Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing

*Juin-Hong Cherng*

## **Abstract**

Patients with burn injuries suffer from pain and an inflammatory response; however, treatment methods are still not satisfactory and remain challenging. Due to the long stage of burn wound rehabilitation, which contributes to the long-term sensory problems, an effective treatment must begin at the outset of burn wound care. The functionalized wound dressing is expected to be a great treatment strategy over the commercialization wound dressing products and engineered skin substitutes nowadays. Some studies revealed the use of calcium alginate polysaccharide (CAPS) as an "active" dressing due to its calcium richness for wound healing and scar tissue formation. The outstanding outcome of CAPS dressing for severe burn injuries was indicated by natural wound healing and less scarring formation, minimum bacterial infection, cytokine enhancement regulation, and appropriate inflammatory response and pain regulation. These advantages affirmed the phytopolysaccharide dressing as the next generation of wound dressing materials with highly desirable properties.

**Keywords:** severe burn injuries, wound dressing, wound management, calcium alginate polysaccharide, inflammatory response

### **1. Introduction**

Burns are the most traumatic injuries and physically harmful because of long hospitalization and rehabilitation, which lead to significant morbidity and mortality [1, 2]. The development of effective treatment associated with burn injury is a major unmet medical problem. Current burn wound treatment methods, such as eschar excision, split-thickness skin autograft, and cell-based skin constructs, are still not satisfactory and remain challenging. Not only causing painful and relative costly treatment, but those methods are also very difficult to perform in patients due to poor availability of healthy tissue [3–5].

Despite any advances in burn management, how to treat wound properly at the outset of burn injury is the important key of an effective treatment. Most patients with burn injuries suffer from long-term pain and posttraumatic situation; therefore, an appropriate burn wound handling with a good dressing initially is expected to be a great way to minimize scar formation and accelerate burn wound healing.

A good clinical dressing must be easy to handle, avoids infection and inflammation, has no toxicity, causes no allergic reactions, and permits easy and early mobilization [6, 7].

requires a supportive microenvironment to avoid infection. Bacterial infection was well known as a common cause of death after burns [13]. Commonly, antimicrobial creams and occlusive dressings are applied on the wound to avoid infection, to limit

*Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing*

Despite any advances in burn management, how to treat wound properly at the outset of burn injury is the important key of an effective treatment. The proper burn wound handling in the beginning with the functionalized wound dressing may enhance reepithelialization progress and accelerate an intact epithelium formation with minimal scar appearance. Not only should achieve rapid healing at reasonable cost with less inconvenience to the patient, but the use of clinical dressing also must be easy to handle, avoids infection and inflammation, has no toxicity, causes no

Based on its natural action, wound dressings are normally classified as passive products, interactive products, and bioactive products [9]. Passive products consist of traditional dressings like gauze and tulle dressings which account for the largest market segment. Interactive products consist of polymeric films and forms, which are recommended for low exuding wounds due to its characteristics. Bioactive products are which deliver either bioactive compounds or dressings are constructed from a material having endogenous activity in wound healing. These materials include proteoglycans, collagen, non-collagenous protein, chitosan, or alginate. They are considered to contribute not only a matrix for repair but also growth factors and cytokines to enhance the healing process [8]. Commercially, various types of those bioactive wound dressings are currently used in the clinical setting with their advantages and disadvantages for some types of wounds. In the case of burn wound, the dressing with rich glycosaminoglycan (GAG) is expected to encourage the efficient and rapid healing process. GAG has a significant role in wound healing phases which acts as a regulator of early inflammation to modulate inflammatory cell and fibroblast cell migration, pro-inflammatory cytokine synthe-

Alginate, commonly derived from seaweed, is a rich natural anionic phytol polysaccharide (APS) that consists of mainly differing ratios of D-mannuronic and L-guluronic acid, which are covalently bound through 1,4-glycosidic linkages. Polysaccharides and proteins are the most common natural polymers used in the tissue engineering field for the regeneration of full-thickness wounds because of their biocompatibility, biodegradability, and similarity with ECM [16, 17].

Containing glycosaminoglycan (GAG), they play a key role in wound healing due to their ability to encourage activation of the immune system that cleans up the wound site after injury and reduces the pain simultaneously. It provides a moist environment around the wound site that leads to rapid granulation and reepithelialization. Alginate-based wound dressings have also been demonstrated for their hemostatic properties in exudation/bleeding wounds and burns [9]. Alginate can easily form gels by binding with divalent cations, especially calcium ions [18]. The gelling property of alginate helps in the dressing removal without much trauma [19]. Alginate dressings were originally presented as formed from calcium alginate fibers and have been technically fabricated with fibers woven to form a more solid and strengthen structure to obtain an applicable wound dressing. As wound dressing, treatment with calcium alginate polysaccharide (CAPS) dressings had shown great wound recovery outcome in various types of skin wounds [20–23]. They promoted healing via a direct modulatory effect on wound macrophage activation that secretes pro-inflammatory cytokines within the chronic wound bed which may

initiate a delayed inflammatory phase [24]. Additionally, numerous studies revealed that CAPS-containing dressing for severe burn injuries has outstanding outcomes such as rapid wound closure with less scarring formation, minimum

**5**

wound progression, and to improve epithelialization progression [14].

*DOI: http://dx.doi.org/10.5772/intechopen.80875*

allergic reactions, and permits easy and early mobilization [6, 7].

sis, and the phagocytosis of invading microbes [15].

Bioactive wound dressing, or functionalized wound dressing, is expected to overcome the limitations of the current treatment in burn wound management. This dressing delivers either bioactive compounds or dressing that is constructed from a material having endogenous activity in wound healing, which contribute not only a matrix for repair but also growth factors and cytokines to enhance the healing process [8]. Various types of bioactive wound dressings are available on the market and are used clinically. However, bioactive wound dressings have advantages and disadvantages, so choosing the suitable wound dressing as needed is advised.

Alginate, commonly derived from seaweed, has been widely investigated by many researchers for possible new alternative in wound management field. Alginate, a rich natural polysaccharide, which contains glycosaminoglycan (GAG), has several major properties such as biocompatibility, gelling, and swelling that keep the wound site moist enough for proper healing and then able to reduce healing times of wounds [9, 10]. When attached with wound, an ion-exchange reaction occurs between the calcium in the alginate and the sodium in the exudate, thus producing a soluble gel that help maintain a moist wound environment and also hold bacterial infection in absorbed wound fluid at the same time. This is why alginate is recommended for the treatment of moderate to highly exuding wounds [11].

Calcium alginate polysaccharide (CAPS) has been found suitable for use in pharmaceutical drugs, as a bioactive food ingredient, and for cell encapsulation or tissue regeneration [12]. Numerous studies revealed that CAPS-containing dressing for severe burn injuries has outstanding outcomes such as rapid wound closure with less scarring formation, minimum bacterial infection, cytokine enhancement regulation, and appropriate inflammatory response and pain regulation. In addition, this material becomes substantial to be considered as optimal burn wound dressing treatment because it maintains a great moist microenvironment at the wound site. Therefore, the detail mechanisms and involvement of CAPS dressing in accelerating burn wound healing will be further discussed in this chapter.

### **2. Medical dressing for the treatment of burn injury**

Generally, the treatment of burn injury depends on both depth and surface area of burn wounds, which reepithelialization is the most important stage of burn wound repair. For the severe burn injury such as deep partial-thickness or fullthickness burn, there is a need of special treatment to prevent delayed reepithelialization due to the destruction of epithelial regenerative elements in the basal layer of the epidermis and in the dermis. To date, eschar excision and split-thickness skin autograft taken from a healthy skin of the same patient are medical standard treatments for severe burn injury [3, 4]. However, the grafts are causing pain and very difficult to perform in patients due to poor availability of healthy tissue. In addition, many types of cell-based skin constructs have been developed for fullthickness burn injury, but poor survival rate of the keratinocytes in cell sheets has been a major concern in these discoveries [5].

On the other hand, for the first or superficial second-degree injury, the reepithelialization remains possible by the migration of keratinocytes from the edges of the wound, followed by their proliferation, stratification, and dedifferentiation to form an intact epithelium [3]. But still, an optimal reepithelialization

#### *Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing DOI: http://dx.doi.org/10.5772/intechopen.80875*

requires a supportive microenvironment to avoid infection. Bacterial infection was well known as a common cause of death after burns [13]. Commonly, antimicrobial creams and occlusive dressings are applied on the wound to avoid infection, to limit wound progression, and to improve epithelialization progression [14].

Despite any advances in burn management, how to treat wound properly at the outset of burn injury is the important key of an effective treatment. The proper burn wound handling in the beginning with the functionalized wound dressing may enhance reepithelialization progress and accelerate an intact epithelium formation with minimal scar appearance. Not only should achieve rapid healing at reasonable cost with less inconvenience to the patient, but the use of clinical dressing also must be easy to handle, avoids infection and inflammation, has no toxicity, causes no allergic reactions, and permits easy and early mobilization [6, 7].

Based on its natural action, wound dressings are normally classified as passive products, interactive products, and bioactive products [9]. Passive products consist of traditional dressings like gauze and tulle dressings which account for the largest market segment. Interactive products consist of polymeric films and forms, which are recommended for low exuding wounds due to its characteristics. Bioactive products are which deliver either bioactive compounds or dressings are constructed from a material having endogenous activity in wound healing. These materials include proteoglycans, collagen, non-collagenous protein, chitosan, or alginate. They are considered to contribute not only a matrix for repair but also growth factors and cytokines to enhance the healing process [8]. Commercially, various types of those bioactive wound dressings are currently used in the clinical setting with their advantages and disadvantages for some types of wounds. In the case of burn wound, the dressing with rich glycosaminoglycan (GAG) is expected to encourage the efficient and rapid healing process. GAG has a significant role in wound healing phases which acts as a regulator of early inflammation to modulate inflammatory cell and fibroblast cell migration, pro-inflammatory cytokine synthesis, and the phagocytosis of invading microbes [15].

Alginate, commonly derived from seaweed, is a rich natural anionic phytol polysaccharide (APS) that consists of mainly differing ratios of D-mannuronic and L-guluronic acid, which are covalently bound through 1,4-glycosidic linkages. Polysaccharides and proteins are the most common natural polymers used in the tissue engineering field for the regeneration of full-thickness wounds because of their biocompatibility, biodegradability, and similarity with ECM [16, 17]. Containing glycosaminoglycan (GAG), they play a key role in wound healing due to their ability to encourage activation of the immune system that cleans up the wound site after injury and reduces the pain simultaneously. It provides a moist environment around the wound site that leads to rapid granulation and reepithelialization. Alginate-based wound dressings have also been demonstrated for their hemostatic properties in exudation/bleeding wounds and burns [9]. Alginate can easily form gels by binding with divalent cations, especially calcium ions [18]. The gelling property of alginate helps in the dressing removal without much trauma [19].

Alginate dressings were originally presented as formed from calcium alginate fibers and have been technically fabricated with fibers woven to form a more solid and strengthen structure to obtain an applicable wound dressing. As wound dressing, treatment with calcium alginate polysaccharide (CAPS) dressings had shown great wound recovery outcome in various types of skin wounds [20–23]. They promoted healing via a direct modulatory effect on wound macrophage activation that secretes pro-inflammatory cytokines within the chronic wound bed which may initiate a delayed inflammatory phase [24]. Additionally, numerous studies revealed that CAPS-containing dressing for severe burn injuries has outstanding outcomes such as rapid wound closure with less scarring formation, minimum

A good clinical dressing must be easy to handle, avoids infection and inflammation, has no toxicity, causes no allergic reactions, and permits easy and early mobilization

Bioactive wound dressing, or functionalized wound dressing, is expected to overcome the limitations of the current treatment in burn wound management. This dressing delivers either bioactive compounds or dressing that is constructed from a material having endogenous activity in wound healing, which contribute not only a matrix for repair but also growth factors and cytokines to enhance the healing process [8]. Various types of bioactive wound dressings are available on the market and are used clinically. However, bioactive wound dressings have advantages and disadvantages, so choosing the suitable wound dressing as needed is

Alginate, commonly derived from seaweed, has been widely investigated by many researchers for possible new alternative in wound management field. Alginate, a rich natural polysaccharide, which contains glycosaminoglycan (GAG), has several major properties such as biocompatibility, gelling, and swelling that keep the wound site moist enough for proper healing and then able to reduce healing times of wounds [9, 10]. When attached with wound, an ion-exchange reaction occurs between the calcium in the alginate and the sodium in the exudate, thus producing a soluble gel that help maintain a moist wound environment and also hold bacterial infection in absorbed wound fluid at the same time. This is why alginate is recommended for the treatment of moderate to highly exuding

Calcium alginate polysaccharide (CAPS) has been found suitable for use in pharmaceutical drugs, as a bioactive food ingredient, and for cell encapsulation or tissue regeneration [12]. Numerous studies revealed that CAPS-containing dressing for severe burn injuries has outstanding outcomes such as rapid wound closure with less scarring formation, minimum bacterial infection, cytokine enhancement regulation, and appropriate inflammatory response and pain regulation. In addition, this material becomes substantial to be considered as optimal burn wound dressing treatment because it maintains a great moist microenvironment at the wound site. Therefore, the detail mechanisms and involvement of CAPS dressing in accelerating

Generally, the treatment of burn injury depends on both depth and surface area

of burn wounds, which reepithelialization is the most important stage of burn wound repair. For the severe burn injury such as deep partial-thickness or fullthickness burn, there is a need of special treatment to prevent delayed reepithelialization due to the destruction of epithelial regenerative elements in the basal layer of the epidermis and in the dermis. To date, eschar excision and split-thickness skin autograft taken from a healthy skin of the same patient are medical standard treatments for severe burn injury [3, 4]. However, the grafts are causing pain and very difficult to perform in patients due to poor availability of healthy tissue. In addition, many types of cell-based skin constructs have been developed for fullthickness burn injury, but poor survival rate of the keratinocytes in cell sheets has

On the other hand, for the first or superficial second-degree injury, the reepithelialization remains possible by the migration of keratinocytes from the edges of the wound, followed by their proliferation, stratification, and dedifferentiation to form an intact epithelium [3]. But still, an optimal reepithelialization

burn wound healing will be further discussed in this chapter.

**2. Medical dressing for the treatment of burn injury**

been a major concern in these discoveries [5].

[6, 7].

*Wound Healing*

advised.

wounds [11].

**4**

bacterial infection, cytokine enhancement regulation, and appropriate inflammatory response and pain regulation. Hence, this material becomes substantial to be considered as an optimal burn wound dressing.

secondary outcomes of the depth of scar formation at postburn, determined by the Vancouver Scar Scale (VSS) which consists of four variables: vascularity, height (thickness), pliability, and pigmentation. The total score ranges from 0 to 14, whereby a score of 0 reflects normal skin. The results showed that wounds dressed with CAPS exhibit a rapid reepithelialization and less scar formation, which

*Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing*

*DOI: http://dx.doi.org/10.5772/intechopen.80875*

appeared with a smooth wound. Based on VSS scores, there was less scar formation in the wounds dressed with CAPS, shown by significantly lower scores up to 6 weeks of observation. Scarring, or fibrosis, is known as an abnormal tissue remodeling. The management of scar formation is one of major complications encountered during the wound healing process. Without the right handling, a hypertrophic scar caused by fibroblastic proliferation will be formed during the healing process [26]. Moreover, healing by fibrosis instead of regeneration often

In line, an obvious wound closure and relative complete reepithelialization were observed to occur on wound dressed with the CAPS dressing in rat group model [37]. Their histological analysis revealed that the new dermis tissue on dressing treated wound area was composed of reorganized and stratified epithelial layer, with fully developed connective tissue, hair follicle, sebaceous glands, and aligned collagen. Another study reported that CAPS dressing treatment accelerated wound closure rate and exhibited a faster epithelialization [38]. They found that the expression of skin tissue collagen I was elevated by CAPS dressing application, and this dressing pro-

The ability of CAPS dressing reduces scar formation in burn injury is attributable to its rich contain of glycosaminoglycan (GAG), which was known to promote wound healing, lead to rapid granulation and reepithelialization, and thus yield a minimum scar formation certainly. Moreover, when attached to the wound, an ionexchange reaction occurs between the calcium in the alginate and the sodium in the exudate, producing a soluble gel that turns to help maintain a moist wound environment [39]. CAPS dressings also have their inherent ability to augment hemostasis, as release of calcium ions leads to platelet activation [40, 41]. Additionally, calcium ions also speed up the wound healing process by modulating cell prolifera-

causes lifelong disability that has a significant economic impact [36].

vides a moist environment and a faster collagen I-related epithelialization.

tion, maturation, and the creation of epidermal lipid barriers [42–44].

As another major challenge in burn injury management, bacterial infection becomes the most common cause of mortality and morbidity [13, 45, 46]. Infection is defined as the presence of high concentrations (>105 organisms/g of tissue) of bacteria in the burn wound and usually progresses to invasion of subjacent tissue within 5 days. Infection can delay wound healing process due to the development of a pronounced immune response, accompanied by sepsis or septic shock, which causes hypotension and impaired perfusion of end organs including the skin. To prevent this condition, wound dressing for burn injury treatment should create an optimal environment, which provides barrier against chronic wound infection. Some studies have demonstrated that CAPS dressings have hemostatic [47] and

some bacteriostatic [48] properties. CAPS dressing for burn wound treatment demonstrated a remarkable inhibition of bacterial growth than CMC dressing treatment, which significantly reduced the amount of bacteria at 3 weeks postburn injury [33]. This reduction was maintained until 6 weeks postburn injury. The infection control functioned by CAPS dressing might be related to its bacterial infection holding in absorbed wound fluid. As they swell, they trap wound debris and bacteria, thereby reducing overall bacterial load within the wound during dressing changes [19]. In addition, the advantages of a new technology conferring a bactericidal effect on CAPS gels for wound dressing have been explored. Poor et al. [49] developed nonthermal-plasma-treated alginate gel wound dressing, and the

**7**

### **3. The problem and historical perspective of burn wound healing**

The proper treatment of wound has attracted the human attention over several decades. Among the various types of wound, severe burn injuries are the most traumatic and physically harmful, which lead to significant morbidity and mortality [1, 2]. Burn injuries can lead to multifarious uncontrolled effects after the accident, and they may have a major impact to the body functions of burn-injured patients. Historically, they were accounted for an estimate of 180,000 deaths every year, which are related to burn injury worldwide, and the vast majority occurs in lowand middle-income countries [25]. Most burn victims face up a long-term hospitalization and suffer major burns covering 25% of their body surface.

The healing process of burn wound, both small burn and large severe burn injuries, occurs through several biological processes, such as hemostasis, inflammation, proliferation, and maturation. Without the right handling, a hypertrophic scar caused by fibroblastic proliferation will be formed during the healing process, which is confined to the wound site [26]. In addition to local wound repair, severe large burns also can stimulate a persistent pathophysiological stress response [27]. Most patients with burn injuries suffer pain during burn wound debridement in the clinic, which they describe as severe to excruciating despite the use of powerful opioid analgesics [28]. Based on local and systemic pathophysiologic responses, burn wound recovery is generally divided into three phases: acute phase, healing phase, and rehabilitation phase. The acute phase may be completely bypassed in smaller injuries, which specifically lasts 2–3 days [29, 30]; the healing phase may be weeks or more, whereas the rehabilitation phase most often takes at least 1 year and sometimes much longer, depending on patient participation in the treatment plan, patient age, and specification of burn [31]. These long phases of recovery often lead burn-injured patients to survive from long-term pain and encounter a posttraumatic situation.

In order to reduce the lifelong burn wound recovery phases which usually contributes to the further problems, an effective treatment must begin at the outset of burn wound care. An appropriate burn wound handling in the beginning is expected to be a great way to minimize scar formation and accelerate burn wound healing.

#### **4. Application of CAPS dressing for accelerating burn injury treatment**

Since burns have a heterogeneous nature, a variety of animal burn models have been developed as valuable tools to observe the pathophysiology of burns. Animal models continue to be explored to uncover the molecular and cellular aspects that characterize human burn trauma [32]. Better understanding of the burn wound healing in animal models and their relation to human wounds will significantly overcome the limited translation of research into practical treatments for burninjured patients.

Wang et al. [33] treated a severe burn injury in swine model with calcium alginate polysaccharide (CAPS) dressing to observe wound repair and scar formation comparing to the use of carboxymethyl cellulose (CMC) as a commonly used wound dressing for many years [34, 35]. These animals were also used to assess the

#### *Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing DOI: http://dx.doi.org/10.5772/intechopen.80875*

secondary outcomes of the depth of scar formation at postburn, determined by the Vancouver Scar Scale (VSS) which consists of four variables: vascularity, height (thickness), pliability, and pigmentation. The total score ranges from 0 to 14, whereby a score of 0 reflects normal skin. The results showed that wounds dressed with CAPS exhibit a rapid reepithelialization and less scar formation, which appeared with a smooth wound. Based on VSS scores, there was less scar formation in the wounds dressed with CAPS, shown by significantly lower scores up to 6 weeks of observation. Scarring, or fibrosis, is known as an abnormal tissue remodeling. The management of scar formation is one of major complications encountered during the wound healing process. Without the right handling, a hypertrophic scar caused by fibroblastic proliferation will be formed during the healing process [26]. Moreover, healing by fibrosis instead of regeneration often causes lifelong disability that has a significant economic impact [36].

In line, an obvious wound closure and relative complete reepithelialization were observed to occur on wound dressed with the CAPS dressing in rat group model [37]. Their histological analysis revealed that the new dermis tissue on dressing treated wound area was composed of reorganized and stratified epithelial layer, with fully developed connective tissue, hair follicle, sebaceous glands, and aligned collagen. Another study reported that CAPS dressing treatment accelerated wound closure rate and exhibited a faster epithelialization [38]. They found that the expression of skin tissue collagen I was elevated by CAPS dressing application, and this dressing provides a moist environment and a faster collagen I-related epithelialization.

The ability of CAPS dressing reduces scar formation in burn injury is attributable to its rich contain of glycosaminoglycan (GAG), which was known to promote wound healing, lead to rapid granulation and reepithelialization, and thus yield a minimum scar formation certainly. Moreover, when attached to the wound, an ionexchange reaction occurs between the calcium in the alginate and the sodium in the exudate, producing a soluble gel that turns to help maintain a moist wound environment [39]. CAPS dressings also have their inherent ability to augment hemostasis, as release of calcium ions leads to platelet activation [40, 41]. Additionally, calcium ions also speed up the wound healing process by modulating cell proliferation, maturation, and the creation of epidermal lipid barriers [42–44].

As another major challenge in burn injury management, bacterial infection becomes the most common cause of mortality and morbidity [13, 45, 46]. Infection is defined as the presence of high concentrations (>105 organisms/g of tissue) of bacteria in the burn wound and usually progresses to invasion of subjacent tissue within 5 days. Infection can delay wound healing process due to the development of a pronounced immune response, accompanied by sepsis or septic shock, which causes hypotension and impaired perfusion of end organs including the skin. To prevent this condition, wound dressing for burn injury treatment should create an optimal environment, which provides barrier against chronic wound infection.

Some studies have demonstrated that CAPS dressings have hemostatic [47] and some bacteriostatic [48] properties. CAPS dressing for burn wound treatment demonstrated a remarkable inhibition of bacterial growth than CMC dressing treatment, which significantly reduced the amount of bacteria at 3 weeks postburn injury [33]. This reduction was maintained until 6 weeks postburn injury. The infection control functioned by CAPS dressing might be related to its bacterial infection holding in absorbed wound fluid. As they swell, they trap wound debris and bacteria, thereby reducing overall bacterial load within the wound during dressing changes [19]. In addition, the advantages of a new technology conferring a bactericidal effect on CAPS gels for wound dressing have been explored. Poor et al. [49] developed nonthermal-plasma-treated alginate gel wound dressing, and the

bacterial infection, cytokine enhancement regulation, and appropriate inflammatory response and pain regulation. Hence, this material becomes substantial to be

**3. The problem and historical perspective of burn wound healing**

ization and suffer major burns covering 25% of their body surface.

burn-injured patients to survive from long-term pain and encounter a

In order to reduce the lifelong burn wound recovery phases which usually contributes to the further problems, an effective treatment must begin at the outset of burn wound care. An appropriate burn wound handling in the beginning is expected to be a great way to minimize scar formation and accelerate burn wound healing.

**4. Application of CAPS dressing for accelerating burn injury treatment**

Wang et al. [33] treated a severe burn injury in swine model with calcium alginate polysaccharide (CAPS) dressing to observe wound repair and scar formation comparing to the use of carboxymethyl cellulose (CMC) as a commonly used wound dressing for many years [34, 35]. These animals were also used to assess the

Since burns have a heterogeneous nature, a variety of animal burn models have been developed as valuable tools to observe the pathophysiology of burns. Animal models continue to be explored to uncover the molecular and cellular aspects that characterize human burn trauma [32]. Better understanding of the burn wound healing in animal models and their relation to human wounds will significantly overcome the limited translation of research into practical treatments for burn-

posttraumatic situation.

injured patients.

**6**

The proper treatment of wound has attracted the human attention over several decades. Among the various types of wound, severe burn injuries are the most traumatic and physically harmful, which lead to significant morbidity and mortality [1, 2]. Burn injuries can lead to multifarious uncontrolled effects after the accident, and they may have a major impact to the body functions of burn-injured patients. Historically, they were accounted for an estimate of 180,000 deaths every year, which are related to burn injury worldwide, and the vast majority occurs in lowand middle-income countries [25]. Most burn victims face up a long-term hospital-

The healing process of burn wound, both small burn and large severe burn injuries, occurs through several biological processes, such as hemostasis, inflammation, proliferation, and maturation. Without the right handling, a hypertrophic scar caused by fibroblastic proliferation will be formed during the healing process, which is confined to the wound site [26]. In addition to local wound repair, severe large burns also can stimulate a persistent pathophysiological stress response [27]. Most patients with burn injuries suffer pain during burn wound debridement in the clinic, which they describe as severe to excruciating despite the use of powerful opioid analgesics [28]. Based on local and systemic pathophysiologic responses, burn wound recovery is generally divided into three phases: acute phase, healing phase, and rehabilitation phase. The acute phase may be completely bypassed in smaller injuries, which specifically lasts 2–3 days [29, 30]; the healing phase may be weeks or more, whereas the rehabilitation phase most often takes at least 1 year and sometimes much longer, depending on patient participation in the treatment plan, patient age, and specification of burn [31]. These long phases of recovery often lead

considered as an optimal burn wound dressing.

*Wound Healing*

results showed that this treatment has better wound decontamination and wound healing capabilities, as well as broad-spectrum antibacterial activity and negligible cytotoxicity.

abscess surgery, which was known as an acute suppurative infectious disease that occurs around the anus, anal canal, and rectum. The results showed that the expression of a variety of proliferative cytokines increases in the wound treated with CAPS dressing and helps promote wound healing [74]. The CAPS dressing treatment also was found to increase the synthesis of collagen and, on the other hand, inhibit the apoptosis of mitochondrial pathway and death receptor pathway. Some literatures revealed that calcium ions from Ca-alginate systems [62] and oligosaccharides derived from polysaccharides (β-glucan, xyloglucan, chitin, pectin, D-mannuronic, and L-guluronic) can stimulate human cells to produce cytokines [75, 76]. Especially, enhancement of IL-1β secretion was expected due to the connection between calcium ion-induced mitochondrial damage and activation of the NLRP3 inflammasome, an important molecular platform expressed by myeloid cells in innate immune defense [77–79]. Besides, alginate-containing dressings have the

*Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing*

*DOI: http://dx.doi.org/10.5772/intechopen.80875*

potential to activate macrophages and have the ability to generate a pro-

arrangement [80].

simultaneously.

**5. Conclusion**

strategies with highly desirable properties.

**Acknowledgements**

**9**

inflammatory signal which promotes granulation tissue formation [24]. However, another factor that may be important in cytokine induction not only relates to the proportions of guluronic to mannuronic acid residues but also their polymeric

In summary, because of these properties, CAPS dressings are considered as a bioactive wound dressing and expected to accelerate the treatment for burn wound healing. There were few products made from CAPS related to surgery and wound management previously but, due to the small amount of these fibers used in total product with high-cost manufacture, it seems not profitable to continue the production. With the improved technology lately, CAPS has been developed into spinning fine dressing as an applicable wound dressing. Together with the increased understanding of CAPS beneficials in accelerating burn injury treatment, it is expected that CAPS dressing will give potential value for medical and business field

As the glycosaminoglycan (GAG) has influential roles in the stimulation of rapid

The author would like to thank Dr. Chih-Hsin Wang (Department of Plastic and Reconstructive Surgery) and Dr. Cheng-Che Liu (Department of Physiology and Biophysics, Graduate Institute of Physiology) at Tri-Service General Hospital,

wound healing, calcium alginate polysaccharide (CAPS), which contains a rich amount of GAG, can be regarded as a remarkable material-based wound dressing option. Since this material had technically actualized into spinning fibers woven or non-woven, it is expected that CAPS-containing wound dressing not only gives an optimal burn injury treatment alternative in medical field but also can rise up the textile industry value from the business perspective. Owing the significant benefits as an "active" dressing for burn wound recovery, such as rapid wound closure with less scarring formation, minimum bacterial infection, cytokine enhancement regulation, and appropriate inflammatory response and pain regulation, which have been demonstrated in several studies and clinical trials, therefore, the CAPS dressing holds a promising potential as the advisable preference of burn injury treatment

CAPS dressing reduced the bacterial growth through the release of calcium, which has been recommended as an antimicrobial agent [50–55], resulting in superior bactericidal and bacteriolytic effects compared with other antimicrobial agents [52–55]. Moreover, the use of alginate derivatives such as antibacterial, antiviral, and antifungal agents has been revealed by numerous data [56, 57]. Negatively charged alginates were found to interact with the outer bacterial cellular surface, which causes disruption and leakage of intracellular substances [58, 59]. Additionally, the ability of alginate modulating the production of toxins, microbial growth, and factors crucial for microorganism's stability could be the reasons for its antibacterial efficacy characteristic. Some varieties of bacteria such as *Pseudomonas*, *Escherichia*, *Proteus*, and *Acinetobacter* have been proven to be detained by bacteriostatic activity of alginate [60, 61].

Further, the CAPS dressing treatment has also demonstrated its critical role in inflammation. Inflammation is a crucial stage to successful burn wound healing. The release of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, interferon (INF)-γ, and tumor necrosis factor (TNF)-α, after thermal injury is one of the important systemic inflammatory responses in burn-induced skin damages [62, 63]. Pro-/anti-inflammatory cytokines act as important modulators of immune cell proliferation, differentiation, and clonal growth of lymphocyte subpopulations and also attract immune cells to the site of burn injuries [64], which are substantial in the process of burn wound recovery.

The involvement of IL-4, IL-6, TNF-α, and MCP-1 was found in the early stages of the rat's response to burn injury treated with CAPS dressing [33]. Immune cells were attracted by these cytokines to the site of injuries to initiate an immune response right away after burning. The ratio of IL-6 to TNF-α can be used to predict mortality from sepsis following burn injury [65]. IL-4 and IL-8 may serve as predictive biomarkers of mortality from sepsis and/or multiple organ failure (MOF) [66]. In addition, MCP-1, an initiator of typ. 2 T-cell generation and an indicator of bacterial infection, is essential for optimal microbial elimination [52]. The involvement of MCP-1 in Gram-positive bacterial infections has been demonstrated in the control of *Listeria monocytogenes* infections [53]. Chan et al. [67] and Thomas et al. [24] have also revealed the similar results both in vitro and in vivo. Particularly, aside from the other chemokines and cytokines, at least fivefold more of IL-1β secretion was found from CAPS gel treatment compared to agarose and collagen gel treatment [67]. IL-1β is known as a critical mediator of inflammation which has substantial roles in neutrophil mobilization, cellular adhesion to the endothelium, and white blood cell infiltration [68, 69].

Furthermore, the pain is related with the modulation of transforming growth factor (TGF-β), an important inflammatory cytokine and anti-inflammatory factor [70–72], that implicated in the pathogenesis of keloids and hypertrophic scarring. TGF-β also participates in the mechanism of pain signals including peripheral and central processing [71]. CAPS dressing for burn wound treatment demonstrated high levels of TGF-β1, TGF-β2, and TGF-β3, suggesting that it might contribute to reduced pain perception [33]. TGF-β1 is responsible for the fibrotic scarring response, whereas TGF-β2 and TGF-β3 are responsible for the scarless wound healing [70]. Another study confirmed that alginate-containing dressings can augment natural wound healing with inhibition of cytokines associated with fibrosis, resulting in decreased wound size and increasing epithelial proliferation [73].

Those data correlated very well with the use of CAPS dressing for human skin wound in the clinical setting recently. CAPS dressings were applied after perianal

#### *Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing DOI: http://dx.doi.org/10.5772/intechopen.80875*

abscess surgery, which was known as an acute suppurative infectious disease that occurs around the anus, anal canal, and rectum. The results showed that the expression of a variety of proliferative cytokines increases in the wound treated with CAPS dressing and helps promote wound healing [74]. The CAPS dressing treatment also was found to increase the synthesis of collagen and, on the other hand, inhibit the apoptosis of mitochondrial pathway and death receptor pathway.

Some literatures revealed that calcium ions from Ca-alginate systems [62] and oligosaccharides derived from polysaccharides (β-glucan, xyloglucan, chitin, pectin, D-mannuronic, and L-guluronic) can stimulate human cells to produce cytokines [75, 76]. Especially, enhancement of IL-1β secretion was expected due to the connection between calcium ion-induced mitochondrial damage and activation of the NLRP3 inflammasome, an important molecular platform expressed by myeloid cells in innate immune defense [77–79]. Besides, alginate-containing dressings have the potential to activate macrophages and have the ability to generate a proinflammatory signal which promotes granulation tissue formation [24]. However, another factor that may be important in cytokine induction not only relates to the proportions of guluronic to mannuronic acid residues but also their polymeric arrangement [80].

In summary, because of these properties, CAPS dressings are considered as a bioactive wound dressing and expected to accelerate the treatment for burn wound healing. There were few products made from CAPS related to surgery and wound management previously but, due to the small amount of these fibers used in total product with high-cost manufacture, it seems not profitable to continue the production. With the improved technology lately, CAPS has been developed into spinning fine dressing as an applicable wound dressing. Together with the increased understanding of CAPS beneficials in accelerating burn injury treatment, it is expected that CAPS dressing will give potential value for medical and business field simultaneously.

### **5. Conclusion**

results showed that this treatment has better wound decontamination and wound healing capabilities, as well as broad-spectrum antibacterial activity and negligible

CAPS dressing reduced the bacterial growth through the release of calcium, which has been recommended as an antimicrobial agent [50–55], resulting in superior bactericidal and bacteriolytic effects compared with other antimicrobial agents [52–55]. Moreover, the use of alginate derivatives such as antibacterial, antiviral, and antifungal agents has been revealed by numerous data [56, 57]. Negatively charged alginates were found to interact with the outer bacterial cellular surface, which causes disruption and leakage of intracellular substances [58, 59]. Additionally, the ability of alginate modulating the production of toxins, microbial growth, and factors crucial for microorganism's stability could be the reasons for its

antibacterial efficacy characteristic. Some varieties of bacteria such as *Pseudomonas*, *Escherichia*, *Proteus*, and *Acinetobacter* have been proven to be detained by bacterio-

Further, the CAPS dressing treatment has also demonstrated its critical role in inflammation. Inflammation is a crucial stage to successful burn wound healing. The release of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, interferon (INF)-γ, and tumor necrosis factor (TNF)-α, after thermal injury is one of the important systemic inflammatory responses in burn-induced skin damages [62, 63]. Pro-/anti-inflammatory cytokines act as important modulators of immune cell proliferation, differentiation, and clonal growth of lymphocyte subpopulations and also attract immune cells to the site of burn injuries [64], which are substantial

The involvement of IL-4, IL-6, TNF-α, and MCP-1 was found in the early stages of the rat's response to burn injury treated with CAPS dressing [33]. Immune cells were attracted by these cytokines to the site of injuries to initiate an immune response right away after burning. The ratio of IL-6 to TNF-α can be used to predict mortality from sepsis following burn injury [65]. IL-4 and IL-8 may serve as predictive biomarkers of mortality from sepsis and/or multiple organ failure (MOF) [66]. In addition, MCP-1, an initiator of typ. 2 T-cell generation and an indicator of bacterial infection, is essential for optimal microbial elimination [52]. The involvement of MCP-1 in Gram-positive bacterial infections has been demonstrated in the control of *Listeria monocytogenes* infections [53]. Chan et al. [67] and Thomas et al. [24] have also revealed the similar results both in vitro and in vivo. Particularly, aside from the other chemokines and cytokines, at least fivefold more of IL-1β secretion was found from CAPS gel treatment compared to agarose and collagen gel treatment [67]. IL-1β is known as a critical mediator of inflammation which has substantial roles in neutrophil mobilization, cellular adhesion to the endothelium,

Furthermore, the pain is related with the modulation of transforming growth factor (TGF-β), an important inflammatory cytokine and anti-inflammatory factor [70–72], that implicated in the pathogenesis of keloids and hypertrophic scarring. TGF-β also participates in the mechanism of pain signals including peripheral and central processing [71]. CAPS dressing for burn wound treatment demonstrated high levels of TGF-β1, TGF-β2, and TGF-β3, suggesting that it might contribute to reduced pain perception [33]. TGF-β1 is responsible for the fibrotic scarring response, whereas TGF-β2 and TGF-β3 are responsible for the scarless wound healing [70]. Another study confirmed that alginate-containing dressings can augment natural wound healing with inhibition of cytokines associated with fibrosis, resulting in decreased wound size and increasing epithelial proliferation [73].

Those data correlated very well with the use of CAPS dressing for human skin wound in the clinical setting recently. CAPS dressings were applied after perianal

cytotoxicity.

*Wound Healing*

static activity of alginate [60, 61].

in the process of burn wound recovery.

and white blood cell infiltration [68, 69].

**8**

As the glycosaminoglycan (GAG) has influential roles in the stimulation of rapid wound healing, calcium alginate polysaccharide (CAPS), which contains a rich amount of GAG, can be regarded as a remarkable material-based wound dressing option. Since this material had technically actualized into spinning fibers woven or non-woven, it is expected that CAPS-containing wound dressing not only gives an optimal burn injury treatment alternative in medical field but also can rise up the textile industry value from the business perspective. Owing the significant benefits as an "active" dressing for burn wound recovery, such as rapid wound closure with less scarring formation, minimum bacterial infection, cytokine enhancement regulation, and appropriate inflammatory response and pain regulation, which have been demonstrated in several studies and clinical trials, therefore, the CAPS dressing holds a promising potential as the advisable preference of burn injury treatment strategies with highly desirable properties.

#### **Acknowledgements**

The author would like to thank Dr. Chih-Hsin Wang (Department of Plastic and Reconstructive Surgery) and Dr. Cheng-Che Liu (Department of Physiology and Biophysics, Graduate Institute of Physiology) at Tri-Service General Hospital,

National Defense Medical Center, Taipei, Taiwan (ROC), for their helpful discussion during this chapter writing.

**References**

[1] Sanchez JL, Pereperez SB, Bastida JL, Martinez MM. Cost-utility analysis applied to the treatment of burn

*DOI: http://dx.doi.org/10.5772/intechopen.80875*

Equine Practice. 2004;**3**(2):148-163. DOI: 10.1053/j.ctep.2004.08.006

[9] Sweeney IR, Miraftab M, Collyer G. A critical review of modern and emerging absorbent dressings used to treat exuding wounds. International Wound Journal. 2012;**9**(6):601-612. DOI: 10.1111/j.1742-481X.2011.00923.x

[10] Fan L, Li M, Gong Y, Peng K, Xie W. Preparation and characterization of alginate/Hydroxypropyl chitosan blend fibers. Journal of Applied Polymer Science. 2012;**125**(2):829-835. DOI:

[11] Andersen T, Markussen C, Dornish

[12] Matricardi P, Meo CD, Coviello T, Alhaique F. Recent advances and perspectives on coated alginate microspheres for modified drug delivery. Expert Opinion on Drug Delivery. 2008;**5**:417-425. DOI: 10.1517/

[13] D'Avignon LC, Hogan BK, Murray CK, Loo FL, Hospenthal DR, et al. Contribution of bacterial and viral infections to attributable mortality in patients with severe burns: An autopsy series. Burns. 2010;**36**:773-779. DOI:

10.1016/j.burns.2009.11.007

[14] Sevgi M, Toklu A, Vecchio D, Hamblin MR. Topical antimicrobials for burn infections-an update. Recent Patents on Anti-Infective Drug Discovery. 2013;**8**(3):161-197. DOI: 10.2174/1574891X08666131112143447

[15] Chen WY, Abatangelo G. Functions of hyaluronan in wound repair. Wound Repair and Regeneration. 1999;**7**(2):

M, et al. In situ gelation for cell immobilization and culture in alginate foam scaffolds. Tissue Engineering. Part

A. 2014;**20**(3–4):600-610. DOI: 10.1089/ten.TEA.2013.0223

10.1002/app.35629

*Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing*

17425247.5.4.417

patients in a specialized center. Archives of Surgery. 2007;**142**:50-57. DOI: 10.1001/archsurg.142.1.50

[2] de Roche R, Luscher NJ, Debrunner HU, Fischer R. Epidemiological data and costs of burn injuries in workers in Switzerland: An argument for

immediate treatment in burn centers. Burns. 1994;**20**:58-60. DOI: 10.1016/

[3] Papini R. Management of burn injuries of various depths. BMJ. 2004; **329**:158. DOI: 10.1136/bmj.329.7458.158

D'Aniello C. Classification and pathophysiology of skin grafts. Clinics in Dermatology. 2005;**23**:332. DOI: 10.1016/j.clindermatol.20

[4] Andreassi A, Bilenchi R, Biagioli M,

[5] Odessey R. Addendum: Multicenter experience with cultured epidermal autograft for treatment of burns. The Journal of Burn Care & Rehabilitation. 1992;**13**(1):174-180. DOI: 10.1097/ 00004630-199201000-00038

[6] Reig A, Tejerina C, Codina J, Hidalgo J, Mirabet V. Application of a new cicatrization dressing in treating second-degree burns and donor sites. Annals of the MBC. 1991;**4**:174-176

[7] Hindy A. Comparative study between sodium carboxymethylcellulose silver, moist exposed burn ointment, and saline-soaked dressing for treatment of facial burns. Annals of Burns and Fire Disasters. 2009;**22**:

[8] Stashak TS, Farstvedt E, Othic A. Update on wound dressings: Indications and best use. Clinical Techniques in

131-137. PMID: 21991168

**11**

0305-4179(94)90108-2

04.07.024

## **Conflict of interest**

The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

### **Author details**

Juin-Hong Cherng1,2,3\*

1 Department and Graduate Institute of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan, ROC

2 General Clinical Research Center for New Drug Trial, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC

3 Department of Gerontological Health Care, National Taipei University of Nursing and Health Sciences, Taipei, Taiwan, ROC

\*Address all correspondence to: i72bbb@gmail.com

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

*Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing DOI: http://dx.doi.org/10.5772/intechopen.80875*

### **References**

National Defense Medical Center, Taipei, Taiwan (ROC), for their helpful discus-

The author declared no potential conflicts of interest with respect to the

1 Department and Graduate Institute of Biology and Anatomy, National Defense

3 Department of Gerontological Health Care, National Taipei University of Nursing

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

2 General Clinical Research Center for New Drug Trial, Tri-Service General

Hospital, National Defense Medical Center, Taipei, Taiwan, ROC

research, authorship, and/or publication of this article.

sion during this chapter writing.

**Conflict of interest**

*Wound Healing*

**Author details**

**10**

Juin-Hong Cherng1,2,3\*

Medical Center, Taipei, Taiwan, ROC

and Health Sciences, Taipei, Taiwan, ROC

provided the original work is properly cited.

\*Address all correspondence to: i72bbb@gmail.com

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[2] de Roche R, Luscher NJ, Debrunner HU, Fischer R. Epidemiological data and costs of burn injuries in workers in Switzerland: An argument for immediate treatment in burn centers. Burns. 1994;**20**:58-60. DOI: 10.1016/ 0305-4179(94)90108-2

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Equine Practice. 2004;**3**(2):148-163. DOI: 10.1053/j.ctep.2004.08.006

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International Association for the Study of Pain (IASP); 1992

79-89. DOI: 10.1046/j.1524-475X.

1996;**22**(1):40-43. DOI: 10.1016/

tumour necrosis factor-alpha. Biomaterials. 2000;**21**:797-802. DOI: 10.1016/S0142-9612(00)00072-7

[25] WHO. Burns: 2018 update

3009337

addr.2017.09.018

[24] Thomas A, Harding KG, Moore K. Alginates from wound dressings activate human macrophages to secrete

[Internet]. 2018. Available from: http:// www.who.int/mediacentre/factsheets/ fs365/en/ [Accessed: 10 April 2018]

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[28] Verhaegen PD, van Zuijlen PP, Pennings NM, van Marle J, Niessen FB, van der Horst CM, et al. Differences in collagen architecture between keloid, hypertrophic scar, normotrophic scar,

and normal skin: An objective histopathological analysis. Wound Repair and Regeneration. 2009;**17**:

[29] Meyer WJ, Marvin JA, Patterson

[30] Ready LB, Edwards WT. Handbook of Management of Acute Pain: A Practical Guide. Seattle, WA:

DR, Thomas C, Blakeney PE. Management of pain and other discomforts in burned patients. In: Herndon D, editor. Handbook of Total Burn Care. 2nd ed. London: WB Saunders; 2001. pp. 747-765

649-656. DOI: 10.1111/ j.1524-475X.2009.00533.x

0305-4179(95)00066-6

[16] Malafaya PB, Silva GA, Reis RL. Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering

applications. Advanced Drug Delivery Reviews. 2007;**59**:207-233. DOI: 10.1016/j.addr.2007.03.012

[17] Wiegand C, Hipler UC. Polymerbased biomaterials as dressings for chronic stagnating wounds.

Macromolecular Symposia. 2010;**294**: 1-13. DOI: 10.1002/masy.200900028

[18] LeRoux MA, Guilak F, Setton LA. Compressive and shear properties of alginate gel: Effects of sodium ions and alginate concentration. Journal of Biomedical Materials Research. 1999; **47**(1):46-53. DOI: 10.1002/(SICI) 1097-4636(199910)47:13.0.CO;2-N

[19] Fanucci D, Seese J. Multi-faceted use of calcium alginates. A painless, cost-effective alternative for wound care management. OWM. 1991;**37**:16-22.

[20] Bale S, Baker N, Crook H, Rayman A, Rayman G, Harding KG. Exploring the use of an alginate dressing for diabetic foot ulcers. Journal of Wound Care. 2001;**10**(3):81-84. DOI: 10.12968/

[21] Sayag J, Meaume S, Bohbot S. Healing properties of calcium alginate dressings. Journal of Wound Care. 1996;

[22] Attwood AI. Calcium alginate dressing accelerates split skin graft donor site healing. British Journal of Plastic Surgery. 1989;**42**(4):373-379. DOI: 10.1016/0007-1226(89)90001-5

[23] Kneafsey B, O'Shaughnessy M, Condon KC. The use of calcium alginate dressings in deep hand burns. Burns.

**5**(8):357-362. DOI: 10.12968/

PMID: 1764155

jowc.2001.10.3.26063

jowc.1996.5.8.357

**12**

1999.00079.x

*Wound Healing*

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[51] Lee RM, Hartman PA, Stahr HM, Olson DG, Williams FD. Antibacterial mechanism of long-chain polyphosphates in Staphylococcus aureus. Journal of Food Protection. 1994;**57**:289-294. DOI: 10.4315/ 0362-028X-57.4.289

[52] Teixeira-da-Cunha MGA, Gomes RN, Roehrs N, Bozza FA, Prescott SM, Stafforini D, et al. Bacterial clearance is improved in septic mice by plateletactivating factor-acetylhydrolase (PAF-AH) administration. PLoS One. 2013;**8**: e74567. DOI: 10.1371/journal. pone.0074567

Effect of the crosslinking degree and oregano essential oil concentration. Journal of Food Engineering. 2012; **110**(2):232-239. DOI: 10.1016/j.

*DOI: http://dx.doi.org/10.5772/intechopen.80875*

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Determination of burn patient outcome by large-scale quantitative discovery proteomics. Critical Care Medicine. 2013;**41**:1421-1434. DOI: 10.1097/

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Kaushal A, Xiao W, Liu T, et al.

CCM.0b013e31827c072e

*Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing*

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[68] Allantaz F, Chaussabel D, Banchereau J, Pascual V. Microarraybased identification of novel biomarkers in IL-1-mediated diseases. Current Opinion in Immunology. 2007;**19**(6): 623-632. DOI: 10.1016/j.coi.2007.10.003

[69] Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996; **87**(6):2095-2147. PMID: 8630372

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neuropathic pain through pleiotropic effects. Molecular Pain. 2009;**5**:16. DOI:

[71] Zhu Y, Colak T, Shenoy M, Liu L, Mehta K, Pai R, et al. Transforming growth factor beta induces sensory neuronal hyperexcitability, and contributes to pancreatic pain and hyperalgesia in rats with chronic pancreatitis. Molecular Pain. 2012;**8**:65.

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10.1186/1744-8069-5-16

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breast cancer. Mediators of

10.1155/2015/129034

[60] Khan S, Tøndervik A, Sletta H, Klinkenberg G, Emanuel C, Onsøyen E, et al. Overcoming drug resistance with alginate oligosaccharides able to potentiate the action of selected antibiotics. Antimicrobial Agents and Chemotherapy. 2012;**56**(10): 5134-5141. DOI: 10.1128/AAC.00525-12

[61] Pritchard MF, Powell LC, Menzies GE, Lewis PD, Hawkins K, Wright C,

oligosaccharide polymer therapy to modify the mucus barrier of chronic respiratory disease. Molecular Pharmaceutics. 2016;**13**(3):863-872.

[62] Despond O, Proulx F, Carcillo JA, Lacroix J. Pediatric sepsis and multiple organ dysfunction syndrome. Current Opinion in Pediatrics. 2001;**13**:247-253. DOI: 10.1097/00008480-200106000-

[63] Gauglitz GG, Song J, Herndon DN, Finnerty CC, Boehning D, Barral JM,

inflammatory response during acute and post-acute phases after severe burn. Shock. 2008;**30**:503-507. DOI: 10.1016/j.

[64] Finnerty CC, Przkora R, Herndon DN, Jeschke MG. Cytokine expression profile over time in burned mice. Cytokine. 2009;**45**:20-25. DOI: 10.1016/

[65] Finnerty CC, Herndon DN, Chinkes DL, Jeschke MG. Serum cytokine differences in severely burned children with and without sepsis. Shock. 2007;**27**:

et al. Characterization of the

et al. A new class of safe

molpharmaceut.5b00794

DOI: 10.1021/acs.

00006

jss.2007.12.440

j.cyto.2008.10.005

4-9. DOI: 10.1097/01. shk.0000235138.20775.36

**15**

jfoodeng.2011.05.023

[53] Serbina NV, Jia T, Hohl TM, Pamer EG. Monocyte-mediated defense against microbial pathogens. Annual Review of Immunology. 2008;**26**:421-452. DOI: 10.1146/annurev. immunol.26.021607.090326

[54] Sjögren U, Figdor D, Spångberg L, Sundqvist G. The antimicrobial effect of calcium hydroxide as a short-term intracanal dressing. International Endodontic Journal. 1991;**24**:119-125. DOI: 10.1111/j.1365-2591.1991.tb00117.x

[55] Goh CH, Heng PW, Huang EP, Li BK, Chan LW. Interactions of antimicrobial compounds with crosslinking agents of alginate dressings. The Journal of Antimicrobial Chemotherapy. 2008;**62**:105-108. DOI: 10.1093/jac/ dkn168

[56] Ngo DH, Kim SK. Sulfated polysaccharides as bioactive agents from marine algae. International Journal of Biological Macromolecules. 2013;**62**: 70-75. DOI: 10.1016/j. ijbiomac.2013.08.036

[57] Lee JB, Takeshita A, Hayashi K, Hayashi T. Structures and antiviral activities of polysaccharides from *Sargassum trichophyllum*. Carbohydrate Polymers. 2011;**86**:995-999. DOI: 10.1016/j.carbpol.2011.05.059

[58] Yan GL, Guo YM, Yuan JM, Liu D, Zhang BK. Sodium alginate oligosaccharides from brown algae inhibit Salmonella enteritidis colonization in broiler chickens. Poultry Science. 2011;**90**(7):1441-1448. DOI: 10.3382/ps.2011-01364

[59] Benavides S, Villalobos-Carvajal R, Reyes JE. Physical, mechanical and antibacterial properties of alginate film: *Calcium Alginate Polysaccharide Dressing as an Accelerated Treatment for Burn Wound Healing DOI: http://dx.doi.org/10.5772/intechopen.80875*

Effect of the crosslinking degree and oregano essential oil concentration. Journal of Food Engineering. 2012; **110**(2):232-239. DOI: 10.1016/j. jfoodeng.2011.05.023

lives: Infection in burns. Surgical Infections. 2015;**16**(4):380-387. DOI:

[46] Norbury W, Herndon DN, Tanksley J, Jeschke MG, Finnerty CC. Infection in burns. Surgical Infections. 2016;**17**(2): 250-255. DOI: 10.1089/sur.2013.134

improved in septic mice by plateletactivating factor-acetylhydrolase (PAF-AH) administration. PLoS One. 2013;**8**:

[53] Serbina NV, Jia T, Hohl TM, Pamer EG. Monocyte-mediated defense against microbial pathogens. Annual Review of Immunology. 2008;**26**:421-452. DOI:

[54] Sjögren U, Figdor D, Spångberg L, Sundqvist G. The antimicrobial effect of calcium hydroxide as a short-term intracanal dressing. International Endodontic Journal. 1991;**24**:119-125. DOI: 10.1111/j.1365-2591.1991.tb00117.x

[55] Goh CH, Heng PW, Huang EP, Li

BK, Chan LW. Interactions of antimicrobial compounds with crosslinking agents of alginate dressings. The Journal of Antimicrobial Chemotherapy. 2008;**62**:105-108. DOI: 10.1093/jac/

[56] Ngo DH, Kim SK. Sulfated

70-75. DOI: 10.1016/j. ijbiomac.2013.08.036

polysaccharides as bioactive agents from marine algae. International Journal of Biological Macromolecules. 2013;**62**:

[57] Lee JB, Takeshita A, Hayashi K, Hayashi T. Structures and antiviral activities of polysaccharides from *Sargassum trichophyllum*. Carbohydrate Polymers. 2011;**86**:995-999. DOI: 10.1016/j.carbpol.2011.05.059

[58] Yan GL, Guo YM, Yuan JM, Liu D,

colonization in broiler chickens. Poultry Science. 2011;**90**(7):1441-1448. DOI:

[59] Benavides S, Villalobos-Carvajal R, Reyes JE. Physical, mechanical and antibacterial properties of alginate film:

Zhang BK. Sodium alginate oligosaccharides from brown algae inhibit Salmonella enteritidis

10.3382/ps.2011-01364

e74567. DOI: 10.1371/journal.

immunol.26.021607.090326

pone.0074567

10.1146/annurev.

dkn168

[47] Piacquadio D, Nelson DB. Alginates. A "new" dressing alternative. The Journal of Dermatologic Surgery and Oncology. 1992;**18**(11):992-995. DOI: 10.1111/j.1524-4725.1992.tb02773.x

[48] Wiegand C, Heinze T, Hipler UC.

cytotoxicity, antimicrobial activity, and binding capacity for pathophysiological factors in chronic wounds of alginate and silver-containing alginate. Wound Repair and Regeneration. 2009;**17**(4):

[49] Poor AE, Ercan UK, Yost A, Brooks AD, Joshi SG. Control of multi-drugresistant pathogens with non-

thermal-plasma-treated alginate wound dressing. Surgical Infections. 2014; **15**(3):233-243. DOI: 10.1089/

[50] Bystrom A, Claesson R, Sundqvist

camphorated paramonochlorophenol, camphorated phenol and calcium hydroxide in the treatment of infected root canals. Endodontics & Dental Traumatology. 1985;**1**:170-175. DOI: 10.1111/j.1600-9657.1985.tb00652.x

[51] Lee RM, Hartman PA, Stahr HM, Olson DG, Williams FD. Antibacterial

polyphosphates in Staphylococcus aureus. Journal of Food Protection. 1994;**57**:289-294. DOI: 10.4315/

[52] Teixeira-da-Cunha MGA, Gomes RN, Roehrs N, Bozza FA, Prescott SM, Stafforini D, et al. Bacterial clearance is

mechanism of long-chain

0362-028X-57.4.289

**14**

G. The antibacterial effect of

Comparative *in vitro* study on

511-521. DOI: 10.1111/ j.1524-475X.2009.00503.x

sur.2013.050

10.1089/sur.2013.135

*Wound Healing*

[60] Khan S, Tøndervik A, Sletta H, Klinkenberg G, Emanuel C, Onsøyen E, et al. Overcoming drug resistance with alginate oligosaccharides able to potentiate the action of selected antibiotics. Antimicrobial Agents and Chemotherapy. 2012;**56**(10): 5134-5141. DOI: 10.1128/AAC.00525-12

[61] Pritchard MF, Powell LC, Menzies GE, Lewis PD, Hawkins K, Wright C, et al. A new class of safe oligosaccharide polymer therapy to modify the mucus barrier of chronic respiratory disease. Molecular Pharmaceutics. 2016;**13**(3):863-872. DOI: 10.1021/acs. molpharmaceut.5b00794

[62] Despond O, Proulx F, Carcillo JA, Lacroix J. Pediatric sepsis and multiple organ dysfunction syndrome. Current Opinion in Pediatrics. 2001;**13**:247-253. DOI: 10.1097/00008480-200106000- 00006

[63] Gauglitz GG, Song J, Herndon DN, Finnerty CC, Boehning D, Barral JM, et al. Characterization of the inflammatory response during acute and post-acute phases after severe burn. Shock. 2008;**30**:503-507. DOI: 10.1016/j. jss.2007.12.440

[64] Finnerty CC, Przkora R, Herndon DN, Jeschke MG. Cytokine expression profile over time in burned mice. Cytokine. 2009;**45**:20-25. DOI: 10.1016/ j.cyto.2008.10.005

[65] Finnerty CC, Herndon DN, Chinkes DL, Jeschke MG. Serum cytokine differences in severely burned children with and without sepsis. Shock. 2007;**27**: 4-9. DOI: 10.1097/01. shk.0000235138.20775.36

[66] Finnerty CC, Jeschke MG, Qian WJ, Kaushal A, Xiao W, Liu T, et al. Determination of burn patient outcome by large-scale quantitative discovery proteomics. Critical Care Medicine. 2013;**41**:1421-1434. DOI: 10.1097/ CCM.0b013e31827c072e

[67] Chan G, Mooney DJ. Ca2+ released from calcium alginate gels can promote inflammatory responses *in vitro* and *in vivo*. Acta Biomaterialia. 2013;**9**: 9281-9291. DOI: 10.1016/j. actbio.2013.08.002

[68] Allantaz F, Chaussabel D, Banchereau J, Pascual V. Microarraybased identification of novel biomarkers in IL-1-mediated diseases. Current Opinion in Immunology. 2007;**19**(6): 623-632. DOI: 10.1016/j.coi.2007.10.003

[69] Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996; **87**(6):2095-2147. PMID: 8630372

[70] Echeverry S, Shi XQ, Haw A, Liu H, Zhang ZW, Zhang J. Transforming growth factor-beta1 impairs neuropathic pain through pleiotropic effects. Molecular Pain. 2009;**5**:16. DOI: 10.1186/1744-8069-5-16

[71] Zhu Y, Colak T, Shenoy M, Liu L, Mehta K, Pai R, et al. Transforming growth factor beta induces sensory neuronal hyperexcitability, and contributes to pancreatic pain and hyperalgesia in rats with chronic pancreatitis. Molecular Pain. 2012;**8**:65. DOI: 10.1186/1744-8069-8-65

[72] Panis C, Pavanelli WR. Cytokines as mediators of pain-related process in breast cancer. Mediators of Inflammation. 2015;**2015**:129034. DOI: 10.1155/2015/129034

[73] Lee WR, Park JH, Kim KH, Kim SJ, Park DH, Chae MH, et al. The biological effects of topical alginate treatment in an animal model of skin wound healing. Wound Repair and Regeneration. 2009;

**17**(4):505-510. DOI: 10.1111/ j.1524-475X.2009.00496.x

[74] Lu Y, Huang CL, Yu F, Xu YJ. Effect of calcium alginate dressing on the cytokine contents, collagen synthesis degradation balance and apoptosis gene expression in the wound after perianal abscess surgery. Journal of Hainan Medical University. 2017;**23**(18):65-68

[75] Iwamoto M, Kurachi M, Nakashima T, Kim D, Yamaguchi K, Oda T, et al. Structure–activity relationship of alginate oligosaccharides in the induction of cytokine production from RAW264. 7 cells. FEBS Letters. 2005; **579**:4423-4429. DOI: 10.1016/j. febslet.2005.07.007

[76] Ryan CA, Farmer EE. Oligosaccharide signals in plants: A current assessment. Annual Review of Plant Physiology and Plant Molecular Biology. 1991;**42**:651-674. DOI: 10.1146/ annurev.pp.42.060191.003251

[77] Davis BK, Wen HT, Ting JPY. The Inflammasome NLRs in immunity, inflammation, and associated diseases. Annual Review of Immunology. 2011; **29**:707-735. DOI: 10.1146/annurevimmunol-031210-101405

[78] Murakami T, Ockinger J, Yu J, Byles V, McColl A, Hofer AM, et al. Critical role for calcium mobilization in activation of the NLRP3 inflammasome. Proceedings of the National Academy of Sciences of the United States of America. 2012;**109**(28):11282-11287. DOI: 10.1073/pnas.1117765109

[79] Zhou RB, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;**469**(7354):221-225. DOI: 10.1038/nature09663

[80] Haug A, Myklastade S, Larsen B, Smidrod O. Correlation between chemical structure and physical properties of alginates. Acta Chemica Scandinavica. 1967;**21**:768-778. DOI: 10.3891/acta.chem.scand.21-0768

**17**

**Chapter 2**

**Abstract**

Products

availability of raw materials.

**1. Introduction**

(personal hygiene).

deodorization, collagen, substances, fish raw materials

A Study of the Use of Modified

Collagen of Freshwater Fish as

*L.V. Antipova, S.A. Storublevtsev, S.A. Titov, S.S. Antipov,* 

The work is devoted to the use of collagen materials produced on the basis of connective tissues of hydrobionts. Their characteristics as potential means of personal hygiene and wound healing are investigated. The results of studies of physical and chemical characteristics of collagen materials from freshwater fish with a modified structure obtained in this paper indicate the prospects of their use as an absorbent layer of personal hygiene products, due to the high moisture absorption capacity, which is an order of magnitude higher than the moisture capacity of untreated collagen and higher moisture capacity of superadsorbing polymers required for use in personal hygiene products. The resulting material meets the requirements of sanitary and epidemiological safety, allergenic action on the skin, as can be concluded from the results of tests on animals, it does not. This material accelerates reparative processes to the same extent as collagen used in standard hemostatic sponges with the simplicity of its production technology, low cost, and

**Keywords:** hygiene, human, safety, hydration, moisture capacity, sorption capacity,

Absorbing and deodorizing properties are especially important when improving and creating new medical means and materials, including those for individual use

Presently, the improvement of, for example, the napkins is focused primarily on the modification of their shape and design [1–3]; however, less attention is paid to a selection of moisture-absorbing layer materials for personal hygiene means, and their domestic production (in Russia) is absent. These materials can be divided now into three categories, i.e., the synthetics—for example, polyvinyl alcohols, polyethylene oxides, cross-linked polyacrylic esters [2]; natural materials—cellulose, guaric or xanthan gum; and modified natural materials—the cross-linked starches, sulphitic cellulose, Kraft cellulose [1]. The mixes of polymers of either synthetic or natural origin can be used. Particles of these polymers (they are called

a Material for Personal Care

*M.G. Khatkhokhu, M.S. Bolokov and V.V. Loboda*

### **Chapter 2**

**17**(4):505-510. DOI: 10.1111/ j.1524-475X.2009.00496.x

*Wound Healing*

[74] Lu Y, Huang CL, Yu F, Xu YJ. Effect of calcium alginate dressing on the cytokine contents, collagen synthesis degradation balance and apoptosis gene expression in the wound after perianal abscess surgery. Journal of Hainan Medical University. 2017;**23**(18):65-68

[75] Iwamoto M, Kurachi M, Nakashima T, Kim D, Yamaguchi K, Oda T, et al. Structure–activity relationship of alginate oligosaccharides in the

induction of cytokine production from RAW264. 7 cells. FEBS Letters. 2005; **579**:4423-4429. DOI: 10.1016/j.

Oligosaccharide signals in plants: A current assessment. Annual Review of Plant Physiology and Plant Molecular Biology. 1991;**42**:651-674. DOI: 10.1146/

[77] Davis BK, Wen HT, Ting JPY. The Inflammasome NLRs in immunity, inflammation, and associated diseases. Annual Review of Immunology. 2011; **29**:707-735. DOI: 10.1146/annurev-

[78] Murakami T, Ockinger J, Yu J, Byles V, McColl A, Hofer AM, et al. Critical role for calcium mobilization in

activation of the NLRP3 inflammasome. Proceedings of the National Academy of

Sciences of the United States of America. 2012;**109**(28):11282-11287. DOI: 10.1073/pnas.1117765109

[79] Zhou RB, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;**469**(7354):221-225. DOI:

[80] Haug A, Myklastade S, Larsen B, Smidrod O. Correlation between chemical structure and physical properties of alginates. Acta Chemica Scandinavica. 1967;**21**:768-778. DOI: 10.3891/acta.chem.scand.21-0768

10.1038/nature09663

**16**

annurev.pp.42.060191.003251

immunol-031210-101405

febslet.2005.07.007

[76] Ryan CA, Farmer EE.
