Principles of Wound Healing

WHAT IS A WOUND?

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

tissues.

Common chronic wounds of the skin and soft tissues

Arterial

Venous

Pressure

Diabetes

Collagen Vascular disease

Udder

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.

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.

Chronic Versus Acute WoundsChronic Versus Acute Wounds

Reference: Lazarus GS, Cooper DM, Knighton DR et al. Definitions and Guidelines for Assessment of Wounds and Evaluation of

Healing. Arch Dermatol. 1994;130:489-493.

Reference: Lazarus GS, Cooper DM, Knighton DR et al. Definitions and Guidelines for Assessment of Wounds and Evaluation of

Healing. Arch Dermatol. 1994;130:489-493.

Acute WoundsAcute 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

tissueReference: 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.

Chronic WoundsChronic 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)

References:

Stanley A, Osler T. Senescence and the healing rates of venous ulcers. J Vasc Surg 2001 Jun;33(6):1206-11

Mulder GD, Vande Berg JS. Cellular senescence and matrix metalloproteinase activity in chronic wounds. Journal of the

American Podiatirc Medical Association. Jan 2002 92(1):34-37.

References:

Stanley A, Osler T. Senescence and the healing rates of venous ulcers. J Vasc Surg 2001 Jun;33(6):1206-11

Mulder GD, Vande Berg JS. Cellular senescence and matrix metalloproteinase activity in chronic wounds. Journal of the

American Podiatirc Medical Association. Jan 2002 92(1):34-37.

Biological and Chemical Defects in Chronic Wounds

• Deficient growth factors• Diminished granulation tissue• Delayed epithelialization• Defective extracellular matrix formation• Excessive proteases (MMPs)

Reference: Nwomeh BC, Yager DR, Cohen,IKC. Physiology of the chronic wound. Clinics in Plastic Surgery July 1998 25(3):341-356.Reference: Nwomeh BC, Yager DR, Cohen,IKC. Physiology of the chronic wound. Clinics in Plastic Surgery July 1998 25(3):341-356.

Growth factor deficiencies found

in chronic wounds include:

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)

Reference: Robson MC, Smith PD. Topical use of growth factors to enhance healing. In Cutaneous Wound Healing editor V.

Falanga Martin Dunitz, London 2001 pp379-398.

Reference: Robson MC, Smith PD. Topical use of growth factors to enhance healing. In Cutaneous Wound Healing editor V.

Falanga Martin Dunitz, London 2001 pp379-398.

Good Wound Care:

Clinical practices which support the normal healing process

Good Wound Care:

Clinical practices which support the normal healing process

Key Considerations – Good Wound Care

• Infection control

• Sharp Debridement

• Moist wound environment

• Off-loading/compression therapy

• Nutritional status

Sharp Debridement

Removes:• Devitalized tissues• Bacteria and

proteolytic enzymes• Senescent cells

Know the wound etiology!

Venous stasis etiology

Arterial etiology

Neuropathic (Diabetic) Etiology

Pressure etiology

Collagen vascular etiology

Hypercoagulopathy

Phases of Normal Wound Healing

• Hemostasis

• Inflammation

• Proliferation

• Remodeling

Hemostasis

• Immediate reaction of small vessels in the area of injury is vasoconstriction

• Release of platelet cytokines (growth factors)

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 24-48 hours

• Macrophages appear at 48-96 hours

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

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

Remodeling Phase

• Usually starts from month 3 and can last up to a year or more

• Reorganization of collagen

• Increase in tensile strength

Why won’t this wound heal?

Why won’t this wound heal?

Why won’t this wound heal?

Factors Affecting Normal Wound Healing

• Poor arterial circulation

• Infection

• Venous hypertension

• Diabetes

• Steroid usage

• Continued pressure

• Poor nutrition

• Cytotoxic substances

• Malignancies

Factors Affecting Normal Wound Healing

• Foreign bodies

• Cigarette smoking

• Radiation

• Alcoholism

• Aging

•Compliance

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

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

Infection

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

Venous Stasis

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

CHARCOT ARTHROPATHY

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

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

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.

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

Foreign Bodies

• Nidus for infection: Hematomas, Dysvascularized bone, tendon, cartilage,

metal objects, glass, wood, thorns

Smoking

• Limits functional tissue perfusion

• Cutaneous vasoconstriction and decreased wound contraction as a direct effect of nicotine

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

Osteoradionecrosis

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

CalciphylaxisPyoderma gangrenosum

Be aware!

Compliance

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