The Story behind Chronic Wounds

The Healing Process

When healthy, the body heals itself in 4 consecutive steps:

1. Hemostasis & Coagulation: the primary focus for this step is to reduce blood loss. This is done by the formation of a blood clot, creating a sort of plug in the blood vessel. The clot is a result of an accumulation of platelets, that are meshed with a protein called fibrin.
2. Inflammation: Once the wound has been plugged, the body proceeds to “cleaning out” any foreign entities; these are known as pathogens. The removal of pathogens is overseen by macrophages. Simultaneously, the repair of the damaged tissue begins. Platelets are activated and growth factors are released, that in turn signal and recruit the necessary cells at the wound site. A process known as vasodilation also takes place, which increased the blood flow to the affected area, increasing the supply of oxygen and nutrient, and therefore favouring wound healing.
3. Proliferative & Migration: the cells recruited by the growth factors get to work; new tissue is formed, blood vessels are grown, the skin structure is restored. Neutrophils are recruited to help with the immune defence by removing dead tissue and pathogens, and simultaneously support wound repair by promoting collagen formation. During this stage, a temporary matrix is created to provide structure to the reconstruction. An important aspect to remember is the layer of cells that covers the wound, which act as a barrier to any foreign bodies and provides the wound with protection.
4. Remodelling: once the wound has been filled in, the body then progressively breaks down and rebuilds the new tissue, to improve its overall structure and strength. Fibroblasts, which were recruited in the previous step to deposit collagen, will gradually replace the temporary structure built in the previous step with a more layered and complete structure.

Key Players

Platelets:

One of the three major blood cells, alongside Red Blood Cells and Plasma; recruited during first phase of wound healing; play pivotal role, acting initially as plug to stop flow, and then as a cell signaller to recruit the required cells.
VEGF: Stimulates angiogenesis, increases vascular permeability for entry of other cells to wound area.
PDGF: Activates monocytes, macrophages, fibroblasts, induces production of ECM molecules, enhances healing.

Macrophages:

A type of White Blood Cells that acts as first line of defence; two types of macrophages, the first initiating pro-inflammatory response, and the second an anti-inflammatory response; balance between both during the wound healing process. Primary function is targeting pathogens introduced into system, and digesting them to produce:

• Waste (dead cells, cellular debris, …)
• Cytokines that promote angiogenesis
• PDGF

Neutrophils:

Another type of White Blood Cell, but this time much more short-lived than macrophages, and highly motile.

2 main functions:

• Phagocytosis: the process of degrading pathogens and non-viable tissue; a function overseen by macrophages that is supported by neutrophils.
• Release of granule contents to help progress wound closure.

Fibroblasts:

Acts as the glue, connecting tissue and organs in the body; recruited at the end of the Proliferative & Migration step to create collagen, fibroblasts will eventually rebuild the temporary matrix with new, stronger and more structure collagen strands.