Discuss the Epidermal Barrier Function and its relevance to three aesthetic techniques
Dr MJ Rowland-Warmann BSc BDS MSc Aes.Med. PGDip Endod. MJDF RCS (Eng)
For her MSc Masters Degree in Aesthetic Medicine for the Queen Mary University of London. Â The following essay received a Distinction – the highest mark awarded.
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The skin makes up approximately 16% of total body weight and is the largest organ of the body.  Functions of the skin include prevention of water loss, protection from the environment, immune and sensory function, regulation of body temperature and vitamin D synthesis (4,6).
Epidermis
The epidermis protects internal organs from both mechanical and chemical insults such as trauma, UV radiation and attack by microorganisms, but also regulates transepidermal water and electrolyte movement (1).  The Epidermis consists of stratum basale, stratum spinosum, stratum granulosum and stratum corneum in order from the deepest to the uppermost. It is a physical, chemical, biochemical and adaptive immunologic barrier (2). Cells are shed on average every 28 days, which serves to continually renew the skin.
Stratum corneum
The end point of differentiation of the epidermal layers is arguably for its most important function in producing the stratum corneum (SC), a densely packed layer which serves to provide the so-called epidermal barrier (8).
The keratinocyte is the main cell found in the epidermis and cycles upwards from stratum basale to SC, becoming increasingly differentiated and flattened (2,6). The final maturation of keratinocytes turns them into protein-enriched corneocytes in the SC, which are dead cells containing keratin filaments and water surrounded by protein and lipid layers.
The lead role in epidermal barrier function is performed by SC. Corneocytes serve as moisture reservoirs, mechanical protection and structural support for the skin and underlying tissues. They are surrounded by a lipid matrix, containing ceramides, cholesterol and free fatty acids which forms a barrier contributing to antimicrobial, antioxidant and skin permeability functions and preventing water loss and thus dehydration (1,5,8). The lipids of the SC assist enzyme function (10). Intercellular spaces also contain keratin filaments, increasing the framework’s resilience. Any alteration of the epidermal differentiation or lipid composition results in changes to the barrier function, such as fatty acid deficiency reducing it (2,5,8).
Activity of the SC is pH dependent, with changes resulting in desquamation. Barrier function is enhanced in acid conditions, down regulating lysosomal enzymes involved in desquamation but is also important in preventing infection by providing the acid mantle (8). The desquamation process is normal, and prevents bacteria from colonising the SC. Changes in the pH of the skin, which can be brought about by external influences such as soaps, cosmetics and antibiotics can alter the skin’s behaviour and cause skin conditions such as dermatitis, acne and thrush.
Epidermal components
Langerhans cells, Merkel cells, melanocytes and lymphocytes are also found in the epidermis. Langerhans cells serve an immune function. Merkel cells assist the sensory nerve function. Melanocytes produce pigmentation protecting the skin from UV radiation. Lymphocytes are active components of the cellular immune response (2). Whilst not a direct barrier, these cells all serve to ensure the correct functioning of the SC.
Dermis
The dermis supports epidermal structure with connective tissue, collagen and elastin, lymphatics and vascular structures. Fibrobasts are the main cells of the dermis, synthesising collagen and elastin. The layer of subcutaneous fat immediately below the dermis, or hypodermis, insulates the body, protects from mechanical shock and is vital in energy metabolism. The supporting structure to the epidermis, the dermis displays changes with age, affecting the composition of both structures (4).
Ageing
The two types of ageing are chronologic and photoageing. Both affect the skin, causing dryness, wrinkling, atrophy and laxity. Both epidermis and dermis thin with age and collagen decreases (12). Simultaneously the SC thickens. With age, glycosaminoglycans (GAG), collagen and elastic fibres decrease/degenerate. With photo ageing, melanin becomes irregularly distributed giving rise to hyperpigmentation, actinic keratoses, wrinkles and leathery skin (16).  Lipid synthesis and content also decreases with age and the skin’s pH increases. This decreases the skin’s barrier ability by disrupting the lipid layer and protection against infection (3).
Aesthetic Procedures
The desire to look and feel good has caused a surge in aesthetic procedures while maintaining healthy and youthful looking skin is crucial. Skin that maintains its youthful characteristics is able to aid protection of the body and aesthetic procedures are aimed at improving epidermal barrier function with age.
Cosmeceuticals
The term ‘cosmeceuticals’ was coined by Kligman, combining aesthetic needs and function of products, where cosmetics and pharmaceuticals combine to have a positive effect on skin (11).  Cosmeceuticals are the ideal gateway for the concerned individual who is looking to reverse signs of ageing without the need for invasive procedures. It places individuals on a path to self-improvement and skin awareness which oftentimes leads to an acceptance of further aesthetic procedures.  There are many compounds used in cosmeceuticals today that have beneficial effects on barrier function and this enables these products to have an advantage over commonly available lotions.
Bases
Bases are used to stabilise and transport substances in cosmeceuticals to their active sites. Emollients, such as petrolatum and lanolin, are barrier creams penetrating the SC and acting on corneocyte cohesion (8). Paraffin, soy bean oil and petrolatum are occlusive preparations, which inhibit transepithelial water loss. Glycerol, hyaluronic acid and urea increase the SC’s hydration and are known for their moisture-retaining properties (11). They simultaneously act as exfoliants increasing desquamation (8). The base itself is useful in increasing the hydration of the upper skin layers, but combining it with further active substances improves a barrier function.
Antioxidants
Skin-damaging free radicals, released in response to oxidative stress, are cause by factors including sunlight, smoking and pollution (13). Antioxidants, including vitamins, coenzymes and plant extracts, reduce oxidative stress from destructive free radicals in tissue. They influence fibroblast metabolism, decreasing the activity of the collagen degrading compounds, Matrix metalloproteinases (MMP).
Vitamin C is an antioxidant which stimulates dermal connective tissue metabolism by induction of type I and III collagen, while increasing ceramides in the SC, contributing to enhanced barrier function (11).  Niacinamide is an antioxidant which regulates cell metabolism. It increases the synthesis of free fatty acids, ceramides and cholesterol which serves to improve the lipid envelope and decreases TEWL (11). Niacinamide also boasts anti-sebum and anti-inflammatory actions, decreasing pore size and acting further to reduce TEWL, making it useful in treatment of acne.
Other antioxidants found in cosmeceuticals are vitamin E, which increases moisture retention and promotes healing of the epidermis, and green tea extract, which stimulates keratinocytes in the epidermis (13).
Cell Regulators
The vitamin A group of compounds, including retinol and tretinoin, are the gold standard treatment for photoageing. They normalise cell keratinisation by modulating cell differentiation, induce collagen synthesis and reduce degradation of collagen by downregulating MMP (11). Other actions of vitamin A compounds are decreased corneocyte adhesion, reducing the thickness of SC, and promoting epidermal hyperplasia, thickening the epidermis. The latter results in an increase in Langerhans cells, collagen and elastin. Retinoids increase turnover of the epidermis, disrupting the contact between keratinocytes and melanocytes to cause depigmentation and are the only substances that can truly repair photoaged skin in cosmeceuticals (13)
Alpha-hydroxy acids (AHAs)
AHAs are commonly used in cosmeceutical preparations in order to stimulate turnover of the SC, their keratolytic action reducing the adhesion of keratocytes. They include malic, lactic, tartaric and citric acids, of which glycolic acid is the most commonly used (11).
The stimulation of targeted pathways in skin regeneration by cosmeceuticals is remarkable and can provide great benefit to the skin’s functioning and wellbeing of the patient. It is important to begin treatment of ageing with methods that are non-invasive and atraumatic in order to build patient confidence in aesthetic medicine. Cosmeceuticals are invaluable in this respect.
Peels
Chemical peels have gained popularity due to their simplicity, versatility and effectiveness at combatting photoageing. Peels have been used since 1871, when Fox used Phenol peels to lighten skin, and have evolved into the hundreds of varieties we see today. They are useful to decrease the signs of photoaging caused by a thickened SC and thinning epidermis with irregular melanin distribution (16).  Peels cause destruction of the outer layers of the skin to increase exfoliation of some or all of the epidermis and dermis, causing regeneration and skin tightening (21).
If you are a patient looking for chemical peels at Smileworks then follow the link here to our main page: chemical peel Liverpool.
Peels can be classified as follows:
- Very Superficial – SC is destroyed to below stratum granulosum.
- Superficial – epidermis destroyed to basal layer.
- Medium – destruction to part of papillary dermis
- Deep – enhanced destruction to the papillary dermis (16)
Destruction of skin layers has implications for the epidermal barrier and damage to the epidermis and dermis carries risks and benefits. For noticeable improvement, a peel must reach into the layer of the skin that exhibits damage, whilst respecting the overarching architecture of the skin.  The goal of peels is to regenerate the epidermis rapidly – usually within 7 to 10 days, and cause slower, more long-term regeneration in the dermis (16).
Alpha-hydroxy Acids (AHA)
AHAs such as glycolic, lactic or malic acid cause superficial exfoliation and thinning of the SC by causing dyscohesion of overly-sticky keratinocytes in the stratum granulosum. Compaction of the SC increases GAG in fibroblasts and keratinocytes, increasing hydration of the skin and improving skin tone (22). AHAs have keratolytic, ant-inflammatory and antioxidant properties which increase the level of enzyme activity in the SC, causing epidermolysis (21).
Beta-hydroxy Acids (BHA)
Salicylic acid, a beta-hydroxy acid, is used to exfoliate the epidermis in superficial peels without causing inflammation. It reduces corneocyte adhesion, resulting in thinning of the SC, increasing epidermal turnover and thickening the epidermis.
Trichloroacetic acid (TCA)
Applied layer by later, TCA penetrates the skin and is neutralised by coagulation of skin proteins (19). This restores keratinocyte polarity and increases type I collagen content (17). There is marked desquamation after the peel, disrupting epidermal barrier function. It is important to aid regeneration after TCA peeling with adjunct use of cosmeceutical preparations to improve the skin’s response. Regeneration in medium depth peels is from adnexal structures such as hair follicles, which are lined with epithelium (21).
Phenol
Phenol peels exert their effects by causing epidermal necrosis by keratocoagulation. The epidermis is separated from the dermis by an inflammatory exudate (18,19). Phenol peels are the deepest peels and can cause significant damage. After application the epidermal barrier is destroyed and the resulting improvement is seen by its effects on the deeper layers, causing a response to injury and fibrosis of the papillary dermis with collagen formation. The upper layers of the skin must reform and the healing period leaves the skin exposed to increased risk of damage. If the adnexal structures that promote healing of the skin are damaged, the healing response will be poor, resulting in scarring.
Peels stimulate a response proportional to the damage caused – in superficial peels the epidermis is stimulated, whereas deeper peels stimulate the dermis, causing more long term effects by stimulating the contraction of collagen (23). Peels are more invasive than topically applied treatments and by virtue of this fact, cause more significant improvements in skin function and appearance.
Microneedling
The belief is that tight, thick skin is youthful and whilst we have an arsenal of aesthetic procedures at our disposal, microneedling, introduced in 1997, has arisen with the intention to keep the epidermis intact. Whilst peels destroy the epidermis, microneedling can bring about collagen induction without scarring and risks associated with peels (23).  Normal skin has a lattice network of collagen. In scar reactions, also noted in the response to peels, fibroblasts produce collagen in a parallel orientation, bringing about about tighter skin by fibrosis (23, 24).
Microneedling, or percutaneous collagen induction, disrupts collagen strands in the papillary dermis to stimulate collagen and elastin formation. Healing is rapid as the epidermal barrier is not destroyed. Tiny puncture wounds in the skin make a scatter of GAG in the epidermis, which enables better binding of GAG to water, increasing skin hydration (26).
Post-procedure, the wound healing cascade is started. Trauma and minimal bleeding from microneedling engages platelets and neutrophils to alter keratinocyte and fibroblast activity. Thereafter, monocytes cause epithelialisation and production of type III collagen, elastin, GAG and proteoglycans. Maturation of the site due to growth factors causes further collagenesis and the conversion of type III collagen to type I by MMP and hence tightening of the skin (23). Due to the increase in keratinocyte and fibroblasts, the epidermis is thickened, especially the stratum granulosum (25). Growth factors play an important role in the type of collagen formed – TGF-B3 is thought to be involved in the key part of healing in microneedling that directs normal collagen formation rather than the scarring seen often in peels with activation of TGF-B1 (25)
For best results, microneedling is combined with products commonly found in many cosmeceuticals. Topical vitamin A improves collagen production, promoting TGF-B3 which is important in normal collagen formation (23). Vitamin C maximises collagen production and has been shown to increase the thickness of the epidermis by 140% over conventional microneedling (24, 26)
The key idea in microneedling is improvement of the epidermis without injury to the barrier and achievement of an improvement in the connective tissue substructure of the skin.
Conclusions
The epidermal barrier performs essential protective functions of the skin but also mirrors the stresses that the body is subjected to during life.  Aesthetic procedures must consider the skin as not simply an envelope but an integral part of rejuvenating procedures. Rejuvenation of the skin will oftentimes have as profound an effect as any toxin or filler treatment and will certainly aid in promoting better health.
The interaction of cosmeceuticals, peels and microneedling will produce excellent results and it can be argued that none on their own will be as beneficial as the combination of all three. Priming the skin with a suitable topical preparation prior to peeling, and stimulating the collagen production with microneedling thereafter will bring about an extensive improvement that is beneficial for appearance and epidermal barrier function.
Focusing on the treatment of skin to achieve a compacter stratum corneum and a thicker epidermis which ensures improved cell quality and better turnover will result in a skin that is leaner, meaner and better suited to withstand the stresses that daily life throws our way.
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