Inservice Exam - 2005
Wound Healing

Which of the following processes of healing provides maximal tensile strength of a wound?

(A) Accumulation of collagen
(B) Addition of sugar moieties
(C) Hydroxylation of lysine
(D) Hydroxylation of proline
(E) Molecular cross-linking


The correct response is Option E.

Intramolecular and intermolecular cross-linking between collagen fibers accounts for the maximal tensile strength of a wound. Maximal strength occurs during the remodeling phase of wound healing. Peak increase in tensile strength occurs three to six weeks after injury but approaches maximal after about three months when it achieves up to 80% of the normal skin strength.

Collagen synthesis peaks at about three weeks, and collagen accumulates to its maximum at six weeks; however, intramolecular and intermolecular cross-linking between collagen fibers provides the tensile strength of the wound.

The addition of sugar moieties occurs just before cleavage of amino and carboxy terminal ends. After this, the molecules are termed collagen, which then develops further intermolecular and intramolecular bonds for strength.

The hydroxylation of lysine and proline in the endoplasmic reticulum of the fibroblasts is a crucial step in collagen production and is important in future intermolecular cross-linking. However, this step occurs much earlier in wound healing, primarily during the proliferative phase.


References:
1. Peacock EE, Cohen IK. Wound healing. In: McCarthy JG, May JW, Littler JW, eds. Plastic Surgery. Vol 1. Philadelphia: WB Saunders; 1990:161-185.
2. Lawrence TH. Physiology of the acute wound. Clin Plast Surg. 1998;25:321-340.
3. Monaco JL, Lawrence TH. Acute wound healing: an overview. Clin Plast Surg. 2003;30:1-12.



Which of the following types of cells has been shown to mediate wound contraction?

(A) Epithelial cells
(B) Lymphocytes
(C) Macrophages
(D) Myofibroblasts
(E) Polymorphonuclear cells

The correct response is Option D.

Myofibroblasts, described by Gabbiani in 1971, are thought by most people to mediate wound contraction. They are derived from fibroblasts in the wound, which under conditions of stress elongate and show features of a myocyte. Through interaction with the matrix, they effectively retract collagen fibrils. Various mediators such as transforming growth factor-beta (TGF-_) and platelet-derived growth factor (PDGF) are involved in the process. Myofibroblasts first appear in the wound by the third day after injury and persist for approximately 21 days, after which time they slowly disappear. They persist longer in open contracting wounds.

Epithelial cells are required to cover a wound but play no role in the wound contraction process. Polymorphonuclear cells, lymphocytes, and macrophages are leukocytes involved in the inflammatory response to injury.

References:
1. Fine NA, Mustoe TA. Wound healing. In: Greenfield LJ, ed. Surgery: Scientific Principles and Practice. Vol 1. 2nd ed. Philadelphia: Lippincott Raven Publishers; 1997:67-83.
2. Glat PM, Longaker MT. Wound healing. In: Aston SJ, Beasley RW, Thorne CH, eds. Grabb & Smith’s Plastic Surgery. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 1997:3-12.
3. Lawrence TW. Wound healing biology and its application to wound management. In: O’Leary JP, Capote LR, eds. The Physiologic Basis of Surgery. Baltimore: Lippincott Williams & Wilkins; 1996:118-140.




Which of the following types of collagen is most abundant in a healed scar?

(A) I
(B) II
(C) III
(D) IV
(E) V


The correct response is Option A.


The most abundant type of collagen in a healed scar is Type I. This type is the most abundant collagen in the body, including the skin. Type II collagen is found predominantly in cartilage and vitreous. Type III collagen is the second most abundant collagen in a healed scar. It also exists in elastic tissues, such as blood vessels. Type IV collagen is located mainly in the basement membranes. Type V collagen is widespread.

References:
1. Fine NA, Mustoe TA. Wound healing. In: Greenfield LJ, ed. Surgery: Scientific Principles and Practice. Vol 1. 2nd ed. Philadelphia: Lippincott-Raven; 1997:67-83.
2. Glat PM, Longaker MT. Wound healing. In: Aston SJ, Beasley RW, Thorne CH, eds. Grabb & Smith’s Plastic Surgery. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 1997:3-12.




Which of the following is the predominant cell responsible for the intermediate phase of wound healing and collagen synthesis (days 3 through 21)?

(A) Erythrocyte
(B) Fibroblast
(C) Myoepithelial cell
(D) Neutrophil
(E) Platelet


The correct response is Option B.


The intermediate phase of wound healing begins on the second or third day after injury and continues until approximately 21 days after injury. This phase begins with chemotaxis and proliferation of mesenchymal cells, angiogenesis, and epithelialization. Ultimately, collagen synthesis, wound contraction, and proteoglycan synthesis predominate in this phase; fibroblasts and macrophages are the primary cells involved. Before this phase, the primary effects of wound healing involve hemostasis and inflammation. Initially, the cellular elements involved in this initial phase are erythrocytes and platelets. Neutrophils are the first of the leukocytes found in the area and are mobilized not long after the erythrocytes and platelets. After approximately 21 days, wound remodeling permeates the overall healing environment. This phase is said to end after approximately one year, although wound remodeling is actually a lifelong process.


References:
1. Lawrence WT. Physiology of the acute wound. Clin Plast Surg. 1998;25:321-340.
2. Monaco JL, Lawrence WT. Acute wound healing: an overview. Clin Plast Surg. 2003;30:1.
3. Steed DL. Modifying the wound healing response with exogenous growth factors. Clin Plast Surg. 1998;25:397.




Which of the following interventions is LEAST likely to improve the appearance of a hypertrophic scar?

(A) Application of silicone gel sheeting
(B) Application of vitamin E gel
(C) Intralesional injection of a corticosteroid
(D) Pressure therapy
(E) Prolonged application of paper tape


The correct response is Option B.


Application of vitamin E products is popular in the skin-care industry despite the paucity of scientific evidence about its effectiveness. Some animal models have demonstrated improvement in healing of radiation-induced wounds with vitamin E. However, no studies have shown clear-cut improvement in hypertrophic or normal scars. In fact, the only controlled study showed no benefit. Localized dermatitis may occur with application of vitamin E products.

Although various treatments have been used to improve the appearance and texture of hypertrophic scars, no single method has shown uniform success. Response rates greater than 50% are considered successful. Application of silicone gel sheeting has shown significant improvement in fibroproliferative scars in several controlled trials, although the mechanism is unknown.


Intralesional injection of triamcinolone and other corticosteroids typically have a response rate greater than 50% but can cause skin atrophy, depigmentation, telangiectasis, and pain.


Pressure therapy has been used to manage keloids and hypertrophic scars since the early 1970s. The use of pressure garments (specially fitted elastic garments often with silicone inserts) to treat postburn scarring and contractures is a standard of care.


Application of adhesive microporous tape to fresh surgical wounds has been endorsed by an international panel on scar management. Uncontrolled clinical trials have shown its efficacy. The mechanism is unknown but may be similar to the action of silicone gel sheeting.


References:
1. Havlik RJ. Vitamin E and wound healing: safety and efficacy reports. Plast Reconstr Surg. 1997;100:1901-1902.
2. Mustoe TA, Cooter RD, Gold MH, et al. International clinical recommendations on scar management. Plast Reconstr Surg. 2002;110:560-571.
3. Rahban SR, Garner WL. Fibroproliferative scars. Clin Plast Surg. 2003;30:77-89.