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Anterior Segment Cornea
Figure 1: PLGA–PEG–PLGA Is Liquid at 4ºC (A) and substitute basement membrane to permit host epithelial cell
Gel at 37ºC (B)
migration; thus, it is envisaged that the membrane will become
incorporated onto the ocular surface.
10,11
Although many reports have described the successful use of amniotic
membrane in ocular surface reconstruction, there have also been
several documented cases of sub-optimal results.
11,14
As such, further
investigations of the structural and biochemical properties have
revealed significant intra- and inter-donor variations, which may
account for the failures that have been reported. Moreover, there is
significant variation in the procurement and subsequent preparation of
the amniotic membrane for surgery, thus the membrane is less than
A B
standardised.
15
These problems are further compounded by the fact
that the amniotic membrane, being a biological tissue, must be
screened for transmissible diseases and be quarantined prior to clinical
PLGA = poly(DL-lactide-co-glycolide); PEG = poly(ethylene glycol).
use. Nevertheless, transmission of micro-organisms may still be a
Figure 2: Application of the PLGA–PEG–PLGA Hydrogel to significant risk.
10,11,15
These shortfalls have led researchers to consider
an Intra-lamellar Wound Made in a Rabbit Cornea (A)
synthetic alternatives that can be used as readily available
and Following 14 Days In Situ (B)
standardised alternatives to the native amniotic membrane. As such,
A B
hydrogel polymers have frequently been exploited: not only can they be
used to act as scaffolds to support cell migration and growth, but also
they can act as drug delivery vehicles for the release of medications,
growth factors and/or cytokines.
Hydrogels in Ophthalmology
Hydrogels are hydrophilic polymeric networks that are capable of
imbibing large quantities of fluid. They exist in a liquid state (sol), but
PLGA = poly(DL-lactide-co-glycolide); PEG = poly(ethylene glycol).
can be induced to convert to a semi-solid state (gel) by various
surface. As less than 5% of the applied medication reaches the chemical or physical cross-linking methods.
16
Since their original
intraocular tissues, the requirement for more frequent instillation of introduction as soft contact lenses in the 1960s,
17
hydrogel polymers
topical medication inevitably leads to increased systemic absorption of have gained increasing popularity in many biomedical applications.
16,18–21
the drug, thereby increasing the risk of systemic side effects.
12
This has As such, there is a vast diversity of hydrogels being used and studied in
necessitated the development of alternative modes of drug delivery that the biomedical field. Corneal wounds secondary to trauma and surgery
maximise ocular drug bioavailability and minimise systemic absorption are currently secured with nylon sutures, which are left in situ or
by reducing the need for frequent topical drug administration. These removed at a later date. This extra surgical step has warranted the
new modes of drug delivery include nano- and microparticles, development of hydrogel adhesives – highly branched biocompatible
liposomes, collagen shields and hydrogels,
12
all of which have been dendrimer polymers that exhibit high tensile strength and that can be
shown to be successful in prolonging drug release. Although collagen utilised to secure corneal wounds. These polymers consist of a central
shields are commercially available and have been successfully used in core component upon which additional generations of monomers are
the administration of drugs to the ocular surface, there are reservations coupled in a divergent manner. Research has focused mainly on the
regarding their use due to their bovine or porcine origins.
13
synthesis and characterisation of biocompatible polyesters,
polyester–ether and polyamide dendrimers. These polymers are
An additional treatment modality is the use of amniotic membrane, frequently cross-linked and polymerised using an argon ion laser (i.e.
which has a growing role in the management of many ocular surface they are not thermosensitive) and, although they have demonstrated
conditions. In particular, it has a distinct role in the adjuvant some promising results, they remain at the experimental stage and
management of chemical and thermal burns and persistent epithelial have yet to reach clinical practice or applications.
22
defects, as well as acting as a carrier for ex vivo expanded corneal
epithelial cells for use in ocular surface reconstruction. The amniotic Thermosensitive Hydrogel Polymers
membrane is believed to promote wound healing, reduce scarring, aid Stimuli-responsive hydrogel polymers can be induced to switch from a
epithelialisation and reduce pain. It also possesses antiangiogenic liquid to a stable gel by changes in pH, ionic strength, light and/or
and antimicrobial properties (for a review see Dua et al.
10
). Amniotic temperature. Thermosensitive hydrogels are of particular interest in
membrane consists of an epithelium, an associated basement biomedical applications due to the fact that they remain in the liquid
membrane and a thick stroma layer; clinically, it can be used as a (sol) state outside the body but, on injection or application to part of
patch or a graft. When applied basement-membrane-side-down on the human body, the increase in temperature results in formation of a
the ocular surface to act as a biological bandage, it is described as a gel that is in direct contact with the desired body cavity or surface.
patch. The aim of such a patch is to protect the ocular surface and These gels can also potentially be exploited as synthetic scaffolds for
promote epithelialisation, but, ultimately, it never becomes tissue regeneration, as well as acting as a mode of controlled delivery
incorporated onto the ocular surface. When utilised as a graft, the for a variety of therapeutic agents.
19,20,23,24
As many thermosensitive
amniotic membrane is applied stromal-side-down and basement- hydrogel systems are currently in existence, it is beyond the scope of
membrane-side-up. Here, the amniotic membrane is acting as a this article to highlight all of them (for a review see Ruel-Gariepy et
62 EUROPEAN OPHTHALMIC REVIEW