Biomedical Engineering Reference
In-Depth Information
3.10 New Biomaterials in Transplanted LESC Therapy
The field of tissue engineering in general has rapidly expanded in recent times
combining materials design and engineering with cell therapy and LESC therapy is
no exception. As mentioned previously, the favoured carrier material for LESC
transplantation has been amniotic membrane. Its use as a topical bandage for
surgical wounds, ulcers or burns has exploited its natural anti-inflammatory, anti-
angiogenic, anti-microbial and anti-viral properties in general medicine as well as
ophthalmology (reviewed in [
50
]). However, as growing numbers of new materials
with tuneable properties become available, the limitations of amniotic membrane
as a substrate become increasingly apparent. As expected with any biological
material there is considerable variation between different donors, often dependent
on donor age, but also in the case of amniotic membrane there is even variation
within the same donor depending on whether the material is taken from a distal or
proximal location [
51
]. The processing of amniotic membrane by tissue banks is
not optimal for LESC therapy and the extensive donor screening processes that are
required are costly. Even if you do manage to obtain a suitable piece of amniotic
membrane for use clinically, its mechanical properties make the material difficult
to handle in surgery and its transparency is suboptimal, which is obviously a
particularly important consideration when using this material for ocular surface
repair. A worthy alternative to amniotic membrane must be optically transparent,
mechanically strong in order to withstand manipulation in culture, irrigation and
handling in surgery and also be able to conform to the concave surface of the eye.
It must be cytocompatible and able to be produced with consistent quality pref-
erably at high speed and low cost. These are the considerable challenges tissue
engineers are currently facing in the field of LESC therapy and as a result, many
innovative solutions have been proposed.
First, although the limitations of amniotic membrane have been highlighted, it
has the potential to be enhanced with modifications—a worthwhile endeavour if its
useful anti-inflammatory properties are retained. The shelf life of amniotic
membrane can be enhanced by lyophilisation and this also allows sterilisation by
gamma irradiation or peracetic acid [
52
,
53
]. The freeze-drying process can affect
some of the useful properties of amniotic membrane but treatment with a non-
reducing disaccharide, trehalose, was found to significantly improve its quality
[
54
]. Amniotic membrane can be combined with a polymer to create a hybrid,
exploiting the biocompability of a natural material but enhancing its stability
by cross-linking with substances such as polyvinyl alcohol (PVA) hydrogels or
1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide hydrochloride (EDC)/N-
hydroxysuccinimide (NHS). These mechanically strengthened materials are able to
support stratified epithelia [
55
,
56
].
Fibrin glue has historically been used in ocular surgery to aid sutureless
attachment of amniotic membrane to the corneal surface but increasingly investi-
gators are cutting out the middle man and using fibrin clots alone as a substrate for
LESC culture for transplantation [
57
-
59
]. Fibrin glue is the product of fibrinogen
