a critical structure in interaction of the human body with the environment represents the skin surface with the stratum corneum . without the horny layer a terrestrial life would be impossible .
on the other hand the stratum corneum becomes impaired in any kind of superficial or deep injuries . to retain body homeostasis recovery of stratum corneum
other important protective functions of skin are protection against infection and irradiation , in particular ultraviolet ( uv ) irradiation . in the following chapters
the epidermal thickness of an -immature newborn is about 29 m , in mature newborns and adults the thickness is about 50 m .
the skin surface of the newborn is covered by protective gelatinous vernix caseosa whereas the skin surface of adults is rather dry .
about 20 layers of nucleus - free corneocytes densely packed with keratin filaments are surrounded by a matrix .
the matrix is composed of filaggrin and -derivates , and lipid - rich lamellar bodies .
ceramides stand for about 50% of horny layer lipids and are essential for the lamellar structure of the epidermis .
the free fatty acids are mostly long chained molecules with more than 20 c atoms .
the water exchange is realized by migrating pores , i.e. polar transport pathways within the lipid mosaic .
the matrix develops under influences of ph gradients , sodium ions and enzymes ( synthetases , reductases , hydrolases , lipases ) . in a simplistic
more recent studies discovered subunits of octaeders of corneocytes within the horny layer which may migrate .
the horny layer is covered on its surface by a thin amorphous film contributing to stratum corneum structure and function . in newborns
there is an almost neutral skin surface ph of 6.6 that changes within days or weeks into an acidic ph of 5.9 ( acid skin surface film ) .
this leads to activation of ph - dependent hydrolytic enzymes like -glucocerebrosidase and stratum corneum secretory phospholipase a2 , .
skin surface ph is modulated by microbial harvest , eccrine and sebaceous gland secretions , and endogenous catabolic pathways .
exposure of horny layer to neutral buffers ( i.e. wet work ) or blocking of acidification increases the ph .
prolonged exposure of human skin to wetness ( water ) and/ or occlusion leads to measurable disturbances of barrier function .
the transepidermal water loss ( tewl ) increases in relation to duration of exposure and temperature , .
initially the epidermis comes as a monolayer . in the first trimenon the epidermis is covered by single layered periderm .
the epidermal thickness of an -immature newborn is about 29 m , in mature newborns and adults the thickness is about 50 m .
the skin surface of the newborn is covered by protective gelatinous vernix caseosa whereas the skin surface of adults is rather dry .
about 20 layers of nucleus - free corneocytes densely packed with keratin filaments are surrounded by a matrix .
the matrix is composed of filaggrin and -derivates , and lipid - rich lamellar bodies .
ceramides stand for about 50% of horny layer lipids and are essential for the lamellar structure of the epidermis .
the free fatty acids are mostly long chained molecules with more than 20 c atoms .
the water exchange is realized by migrating pores , i.e. polar transport pathways within the lipid mosaic .
the matrix develops under influences of ph gradients , sodium ions and enzymes ( synthetases , reductases , hydrolases , lipases ) . in a simplistic
more recent studies discovered subunits of octaeders of corneocytes within the horny layer which may migrate .
the horny layer is covered on its surface by a thin amorphous film contributing to stratum corneum structure and function . in newborns
there is an almost neutral skin surface ph of 6.6 that changes within days or weeks into an acidic ph of 5.9 ( acid skin surface film ) .
this leads to activation of ph - dependent hydrolytic enzymes like -glucocerebrosidase and stratum corneum secretory phospholipase a2 , .
skin surface ph is modulated by microbial harvest , eccrine and sebaceous gland secretions , and endogenous catabolic pathways .
exposure of horny layer to neutral buffers ( i.e. wet work ) or blocking of acidification increases the ph .
prolonged exposure of human skin to wetness ( water ) and/ or occlusion leads to measurable disturbances of barrier function .
the transepidermal water loss ( tewl ) increases in relation to duration of exposure and temperature , .
2.1.1 dry skin - xerosis cutis xerosis cutis is a consequence in epidermal water content reduction ( < 10% of stratum corneum ) .
an increased transepidermal water loss ( tewl ) leads to itch , scaling , roughness and fissuring .
the basic principle of treatment of dry skin is the use of emollients and moisturizers .
occlusive substances are for instance vaseline , mineral oils , paraffin , silicon , oils and fatty acids from both animals or vegetables .
ceramides are of particular interest in cosmeceutical since they represent a major physiological constituent of stratum corneum barrier . hydrogenated polydecenes are chemically better defined substances as mineral mixtures like vaseline without their stickiness .
the more and more popular vegetable oils and fatty acids are not without their own problems .
some like coconut butter exert a comedogenic potential , others like peanut butter can cause allergic contact dermatitis . among water binding substances , known as humectants ,
urea that is also a normal components of the natural moisturizing factor ( nmf ) of human skin may be released from oil in water and water in oil emulsions and than penetrate into the horny layer . on average ,
a six - fold increase of urea concentration by topical application doubles the water content of the horny layer .
vehicles are used as drug carriers as well as skincare products without a specific drug constituent . for a long time lipid combinations
are designed to specifically modulate the horny layer and support barrier recovery . in recent times
new pharmaceutical technologies were introduced like liposomes , nano particles , cyclodextrines , and microemulsions .
however , their percutaneous penetration is limited . because of solubility problems , uv- and oxygen - instability vitamins are a challenge for topical use .
percutaneous resorption of tocopheral has been demonstrated . in most cases of vitamins , however , scientific investigations of topical application are missing .
a rather extensive data file , scientific and clinical , is available in case of dexpanthenol that is transformed in skin into panthothenic acid also known as vitamin b5 .
panthothenic acid is a component of coenzyme a involved in the synthesis of fatty acids , sterols , proteins etc .
itch relief was fates and pain was reduced . in randomized , placebo - controlled studies among healthy subjects dexpanthenol significantly increased the horny layer water binding and reduced transepidermal water loss . on experimental damaged skin dexpanthenol ointment improved the stratum corneum water content more rapid and significant compared to its vehicle .
2.1.2 inflammation - radiodermatitis radiodermatitis is defined as the whole range of cutaneous reactions due ionizing irradiation .
exposure of skin to ionizing irradiation activates transcription factor nf-b by formation of intracellular oxygen radicals .
soaps should be avoided for skin cleansing since they may change skin surface ph into the basic range .
non - erosive radiodermatitis can be treated with water - in - oil emulsions . in open trials with breast cancer patients and radiotherapy after tumour
moisturizers are not capable to prevent radiodermatitis , . comparing skin cleansing and skin care with the traditional method to keep skin dry during radiotherapy of breast cancer cleansing with water was superior .
in particular wet desquamation occurred less often when washing was allowed . in a study on skin care during radiation therapy a mild aloe vera - containing soap alone
a protective effective has been described for panthothenol in models of oxygen radical - induced cell and tissue damage such as lipid oxidation of cell membranes treated by gamma irradiation . using a moisturizing concept with dexpanthenol topically in more than 1,000 radiotherapy patients both tolerance to treatment and acceptance of treatment by patients
allergic reactions , super infections , epidermolysis , and xerosis cutis were either less frequent or even completely prevented .
in contrast , a randomized study including 86 patients with larynx or breast cancer and radiotherapy dexpanthenol ointment alone had no significant effect on eortc / rtog - score of radiodermatitis , pain and itch . in this study quality of life , super infection and tolerability of irradiation
the topical steroid was significantly more effective than the vehicle in the reduction of inflammation .
there is no such data available for the use of other topical steroids . in erosive radiodermatitis
wet compressions with black tee or eosin 1 - 2% and a short course of hydrocortisone foam have been recommended .
2.1.3 protection against skin infection and antimicrobial peptides there is a close relationship between horny layer barrier function and the risk of skin infection .
a cochrane group analysis has shown that in newborns emollients alone are capable to stabilize the stratum corneum barrier thereby preventing skin infections .
they may also be used as an adjuvant in management of chronic wounds that are at risk of infection or are infected without replacement of systemic antibiotics when necessary .
iodine is contraindicated during pregnancy , in newborns and patients with thyroid disease since there is a significant percutaneous absorption of iodine . among topical antibiotics for the head and neck region mupirocine
the drug exerts an excellent activity against staphylococcus aureus that makes it the first choice for eradication of a nasal staphyloccous reservoir .
the use of other topical antibiotics like neomycine , bacitracine , polymyxine etc . is better avoided since contact - allergic reactions are not uncommon and they are not effective in deeper infections . in these cases
interestingly enough , the new calls of topical calcineurin - inhibitors used for atopic dermatitis reduces the microbial settlement of skin by staphylococci and restores the barrier function , . in recent years research
the human cathelicidin ll-37 is chemotactic for neutrophils , monocytes , mast cells , and t - lymphocytes , causes mast cell degranulation and supports vascularization and re - epithelialization of wounds . in human skin appendages genes like dcd and camp
in addition , such substances are secreted together with the sweat and spread on the skin surface , . in newborns
there is a 10- to 100-fold increase of expression of cathelicidin ll-37 and -defensin-2 compared with adult skin .
this explains as a compensatory mechanism of a still immature immune system in adapting to post - uterine life .
both -defensin-1 to -3 and cathelicidin ll-37 have been detected there . during the recovery of barrier function after wounding or inflammatory disease ( eczema , psoriasis )
the microbial settlement induces antimicrobial control mechanisms : for instance saprophytic yeast malasezzia furfur , but bacteria as well , induce the expression of -defensin-2 in human epidermal keratinocytes , .   in acute wounds surgery
in chronic non - infected wounds and chronic wounds not at risk of infection the principle of moist wound healing has become the standard .
the use of wound dressings is a part of the concept of wound bed preparation - time .
time includes the following aspects : is the tissue viable or necrotic ? in cases of necrosis debridement is necessary either with the by surgery , application of maggots ( biosurgery ) , or enzymatic .
however , the beneficial effect of regular debridement has been proven scientifically only in the treatment of diabetic foot ulcers yet .
i = infection , inflammation in any case of infection and / or inflammation infection control is need either by antibiosis , removal of the bacterial biofilm or disinfection .
in addition the basic pathogenic factors like hypoxia , impaired circulation , metabolic disease and oedema have to be treated as well . in chronic wounds at risk of infection silver - containing wound dressings are useful and effective , .
in particular re - epithelialization of skin is supported by a moist but not wet wound milieu .
the aim of moisture balance is protection against secondary infection and balancing fluid in the wound bed . for this purpose wound dressings with a semi - occlusive surface membrane combined with polyurethane foams , alginates or hydro fibres
the major effects are improvement of granulation and re - epithelialization , pain reduction , reduction of dressing change frequency and thereby decreasing the nursing time , . in recent years
more and more interactive dressings have been developed , that balance the content and activity of matrix metalloproteinases in the wound fluid , .
the wound edge can be undermined like in pyoderma gangraenosum , hyperplastic like in plantar ulcers or growing onto the wound bed like in healing wounds ( edge effect ) .
the edge effect can also be observed after skin transplant ( i.e. in full thickness reverdin islands ) .
platelet - derived growth factor ( pdgf - bb ) increases the speed of re - epithelialization in diabetic and varicose ulcers .
the basic mechanisms of action are neoangiogenesis and increased fibroblast activity . on the other hand
, dermal matrix components like hyaluronic acid , oxygen partial pressure and other growth factors may stimulate keratinocyte proliferation and migration , .
inter linked hyaluronic acid has been used as wound dressing and as a keratinocyte delivery system in tissue - engineered skin .
2.1.1 dry skin - xerosis cutis xerosis cutis is a consequence in epidermal water content reduction ( < 10% of stratum corneum ) .
an increased transepidermal water loss ( tewl ) leads to itch , scaling , roughness and fissuring .
the basic principle of treatment of dry skin is the use of emollients and moisturizers .
occlusive substances are for instance vaseline , mineral oils , paraffin , silicon , oils and fatty acids from both animals or vegetables .
ceramides are of particular interest in cosmeceutical since they represent a major physiological constituent of stratum corneum barrier . hydrogenated polydecenes are chemically better defined substances as mineral mixtures like vaseline without their stickiness .
the more and more popular vegetable oils and fatty acids are not without their own problems .
some like coconut butter exert a comedogenic potential , others like peanut butter can cause allergic contact dermatitis . among water binding substances , known as humectants ,
urea that is also a normal components of the natural moisturizing factor ( nmf ) of human skin may be released from oil in water and water in oil emulsions and than penetrate into the horny layer . on average ,
a six - fold increase of urea concentration by topical application doubles the water content of the horny layer .
vehicles are used as drug carriers as well as skincare products without a specific drug constituent . for a long time lipid combinations
are designed to specifically modulate the horny layer and support barrier recovery . in recent times
new pharmaceutical technologies were introduced like liposomes , nano particles , cyclodextrines , and microemulsions .
however , their percutaneous penetration is limited . because of solubility problems , uv- and oxygen - instability vitamins are a challenge for topical use .
percutaneous resorption of tocopheral has been demonstrated . in most cases of vitamins , however , scientific investigations of topical application are missing .
a rather extensive data file , scientific and clinical , is available in case of dexpanthenol that is transformed in skin into panthothenic acid also known as vitamin b5 .
panthothenic acid is a component of coenzyme a involved in the synthesis of fatty acids , sterols , proteins etc .
itch relief was fates and pain was reduced . in randomized , placebo - controlled studies among healthy subjects dexpanthenol significantly increased the horny layer water binding and reduced transepidermal water loss . on experimental damaged skin dexpanthenol ointment improved the stratum corneum water content more rapid and significant compared to its vehicle .
2.1.2 inflammation - radiodermatitis radiodermatitis is defined as the whole range of cutaneous reactions due ionizing irradiation .
exposure of skin to ionizing irradiation activates transcription factor nf-b by formation of intracellular oxygen radicals .
soaps should be avoided for skin cleansing since they may change skin surface ph into the basic range .
non - erosive radiodermatitis can be treated with water - in - oil emulsions . in open trials with breast cancer patients and radiotherapy after tumour
moisturizers are not capable to prevent radiodermatitis , . comparing skin cleansing and skin care with the traditional method to keep skin dry during radiotherapy of breast cancer cleansing with water was superior .
in particular wet desquamation occurred less often when washing was allowed . in a study on skin care during radiation therapy a mild aloe vera - containing soap alone
a protective effective has been described for panthothenol in models of oxygen radical - induced cell and tissue damage such as lipid oxidation of cell membranes treated by gamma irradiation . using a moisturizing concept with dexpanthenol topically in more than 1,000 radiotherapy patients both tolerance to treatment and acceptance of treatment by patients
allergic reactions , super infections , epidermolysis , and xerosis cutis were either less frequent or even completely prevented .
in contrast , a randomized study including 86 patients with larynx or breast cancer and radiotherapy dexpanthenol ointment alone had no significant effect on eortc / rtog - score of radiodermatitis , pain and itch . in this study quality of life , super infection and tolerability of irradiation
the topical steroid was significantly more effective than the vehicle in the reduction of inflammation .
there is no such data available for the use of other topical steroids . in erosive radiodermatitis
wet compressions with black tee or eosin 1 - 2% and a short course of hydrocortisone foam have been recommended .
2.1.3 protection against skin infection and antimicrobial peptides there is a close relationship between horny layer barrier function and the risk of skin infection .
a cochrane group analysis has shown that in newborns emollients alone are capable to stabilize the stratum corneum barrier thereby preventing skin infections .
they may also be used as an adjuvant in management of chronic wounds that are at risk of infection or are infected without replacement of systemic antibiotics when necessary .
iodine is contraindicated during pregnancy , in newborns and patients with thyroid disease since there is a significant percutaneous absorption of iodine . among topical antibiotics for the head and neck region mupirocine
the drug exerts an excellent activity against staphylococcus aureus that makes it the first choice for eradication of a nasal staphyloccous reservoir .
the use of other topical antibiotics like neomycine , bacitracine , polymyxine etc . is better avoided since contact - allergic reactions are not uncommon and they are not effective in deeper infections . in these cases
interestingly enough , the new calls of topical calcineurin - inhibitors used for atopic dermatitis reduces the microbial settlement of skin by staphylococci and restores the barrier function , . in recent years research
the human cathelicidin ll-37 is chemotactic for neutrophils , monocytes , mast cells , and t - lymphocytes , causes mast cell degranulation and supports vascularization and re - epithelialization of wounds . in human skin appendages genes like dcd and camp
in addition , such substances are secreted together with the sweat and spread on the skin surface , . in newborns
there is a 10- to 100-fold increase of expression of cathelicidin ll-37 and -defensin-2 compared with adult skin .
this explains as a compensatory mechanism of a still immature immune system in adapting to post - uterine life .
both -defensin-1 to -3 and cathelicidin ll-37 have been detected there . during the recovery of barrier function after wounding or inflammatory disease ( eczema , psoriasis )
the microbial settlement induces antimicrobial control mechanisms : for instance saprophytic yeast malasezzia furfur , but bacteria as well , induce the expression of -defensin-2 in human epidermal keratinocytes , .
in acute wounds surgery is the treatment of choice . in the management of chronic wounds conservative treatments may be successful as well . in chronic non - infected wounds and chronic wounds not at risk of infection the principle of moist wound healing has become the standard . the use of wound dressings is a part of the concept of wound bed preparation - time .
time includes the following aspects : is the tissue viable or necrotic ? in cases of necrosis debridement is necessary either with the by surgery , application of maggots ( biosurgery ) , or enzymatic .
however , the beneficial effect of regular debridement has been proven scientifically only in the treatment of diabetic foot ulcers yet .
i = infection , inflammation in any case of infection and / or inflammation infection control is need either by antibiosis , removal of the bacterial biofilm or disinfection .
in addition the basic pathogenic factors like hypoxia , impaired circulation , metabolic disease and oedema have to be treated as well . in chronic wounds at risk of infection silver - containing wound dressings are useful and effective , .
in particular re - epithelialization of skin is supported by a moist but not wet wound milieu .
the aim of moisture balance is protection against secondary infection and balancing fluid in the wound bed . for this purpose wound dressings with a semi - occlusive surface membrane combined with polyurethane foams , alginates or hydro fibres are useful .
the major effects are improvement of granulation and re - epithelialization , pain reduction , reduction of dressing change frequency and thereby decreasing the nursing time , . in recent years
more and more interactive dressings have been developed , that balance the content and activity of matrix metalloproteinases in the wound fluid , .
the wound edge can be undermined like in pyoderma gangraenosum , hyperplastic like in plantar ulcers or growing onto the wound bed like in healing wounds ( edge effect ) .
the edge effect can also be observed after skin transplant ( i.e. in full thickness reverdin islands ) .
platelet - derived growth factor ( pdgf - bb ) increases the speed of re - epithelialization in diabetic and varicose ulcers .
the basic mechanisms of action are neoangiogenesis and increased fibroblast activity . on the other hand , dermal matrix components like hyaluronic acid
, oxygen partial pressure and other growth factors may stimulate keratinocyte proliferation and migration , .
inter linked hyaluronic acid has been used as wound dressing and as a keratinocyte delivery system in tissue - engineered skin .
 skin exerts a number of essential protective functions ensuring homeostasis of the whole body . in the present review barrier function of skin and its expression of antimicrobial peptides 
 are discussed . 
 barrier function is provided by the dynamic stratum corneum structure composed of lipids and corneocytes . 
 stratum corneum is a conditio sine qua non for terrestrial life . 
 impairment of barrier function can be due to injury and inflammatory skin diseases . 
 therapeutic options are discussed with special emphasis of radiodermatitis and irritant contact dermatitis in patients with hearing device . 
 the use of antimicrobial peptides is illustrated by facial inflammatory skin diseases . in wound healing 
 new developments include biotechnological developments of matrix- and growth factors and tissue - engineered skin substitutes . in everyday wound care of chronic wounds 
 the concept of wound bed preparation ( time ) constitutes the base of successful treatment . 
1. Introduction
1.1 Embryology
1.2 Stratum corneum barrier and skin surface
2. Therapeutic aspects
2.1 Reconstitution of barrier function
2.2 Wound healing - TIME concept