Medical Programs
Infant Skin Development
Infant skin represents the ideal skin state and condition in
many ways. Although complex, infant skin presents less variability
than adult skin does. The effects of the environment, occupation,
and age are not yet apparent; and the dynamic input of emotional
state to alter the properties of the skin are not well
established.
One of the main goals of the Skin Sciences Institute is to
establish quantitative standards for determining skin condition as
a function of anatomical site, age, and disease. The delineation of
standards characterizing normal infant skin represents an important
part of this mission. Such an understanding is important in caring
for premature infants whose skin is immature and liable to damage
compared to older infants and adults.
The skin of the fetus undergoes important changes during the
latter part of pregnancy resulting in the development before birth
of skin surface which is critical for survival after birth. These
changes are linked to the formation of a water repelling surface
layer and maturation of the outermost skin boundary. One mechanism
underlying these changes is the production by the skin of the fetus
of an oily surface covering called the "vernix" which confers a
hydrophobic property to the surface of the skin in contact with the
amniotic fluid. This oily surface layer, we believe, has an
important effect to promote maturation of the underlying skin cells
and the formation of a skin barrier before birth.
Following birth, a second change occurs with the appearance of
the skin's acid mantle and the development of important defense
mechanisms against infection.
Additional data show racial differences in skin barrier
function. Black infants were shown to have a greater barrier to
water loss compared to white infants. We have shown the ability of
hormones such as steroids given to the mother before birth to
accelerate skin barrier maturation in the infant.
These hypotheses can be tested directly using noninvasive
biophysical methods of measurement. These bedside detection methods
include measurement of surface hydration by electrical capacitance
and transepidermal water loss, skin viscoelasticity, blood flow,
surface pH, and temperature. The environment of the neonatal
intensive care unit offers many advantages for quantifying these
skin surface biophysical properties. Temperature and humidity are
well controlled. Moreover, infants in this environment are cared
for on a 24-hour basis by medical personnel familiar with
skin-based monitoring systems.
Quantitative focus on skin structure and function in the newborn
intensive care unit will provide important measures of neonatal
mortality, morbidity, and cost. Reliable noninvasive bedside
monitoring of skin barrier function will lead to optimization of
nursing care, improved patient outcome, and earlier discharge in
hospitalized infants. Proof of this concept will allow extension to
older patient populations.
Wound Healing, Chronic Wounds / Ulcers
Rapid and effective healing of chronic skin wounds is a key area
of research. Medical benefits from improved healing may
include:
- Reduced long-term debilitation
- Accelerated recovery of function
- Decreased need for conventional skin graft procedures and
hospitalization
Closure of these skin wounds has been demonstrated with refined
skin culture systems. The vascular supply must be sufficient in a
debrided wound to support and stabilize the newly growing epidermal
tissue. However, allogenic keratinocytes do not persist on the
wounds. The mechanisms for maintaining epidermal closure are not
known.
It is hypothesized that allogenic keratinocytes deliver
cytokines to wounds. They promote angiogenesis and deposit basement
membrane on wound surfaces. This promotes migration of autologous
keratinocytes to replace allogenic epithelium and wounds close
indefinitely. Identification of mechanisms involved in this process
is a focal area of the Skin Sciences Institute.
The current model of cultured skin is a collagen-based sponge
filled with cultured human keratinocytes and fibroblasts. It
regenerates connective tissue and epidermis on excised,
full-thickness burns. Engraftment is enhanced by topical use of
essential nutrient formulations and non-cytotoxic antimicrobial
agents.
This cultured cell-biopolymer material will be studied for its
utility to improve healing of selected chronic wounds. Studies are
proposed to utilize biophysical instrumentation to evaluate factors
that contribute to the development of chronic wounds and to assess
healing after application of cultured skin substitutes or other
experimental therapies. Parameters of healing include, but are not
limited to:
- Epidermal barrier
- Mechanical strength of healed skin
- Blood flow in treated wounds
- Rythema
- Pigmentation
Data collected from these studies will become part of the Skin
Measurement Space.
Clinical patients will be selected for local and systemic
factors contributing to the chronic nature of their wounds. Those
patients with optimal vascular condition will receive allogeneic
cultured skin or conventional treatment. Engraftment of skin
substitutes (incidence of failure, degree of infection, time to
wound closure, need for reconstruction) and long-term results
(function, contraction, and cosmesis) will be evaluated.
Positive results may lead to reduced morbidity from chronic
wounds, improved materials for plastic and reconstructive surgery,
and greater understanding of mechanisms of wound healing.
Pigmentation
Pigmentation of humans (i.e., skin complexion and hair color) is
extremely variable and under the control of many genetic and
environmental factors. Both complexion and hair color result from
melanin pigments which are synthesized by the melanocyte and
subsequently transferred into keratinocytes.
One of the primary goals in studying pigmentation is to
standardize categories of skin pigmentation using noninvasive
biophysical instruments. Such standardization permits correlation
of these categories with biological, biochemical, disease,
therapeutic, and cosmetic properties of the skin and hair.
We propose to evaluate and understand how the melanocyte and
pigment participate in the following areas:
- Protection of skin from the cancer-causing effects of
sunlight
- Blocking the effect of free radicals which cause aging of the
skin
- Improvement in the process of wound healing
- Influence of the immune response in the skin
- Damage that results as a response to cosmetics and
environmental chemicals
Hydration
Appropriate hydration of the stratum corneum is essential for
good skin condition and health. Understanding the mechanisms of
skin hydration and measuring this property in a noninvasive fashion
are important for developing technologies that optimize the
contributions of moisture to skin condition.
Mechanisms of hydration are believed to involve both the stratum
corneum lipids and the natural moisturizing factors (NMF), i.e.,
the low molecular weight metabolic products. The mechanical
properties of the stratum corneum are highly dependent on the water
content. Well-hydrated skin is much more elastic and extensible
than dry skin.
Treatment and materials that increase skin elasticity could do
so by:
- Increasing the stratum corneum water content
- Plasticising the stratum corneum proteins through direct
interactions
- Both mechanisms
In vitro and in vivo techniques have been used to measure skin
elasticity and the influence of various compounds.
Effect of Race on Skin Condition
An increasing base of information indicates that there are
differences between black and white skin. Variations in color
importantly influence the skin's response to sunlight.
Black skin produces more melanosomes that are larger and more
well dispersed than those in white skin. Black skin absorbs more
solar radiation, but has a lower incidence on sun-induced skin
cancer.
The condition of black and white skin was evaluated with a set
of noninvasive biophysical measurements, including barrier
integrity and function, mechanical properties, sebum production,
and surface microflora. Differences in black and white skin were
observed in the following:
- Stratum corneum barrier integrity was significantly lower on
the cheeks and legs in black subjects compared to that in white
subjects
- Black facial skin had higher hydration, elasticity and sebum
production values
- The desquamation index was higher in white subjects on the
cheeks and forehead, whereas, dryness scores were significantly
higher for black subjects on the legs
Though no overall significant differences in the density of
Propionibacterium acnes were found between the two races, the
density of P. acnes was significantly higher on the cheeks for
black subjects in the 18-30 age group than white subjects in the
same age group. Though the hydration level in black subjects varied
in the sites evaluated, transepidermal water loss seems to be lower
in black subjects irrespective of the water content and sun-induced
damage. This supports the idea that black skin has a superior horny
layer barrier.
Effects of Drugs and Cosmetics
Identifying and understanding the effects of drugs and cosmetics
on skin structure and function using noninvasive biophysical
measurements is a key research area. Previous studies have
indicated that changes in skin structure and function occur long
before the changes are visible. These measurement techniques are
invaluable in detecting skin breakdown and susceptible skin early
and with sufficient time for corrective treatments to be
implemented.
Methods have been established to evaluate the effects of
materials, such as liposomes, designed for targeted or topical drug
delivery. These methods serve as model systems for evaluation of
new technologies, such as trans-retinoic acid encapsulated in
liposomes. Effectiveness of new actives and ingredients can readily
be assessed with these techniques.
Noninvasive Skin Monitoring and Imaging
Evaluation of skin characteristics with noninvasive monitoring
techniques is a fundamental area of interest and development for
The Skin Sciences Institute. A wide variety of methods and
instrumentation are used in basic and clinical research
projects.
Epidermal hydration and barrier integrity are assessed by
measuring surface hydration, transepidermal water loss, water
binding capacity, water holding capacity, surface hydrophobicity,
and corneocyte size.
Vascularization and inflammatory response are evaluated by
measuring blood flow in both static and dynamic situations.
Mechanical properties, including elastic deformation and recovery,
are routinely measured.
The Skin Measurement Space project utilizes multiple assessments
to determine overall skin condition as a function of age, race,
body site, and presence of damage or disease. The Instrumental
Capabilities are listed.
Optical Imaging
The knowledge-based interpretation of medical images has
recently emerged as a promising area of research with potential
application for helping the physician in improving diagnoses
through computerized analysis. An example of computerized analysis
and interpretation of biomedical images is the evaluation of images
of skin lesions for detecting melanoma.
An optical instrument, called the Nevoscope, was developed to
obtain three-dimensional views of a skin lesion transilluminated
through a fiber optics directed visible light source. Appropriate
image processing and analysis is required to extract all features
of diagnostic information and then to analyze them intelligently to
provide quantitative information to the physician in making the
final diagnosis.
At the most sophisticated level, image analysis techniques such
as three dimensional reconstruction and texture and color
segmentation will provide quantitative information about important
diagnostic parameters. This approach can also be applied to the
evaluation of other skin features, both in the healthy and damaged
states. This method for the quantitation of skin characteristics
can be used to assess the effects of products and therapies on the
skin, both in a comparative context and as a function of time.
