Preface

Wound healing is a multifaceted and dynamic procedure of revitalizing lost cellular organizations and flesh layers in the human body [1]. The human wound-healing process could be divided into three or four discrete phases. Formerly, contributors denoted three phases, that is, inflammatory, fibroblastic, and maturation, but the human wound-healing process has also been indicated as inflammatory, proliferation, and remodeling [2]. In the four-phase model, there are the hemostasis, the inflammatory, the proliferation, and the remodeling phase. In the three-phase approach, the hemostasis phase is enclosed within the inflammatory phase [3].

For a wound to be healed efficaciously, all four phases must sequentially happen at an expected time setting. Numerous aspects can hinder one or more stages of this procedure and thus can cause inappropriate or diminished wound healing. This book reviews the recent literature on the most significant factors that affect wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include physiology of wound healing, interferon, stem cells and photobiomodulation, a chronic venous ulcer, chronic fistula, bionanomaterials, topical antiseptic agents, including silver and sodium hypochlorite solution, diabetic ulcers, and nutritional supplements such as copper. A better understanding of the effects of these elements on wound mending may lead to therapeutics that progress wound healing and resolve compromised wounds [4]. This book includes 4 sections and 10 chapters as follows:

## **Section 1: Hypertrophic Scars and Keloids**

Chapter 1 "Interferon Therapy for Hypertrophic Scars and Keloids"

Interferons (IFNs) from the family of cytokines are widely used to treat keloids because of their ability to increase collagenase activity, thereby reducing the production of collagen and other extracellular matrices (ECM). In this chapter, the benefits and limitations of IFN-mediated therapy for the treatment of scars and keloids and the advantages of combinatorial therapy with the appropriate literature support are discussed.

Chapter 2 "The Need for Basic, Translational, and Clinical Research in the Field of Hypertrophic Scars"

Hypertrophic scar (HTS) is a fibrotic skin disorder marked by excessive inflammation and extracellular matrix deposition in response to cutaneous traumatic injuries such as burns, lacerations, incisions, and abrasions. Additional fibrotic skin disorders such as keloid scars are often thought of as being the same pathophysiology existing along the continuum of severity of HTS and hence are often studied as one scar type, despite their varied etiology. This chapter will review current in vitro and in vivo modeling and highlight research needs to address gaps in the study of HTS.

## **Section 2: Chronic Ulcers**

Chapter 3 "Pharyngocutaneous Fistulas Following Total Laryngectomy"

Total laryngectomy is still the final therapeutic solution for locally advanced laryngeal cancer cases. Following excision of the larynx, the remaining pharynx is reconstructed to obtain continuity of the upper digestive tract. One of the most common complications seen in patients, despite constant refinement of the procedure, is the development of a pharyngocutaneous fistula. The development of the fistula prolongs hospital stay and often requires a second surgical procedure, increasing hospitalization cost and morbidity and impairing the quality of life of patients. Only some among the risk factors identified before surgery may be corrected. Managing the fistula once present depends on multiple factors, essential being the size of the fistula as well as the position and concomitant factors. Understanding the healing mechanisms of these structures is important in the proper management of this complication.

Chapter 4 "Combined Administration of Stem Cells and Photobiomodulation on Wound Healing in Diabetes"

Wound healing is an active and compound biological course divided into four steps: hemostasis, inflammation, proliferation, and remodeling. Diabetes mellitus induces weakened wound healing by disturbing one or more of the biological functions of these steps. And based on the current study that analyzes results from studies that used separate and combined administrations of stem cells and photobiomodulation for diabetic wound healing in patients and animal models, we hypothesize that the combined application of photobiomodulation and stem cells will accelerate the repair process and assist the healing of foot ulcers in diabetes mellitus patients.

## Chapter 5 "Chronic Venous Ulcer"

This research review is endeavoring to shed light on the cause and effect of chronic venous ulcer (CVU) in line with its therapeutic procedures. In the last two decades, a lot has changed in the strategy of wound management due to the development of adjunctive therapy that supported wound healing. Eventually, the latest development was in platelet concentration technology that produced platelet-rich fibrin (PRF). The first therapeutic procedure used in the treatment of venous leg ulceration (VLU) was compression therapy where the application of effective graduated compression decreased the overload in the venous system and venous reflux. Furthermore, it accelerated blood flow and decreased fluid leakage in the capillary, which in return alleviated limb edema.

## **Section 3: Biomaterials for Wound Healing**

Chapter 6 "Polymeric Biomaterials for Wound Healing Incorporating Plant Extracts and Extracellular Matrix Components"

Biomaterials are constructed to promote or stimulate the processes of wound healing. Polymeric biomaterials can be used to hydrate the wound and serve as a barrier to pathogens, with plant extracts, antimicrobial agents, and extracellular components incorporated to stimulate the healing process. The biological and physical augmentation provided by extracellular matrix–derived implants

**V**

healing.

continues to facilitate innovation in biomaterials utilized in the management of nonhealing wounds. Extracellular matrix components and plant extracts have been shown to possess pharmacological properties with potential for use in the treatment of skin diseases and wound healing. Antioxidant, anti-inflammatory assays, and wound-healing assays have been shown to support the dermatological

Chapter 7 "Bionanomaterials: Advancements in Wound Healing and Tissue

Abnormal wound healing is an indication of a major healthcare issue owing to an upsurge in a number of traumas and morbid physiology that ultimately posed a health-care burden on patients, society, and health-care organizations. As wound healing is a complex process, effective management of chronic wounds is often hard. Recently, in addition to many conventional wound treatments, advances in bionanomaterials are attaining much attention in wound care and skin tissue engineering. In this chapter, we highlight the sources, biological role, and bioengineering approaches adapted for biopolymers for the facilitation of

Chapter 8 "Current Understanding to Accelerate Wound Healing: Mechanism and

Chapter 9 "Copper, an Abandoned Player Returning to the Wound Healing Battle"

Copper has two key properties that endow it as an excellent active ingredient to be used in the wound-healing battle. First, copper plays a key role in angiogenesis, dermal fibroblasts proliferation, upregulation of collagen, and elastin fiber production by dermal fibroblasts, and it serves as a cofactor of lysyl oxidase needed for efficient dermal extracellular matrix (ECM) protein cross-linking. Second, copper has potent wide-spectrum biocidal properties. Both Gram-positive and Gramnegative bacteria, including antibiotic-resistant bacteria and hard-to-kill bacterial spores, fungi, and viruses, when exposed to high copper concentrations are killed. Copper has been used as a biocide for centuries by many different civilizations. The positive outcome at all wound-healing stages of using copper-impregnated wound dressings is shown, indicating the neglected critical role copper plays in wound

Chapter 10 "Contribution of Topical Agents to Wound Healing"

The process of wound healing is often accompanied by a bacterial infection or critical colonization, which leads to an extension of the inflammatory response

Wound mending is a complex organic cycle that brings about the reclamation of tissue honesty. Physiologically, it may be very well separated into four particular periods: hemostasis, inflammation, proliferation, and tissue remodeling (redesigning). This chapter portrays the cellular premise of wound mending and extracellular flagging cycles that are responsible for controlling the periods. The capacity of fibroblasts, neutrophils, platelets, and macrophages is contemplated

and wound-healing usage of these medicinal plant extracts.

Regeneration"

the wound-healing process.

**Section 4: Wound Healing and Treatments**

Clinical Importance"

exhaustively.

continues to facilitate innovation in biomaterials utilized in the management of nonhealing wounds. Extracellular matrix components and plant extracts have been shown to possess pharmacological properties with potential for use in the treatment of skin diseases and wound healing. Antioxidant, anti-inflammatory assays, and wound-healing assays have been shown to support the dermatological and wound-healing usage of these medicinal plant extracts.

Chapter 7 "Bionanomaterials: Advancements in Wound Healing and Tissue Regeneration"

Abnormal wound healing is an indication of a major healthcare issue owing to an upsurge in a number of traumas and morbid physiology that ultimately posed a health-care burden on patients, society, and health-care organizations. As wound healing is a complex process, effective management of chronic wounds is often hard. Recently, in addition to many conventional wound treatments, advances in bionanomaterials are attaining much attention in wound care and skin tissue engineering. In this chapter, we highlight the sources, biological role, and bioengineering approaches adapted for biopolymers for the facilitation of the wound-healing process.

Chapter 8 "Current Understanding to Accelerate Wound Healing: Mechanism and Clinical Importance"

Wound mending is a complex organic cycle that brings about the reclamation of tissue honesty. Physiologically, it may be very well separated into four particular periods: hemostasis, inflammation, proliferation, and tissue remodeling (redesigning). This chapter portrays the cellular premise of wound mending and extracellular flagging cycles that are responsible for controlling the periods. The capacity of fibroblasts, neutrophils, platelets, and macrophages is contemplated exhaustively.

## **Section 4: Wound Healing and Treatments**

Chapter 9 "Copper, an Abandoned Player Returning to the Wound Healing Battle"

Copper has two key properties that endow it as an excellent active ingredient to be used in the wound-healing battle. First, copper plays a key role in angiogenesis, dermal fibroblasts proliferation, upregulation of collagen, and elastin fiber production by dermal fibroblasts, and it serves as a cofactor of lysyl oxidase needed for efficient dermal extracellular matrix (ECM) protein cross-linking. Second, copper has potent wide-spectrum biocidal properties. Both Gram-positive and Gramnegative bacteria, including antibiotic-resistant bacteria and hard-to-kill bacterial spores, fungi, and viruses, when exposed to high copper concentrations are killed. Copper has been used as a biocide for centuries by many different civilizations. The positive outcome at all wound-healing stages of using copper-impregnated wound dressings is shown, indicating the neglected critical role copper plays in wound healing.

Chapter 10 "Contribution of Topical Agents to Wound Healing"

The process of wound healing is often accompanied by a bacterial infection or critical colonization, which leads to an extension of the inflammatory response phase and delayed epithelization. In the review of scientific articles, we found the description and mode of action of topical antiseptic agents, including silver and sodium hypochlorite solution, in controlling the spread of microorganisms. The value of hyaluronic acid for wound healing is described. Furthermore, a novel treatment option with microspheres is mentioned.

## **Shahin Aghaei, MD**

**VII**

**References**

(1-2):81-94.

5(3):32-4.

[1] Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. *Skin Wound Healing: An Update on the Current Knowledge and Concepts*. Eur Surg Res. 2017. 58

[2] Gilmore MA. *Phases of Wound Healing*. Dimens Oncol Nurs. 1991.

Reference. June 20, 2012.

2010 Mar; 89(3): 219-229.

[3] Romo T, Al Moutran H, Pearson JM, Yalamanchili H, Pafford W, Zoumalan RA. *Skin Wound Healing*. Medscape

[4] Guo S. and DiPietro LA. *Factors Affecting Wound Healing*. J Dent Res.

Associate Professor of Dermatology and Dermatologic Surgery, Department of Dermatology, Iran University of Medical Sciences, Tehran, Iran

## **References**

[1] Sorg H, Tilkorn DJ, Hager S, Hauser J, Mirastschijski U. *Skin Wound Healing: An Update on the Current Knowledge and Concepts*. Eur Surg Res. 2017. 58 (1-2):81-94.

[2] Gilmore MA. *Phases of Wound Healing*. Dimens Oncol Nurs. 1991. 5(3):32-4.

[3] Romo T, Al Moutran H, Pearson JM, Yalamanchili H, Pafford W, Zoumalan RA. *Skin Wound Healing*. Medscape Reference. June 20, 2012.

[4] Guo S. and DiPietro LA. *Factors Affecting Wound Healing*. J Dent Res. 2010 Mar; 89(3): 219-229.

Section 1
