Volume 31, Issue 1 (3-2024)
RJMS 2024, 31(1): 1-24 |
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Research code: این مقاله مروری مورد تایید معاونت پژوهشی دانشگاه محقق
Ethics code: IR.UMA.REC.1400.084
Clinical trials code: کارآزمایی بالینی نداشتیم
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Taghizadeh Momen L, Asadi A, A.Ghanimi H, Abdolmaleki A. A Review of the Types of Skin Substitutes for Regenerating Skin Wounds. RJMS 2024; 31 (1) :1-24
URL: http://rjms.iums.ac.ir/article-1-7736-en.html
URL: http://rjms.iums.ac.ir/article-1-7736-en.html
Associate Professor, Department of Biophysics, Faculty of Advanced Technologies, University of Mohaghegh Ardabili, Namin, Iran , abdolmalekiarash1364@gmail.com
Abstract: (1181 Views)
The skin is important in maintaining the physiological homeostasis of the human body and serves as a protective barrier against infectious microorganisms, ultraviolet radiation, and mechanical injury. It is made up of three main layers: epiderm, derm, and hypoderm. Epiderm is the outer layer of skin that contains various types of keratinocytes (over 90% of epiderm) and non-keratinocytes (langerhans, melanocytes, and merkel cells). This layer plays a crucial role in skin regeneration and immunity. The dermal layer is made up primarily of collagen and elastic fibers, as well as a vascular network and nerves that provide skin strength and elasticity. Furthermore, it is divided into two layers based on collagen content thickness: upper papillary stratum and lower reticular stratum. The dermis is made up of two layers: fibroblasts and myofibroblasts, as well as immune cells like macrophages, lymphocytes, and mast cells. Hypodermis, the deepest and thickest layer of skin, composed of loose connective tissue. It protects blood capillaries and nerve terminals due to the abundance of fat cells. In addition, the hypodermis is a good source of mature mesenchymal stem cells known as adipose-derived stem cells with pluripotency.
The natural mechanism for wound healing is an interconnected and complex process that includes blood elements, extracellular matrix, parenchymal cells, and mediators. Wound healing is typically divided into three stages: inflammation, tissue formation, and tissue remodeling, all overlap each other. Skin wounds are divided into two categories: acute and chronic wounds. Acute wounds are classified into four types based on depth: superficial or epidermal, superficial partial thickness, deep partial thickness, and full thickness. Acute wound regeneration occurs at a specific time as part of the body's overall wound healing process. However, long-term use of any of the wound healing processes eventually results in the formation of chronic wounds such as diabetic foot ulcers and venous ulcers.
Initial efforts to accelerate wound healing and improve the healing process of chronic wounds and burns included the application of synthetic and biological temporary coatings. Furthermore, limited resources for autografts, allografts, and xenografts, as well as severe graft rejection issues, prompted researchers to develop tissue engineering structures. Low regeneration capacity of dermal layer results in the necessity to use skin substitutes for large skin wounds. Scar tissue formed in the absence of dermis lacks natural dermal elasticity and strength. As a result, scar tissue has limited movement, causing pain and an unappealing appearance. Tissue-engineered structures not only close wounds, but also promote dermal reformation. In general, key points to consider when developing skin substitutes include a dermal component for dermal regeneration and supporting epiderm, an epidermal component for fascilitating wound closure and establishing barrier properties, a permeable part for immune, nerve, and vascular system components, active cellular components capable of responding to various types of wounds and conditions, and adequate mechanical strength. Significant advances in skin tissue engineering have occurred in recent decades, with the ultimate goal of creating skin substitutes that resemble natural skin tissue in order to heal skin wounds. Skin substitutes are classified according to a variety of criteria. The first classification is determined by the presence or absence of cellular content in the skin substitute. They are classified as either cellular or non-cellular analogues based on their cellular content. Acellular substitutes are primarily used to prevent environmental contamination and fluid loss. Cellular substitutes are more complex and consist of one or two layers of scaffolds together with autologous or allogeneic cells They improve the healing process, resulting in long-term and complete repair of the damaged tissue, as well as a lower graft rejection rate. Another important consideration in the classification of skin substitutes is the nature of their biomaterials. Natural and synthetic biomaterials are applied in skin tissue engineering. Protein or carbohydrate-based natural biomaterials can be utilized in skin regeneration procedures. The most commonly utilized natural protein biomaterials in skin tissue engineering are fibrinogen, collagen, gelatin, and silk. The four categories of polysaccharide biomaterials—neutral (glucan, dextran, cellulose), acidic (hyaluronic acid and alginic acid), basic (chitosan), or poly sulfated saccharides (heparin, chondroitin)—are used mostly in the form of hydrogels for the efficient healing of skin wounds and burns. The most widely used biomaterials derived from polysaccharides are alginate, hyaluronic acid, and chitosan.
The building block of synthetic biomaterials is hydrocarbons. Despite lacking the biological characteristics of natural biopolymers their easier manufacturing process and more controllable composition make them useful for wound healing. Synthetic biomaterials, including polyglycolic acid, poly-ε-caprolactone, poly-β-hydroxybutyrate, and polyvinyl alcohol, are members of the polyhydroxy orthoester family and are utilized in the production of skin substitutes. The third classification of skin substitutes is based on the anatomical structure of the skin. This type of classification includes epidermal, dermal or bilayer dermoepidermal substitutes. In order to cultivate a mass of keratinocytes in the shortest time, in large number, and transfer them to the clinic, creating epidermal substitutes was considered. The main point in this thechnology is the separation and cultivation of keratinocytes and transformation to the patient. The majority of dermal substitutions are decellularized (mostly allogeneic or xenogeneic).
Decellularized substitutions are more easily manufactured and the license for clinical trials is more achievable than cellular double-layered structures. The main benefits of preparing dermal substitutions are the short preparation time, mass production, and low cost. Dermoepidermal substitutes, also known as composite analogues, are created by replicating the anatomical structure of the skin. Dermoepidermal substitutes are more complex and expensive than epidermal and dermal substitutes. Most of these products contain allogeneic cells and function as temporary wound dressings. Studies showed that allogeneic fibroblasts can function for up to three weeks without stimulating the immune system. Allogeneic keratinocytes are also effective at reducing pain and speeding up wound healing, but they are rejected by the immune system after a few weeks. Only dermoepidermal substitutes containing autologous or allogeneic fibroblasts and autologous keratinocytes have been shown in studies to have long-term effects. Tissue tech autograft system substitute is a dermoepidermal substitute with a permanent effect that consists of a scaffold composed of hyaluronic acid membrane, autologous fibroblasts, and keratinocytes. Since the advent of skin substitutes in 1979, investigations and clinical trials have begun in the 1980s. Following their approval in 1997, engineered skin products entered the market. The first product was named Transcyte. After that, in 1998, the Apligraf product was introduced as the first living tissue engineering product, followed by Dermagraft in 2000 and Orcell in 2001. However, the appropriate skin substitute has yet to be developed and studies are currently being conducted to create a suitable thick-skinned substitute with high-speed angiogenesis. Redesigning commercial substitutes is also required for improved ease of use, cost-effectiveness, and shelf life. The current article provides an overview of advances in skin tissue engineering as they relate to the production of numerous skin substitutes and commercially available products.
The natural mechanism for wound healing is an interconnected and complex process that includes blood elements, extracellular matrix, parenchymal cells, and mediators. Wound healing is typically divided into three stages: inflammation, tissue formation, and tissue remodeling, all overlap each other. Skin wounds are divided into two categories: acute and chronic wounds. Acute wounds are classified into four types based on depth: superficial or epidermal, superficial partial thickness, deep partial thickness, and full thickness. Acute wound regeneration occurs at a specific time as part of the body's overall wound healing process. However, long-term use of any of the wound healing processes eventually results in the formation of chronic wounds such as diabetic foot ulcers and venous ulcers.
Initial efforts to accelerate wound healing and improve the healing process of chronic wounds and burns included the application of synthetic and biological temporary coatings. Furthermore, limited resources for autografts, allografts, and xenografts, as well as severe graft rejection issues, prompted researchers to develop tissue engineering structures. Low regeneration capacity of dermal layer results in the necessity to use skin substitutes for large skin wounds. Scar tissue formed in the absence of dermis lacks natural dermal elasticity and strength. As a result, scar tissue has limited movement, causing pain and an unappealing appearance. Tissue-engineered structures not only close wounds, but also promote dermal reformation. In general, key points to consider when developing skin substitutes include a dermal component for dermal regeneration and supporting epiderm, an epidermal component for fascilitating wound closure and establishing barrier properties, a permeable part for immune, nerve, and vascular system components, active cellular components capable of responding to various types of wounds and conditions, and adequate mechanical strength. Significant advances in skin tissue engineering have occurred in recent decades, with the ultimate goal of creating skin substitutes that resemble natural skin tissue in order to heal skin wounds. Skin substitutes are classified according to a variety of criteria. The first classification is determined by the presence or absence of cellular content in the skin substitute. They are classified as either cellular or non-cellular analogues based on their cellular content. Acellular substitutes are primarily used to prevent environmental contamination and fluid loss. Cellular substitutes are more complex and consist of one or two layers of scaffolds together with autologous or allogeneic cells They improve the healing process, resulting in long-term and complete repair of the damaged tissue, as well as a lower graft rejection rate. Another important consideration in the classification of skin substitutes is the nature of their biomaterials. Natural and synthetic biomaterials are applied in skin tissue engineering. Protein or carbohydrate-based natural biomaterials can be utilized in skin regeneration procedures. The most commonly utilized natural protein biomaterials in skin tissue engineering are fibrinogen, collagen, gelatin, and silk. The four categories of polysaccharide biomaterials—neutral (glucan, dextran, cellulose), acidic (hyaluronic acid and alginic acid), basic (chitosan), or poly sulfated saccharides (heparin, chondroitin)—are used mostly in the form of hydrogels for the efficient healing of skin wounds and burns. The most widely used biomaterials derived from polysaccharides are alginate, hyaluronic acid, and chitosan.
The building block of synthetic biomaterials is hydrocarbons. Despite lacking the biological characteristics of natural biopolymers their easier manufacturing process and more controllable composition make them useful for wound healing. Synthetic biomaterials, including polyglycolic acid, poly-ε-caprolactone, poly-β-hydroxybutyrate, and polyvinyl alcohol, are members of the polyhydroxy orthoester family and are utilized in the production of skin substitutes. The third classification of skin substitutes is based on the anatomical structure of the skin. This type of classification includes epidermal, dermal or bilayer dermoepidermal substitutes. In order to cultivate a mass of keratinocytes in the shortest time, in large number, and transfer them to the clinic, creating epidermal substitutes was considered. The main point in this thechnology is the separation and cultivation of keratinocytes and transformation to the patient. The majority of dermal substitutions are decellularized (mostly allogeneic or xenogeneic).
Decellularized substitutions are more easily manufactured and the license for clinical trials is more achievable than cellular double-layered structures. The main benefits of preparing dermal substitutions are the short preparation time, mass production, and low cost. Dermoepidermal substitutes, also known as composite analogues, are created by replicating the anatomical structure of the skin. Dermoepidermal substitutes are more complex and expensive than epidermal and dermal substitutes. Most of these products contain allogeneic cells and function as temporary wound dressings. Studies showed that allogeneic fibroblasts can function for up to three weeks without stimulating the immune system. Allogeneic keratinocytes are also effective at reducing pain and speeding up wound healing, but they are rejected by the immune system after a few weeks. Only dermoepidermal substitutes containing autologous or allogeneic fibroblasts and autologous keratinocytes have been shown in studies to have long-term effects. Tissue tech autograft system substitute is a dermoepidermal substitute with a permanent effect that consists of a scaffold composed of hyaluronic acid membrane, autologous fibroblasts, and keratinocytes. Since the advent of skin substitutes in 1979, investigations and clinical trials have begun in the 1980s. Following their approval in 1997, engineered skin products entered the market. The first product was named Transcyte. After that, in 1998, the Apligraf product was introduced as the first living tissue engineering product, followed by Dermagraft in 2000 and Orcell in 2001. However, the appropriate skin substitute has yet to be developed and studies are currently being conducted to create a suitable thick-skinned substitute with high-speed angiogenesis. Redesigning commercial substitutes is also required for improved ease of use, cost-effectiveness, and shelf life. The current article provides an overview of advances in skin tissue engineering as they relate to the production of numerous skin substitutes and commercially available products.
Type of Study: review article |
Subject:
Dermatology
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