Biomedical Engineering Reference
In-Depth Information
5.1.1
Anatomically Well-Defined Skin Wounds (“Defects”)
The selection of an experimental volume was previously based on four criteria that
will be briefly reviewed and specifically applied to the study of induced skin regen-
eration.
First, the experimental volume is selected based on whether reactants with pre-
sumptive regenerative activity can be inserted reproducibly as well as one in which
the outcome of the experiment will be correctly recognized. The second criterion
is thorough deletion of the non-regenerative tissue that the investigator wishes to
synthesize. The third criterion is the choice of an anatomically well-bounded defect.
Fourth, the exudate flowing away from the defect will have to be contained by use
of a physical barrier that prevents transfer of matter, including microorganisms, to
or from the environment. This barrier should have, if possible, a negligible effect
on the outcome of an experiment in induced regeneration of the dermis (e.g., a
biologically inert cover, such as a thin sheet of silicone elastomer, as cover for skin
defects).
All four of the above criteria for an anatomically well-defined skin defect are
adequately met by the dermis-free defect, also known as the full-thickness skin
wound, prepared by excision of the epidermis, the dermis with all its appendages,
and fat down to muscle fascia, and covered with a silicone film or another cover
that is biologically inert. This defect has been described in anatomical detail in the
rodent (Billingham and Medawar 1951; Billingham and Reynolds 1952; Billingham
and Russell 1956) and in the swine (Carver et al. 1993b). Only data obtained with
the dermis-free defect by various investigators will be presented in this chapter.
5.1.2
Timescale of Observations
Investigators of healing skin defects have had widely divergent objectives. This
has led to a variety of morphological and functional observations over a very broad
range of timescales, extending from about 8 to 720 days. As discussed in Chap. 4,
the core of the healing process is contained between the time that the defect has
been generated (initial state) and closed (final state).The time for wound closure is
typically about 3-5 weeks for a large number of the experimental protocols reported
in the literature. The data presented in this chapter refer to the final state.
Since remodeling of newly synthesized connective tissue, whether scar (Pea-
cock and Van Winkle 1976; Mast 1992) or regenerated dermis (Yannas et al. 1989),
continues for several months, investigators occasionally have reported data much
beyond the time of defect closure. Important tissue maturation processes continue
long after defect closure. Long-term data should therefore be indispensable in es-
tablishing the fidelity of the regeneration process in the long term. The available
evidence suggests strongly that the outcome of the healing process of skin defects
has been largely determined, at least with respect to the incidence of repair or regen-
eration, by the time that the defect has fully closed (final state). Nevertheless, out-
come data that are reported at the time of defect closure (e.g., the fraction of initial
