Experimental pig model of clinically relevant wound healing delay by intrinsic factors

Abstract

The intrinsic factors associated with delayed wounds are ischaemia, infection, the presence of necrotic tissue and the presence of foreign bodies. This study was designed to create adaptable intrinsic factors induced delayed wound healing model in the pig, similar to clinical conditions. Four pigs were used in this study. Ten 4 × 4cm fresh full-thickness skin defect wounds were made on the back of each pig. Double- flanged blocks made of silicon, a material that induces foreign body reactions, tissue ischaemia and causes local wound infection, were inserted into half of the wounds (n = 5) and removed at weeks 1, 2 or 3. The other wounds (n = 5) were left open for control purposes. Biopsies were obtained at weeks 1–4 for histological examinations and to evaluate inflammatory cytokines, which included tumour necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. A Periscan PIM 3 Laser was used to measure degrees of ischaemia. A Visitrak Digital  device was used to measure the sizes of unhealed wounds. After 3 weeks, unhealed mean wound sizes were 30·72 ± 3·36 and 2·91 ± 1·51 cm 2 , in the experimental and control groups, respectively. Laser Doppler showed limited perfusion at wound margins in wounds containing silicone blocks. Histological findings corresponding to the severity of chronic inflammation were markedly higher and persisted until week 3 in the experimental group. The levels of IL-1 and TNF-α in the third week were statistically significantly higher in the model group. Also, in the fourth week, the level of TNF-α in the model group was significantly higher. Epithelialisation was not complete at the end of the fourth week despite removing silicone blocks in the experimental group. On the basis of macroscopic and histological evaluations and molecular assessments, the described wound model has the characteristics of wound ischaemia and necrosis and persistent inflammation, which are very similar to delayed wounds of patients