Biomedical Engineering Reference
In-Depth Information
12.4.1
Release criteria for use of cultured skin substitutes
A definitive requirement for the closure and healing of full-thickness skin wounds
is the restoration of the epidermal barrier which protects the body from microbial
infection and loss of endogenous fluids. The barrier properties of human skin have
been largely attributed to the presence of the stratum corneum (SC) in the upper
epidermis.
69-72
In human skin, a water gradient exists across the SC in which
hydration levels are lowest at the surface of the skin and highest within more distal
layers. Studies have shown that surface electrical capacitance (SEC) can be used as
a direct, convenient and inexpensive method of measuring skin surface hydration
which is related to barrier function.
73,74
Within CSS, cells organize by morphogenesis into a tissue analog with expres-
sion of tissue-specific phenotypes to partially restore the structure and function of
skin. Measurement of SEC on CSS is one of two parameters currently being used
for quality assurance in the clinical CSS. SEC measurements, collected over a
2-3 day interval are recorded at four points per graph and averaged. The SEC
values of the CSS must decrease during the interval to be eligible for release for
surgery, with most CSS approaching SEC values for normal human skin by the end
of the interval. In addition, brightfield microscopy of standard histological sec-
tions is used as a qualitative assessment. Histologic evaluations consisted of
examination of CSS prepared for each surgical procedure. CSS epithelia are scored
as either excellent (well organized and stratified epithelium), good (organized and
stratified epithelium), fair (multilayered, continuous epithelium) or poor (discon-
tinuous, heterogeneous epithelium). CSS with a histological score between excellent
and fair along with SEC measurements which decrease from day 6 to 9 are
considered acceptable for transplantation. Poor (non-nucleated epithelium) CSS
are not released for transplantation. These analyses are utilized to ensure that only
optimal quality CSS are applied to the patient.
12.4.2 Surgical considerations
Clinical complications with engineered skin often result from anatomic and
physiologic deficiencies that compromise responses to the wound healing process.
Split-thickness autograft contains a vascular plexus and adheres to a debrided
wound by coagulum, followed by inosculation of vessels within 2-5 days. In
comparison, CSS are avascular and reperfusion results from
de novo
angiogenesis.
The additional time required for vascularization may result in cell loss from
microbial infection and/or nutrient deprivation. Therefore, nutrients and
antimicrobials must be supplied to the CSS while vascularization is taking place.
CSS are delivered to the operating room with a covering of N-Terface, a non-
adherent dressing that is stapled to the wound together with the CSS. CSS are
placed onto the patient in a patchwork fashion by approximating each CSS on the
wound bed until the entire excised wound is covered. For comparison, split-
