A suppressed early innate immune reaction during wound healing is associated with an ultimate hypertrophic scar outcome

Excessive scarring is a challenging problem that causes both functional and esthetic complaints for patients. In predisposed individuals on prone regions healing can end with red, raised, disfiguring and painful itching scars. The immune system is thought to be involved in this derailment of wound healing, although the exact mechanism and time of onset remains to be elucidated. If we know the differences between normal and hypertrophic scar formation, and the exact onset of these differences, can it be possible to prevent excessive scarring?

In a prospective observational study on 120 patients, pre-sternal skin biopsies were taken directly at the start and 3 hours later during elective cardiothoracic surgery. The skin biopsies were analyzed for mRNA, proteins and cells involved in the early inflammatory phase of wound healing. The endpoint was scar outcome (normal (n = 7) or hypertrophic (n = 9)) at one year following surgery.

Skin of ultimately hypertrophic scar formers showed a significant higher fold change mRNA expression of P-selectin during surgery (p< 0.05). Post-operative skin concentrations of inflammatory proteins IL-6, IL-8 and CCL2 were significantly lower (p < 0.03/0.003/0,02), whereas a trend of higher pre-operative MR positive macrophage (M2) numbers was observed. Neutrophil numbers increased equally during surgery in both types of wound healing.

The increase of P-selectin mRNA in hypertrophic wound healing shows early endothelial cell activation, which could affect leukocyte migration. However, the observed differences are not (yet) reflected by differences in neutrophil numbers. The decreased concentrations of inflammatory proteins in hypertrophic wound healing as early as three hours following surgery already, indicate an inhibited or delayed inflammatory response. This reduced response has consequences for treatment and may indicate that pre-operative immune stimulating therapies can help to prevent excessive scarring.

In conclusion, alterations of wound healing associated with hypertrophic scarring are visible as early as three hours after wounding and include an inhibited rather than an excessive inflammatory response.

This lecture is presented by: Dr. Frank Niessen, The Netherlands

Frank B Niessen MD PhD 
Plastic- and regenerative surgeon 
Dep of Plastic Reconstructive and Handsurgery VU University Medical Center 
P.O. Box 7057 | 1007 MB Amsterdam  the Netherlands