as one that has failed to heal after 4-6 weeks of conservative management but we should increasingly adhere to the definitions
Reference: Lazarus GS, Cooper DM, Knighton DR et al. Definitions and Guidelines for Assessment of Wounds and Evaluation of Healing. Arch Dermatol. 1994;130:
Reference: Lazarus GS, Cooper DM, Knighton DR et al. Definitions and Guidelines for Assessment of Wounds and Evaluation of Healing. Arch Dermatol. 1994;130:

6. Acute Wounds Cells are viable, able to respond to growth stimuli
Sufficient growth factors are released in the wound environment
Cells proliferate and can migrate and synthesize components of new tissue
Chronic wounds differ in their healing patterns from normal wound healing in many important features.
Normal healing results from the interaction of sufficient growth factor signals with viable, responsive cells that can divide, migrate and synthesize components of new tissue. Acute wounds that heal normally progress rapidly through the sequence of events previously discussed. Analyses of tissue biopsies and wound fluid from healing wounds in comparison to wound fluid from non-healing wounds have revealed quantitative and qualitative differences.
Reference:
5. Monaco JL, Lawrence TL. Acute wound healing; an overview. Clinics in Plastic Surgery 30 (2003): 1-12. .
Reference: Monaco JL, Lawrence TL. Acute wound healing; an overview. Clinics in Plastic Surgery 30 (2003): 1-12.

7. Chronic Wounds Growth factors may be deficient Increased Bacteria
Decreased oxygen
Cells are senescent, unable to respond to growth factors
Cells may be slow to proliferate and migrate (< 0.5 mm/week wound closure rate)
Chronic wounds are characterized by “senescence.” Key cells are incapable of dividing, and have only a muted ability to respond to growth factor stimulation. Studies of venous stasis ulcers have shown that one marker for ”difficult to heal” ulcers is when the percentage of cell populations that are senescent is > 15%. It has been shown that cells from biopsy specimens obtained from the margins of chronic wounds are significantly less capable of proliferating in response to exogenous growth factors than corresponding cells from acute wounds. Additionally, growth factor levels in the chronic wound appear to be insufficient to sustain proper levels of cell proliferation. In contrast to normally healing wounds that have a high level of mitogenic activity, wound fluid collected from chronic wounds does not stimulate DNA synthesis (Ref 4). Epithelial cells from chronic wounds have a reduced capacity for migration. It has been shown that wounds that do not close (epithelialize) faster than 0.5mm/week are likely not to heal.
Explain proliferation & migration
References:
15. Stanley A, Osler T. Senescence and the healing rates of venous ulcers. J Vasc Surg 2001 Jun;33(6):
16. Mulder GD, Vande Berg JS. Cellular senescence and matrix metalloproteinase activity in chronic wounds. Journal of the American Podiatirc Medical Association. Jan (1):34-37.
References:
Stanley A, Osler T. Senescence and the healing rates of venous ulcers. J Vasc Surg 2001 Jun;33(6):
Mulder GD, Vande Berg JS. Cellular senescence and matrix metalloproteinase activity in chronic wounds. Journal of the American Podiatirc Medical Association. Jan (1):34-37.

8. Biological and Chemical Defects in Chronic Wounds
Deficient growth factors
Diminished granulation tissue
Delayed epithelialization
Defective extracellular matrix formation
Excessive proteases (MMPs)
Chronic wounds show a number of other defects that together impair their ability to heal properly.
They are deficient in granulation tissue, which is essential for establishing the nutritional network needed to support reparative tissue. Chronic wounds also show delayed epithelialization as a result of decreased cellular proliferative and migratory capacity. They have defective formation of the supporting stroma. Chronic wounds also often exhibit excessive protease production, which can lead to growth factor degradation and diminution of the proliferative capacity of the wound.
These defects, coupled with cellular senescence, help to explain why chronic wounds are so difficult to heal.
Let’s focus on the growth factor deficiencies first.
References: 10. Nwomeh BC, Yager DR, Cohen,IKC. Physiology of the chronic wound. Clinics in Plastic Surgery July (3):
Reference: Nwomeh BC, Yager DR, Cohen,IKC. Physiology of the chronic wound. Clinics in Plastic Surgery July (3):

9. Growth factor deficiencies found in chronic wounds include:
Platelet Derived Growth Factor (PDGF)
Transforming Growth Factor Beta (TGFß)
Vascular Endothelial Growth Factor (VEGF)
Insulin-like Growth Factor (IGF-1)
Keratinocyte Growth Factor (KGF)
Some of the specific deficiencies found in chronic wounds include deficiencies in PDGF -- which as a key growth factor involved in wound healing.
Other deficiencies include transforming growth factor beta - which in addition to its role in angiogenesis plays an important role in extracellular matrix formation -- and keratinocyte growth factor, which plays a prominent role in the process of re-epithelialization.
Reference: 18. Robson MC, Smith PD. Topical use of growth factors to enhance healing. In Cutaneous Wound Healing editor V. Falanga Martin Dunitz, London 2001 pp
Reference: Robson MC, Smith PD. Topical use of growth factors to enhance healing. In Cutaneous Wound Healing editor V. Falanga Martin Dunitz, London 2001 pp

10. Good Wound Care: Clinical practices which support the normal healing process

11. Key Considerations – Good Wound Care
Infection control
Sharp Debridement
Moist wound environment
Off-loading/compression therapy
Nutritional status
In the clinical management of any type of wound, especially chronic wounds, a number of basic issues must be considered. These include: the need for infection control, sharp debridement, maintaining a moist wound environment, appropriate off-loading or compression therapy, and maintaining an adequate nutritional status of the patient. Collectively addressing these issues can be considered as the foundation of “good wound care.”

12. Sharp Debridement Removes: Devitalized tissues
Bacteria and proteolytic enzymes
Senescent cells
An important step in the management of any wound type is keeping it free of devitalized, necrotic tissue. Devitalized tissues present both physical and chemical impediments to granulation tissue formation and epithelialization. Debridement removes foreign bodies and necrotic tissue, callus, infected or avascular, down to healthy bleeding tissue the urgency and the location of care.
Debridement can be accomplished by using a variety of techniques – surgical or sharp, mechanical, chemical or enzymatic, and autolytic may be appropriate depending on the nature and extent of the devitalized tissue.
The most efficient and aggressive method of debridement is sharp debridement, in which the necrotic tissue is removed with a scalpel, scissor, forceps, or curette. This converts the chronic wound to a more acute wound state that is, in many cases, more capable of healing.
Mechanical debridement involves the use of an external force to remove devitalized tissue. Wet-to-dry dressings are a traditional method of mechanical debridement. Unfortunately, wet-to-dry dressings are nonselective and may tear away new, healthy tissue. It can also be painful.
Proteolytic enzymes are also common chemical agents for debridement. Enzymes are indicated for debridement of necrotic tissue and for liquefaction of slough in acute and chronic wounds. As with any debriding method, these agents should be used only for a limited period. When the wound is clear of debris, a reassessment must be done and another wound management plan should be implemented. Enzymes usually take longer to work than mechanical debridement.
With the autolytic debridement method, the body uses its own endogenous enzymes and phagocytic cells to break down necrotic debris under a moisture-retentive dressing, such as transparent film, hydrocolloid, or hydrogel dressings.

13. Sharp Debridement Improves Incidence of Complete Healing with Becaplermin
A study was published in 1996 showing that sharp debridement alone can improve the incidence of complete wound closure in a clinical trial studying diabetic neuropathic ulcers.
Importantly, the addition of sharp debridement to REGRANEX Gel therapy nearly tripled the incidence of completely healed wounds (>80%) when compared with debridement alone (25%).
Reference:
22. Steed DL, Donohoe D, Webster MW, Lindsley L. Effect of extensive debridement and treatment on the healing of diabetic foot ulcers. Diabetic Ulcer Study Group. J Am Coll Surg. 1996;183:61–64.
— Adapted from Steed DL. et. al. J Am Coll Surg 1996;183:61-64.

14. Know the wound etiology!

15. Venous stasis etiology

16. Arterial etiology
HIPAA

17. Neuropathic (Diabetic) Etiology

18. Pressure etiology

19. Collagen vascular etiology

20. Hypercoagulopathy

21. Phases of Normal Wound Healing
Hemostasis
Inflammation
Proliferation
Remodeling

22. Hemostasis
Immediate reaction of small vessels in the area of injury is vasoconstriction
Release of platelet cytokines (growth factors)

23. Inflammatory Phase
Usually lasts from time of injury through 3 days
Polymorphonuclear leukocytes (PMN’s) are the first white blood cells to enter the wound
Peak in hours
Macrophages appear at hours

24. Proliferative Phase
Fibroblasts appear in the wound on day 3, peaking on day 7
Granulation tissue forms consisting of fibroblasts, inflammatory cells and capillaries in an extracellular matrix of collagen, fibronectin and glycosaminoglycans (GAGs)
Fibroblasts are attracted to the wound and stimulated to proliferate by cytokines (growth factors) produced by platelets, macrophages and lymphocytes

25. Proliferative Phase
Fibroblasts lay down the extracelluar matrix (collagen)
Endothelial cells migrate in response to angiogenic stimuli and form new capillaries
Epithelial cells migrate and begin the process of reepithelialization

26. Remodeling Phase
Usually starts from month 3 and can last up to a year or more
Reorganization of collagen
Increase in tensile strength

27. Why won’t this wound heal?

28. Why won’t this wound heal?

29. Why won’t this wound heal?

30. Factors Affecting Normal Wound Healing
Poor arterial circulation
Infection
Venous hypertension
Diabetes
Steroid usage
Continued pressure
Poor nutrition
Cytotoxic substances
Malignancies

31. Factors Affecting Normal Wound Healing
Foreign bodies
Cigarette smoking
Radiation
Alcoholism
Aging
Compliance

32. Poor Arterial Circulation
inadequate supply of oxygen and nutrients required for healing
Hypoxia impairs neutrophil function
decreases collagen synthesis and cross linking
decrease in tensile strength
increases susceptibility to infection

33. Infection
100,000 bacteria/gram of tissue or greater and the body cannot control without intervention
Beta hemolytic Strep is an exception. Wound healing is affected no matter what the concentration
Bacteria secrete proteases, hemolysins and inhibitors of leukocyte chemotaxis

34. Infection

35. Venous hypertension
superficial venous insufficiency
incompetent perforator vein with normal deep vein
venous hypertension:capillary distention, leakage of fibrinogen from the blood to dermis. Prevents oxygen diffusion nutrient transport, chronic leg edema
periwound inflammation
compression is the cornerstone of treatment
color duplex Doppler's are the gold standard for diagnosis

36. Venous Stasis

38. Diabetes
Peripheral neuropathy with sensory impairment
Motor neuropathy leading to foot deformity
Autonomic neuropathy (decreased sweating and suppleness of the skin)
Peripheral vascular disease (atherosclerosis)
Immunodeficiency
Poor glucose control
Denial of the disease
Charcot arthropathy

40. CHARCOT ARTHROPATHY

41. Glucocorticoid Usage
Prednisone use: Increased risk of infection
Use of steroids can increase wound complications 2-5 times
Suppression of inflammation
Decreased wound strength
Inhibition of wound contracture
Delayed epithelialization
Topical vitamin A enhance epithelialization
Oral vitamin A can increase collagen deposition

42. Continued Pressure
Pressure, friction, shear
Tissue hypoxia
Tissue death
Inhibition of normal wound healing mechanism to proceed
Muscle can degenerate with as little as 60 mm Hg
Pressure over some bony prominences can reach 2600 mm Hg

43. Cytotoxic Substances
Topical products such as hydrogen peroxide, vinegar, povidone-iodine (Betadine), Gentian Violet solution, Phisohex, Dakins solution.
OK to use for a couple of days if your goal is to reduce bacterial count. SHOULD NOT be used on wounds once they are clean and in the healing phase.

45. Malignancies
Wounds that do not fit the profile of a typical chronic wound or is not progressing in the time frame that one might expect
Squamous cell carcinoma, basal cell carcinoma, sarcomas, malignant melanomas, leukemias

48. Foreign Bodies
Nidus for infection: Hematomas, Dysvascularized bone, tendon, cartilage, metal objects, glass, wood, thorns

49. HIPAA Smoking Limits functional tissue perfusion
Cutaneous vasoconstriction and decreased wound contraction as a direct effect of nicotine
HIPAA

50. Radiation
Thinning of the epidermis
Decrease in quantity of blood vessels
Increase fibrosis in dermis
Fibroblasts permanently damaged
Irradiated site becomes relatively ischemic
Radiation damaged skin is easily damaged
Poor inflammatory response after injury
Poor angiogenesis

51. Osteoradionecrosis

52. Alcoholism
Chronic alcohol usage can cause slow cellular growth and slower collagen accumulation
Aging
Affects every stage of healing
Decrease in wound tensile strength, delayed epithelialization, more tissue breakdown than synthesis

53. Calciphylaxis Pyoderma gangrenosum
Be aware!

54. Compliance

55. Current Wound Healing Concepts
Determine the wound etiology
Take wound biopsies
Ensure adequate perfusion
Treat infection (take tissue cultures not swab cultures)
Remove pressure from the wound
Aggressive frequent debridements
Keep wounds moist
Compression is the key to venous stasis ulcers

56. Darco wedge Shoe

57. Reverse IPOS

58. Total Contact Cast

59. Total Contact Cast: Holiday Version

60. Total Contact Cast: Sports Version

61. Diabetic Shoes

62. Wheelchair

63. Canes, crutches, walkers

64. Roll a Bout

65. PRAFO Splint

66. REGRANEX* Gel (becaplermin) 0.01%
Description:
15 gram tube
Contains 100 mg/g rhPDGF-BB (0.01%)
Store at 36°-46°F / 2°-8°C (refrigeration)
REGRANEX Gel is available in 15 gram tubes. It contains active recombinant human PDGF-BB in a concentration of 0.01%.
Because it is a protein product that is temperature-sensitive, REGRANEX Gel must be stored in the refrigerator.
* trademark

67. ORC/Collagen (Promogran* Matrix Wound Dressing)
• 45% Oxidized Regenerated Cellulose / 55% Collagen
A bioresorbable, amorphous, open-pored matrix
PROMOGRAN Matrix is a medical device that inhibits excess protease activity in wounds. This product is a bioresorbable, open-pored matrix comprised of oxidized regenerated cellulose and collagen (ORC/Collagen).
Because it adsorbs wound fluid, PROMOGRAN Matrix also helps maintain the moist wound environment, an important wound healing factor we’ve already discussed.
PROMOGRAN Matrix helps to control the wound environment through a variety of mechanisms. It binds to and protects growth factors by binding and inactivating proteases in the wound environment, and it also directly binds growth factors and then sustain releases them back into the wound bed.
Reference:
23. Cullen B, Smith R, McCullochE, Silcock D, Morrison L. Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Rep Reg 2002;10:16-25.
9. Ovington L, Cullen B. Matrix metalloprotease modulation and growth factor protection. Podiatry Today 2002 Oct(Suppl): 2-13.
Source: Angiogenesis Clinic, Boston
Reference:
Cullen B, Smith R, McCullochE, Silcock D, Morrison L. Mechanism of action of PROMOGRAN, a protease modulating matrix, for the treatment of diabetic foot ulcers. Wound Rep Reg 2002;10:16-25.
Ovington L, Cullen B. Matrix metalloprotease modulation and growth factor protection. Podiatry Today 2002 Oct(Suppl): 2-13.
* Trademark

68. PRISMA Matrix Components
PRISMA Matrix is composed of 55% Type 1 bovine collagen (derived from cow hide), 44% Oxidized regenerated cellulose (ORC), and 1% Silver- ORC salt. The Silver-ORC salt releases 0.25% ionic silver.

69. Adjunct Therapies in Wound Healing
Apligraf: Indicated for venous stasis ulcers. It is a bilayered, living skin construct which can be used in place of a split thickness skin graft. Histologically, it is very similar to human skin and has a functional epidermis and dermis.

70. APLIGRAF® (Graftskin) APPROXIMATES SKIN IN STRUCTURE AND BARRIER FUNCTION

71. HISTOLOGIC COMPARISON
APLIGRAF® (Graftskin)
Human Skin
Photomicrographs of hematoxylin-eosine-stained cross-sections of APLIGRAF® (left) and human skin (right) 250.

72. Hyperbaric Oxygen Therapy (HBO)

73. Effects of HBO
Enhances collagen production
Enhances capillary angiogenesis
Increases oxygen tension in infected tissue and bone
Increases effect of neutrophils
Direct lethal effect on strict anaerobes
Inhibits production of exotoxins
Augments antibiotic effectiveness

74. HBO Indications
Clostridial Myonecrosis (gas gangrene)
Osteomyelitis
Necrotizing soft tissue infections
Non operable patient with arterial disease (TCPO2 studies)
Osteoradionecrosis
Necrotizing insect bites (Brown Recluse spider)
Diabetic foot wounds Wagner Grade 3 or more

75. Topical enzymatic debridement agents i. e
Topical enzymatic debridement agents i.e.: Accuzyme, Panafil, Santyl, Gladase
Topical antibiotics: Silvadene, Iodosorb, bacitracin, Bactroban, Neosporin
Dressings: gauze, hydrogels, alginates, foams
Dermagraft
Graftjacket
Anodyne
The VAC (Vacuum Assisted Closure)
Integra (dermal equivalent)

76. Integra

77. Healed

78. Dog Bite

79. Debridement and Skin Graft

80. Healed

81. Bad Dog!

82. Wound Care Centers Hospital based facilities
Podiatry, Plastic Surgeons, Vascular Surgeons, General Surgeons, etc.
Specialty trained nurses in wound care
Latest treatment modalities
Hyperbaric oxygen chambers
Last resort?