Wound Healing and Tissue Expansion


Chapter 20

Wound Healing and Tissue Expansion



1. Wound healing phases


• Hemostasis: Platelet plug, fibrin clot, vasoconstriction. α granules in the platelets release cytokines such as platelet-derived growth factor (PDGF), transforming growth factor (TGF), and basic fibroplast growth factor (bFGF).


• Inflammatory: Activated to cleanse and prepare wound for healing


▪ Polymorphonuclear (PMN) leukocytes: Initial 24 to 48 hours. Act as defensive units, phagocytosing bacteria and foreign debris from the wound to prevent infection


○ Phagocytosed by macrophages and destroyed


▪ Macrophage: Dominant cell between 48 and 72 hours (key regulatory cell). Functions to phagocytose bacteria and dead tissue. Secretes collagenases and cytokines responsible for proliferation of fibroblasts, resulting in collagen production, and endothelial cells, resulting in angiogenesis


• Proliferative/fibroplastic: 3 to 5 days after injury, fibroblasts migrate into the wound and become predominant cell type. They begin to lay down new collagen. At first, type 3 is greater than type 1 but is eventually replaced by type 1 to the normal ratio (4:1, T1:T3).


▪ It is during this time that the greatest rate of collagen synthesis occurs in the wound.


▪ Contraction begins and continues into remodeling phase.


• Remodeling begins day 21. Cross-linking and organization of collagen fibers (procollagen is cleaved into collagen)


▪ Net amount of collagen is constant because there is an equal amount of degradation and synthesis.


▪ Wound becomes stronger because of cross-linking.


○ Maximum tensile strength is achieved after ~12 weeks.


♦ 80% by 60 days


2. Wound healing process


• Epithelial cell migration: Initiated by loss of contact inhibition and occurs from the periphery of the wound and adnexal structures


▪ Cell division occurs in 48 to 72 hours, resulting in a thin epithelial cell bridge across the wound.


▪ Epidermal growth factors play a key role.


▪ Can be delayed by retinoids (Accutane/isotretinoin)


▪ Can be stimulated by tretinoin (Retin-A)


○ Promotes epithelialization by stimulating mitotic activity and decreasing the turnover of follicular epithelial cells


○ Often used as a pretreatment in patients undergoing chemical peeling and laser skin resurfacing to accelerate wound healing


• Myofibroblasts: Involved in wound contraction and play no role in epithelialization


• Collagen deposition is seen in the remodeling phase of wound healing.


• Fibronectin produced by fibroblasts serves as an adhesion molecule, anchoring cells to collagen or proteoglycan substrates.


• Release of cytokines from platelets plays an important role in the initiation of the hemostatic initial phase.


3. Growth factors involved in wound healing process (see Table 20.1)



Table 20.1


Partial List of Growth Factors Present in the Wound Site



















































































Growth Factor Abbreviation Growth Factor Cellular Source Target Cells Biologic Activity
CTGF Connective tissue growth factor Fibroblasts, endothelial cells Fibroblasts Downstream of TGF-β1
EGF Epidermal growth factor Platelets, macrophages, keratinocytes Keratinocytes, fibroblasts, endothelial cells Proliferation, chemotaxis
FGF-1, FGF-2, FGF-4 Fibroblast growth factor-1, -2, and -4 Macrophage, fibroblasts, endothelial cells Keratinocytes, fibroblasts, endothelial cells, chondrocytes Angiogenesis, proliferation, chemotaxis
FGF-7 (KGF-1), FGF-10 (KGF-2) Fibroblast growth factor-7 (keratinocyte growth factor-1), fibroblast growth factor-10 (keratinocyte growth factor-2) Fibroblasts Keratinocytes Proliferation, chemotaxis
IGF-1/Sm-C Insulin-like growth factor-1/somatostatin-C Fibroblasts, macrophages, serum Fibroblasts, endothelial cells Proliferation, collagen synthesis
IL-1α and IL-1β Interleukin-1α and -1β Macrophages, neutrophils Macrophages, fibroblasts, keratinocytes Proliferation, collagenase synthesis, chemotaxis
PDGF Platelet-derived growth factor Macrophage, platelets, fibroblasts, endothelial cells, vascular smooth-muscle cells Neutrophils, macrophages, fibroblasts, endothelial cells, vascular smooth-muscle cells Chemotaxis, proliferation, matrix production
TGF-α Transforming growth factor-α Macrophages, platelets, keratinocytes Keratinocytes, fibroblasts, endothelial cells Proliferation
TGF-β1 and -β2 Transforming growth factor-β1 and β2 Macrophages, platelets, fibroblasts, keratinocytes Inflammatory cells, keratinocytes, fibroblasts Chemotaxis, proliferation, matrix production (fibrosis)
TGF-β3 Transforming growth factor-β3 Macrophages Fibroblasts Antiscarring
TNF-α Tumor necrosis factor-α Neutrophils Macrophages, keratinocytes, fibroblasts Activation of growth factor expression
VEGF Vascular endothelial cell growth factor Macrophages, keratinocytes, fibroblasts Endothelial cells Angiogenesis


image


Modified from Lorenz, H.P., Longaker, M.T., 2000. Wounds: biology, pathology, and management. In: Norton, J., Barie, P., Bollinger, R., et al. (Eds.), Surgery: Basic Science and Clinical Evidence, 2nd ed. Springer, New York, 191–208.


4. Important nutrients for wound healing


• Vitamin C: Collagen cross-linking via the hydroxylation of proline and lysine to hydroxyproline and hydroxylysine, respectively


▪ Lack of cross-linking results in impaired collagen synthesis and a decrease in collagen tensile strength. Collagen-containing tissues, such as skin, dentition, bone, and blood vessels, are therefore affected, leading to the development of scurvy.


○ Hallmark signs of scurvy: Hemorrhaging in any organ (ie, petechiae, swollen gums), loss of dentition, and a lack of osteoid formation


○ Seen in patients who are severely malnourished, have a history of alcoholism, or have restrictive diets for medical, social, or economic reasons


• Folate and vitamin B6 (pyridoxine) are integral in DNA synthesis and cellular proliferation.


• Vitamin A is an essential factor in epithelialization and fibroblast proliferation.


▪ Impairment of wound healing caused by use of corticosteroids can be reversed by the oral administration of vitamin A (retinoic acid), 15,000 IU daily, for 7 days.


• Vitamin E is a strong antioxidant and immune modulator.


• Zinc is one of the most important micronutrients because it acts as a cofactor for numerous metalloenzymes and proteins.


▪ Essential for proper protein (like collagen) and nucleic acid synthesis


• Silicone/silicone sheeting


▪ Exact mechanism of action unknown


▪ Most widely accepted hypothesis is that there is an increase in hydration resulting from occlusion


○ Studies have either ruled out or not supported alteration of cytokine levels, direct chemical effects, increased oxygen tension, or pressure.


▪ Some postulate that their effect is associated with the generation of an increased static electronegative field by the silicone.


▪ To be effective, it must be worn for at least 12 hours/day for 3 months or longer.


5. Systemic factors affecting wound healing (see Table 20.2)


• Diabetes mellitus adversely affects healing by altering circulation, attenuating inflammation, reducing tissue oxygenation, and adversely affecting glucose metabolism, resulting in stress hyperglycemia.


• Malnutrition, including caloric, protein, vitamin, and mineral insufficiency, impairs the immune system, prevents tissue repair, and may lead to progression or recurrence of a wound.


• Aging is associated with reduced production of collagen and angiogenesis and a diminished response to environmental stresses.


• By reducing inflammation, steroids impair angiogenesis, fibrogenesis, and wound contraction; reduce wound strength; and delay healing.


• Other factors such as infection, smoking, poor tissue oxygenation, radiation, chemotherapy, and the presence of foreign bodies or cancer within a wound are also associated with poor healing.


• Anemia, even to severe levels, when circulation is maintained has not been found to impair wound healing.



Table 20.2


Factors that May Impair Normal Healing and Lead to Chronic Nonhealing Wounds












































































Etiopathology
Examples
Vascular Arterial Arteriosclerosis, arterial aneurysm, fat embolism with arterial obstruction, hypertension (Martorell ulcer)

Lymphatic Lymphatic edema, lymphangiodysplasia

Venous Chronic venous insufficiency, necrotizing thrombophlebitis

Mixed arteriovenous Combined arteriosclerosis with venous insufficiency, arteriovenous malformations/dysplasia; steal phenomenon (e.g., arteriovenous shunts, vascular compression/obstruction; due to tumors, enlarged lymphatic nodes, etc.)

Vasculitis Wegener’s granulomatosis, Churg-Strauss vasculitis, Henoch-Schönlein purpura, Sneddon syndrome, systemic lupus erythematosus, rheumatoid arthritis, Felty syndrome, Takayasu arteriitis, polyarteritis nodosa, Kawasaki syndrome, pyoderma gangrenosum, necrobiosis lipoidica diabeticorum, thromboangiitis obliterans (Buerger’s disease), allergic reactions

Vasculopathic syndromes Raynaud’s syndrome, systemic scleroderma, CREST, Klippel-Trenaunay syndrome, proteus syndrome, CLOVES syndrome, Kasabach-Merritt syndrome
Physical, chemical, and biological causes Pressure Immobility, intra- and postoperative bedding, tight shoes and casts, compression therapy
Trauma Lacerations, any type of soft-tissue and bone injury, vascular rupture
Thermal Burns/frostbite, electrical injury (electrical current/high voltage/lightning)
Radiation Radiation therapy
Chemical-toxic Extravasation, chemical burns (acids/bases), sclerotherapy
Infections Erysipelas, necrotizing fasciitis, septic cutaneous embolism, osteomyelitis, complications after cutaneous infection
Herpes simplex, cytomegalovirus, human immunodeficiency virus, syphilis, leprosy, tuberculosis
Tropical ulcers, parasitic and vermicular infections
Neuropathic Posttraumatic Spinal lesions with palsy, peripheral nerve injury

Congenital Spina bifida, syringomyelia, multiple sclerosis, neurological syndromes

Systemic neuropathic diseases Diabetes mellitus, ethylene oxide toxic neuropathy, degenerative central and peripheral neuropathies
Poliomyelitis, leprosy, tabes dorsalis
Hemopathological Systemic diseases Polycythemia vera, sickle-cell anemia, other anemias, thalassemia, thrombocythemia vera, thrombocytopenic purpura, increased blood viscosity (paraneoplastic, paraproteinemia, hyperglobulinemia, leukemia), complication after blood transfusion

Disturbed hemostasiology Factor V Leiden syndrome, antiphospholipid syndrome, disturbed fibrinolysis, factor-XIII deficiency syndrome, antithrombin-III deficiency, proteins C and S deficiency, Marcumar necrosis, disseminated intravascular coagulation, necrosis due to vitamin K antagonist therapy
Neoplastic diseases Cutaneous tumors Basal and squamous cell carcinoma, melanoma, Bowen syndrome, Marjolin ulcer (scar carcinoma), tumors with cutaneous metastasis or penetration (e.g., Paget syndrome)
Therapeutic modalities
Steroids, vaccination ulcer (BCG), cytostatic drugs, NSAIDs, extravasation of various drugs
Systemic diseases
Hepatic and/or renal insufficiency, immunosuppression, sarcoidosis, homocysteinemia, hemochromatosis
Other causes
Alcoholism, obesity, gout, smoking, advanced age, malnutrition (e.g., vitamin, protein, and micronutrient deficiency; scurvy); psychiatric diseases with self-harming, neglect, intravenous drug abuse; foreign bodies/projectiles with fistulas

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Sep 2, 2016 | Posted by in Aesthetic plastic surgery | Comments Off on Wound Healing and Tissue Expansion

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