**3.3 Maturation and remodeling phase (Day 10–1 year)**

Remodeling is the third and the last phase of wound repair that begins around 2 weeks post-injury and may last up to 1 year or longer, based on various factors [10]. During this stage, all the cellular processes activated post-injury wind down and come to an end, the new epithelium is formed, and the final scar tissue develops. The granulation tissue formation ceases *via* cellular apoptosis, leading to an acellular and avascular mature wound [57]. Majority of the cellular components exit from the wound site or undergo apoptosis, and the resulting mass consists of collagen and other ECM proteins. During wound maturation, the ECM components undergo various

*Nanotechnological Interventions and Mechanistic Insights into Wound-Healing Events DOI: http://dx.doi.org/10.5772/intechopen.106481*

changes characterized by collagen deposition in a well-arranged network form (**Figure 1**). 4–5 weeks post-injury, collagen continues to be synthesized. Stronger collagen I replace the previously predominant collagen III produced during the proliferative phase [58]. Normally, around 90% of collagen present in skin is type I, but during the granulation phase in the wounded skin type III, levels reach up to 30% [31]. In cases with excessive collagen formation, generation of hypertrophic scar occurs [31]. The regulation of skin integrity and homeostasis occurs through the epithelial– mesenchymal interactions [59].

Further, myofibroblasts lead to wound contractions thereby decreasing the scar surface [38, 60]. The angiogenesis processes now diminish causing the blood flow in the wound to decline, and the acute metabolic activity in the wound now slows down and finally diminishes. However, the injured tissue never tends to regain the properties of healthy skin. Certain skin components never recover completely such as the hair follicles and sweat glands that possess no potential to heal potential post-injury [61]. The epidermal layer of the scar formed differs from surrounding healthy skin post-healing [33]. Even years after the injury, the collagen in the scar never gets the fully organized structure seen in healthy skin. Furthermore, the wound strength never returns to 100% [31].
