**2.2. Model of incisional wound healing**

collagen deposition, and re‐epithelization [1]. In the very first steps, natural immunity [2] plays an important role through aggregation of inflammasomes. The next step goes through inflammatory cell types, and messages from the first to this step together with monocyte responsivity are able to determine whether inflammation will prolong to a sort of a steady, chronically established state, which freezes the whole process transforming it into a chronic

Monocyte/macrophage sequestration together with their lack of switch to type 2 [3, 4, 6] impairs angiogenesis and cell activities resulting in a delayed re‐epithelialization, reduced call for fibroblasts and diminishing collagen deposition, as well as a decreased cell proliferation. The aim of this chapter is to report our experience on how to modify impaired wound healing, starting from our experimental studies and concluding with our recent clinical experiences.

Following our studies [2] and those by Mirza et al. [4, 5], we started to focus on the role of accumulation and insufficiency of macrophages in wound healing. Macrophage dysfunction has been shown to produce prolonged inflammatory responses in critical wounds, in diabetes through local secretion of proinflammatory cytokines, such as IL‐1β, TNF‐α, MMP‐9, and IL‐6, in particular, lack of switch to a second macrophage phenotype secreting proregenerative

The result is an important interruption of healing with persistence of inflammation, whether

This produces critical wounds. Obviously, single biological steps can be analyzed in experi‐ mental studies, whereas in clinical practice this single factor must often be added to other associated diseases, such as reduction of blood supply due to vascular obstruction. In the latter case, translation from experimental to clinical work must also take into account adding

Our clinical experience deals with persistence of inflammation through both monocyte and

In this section, we report our experimental evidences leading to the results about the above‐ mentioned inflammasome inhibition [2]. Plastic surgeons together with pharmacologists of the University of Messina have been working on wound healing for more than 15 years

For these experiments adult male mice have been chosen, caged alone, and maintained under a controlled environment (12‐hour light cycles day/night and 23°C room temperature, food,

inflammation [2–6].

156 Wound Healing - New insights into Ancient Challenges

**2. Pathophysiology**

vascular insufficiency.

*2.1.1. Animals*

factors, such as IL‐10, IGF‐1, and TGF‐β [6].

hyperglycemia through cascade of ROS is its cause or not.

proangiogenetic factors even to provide a complete care.

**2.1. Our experimental studies on wound healing**

developing some models on rodents.

The animals (mice) underwent general anesthesia with sodium thiopental (80 mg/kg intra‐ peritoneal injection) were scrubbed with iodine povidone on their back – their back skin shaved and rinsed with physiological serum. Two longitudinal parallel 4 cm incisions were performed and sutured with alternate stitches placed 1 cm from one another.

Sacrifices were conducted on Days 7 and 14, respectively, and wounds were divided into three segments of 80 mm large and 120 mm long. Caudal and cranial strips were used for molecular studies, whereas the central one was used for histology and immunohistochemistry.
