Artificial Support and Replacement of Human Organs - Biomimetics: Biologically Inspired Technologies - page 463

18.12 ARTIFICIAL SKIN SUBSTITUTES

Successful application of skin substitutes has been applied widely in the clinical field for a few
decades now. The development of skin substitutes or artificial skin began with growing sheets of
cells in culture media and has progressed to developing complex structures with bi-layered skin that
mimics the human skin. A deeper dermal element is constructed using synthetic epidermis.
Currently there are three approaches used for manufacturing artificial skin, the gel approach where
cells are grown in a gel of extracellular material like collagen; the scaffold approach where porous
scaffolds created from collagen or synthetic material are used to allow cells to be seeded subse-
quently (Jones et al., 2002); the third approach entails, self-assembly, it is still in animal testing
stage and has to await clinical application.
Some of the artificial skin substitutes available are, Alloderm 1 introduced in market in 1992
and is based on treating fresh cadaver skin in which the epidermal layer is removed and cellular
components are destroyed (Bello et al., 2001). The freeze drying of this skin substitute renders it
immunologically inert and hence is not rejected by the recipient (Losee et al., 2005; Terino, 2001).
Integra y approved in 1996 by FDA is another skin substitute available commercially and is made
from cellular collagen and glycosaminoglycans matrix (Winfrey et al., 1999). The dermal compon-
ent is made of collagen and the epidermal element is substituted by synthetic silicon. Dermagraft 1 is
an allogenic dermal substitute, it comprises of a scaffold of polyglactin seeded with allogenic
fibroblasts (Eaglstein, 1998). This is now used to treat skin ulcers and burn wounds. Another
allogenic frozen dermal substitute is TransCyte 1 , which is used as a temporary replacement for
wounds and burns (Noordenbos et al., 1999). It is created by seeding fibroblasts into a scaffold made
from nylon mesh and silicone sheet. Bilayered substitutes are composed of allogenic keratinocytes
seeded on a nonporous collagen gel and covered with a bovine collagen scaffold containing
fibroblasts (OrCel 1 ). They offer the more biologically mimicking skin substitute (Still et al., 2003).

18.13 ARTIFICIAL BLOOD

Inadequate oxygen delivery to the tissues is common sequelae when significant blood loss occurs
due to trauma or surgery. This is commonly treated in clinical practice by administering donated
human blood. However, the availability of donors and the risk of transmission of infections limit this
approach. Fatal reactions can occur due to a mismatch or presence of antibodies in the blood of the
recipient; in addition, repeated blood transfusions can depress the immune function in the host. This
is one of the reasons why an artificial blood substitute is highly desirable since it can avoid these
complications. Two main approaches are used for achieving an artificial blood substitute, bio-
artificial oxygen carriers and totally synthetic oxygen carriers. Bio-artificial oxygen carriers are
hemoglobin-based oxygen carriers and use human, animal, or recombinant hemoglobin. Synthetic
oxygen carriers use metal chelates that mimic the hemoglobin's oxygen binding capacity. Artificial
fluorinated organic compounds can physically dissolve large amounts of oxygen, perflurocarbon-
based oxygen carriers are commonly employed for this purpose. However, in a strict sense they
constitute oxygen carrier substitutes and not blood substitutes since they lack the coagulation
factors and immune cells fighting infection that are essential in aiding coagulation and clot
formation and fighting infection, which can be vital in the patients receiving these therapies.
Examples of bio-artificial oxygen carriers include modified human or animal hemoglobin-based
carriers, stabilized hemoglobin tetramers, polymerized hemoglobin, conjugated hemoglobin, and
liposome encapsulated hemoglobin. Other carriers also include recombinant hemoglobin or from
transgenic studies. Synthetic oxygen carriers include lipid-heme vesicles, hemoglobin aquasoms, and
perflurocarbon based carriers. More detailed review is presented elsewhere (Kim and Greenburg, 2004).