Biomedical Engineering Reference
In-Depth Information
facilitating the adhesion and colonisation of the bacterial cells [15].
Since the HA polymer produced in animals and the aforementioned
bacteria is identical, the host immune defence is not triggered to repel
the pathogenic bacteria in contrast to other bacteria with a different
extracellular capsule. Intriguingly, the non-immunogenic and non-
inflammatory properties of bacterial hyaluronan benefit mammals
indirectly too, since bacterial hyaluronan has been an excellent source
of medical grade hyaluronan [6]. The unique biocompatibility and
physicochemical properties of HA drive scientists to utilise it for
various medical and pharmaceutical applications. The most significant
clinical applications of HA are in the areas of ophthalmology,
rheumatology, otolaryngology, orthopaedics, dermatology and plastic
surgery, wound healing and tissue engineering [8]. The biological
functions of hyaluronan are strongly size-dependent. High molecular
weight hyaluronan polymers (MW > 5 × 10
5
Da) are space filling,
anti-angiogenic, and immunosuppressive, medium size hyaluronans
(MW between 2 × 10
4
and 1 × 10
5
Da) are involved in ovulation,
embryogenesis, and wound repair, while HA oligosaccharides with
15-50 repeating disaccharide units (MW between 6 × 10
3
and
2 × 10
4
Da) are inflammatory, immunostimulatory, and angiogenic.
The smallest HA oligomers (MW from 400-4,000 Da) are anti-
apoptotic and are inducers of heat shock protein synthesis [16].
Commercial production of hyaluronan is carried out by two
methods: first, by extraction from animal tissues, second by microbial
fermentation using bacterial strains. Some of the most accessible
sources for large-scale production of high MW hyaluronan are rooster
combs (MW around 1.2 × 10
6
Da), the human umbilical cord (MW
3.4 × 10
6
Da), the vitreous humour of cattle (MW 7.7 × 10
4
-1.7 ×
10
6
Da), and bovine synovial fluid (MW 14 × 10
6
Da) [17, 18].
The hyaluronan polymer isolated from animals or bacteria is
identical, and since bacterial hyaluronan is not immunogenic, it is an
excellent source for medical grade hyaluronan. Extracting hyaluronan
from microbial fermentation broth is a relatively simple process with
high yields. An additional and important advantage of microbial
hyaluronan production is that microbial cells can be physiologically
and/or metabolically adapted to produce hyaluronan of high MW.
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