What is resolution, regeneration and replacement

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An 80-year-old male presents with resolving decubitus that is now oozing and red. The wound team has been involved. His daughter wants information regarding his skin condition.

Describe the phases of wound healing.

Three phases of wound healing include hemostasis, inflammation, proliferation, proliferation, and remodelling. Each is activated by cytokines and mediators as the previous stage nears completion (Bowers & Franco, 2020).

Stage I: Hemostasis to stop the bleeding through vasoconstriction. Activation of the clotting cascade results from platelet exposure to collagen, which proceed to release chemicals that cause more platelets to become active. Fibrin is also activated, and in conjunction with platelets forms a provisional matrix.

Inflammatory Stage: Inflammation attempts to remove foreign material from the wound and prepares for healing. It is considered the province of the innate immune system, and this stage can be prolonged if there is ineffective decontamination and microbial removal, which is caused by endotoxin levels and/or other microbial products. Neutrophils and M1 macrophages arrive and proceed to phagocytize material and also release massive amounts of pro-inflammatory cytokines, which encourage the secretion of transforming growth factor and platelet-derived growth factor. This promotes the proliferation of fibroblast, angiogenesis, and keratinocyte migration. Chemotaxis of neutrophils and macrophages end the inflammatory phase. With chronic wounds, two mechanisms stall or arrest this orderly progression of events between the inflammation stage and wound closure. One is that the previous step never completes and/or wound closure signals fail to get through and an equilibrium sets up with bacteria that is present. The second is that the signals do get through, but for some reason, the next step that starts isn’t the right one. Prolonged inflammation can cause protease levels to increase, which degrades the extracellular matrix and growth factors. This prevents the proliferation stage and wound closure, leading to chronic wounds (Almadani et al., 2021).

Proliferation/Epithelization Stage: This is the reparative phase when collagen-producing fibroblasts and epithelial cells are replaced at the injury site. MicroRNA (miR-21) appears to be involved in signalling the termination of the inflammatory phase and the start of the proliferation phase. M2 and M2-like macrophages induce regulatory, reparative, and anti-inflammatory functions aimed at wound closure. Keratinocytes proliferate, granulation tissue develops, and keratinocytes migrate. This phase ends when stem cells in the epithelium are finished assembling a new layer of cells, but it is flimsy because dermal layer cells have not yet been repaired (Watts et al., n.d.).

Fibroplasia Stage is when granulation tissue is assembled in the dermal layer. There is collagen remodelling that makes the tissue stronger (MacLeod & Mansbridge, 2016). Fibroblasts proliferate and release collagen, which stimulates angiogenesis, glycoproteins and sugars, and produces collagen fibrils, and those fibrils produce collagen bundles that act as extracellular scaffolding and provide strength (Watts et al., n.d.).

Remodelling/Maturation: The wound receives additional support through collagen cross-linking (covalent bonds form between collagen bundles), which increases the strength of the wound tissue. Collagen remodelling also takes place as fibroblasts remove subpar collagen. Myofibroblasts then produce contractile proteins, which attach to transmembrane proteins, and then attach to interstitial space proteins. Contraction happens and pulls the wound together and is important in large wounds that must heal by secondary intention. Melanocytes then produce pigment restore the damaged skin natural color.

What is resolution, regeneration and replacement?

The type and location of the wound determine which type of scar is formed. For example, if there are burns to the skin, the body will try to replace the damaged tissue with the same type of tissue. However, if the wounds are severe and/or the tissue lacks stem cells, a scar will develop instead (MacLeod & Mansbridge, 2016).

Resolution is when neutrophils and macrophages remove foreign debris and cellular debris from the wound to prevent infection during the inflammation stage.

Regeneration takes place in some tissues like the liver and skin when stem cells that can divide and differentiate produce novel yet similar tissue to replace damaged tissue during the proliferation stage.

Replacement happens during the maturation stage when tissues like skeletal muscle and the heart that lack stem cells develop strong but inflexible collagen-less scar tissue to replace damaged tissue. `

What is the significance of the oozing and discoloration?

Present during the inflammatory and proliferative stages, oozing is when the body tries to remove debris and foreign material by producing and leaking a liquid made of plasma, blood, and WBCs, while discoloration reflects blood that is trapped underneath the skin as the body tires to remove debris and transport new blood cells to the area.

What factors impede the healing process and why? (Bowers & Franco, 2020)

Poor circulation impedes the transportation of oxygen and nutrients to the wound and the removal of waste products due to prolonged compression and/or illnesses like DM and atherosclerosis.

Infection leads to inflammation as bacteria compete for oxygen, and edema disrupts fibroblast activity, collagen deposition and cross-linking, which can create a barrier to the transportation and removal of debris and waste products (Watts et al., n.d.).

Advanced age due to decreasing abilities of the person’s immune system.

Smoking damages the walls of blood vessels and decreases the amount of oxygen available to all tissues, including those repairing the wound.

Diabetes damages blood vessels and nerves required to signal wound damage.

Deficiency in vitamins and minerals, including vitamin C, zinc, and protein means that the cells don’t have the building blocks necessary to repair the wound.

Medications like chemotherapy and steroids suppress the immune system.

References

Almadani, Y. H., Vorstenbosch, J., Davidson, P. G., & Murphy, A. M. (2021). Wound healing: a comprehensive review. Seminars in Plastic Surgery, 35(3), 141-144. https://doi.org/10.1055/s-0041-1731791

Bowers, S., & Franco, E. (2020, February 1). Chronic wounds: evaluation and management. American Family Physician, 101(3), 159-166. https://www.aafp.org/pubs/afp/issues/2020/0201/p159.html

MacLeod, A. S., & Mansbridge, J. N. (2016). The innate immune system in acute and chronic wounds. Advances in Wound Care, 5(2), 65-78, https://doi.org/10.1089/wound.2014.0608

Watts, S., McBundy, S., & Debevec-McKenney, E. (n.d.). Wound healing [Video]. Osmosis, Elsevier. Retrieved August 6, 2023, from https://www.osmosis.org/learn/wound-healin

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