“Whenever you see inflamed skin, regardless of cause, the stratum corneum is leaky and permeable. 
But, if you repair the stratum corneum, that tells the underlying tissues that they
don’t have to 
keep reacting like there’s danger in the environment.”

Albert Kligman, M.D., Ph.D.; 1919-2010



Corneobiology refers to a broad range of experimental studies focused on the anatomy, physiology and biology of the stratum corneum, focused specifically on the horny layer that is very unique to human beings.1 

This science encompasses numerous studies that deal with immunology,endocrinology, neurobiology and psychology. Studies as early as 1964 showed that the horny layer membrane was a coherent tissue of cornified cells (corneocytes) and was not as previously depicted “an amorphous filamentous graveyard of degenerated keratinocytes.”2 In his earlier research and confirmed by Professor Peter M. Elias and other prominent scientists, Dr. Kligman articulated that the stratum corneum (SC) has many diverse functions and that it is very much alive.

AZ-fig-1 Science of the Skin | Corneobiology | Understanding the skinIt is a key player in numerous biological functions and should not be overlooked when assessing skin conditions. Corneocyte structures are bilaminar membranes linked by corneodesmosomes that are tightly bound and separated by narrow intercellular spaces that form a coherent membrane until they reach the upper surface where they progressively undergo a desquamation process.3 The adaptive capability of the SC regulates several key functions: permeability barrier formation, desquamation, maintenance of mechanical integrity,and generating osmotically active humectants (Natural Moisturizing Factors). Additionally, it is also confirmed that the SC is an enriched environment of cytokines and can end up being an inflammatory tissue if its contents are extruded into the dermis as in the case of acne pustules.4 (See Figure 1)


Corneobiology has revolutionized topical therapies for marked improvement for dermatological skin conditions such as atopic dermatitis and other barrier disorders. Corneotherapy aims at the recovery of the SC to improve the function of the skin barrier and overall homeostasis (balance) of the skin. A healthy and functioning skin barrier provides overall protection against dehydration, penetration of germs, allergens, irritants, oxidative radicals and ultraviolet radiation.5 It also supports a gradual healing of inflammation and other skin problems since the external causative agents are blocked through an intact skin barrier.6 Kligman coined a term called “outside-in-therapy” meaning that the long-term effects in the epidermis after a therapeutic treatment of the horny layer with appropriate substances could help repair the underlying dermal structures. (See Figure 2)

AZ-fig-2 Science of the Skin | Corneobiology | Understanding the skinPreventative corneotherapy requires avoidance of skin care products with harmful substances such as irritants and allergens, fragrances, preservatives, colors, emulsifiers and occlusive substances. Formulations should be biologically mimetic, meaning that they imitate the dermal membrane structures. The natural structures within the skin’s bilayers for example consist of water, fatty acids, triglycerides, ceramides and cholesterol. The skin can be enriched through natural mimetic ingredients such as linoleic acid (omega-6) in the form of specialized delivery vehicles such as liposomes that merge easily into the skin’s natural barrier layers that allow active ingredients to penetrate effectively supporting the formation of Ceramide I.
Nanoparticles that are specifically liquid biodegradable and encapsulated into bodes of phosphatidylcholine have similar composition to that of a liposome and are spherical membranes that mimic the skin’s natural barrier. Included in this mix are antioxidants (vitamins A, C, E, superoxide dismutase) and other ingredients (evening primrose oil, boswellia, echinacea and more) that support the epidermal structures.7 Specific skin conditions can be treated with focused actives. Newer delivery system such as liposomes and nanoparticles (derived from phosphatidylcholine) allow for actives to be carried directly to the cellular layers very efficaciously without irritation.8 When choosing raw materials for skin care formulations, we have to “think” like a keratinocyte or the fibroblast in order to determine what constituents are required for optimum function. 

Old Thoughts … New Thoughts

What we know in 2012 – survival for a healthy body and appearance is dependent upon our ability to have flexibility in adjusting to numerous environments. The process of differentiation and keratinization within the epidermis is a strategic process whose purpose is to build a strong barrier defense system for the skin. The skin’s permeability barrier and internal bilayer structures allow for survival of potential risks in an everchanging environment. 

The complexities of the SC between its structural components and adaptive physiological functions are maintained on a daily basis. It can detect even the

slightest of environmental changes, both within and outside of its structures. Skin appearance relies on its normal ability to carry out immune surveillance and response to antimicrobial functions, TEWL (trans-epidermal water loss) adjustments, and other internal tasks.  Acute assaults to the SC include overexposure to UV,wounding, disease, skin care treatments (microdermabrasion,laser rejuvenation, excessive and strong peels), and any aggressive substances in products. The skin incorporates several adaptive mechanisms to restore itself as quickly as possible to structural and functional integrity. It readjusts the TEWL and also increases its lipid barrier during a rebuilding process. When the corrective mechanisms become overly compromised, such as the pH balance along with other deeper structural disturbances, it begins to visibly manifest in the form of irritated, dry and wrinkled skin – as well as the onset of glycation. When these conditions are not corrected at the beginning, biological aging of cells can easily surpass chronological aging.

Shifting paradigms for a new understanding of the skin; as we explore the skin in today’s modern world, we also have to be aware that we have the ability to study the skin in a new light. Let us review some older concepts.

The Stratum Corneum is Dead

As early as 1964 and a thinking process that continued on up through the latter part of the 20th century is that the SC is a dead, inert, passive, metabolically lifeless membrane. It was compared to a plastic wrap-like impermeable shroud protection from chemical and exogenous (external) threats.22 

Unfortunately, marketing practices have continued this concept as well as implanting other misconceptions about the skin. This notion has also driven inappropriate treatment modality choices that are still continued in practices, as well as what may be taught in our schools. Given the role of the SC and the keratinocytes within the epidermis, recent research has disclosed that over-processing the skin may prove to add more stress to an impaired barrier function. The first rule of order is to support repair of the SC for several weeks prior to proceeding to more invasive treatments.

New research and discoveries of innovative ingredients and delivery systems unveil a greater understanding of how we can repair the SC and underlying structures. It sends a strong message to the practitioner that one must maintain the integrity of the epidermis at all times. Conditions such as rough, scaly, brittle, cracked or itchy skin become red flags, which beckon us to explore deeper for underlying causes.
When we perform peeling treatments, microdermabrasion, laser rejuvenation, and other more invasive procedures, one has to be aware that these treatments interfere with the normal skin functioning since it sends a loud immune response signaling that there is interference with its normal functioning. Given that the keratinocytes are critical for communication, removing too many of them adds more stress.

The Skin is Dehydrated

During a consultation, an easy conclusion is to assume that what we are viewing is a sign that the skin is “dehydrated.” While this may be very true to a certain degree, there are other considerations to evaluate including the client’s age,lifestyle and a more in depth assessment to determine the biological age of the cells and the actual level of cellular damage. 
Let us explore the meaning of TEWL. Trans-epidermal water loss is the quantity of water that passes from inside the skin to the surrounding atmosphere. Damage to the skin through injury, infection, burns, many skin treatments and other assaults will impair the functioning of the epidermis and its ability to maintain good water balance.

It is not enough to say that the skin is dehydrated and base a remedy strictly on this observation. Instead we should explore several parameters from a newer paradigm that provides skin indicators based on texture, secretions and color. Within each indicator are parameters relating to skin conditions and understanding their effect on cells and systems. A good diagnostic tool, a skin scanner and the client’s health profile all provide vital information that uncovers possible risk factors and the probability of outcome regarding a treatment program.

Water Movement Within the Skin

The systems that are directly involved with skin secretions within the body are:23

  • Acid mantle
  • Epidermal lipids
  • NMF (natural moisturizing factors) and TEWL
  • Sebaceous secretions
  • Glycosaminoglycans
  • Lymphatic system

We will focus on the structures within the epidermis that are responsible for moisture retention and balance. All tissue must maintain sufficient water balance for proper function including the ability to adjust within one’s environment.24 Balanced hydration is based on the following facts.25

  • Relevant ambient humidity;
  • The retention power of the SC;
  • The amount of water transmitted from the inner to the outer layers of the skin;
  • The time span involving how long water moves from the lower skin layers to the upper regions of the SC.

Relevant Ambient Humidity

Skin hydration depends on a functioning natural moisture factor, the skin barrier and balanced sebum. The skin continuously adjusts between outside atmospheric conditions and the temperatures maintained inside our homes and place of work. Depending upon where you live – arid regions such as high dessert, mountainous or tropical regions – the skin transitions with the atmospheric changes in order to maintain its natural moisture levels. Extreme changes of relative humidity may begin to stress the skin. It begins to have difficulty maintaining internal moisture levels. Air conditioning and heating systems change indoor atmospheric humidity. These transitions can easily become skin stressors as it continuously adjusts between inside and outside atmospheric conditions.

In dry conditions, TEWL is much greater. It stands to reason that facial moisturizers may not be as efficient when there is very low humidity since there is a characteristic threshold for every moisturizer.26 It becomes inefficient and releases the moisture in the surrounding air.

The epidermal tissue must remain as impermeable as possible with the exception of allowing enough water to maintain hydration at the outer layers of the SC as well as supporting the enzymatic processes that facilitate corneodesmosomal degradation and desquamation. The water content within the skin supports flexibility and the ability to adjust to relative humidity (internal and external). The ability for the SC to maintain its water content is dependent upon three things: the thickness of the SC, the organizational and compacting characteristics of the corneocytes that allow them to function properly, and the presence of very hygroscopic (NMF) compounds largely found within the corneocytes.27 Moreover, adequate water consumption on a daily basis is very important.

NMF – Multi-Function Qualities

The natural moisturizing factors (NMF) within the skin are composed primarily of amino acids, PCA, and other compounds. The hygroscopic (ability to attract water) properties of NMF greatly contribute to the corneocytes’ ability retain moisture.28  NMF also facilitates enzymatic processes including the dissolution of the desmosomes.29 NMF consist of amino acids that are not only responsible for the moisture content of the skin, but also for the osmolytic balance (movement of water across a cell membrane). NMFs correct imbalances in the osmotic pressure of the skin. Furthermore, the amino acids and the urea of the NMF protect against ROS (reactive oxygen species – free radicals).30

Skin Moisturizers and Humidity TEWL increases when the air becomes dryer. Balancing the skin barrier during changing environmental conditions becomes challenging. Moisturizers play a significant role by increasing skin elasticity as well as smooth the skin. They also become very inefficient in arid climates. Instead of releasing moisture into the skin, it evaporates into the dry circumambient air.31 Even when we reapply, it is not enough. Wellpenetrating moisturizers that contain ingredients such as urea,glycerin and glycols just cannot compensate due to their low molecular weight.32 An ideal moisturizer for dryer climates is to use hyaluronic acid, CM-Glucan, and other agents that form an additional barrier to prevent TEWL on the skin surface.

When humidity gets even lower with higher temperatures, the quantity of lipid substances (including phytosterols in skin care formulations) should be increased. Precaution should be taken when recommending for cases of rosacea skin conditions. Reapplication with too much moisture on this type of skin may lead to irritations including increasing the risk of creating an environment that encourages the growth of anaerobic bacteria that further perpetuates skin irritation.33

Pigmentation and corneotherapy

AZ-fig-3 Science of the Skin | Corneobiology | Understanding the skinPigmentation is a growing concern among many skin types and the approach to correction must be weighed carefully. There are numerous reasons for pigmentation disorders including UVR exposure and sunburn history, essential fatty acid deficiency, aging and cellular senescence, DNA damage to the melanocyte, hormones and medications.34

There is no simple remedy for this condition. Establishing the leading cause is paramount before beginning a treatment program. Melanocytes are slow cycling and long lived. After the age of 16, the regenerative cycle of these cells become limited. Beginning in our 30s and 40s, the density of active melanocytes is reduced by 10 to 20 percent every 10 years.35,36
Furthermore, during embryonic development, 
there are 120 genes involved in transfer from the neural crest to the eyes, hair and skin. This also means that there could be 120 reasons for something to go wrong, such as seen in a birthmark. Establishing leading causes of pigmentation requires a close analysis of the client’s history and a realistic assessment regarding how much repair is even possible.
Some conditions may require medical intervention to rule out a medical condition. It is safer to take a progressive approach to correction including a careful choice of treatment and products and awareness of newer research concerning controversial ingredients.


Earlier scientific findings and manufacturing of topical remedies have progressed throughout the past 25 to 30 years. The more we understand the dermal sciences and the functioning of the keratinocytes and cells throughout the entire dermal structures, the easier it is to make better decisions. Following the principles of corneotherapy provides a common sense approach to preserving the integrity of the skin and successful treatment.




1 Kligman, A.M. (2011) Corneobiology and Corneotherapy – a final chapter. Intl Jour of Cosmetic Science, 33, 197-209 (written from his notes posthumously)
2 Kligman, A.M. (2011) Chapter 3: How the Dead Stratum Corneum Became Alive. Skin edited by Elias and Feingold. Taylor and Francis, NY, London. p 15
3 See Ref 2, pg. 20
4 See Ref 1 p. 199
5 Lautenschläger, H. (2007) Applied corneotherapy and skin care: Guidelines for the anti-aging treatment. Äesthetische Dermatologie (3), 8-16
6 ibid
7 ibid
8 Lautenschläger, H. (1999). Ceramides – lipids with multiple assignments. Kosmetik International (11, 124-126)
9 Vitamin A. Linus Pauling Institute, Oregon State University. Retrieved from http://lpi.oregonstate.edu/infocenter/vitamins/vitaminA/
10 Thiele, J. J. (2006) Chapter 23: The Epidermal Antioxidant Barrier. Skin Barrier, edited by Peter M. Elias and Kenneth R. Feingold. Taylor and Francis, NY,
London. p. 379
11 ibid, p. 382
12 ibid, p. 381
13 Bardan, A, Nizet, V, Gallo, R. (2004) Antimicrobial peptides and the skin.
Expert Opin. Biol. Ther. 4(4):543-549 Article retrieved from http://nizetlab.ucsd.
14 Nardo, A., Gallo, R. (2006). Chapter 22: Cutaneous Barriers in Defense
Against Microbial Invasion. Skin Barrier, edited by Peter M. Elias and Kenneth
R. Feingold. Taylor and Francis, NY, London. p. 364
15 Elias, P.. M., Steinhoff, M. (2008) “Outside-to-Inside” (and Now Back to
“Outside) Pathogenic Mechanisms in Atopic Dermatitis. J Invest Derm 128,
1067-1070. doi: 10.1038/jid.2008.88 www.jidonline.org
16 See Ref 14 p. 365
17 See Ref 14 p. 365
18 Lautenschläger, H., Jabs, U. (2010) Radio waves and boswellia nanoparticles – a new derma rejuvenation therapy: Consideration on skin physiology and skin aging from the biochemical point of view. Ästhetische Dermatologie (mdm) Verlag) (4), 18-25.
19 Haftek, M., Simon, M., Serre, G. (2006) Chapter 11: Cornedesmosomes: Pivotal Actors in the Stratum Corneum Cohesion and Desquamation. Skin Barrier, edited by Peter M. Elias and Kenneth R. Feingold. Taylor and Francis, NY, London. p. 173
20 Pugliese, P.T. (2006). Advanced Professional Skin Cary – Medical Edition. Topical Agent, Bernville, PA. P. 182
21 Bickle, K. MD, Roark, T.R. MD, Hsu, S. MD (2002) Autoimmune Bullous Dermatoses: A Review. American Family Physician, Vol 65, No. 9 Retrieved from www.aafp.org/afp
22 Kligman, A.M. (2006) Chapter 3: A brief history of how the dead stratum corneum became alive. Skin Barrier, edited by Peter M. Elias and Kenneth R. Feingold. Taylor and Francis, NY, London. pp 15-24
23 Barrett-Hill, F. (2005) Advanced Skin Analysis. Virtual Beauty, New Zealand. p. 102
24 Rawlings, A.V. (2006). Skin Barrier: Chapter 24, Sources and Role of Stratum Corneum Hydration, Chapter 24. Taylor & Francis Group, NY, London.
25 See Ref 24
26 See Ref 24
27 Elias, P.T., Feingold, K.R. (2009) Skin Barrier. (23) Taylor & Francis, New York. p. 399
28 ibid p. 407
29 ibid p. 407
30 Lautenschläger, H. (2007) Applied corneotherapy and skin care: guidelines
for the anti-aging treatment. Äesthetische Dermatologie (3), 8-16
31 Lautenschlager, H. (2011) Moisturizers in skin care. Beauty Forum (3), 86-88 and 2011 (4) 46-69
32 ibid
33 ibid Ref. 31
34 Barrett-Hill, F. (2012) Course: Advanced Skin Analysis.
35 Alam, M., Ashish, B., e al (2004 Cosmetic Dermatology for Skin of Color. McGraw-Hill Medical, NY. P 1-8
36 Barrett-Hill, F. (2005) Advanced Skin Analysis. Virtual Beauty, New Zealand.

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