Volume 31, Issue 1 (3-2024)
RJMS 2024, 31(1): 0-0 |
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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)
URL: http://rjms.iums.ac.ir/article-1-7736-en.html
URL: http://rjms.iums.ac.ir/article-1-7736-en.html
, abdolmalekiarash1364@gmail.com
Abstract: (293 Views)
The skin plays an important role in maintaining the physiological homeostasis of the human body and acts as a covering that protects the body from infectious microorganisms, ultraviolet rays or biomechanical trauma. It consists of three main layers including epiderm, derm, and hypoderm. Epiderm is the outer layer layer of skin which contains different types of keratinocytes. (more than 90% of epiderm) and non-keratinocytes (Langerhans, melanocytes, and mecel cells). This layer has important rules in skin regeneration and immunity. Dermal layer mainly consists of collagen and elastic fiber, vascular network and nerves, which provides skin strength and elasticity. Furthermore, based on the thickness of the collagen content, it is divided into two layers, the upper papillary stratum and the lower reticular stratum. Both layers of the dermis contain fibroblasts, myofibroblasts, and immune cells such as macrophages, lymphocytes, and mast cells. Hypodermis, the deepest and thickest layer of the skin, made of loose connective tissue, has shock absorber role, because of fat cell abundance, for protecting blood capillaries and nerve terminals. In addition, hypodermis is a good source of mature mesenchymal stem cells called adipose-derived stem cells with pluripotent properties.
The natural mechanism for wound healing is an interative and complex process which blood elements, extracellular matrix, parenchymal cells, and mediators involve in it. Generally wound healing ocuurs in three stages, including inflammation, tissue formation, and tissue remodeling, which overlap with each other. Skin wounds are classified into two main groups including acute and chronic wounds. Acute wounds are classified into four categories based on depth: superficial or epidermal, superficial partial thickness, deep partial thickness, and full thickness. Acute wound regeneration occurs in a certain timeline by general wound healing process of the body. However, long-term continuation of any of the wound healing processes eventually leads to the formation of chronic wounds such as diabetic foot ulcer and venous ulcer.
Initial efforts to accelerate wound healing and improvement in the healing process of chronic wounds and burns included the use of synthetic and biological coatings. These coatings are not considered permanent and their effect is temporary. In addition, limited resources of autografts, allografts, and xenografts and severe graft rejection issues, led researchers to create tissue engineering structures. Low regeneration capacity of dermal layer results in the necessity to use skin substitutes for large skin wounds. The scar tissue, which is formed in the absence of derm, do not possess natural dermal elasticity and strength. As a result, scar tissue has limited movement capability that causes pain and undesirable appearance. Tissue engineered structures not only cause wound closure, but they also stimulate dermal reformation. Generally, key points that they have to be considered in preparing skin substitutes includea dermal component for dermal regeneration and supporting epiderm, an epidermal component for fascilitating wound closure and establishing its barrier properties, a permeable part for components of immune, nerve, and vascular systems, active cellular components that are able to respond to various types of wounds and conditions, and sufficient mechanical strength. Significant advances in skin tissue engineering have been made in recent decades, with the ultimate goal of developing skin substitutes that resemble natural skin tissue to heal skin wounds and deal with existing clinical problems. Skin substitutes are classified into different types based on different criteria. The first classification is based on the presence or absence of cellular content in the skin substitute. According to the cellular content, they can be divided into cellular or non-cellular analogues. Acellular substitutes are mainly used as protection against environmental contamination as well as fluid loss. Cellular substitutes are more complex and consist of one or two layers of scaffolds together with autologous or allogeneic cells. They lead to an increase in the healing process with long-term and complete repair of the damaged tissue and a decrease in the graft rejection rate. Another important factor for the classification of skin substitutes is the nature of its constituent biomaterials. Biomaterials can be natural or synthetic. Natural biomaterials used in skin regeneration can be of protein or carbohydrate origin. The dominant natural protein biomaterials used in skin tissue engineering include collagen, gelatin, silk and fibrinogen. Biomaterials based on polysaccharides, which are mainly used in the form of hydrogels for the effective healing of skin wounds and burns, are divided into four categories: neutral (such as glucan, dextran, cellulose), acidic (alginic acid and hyaluronic acid), basic (chitosan) or poly sulfated saccharides (heparin, chondroitin) are classified. The most common polysaccharide-derived biomaterials include chitosan, hyaluronic acid, and alginate. Hydrocarbons are components of synthetic biomaterials. Although they do not exhibit the biological properties of natural biopolymers, their controllable composition and easier manufacturing process highlight their utility for wound healing. Polyhydroxy orthoester family such as polyglycolic acid, poly-ε-caprolactone, poly-β-hydroxybutyrate, and polyvinyl alcohol are examples of synthetic biomaterials used in the manufacture 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 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 in terms of number, growth and transfering to the patient. Most dermal substitutions are decellularized and mostly allogeneic or xenogeneic. It is easier to make these products compared to double-layer and cellular structures, and the license for clinical trials is more achievable. Key advantages of of preparing dermal substitutions are short preparation time, mass production, and low price. Dermoepidermal substitutes are also known as composite analogues, are made by modeling the anatomical structure of the skin. As a result, they show more functional similarity. Dermoepidermal substitutes are more complex and expensive than epidermal and dermal substitutes. Most of these products contain allogeneic cells and are used as temporary wound dressings. Studies showed that allogeneic fibroblasts can function for up to three weeks without stimulating the immune system. Allogeneic keratinocytes also work better in reducing pain and speeding up wound healing, but they are rejected by the immune system after a few weeks. Researches demonstrated that only dermoepidermal substitutes with fibroblasts, either autologous or allogeneic, and autologous keratinocytes can show permanent effects. Tissue tech autograft system substitute, is a dermoepidermal substitiute with permanat effect which has a scaffold made up of hyaluronic acid membrane, autologous fibroblasts and keratinocytes. Since the advent of skin substitutes in 1979, their potential has been investigated and clinical trials began in the 80s. Engineered skin products entered the market after being approved in 1997. The first product was called Transcyte. After that, in 1998, the Apligraf product was launched 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 research is currently underway to develop a suitable thick-skinned substitute with high-speed angiogenesis. Redesigning commercial substitutes is also essential for greater usability, cost-effectiveness, and longer shelf life. The current article provides an overview of the advancements in skin tissue engineering in the production of numerous skin substitutes and commercial products available on the market.
The natural mechanism for wound healing is an interative and complex process which blood elements, extracellular matrix, parenchymal cells, and mediators involve in it. Generally wound healing ocuurs in three stages, including inflammation, tissue formation, and tissue remodeling, which overlap with each other. Skin wounds are classified into two main groups including acute and chronic wounds. Acute wounds are classified into four categories based on depth: superficial or epidermal, superficial partial thickness, deep partial thickness, and full thickness. Acute wound regeneration occurs in a certain timeline by general wound healing process of the body. However, long-term continuation of any of the wound healing processes eventually leads to the formation of chronic wounds such as diabetic foot ulcer and venous ulcer.
Initial efforts to accelerate wound healing and improvement in the healing process of chronic wounds and burns included the use of synthetic and biological coatings. These coatings are not considered permanent and their effect is temporary. In addition, limited resources of autografts, allografts, and xenografts and severe graft rejection issues, led researchers to create tissue engineering structures. Low regeneration capacity of dermal layer results in the necessity to use skin substitutes for large skin wounds. The scar tissue, which is formed in the absence of derm, do not possess natural dermal elasticity and strength. As a result, scar tissue has limited movement capability that causes pain and undesirable appearance. Tissue engineered structures not only cause wound closure, but they also stimulate dermal reformation. Generally, key points that they have to be considered in preparing skin substitutes includea dermal component for dermal regeneration and supporting epiderm, an epidermal component for fascilitating wound closure and establishing its barrier properties, a permeable part for components of immune, nerve, and vascular systems, active cellular components that are able to respond to various types of wounds and conditions, and sufficient mechanical strength. Significant advances in skin tissue engineering have been made in recent decades, with the ultimate goal of developing skin substitutes that resemble natural skin tissue to heal skin wounds and deal with existing clinical problems. Skin substitutes are classified into different types based on different criteria. The first classification is based on the presence or absence of cellular content in the skin substitute. According to the cellular content, they can be divided into cellular or non-cellular analogues. Acellular substitutes are mainly used as protection against environmental contamination as well as fluid loss. Cellular substitutes are more complex and consist of one or two layers of scaffolds together with autologous or allogeneic cells. They lead to an increase in the healing process with long-term and complete repair of the damaged tissue and a decrease in the graft rejection rate. Another important factor for the classification of skin substitutes is the nature of its constituent biomaterials. Biomaterials can be natural or synthetic. Natural biomaterials used in skin regeneration can be of protein or carbohydrate origin. The dominant natural protein biomaterials used in skin tissue engineering include collagen, gelatin, silk and fibrinogen. Biomaterials based on polysaccharides, which are mainly used in the form of hydrogels for the effective healing of skin wounds and burns, are divided into four categories: neutral (such as glucan, dextran, cellulose), acidic (alginic acid and hyaluronic acid), basic (chitosan) or poly sulfated saccharides (heparin, chondroitin) are classified. The most common polysaccharide-derived biomaterials include chitosan, hyaluronic acid, and alginate. Hydrocarbons are components of synthetic biomaterials. Although they do not exhibit the biological properties of natural biopolymers, their controllable composition and easier manufacturing process highlight their utility for wound healing. Polyhydroxy orthoester family such as polyglycolic acid, poly-ε-caprolactone, poly-β-hydroxybutyrate, and polyvinyl alcohol are examples of synthetic biomaterials used in the manufacture 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 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 in terms of number, growth and transfering to the patient. Most dermal substitutions are decellularized and mostly allogeneic or xenogeneic. It is easier to make these products compared to double-layer and cellular structures, and the license for clinical trials is more achievable. Key advantages of of preparing dermal substitutions are short preparation time, mass production, and low price. Dermoepidermal substitutes are also known as composite analogues, are made by modeling the anatomical structure of the skin. As a result, they show more functional similarity. Dermoepidermal substitutes are more complex and expensive than epidermal and dermal substitutes. Most of these products contain allogeneic cells and are used as temporary wound dressings. Studies showed that allogeneic fibroblasts can function for up to three weeks without stimulating the immune system. Allogeneic keratinocytes also work better in reducing pain and speeding up wound healing, but they are rejected by the immune system after a few weeks. Researches demonstrated that only dermoepidermal substitutes with fibroblasts, either autologous or allogeneic, and autologous keratinocytes can show permanent effects. Tissue tech autograft system substitute, is a dermoepidermal substitiute with permanat effect which has a scaffold made up of hyaluronic acid membrane, autologous fibroblasts and keratinocytes. Since the advent of skin substitutes in 1979, their potential has been investigated and clinical trials began in the 80s. Engineered skin products entered the market after being approved in 1997. The first product was called Transcyte. After that, in 1998, the Apligraf product was launched 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 research is currently underway to develop a suitable thick-skinned substitute with high-speed angiogenesis. Redesigning commercial substitutes is also essential for greater usability, cost-effectiveness, and longer shelf life. The current article provides an overview of the advancements in skin tissue engineering in the production of numerous skin substitutes and commercial products available on the market.
Type of Study: review article |
Subject:
Dermatology
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