• Clinical science

Wound healing

Summary

Wounds are a break in the skin and/or a disruption of the skin's normal barrier function. Wound healing is a step-wise cellular response involving fibroblasts, macrophages, endothelial cells, and keratinocytes that restore the structural and functional integrity of the skin. The four general stages of wound healing are exudative, resorptive, proliferative, and maturation. While the three initial stages take place within the first two weeks, the last stage proceeds over months. Many factors affect wound healing, including the size of the wound, tension on wound edges, the presence of foreign bodies or infection, and the baseline health and nutrition of the patient. In addition, chronic health conditions such as diabetes and peripheral vascular disease can slow the wound healing process. Delayed wound healing may lead to the formation of a chronic wound.

Types of wound closure

Primary wound closure

  • Usually a small, straight, and clean incision
  • Primary approximation of the wound edges without irregularities
  • Minimal inflammation
  • Minimal to no granulation tissue
  • Organ-specific tissue forms at the site of healing
  • Hairline scar or no scar formation

Secondary wound closure

  • Usually larger open wounds with irregular edges (most common type of wound)
  • Irregular wound edges that cannot be perfectly approximated
  • Pronounced inflammation
  • Requires the formation of granulation tissue (increase the length of healing)
  • Wound replaced with increased proliferation of fibroblasts
  • Scar formation

Tertiary wound closure (also called delayed primary closure)

  • Due to an interruption in normal wound healing
  • Combination of primary closure and secondary closure: wounds should be cleaned and observed for 2–3 days before surgical closure to ensure there is no infection.
  • Results in a larger scar than with primary or secondary closure
  • Wounds can result from a variety of trauma (e.g., animal bites, lacerations with foreign bodies)

Phases of wound healing

Phases of wound healing [1]
Phase Timing Cells involved Characteristics Involved tissue mediators

Exudative

  • Day 1

Resorptive

  • Days 1–3

Proliferative

  • Days 3–7
Maturation
  • Weeks to 1 year

Wound healing complications

Delayed wound healing or chronic wound formation

  • Usually occurs in patients with multiple risk factors that cause slowing or failure to progress through one or more stages of wound healing
  • The proliferative wound healing phase is delayed in individuals with copper and vitamin C deficiency.
  • Zinc deficiency can delay wound healing because the collagenases responsible for collagen remodeling require zinc to function properly.

Scar formation

  • Occurs when initial injury cannot be repaired solely by cell regeneration
  • Cells that cannot be regenerated (e.g., due to chronic injury or because acute injury is too severe) are replaced by connective tissue.
  • After 3 months, 70–80% of tensile strength is regained. [2]
  • Maximum strength of scar tissue is approx. 80% of that of unwounded skin. [2]

Excessive scar

Hypertrophic scar

Keloid

Contracture

  • Excessive proliferation in myofibroblasts during proliferative and maturation phases leads to contraction of the wound.
  • Excessive contraction can reduce the functionality of the injured limbs or organs.
  • Wounds that cross a joint (e.g., on the hands and fingers) are at high risk for causing functional deficits from contracture. Periodic exercise of the involved limb can help preserve normal function.
  • 1. Stadelmann WK, Digenis AG, Tobin GR. Physiology and healing dynamics of chronic cutaneous wounds. Am J Surg. 1998; 176(2A Suppl): pp. 26S–38S. pmid: 9777970.
  • 2. Thiruvoth F, Mohapatra D, Sivakumar D, Chittoria R, Nandhagopal V. Current concepts in the physiology of adult wound healing. Plastic and Aesthetic Research. 2015; 2(5): p. 250. doi: 10.4103/2347-9264.158851.
  • 3. Zhu Z, Ding J, Tredget EE. The molecular basis of hypertrophic scars. Burns & trauma. 2016; 4: p. 2. doi: 10.1186/s41038-015-0026-4.
  • 4. Leivonen SK, Lazaridis K, Decock J, Chantry A, Edwards DR, Kähäri VM. TGF-β-elicited induction of tissue inhibitor of metalloproteinases (TIMP)-3 expression in fibroblasts involves complex interplay between Smad3, p38α, and ERK1/2. PloS one. 2013; 8(2): p. e57474. doi: 10.1371/journal.pone.0057474.
  • 5. Shah M, Foreman DM, Ferguson MW. Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring. J Cell Sci. 1995; 108 ( Pt 3): pp. 985–1002. pmid: 7542672.
  • 6. Schultz GS, Chin GA, Moldawer L, Diegelmann RF, Fitridge R, Thompson M. Principles of Wound Healing. StatPearls. 2011. pmid: 30485016.
  • 7. Köse O, Waseem A. Keloids and hypertrophic scars: are they two different sides of the same coin?. Dermatol Surg. 2008; 34(3): pp. 336–46. doi: 10.1111/j.1524-4725.2007.34067.x.
  • 8. Verhaegen PD, van Zuijlen PP, Pennings NM, et al. Differences in collagen architecture between keloid, hypertrophic scar, normotrophic scar, and normal skin: An objective histopathological analysis. Wound Repair Regen. ; 17(5): pp. 649–56. doi: 10.1111/j.1524-475X.2009.00533.x.
last updated 11/16/2020
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