The (1986), which permitted growth inside the beads,

The idea of using small beads (0·2 mm),
on which anchorage-dependent cells attach and grow, as a culture system was
first reported by van Wezel (1967). In this first experiment a positively
charged ion-exchanger was utilized (DEAE-Sephadex) as microcarrier. The
properties making this microcarrier effective were a charged surface, a large
surface area/volume ratio, a beaded form, transparency and a relatively low
density. Using the microcarrier at a concentration of 1 g/L, van Wezel proved
that cells (HEL, human embryonic lung) were able to grow to high densities and,
after inoculation with virus, the titres achieved were comparable with those
noted with other growth systems. However, the use of this microcarriers at a
higher concentration could result in toxic effects which simultaneously effects
the cell density.  The first product to
be produced industrially using microcarriers (an inactivated polio vaccine) was
developed by van Wezel himself several years later (Castilho, 2008).

The technology developed rapidly in the 1980s and achieved noticeable
success. The use of Sephadex as starting material and substituting the matrix
with DEAE groups to 1.5 meq/g dry product had brought about the generation of
microcarrier, Cytodex 1 which is appropriate for the growth of many kind of
cells (Hirtenstein, 1980; Hirtenstein & Clark, 1980; Clark &
Hirtenstein, 1980). The use of Cytodex1 microcarriers at a concentration of
more than 1 g/L does not produce toxic effects like DEAE Sephadex A-50 and at
the same time is able to produce high density of cells. This reduced-charge product
was the first to permit the full potential of microcarrier culture to be used
in culture volumes of up to several hundred litres (Meignier, 1980; Van
Wezel & Van Der Velden-de Groot, 1980; Montagnon & Fanget, 1981). It
was specially designed for animal cell culture and fulfilled the general
requirements for an ideal microcarrier (Van Wezel, 1976; Hirtenstein,

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  The prospects for
microcarrier culture of animal cells have been widened by the development of
Cytodex 3. Since charged groups are essential only for cell attachment, they
need to be confined to the surface of the microcarriers. The development of
Cytodex 3 had introduced a new concept in microcarrier culture.   Instead of using synthetic charged groups to
promote cell attachment, it has a surface layer of denatured collagen. The
surface upon which cells attach is thus alike to that found in vivo.
This type of surface provides maximum plating efficiency, growth and function
of certain cell types and affords itself to unique possibilities for harvesting
cells from microcarrier cultures. Nilsson
and Mosbach (1980) have also analysed this approach.

   The following
main step forward was macroporous gelatin microcarriers developed by Nilsson  (1986), which permitted growth inside the
beads, thereby increasing cell density and protecting the cells. Young amd Dean
(1987) then described the use of microcarriers for animal cells in fluidized beds.
This advancement allowed the immobilization of both anchorage and suspension
cells in high cell density production systems. Cytopore was yet a further
development that kept most of the properties similar to Cytodex but increased
the surface area through a macroporous structure. Cytoline was developed for
the fluidized bed application, which is why the particles were weighted with
silica (Blüml, 1992). As a result, the commercialization of microcarriers
had expanded and there are a variety of commercial microcarriers available
today such as Hillex, Glass Coated, Plastic Plus Coated, Rapid Cell P,
Cytodex-3, Cytodex-2, and Cytodex-1.

  According to a
recent study conducted by Arifin (2016) a new microcarrier known as the
Ultraviolet/ozone (UVO3) treated polystyrene (PS) microcarrier had been
developed for animal cell culture using methods that are relatively easy,
simple and very low-cost.  The use of
this UVO3 treated polystyrene microcarriers had resulted in a higher density of
cells compared to the use of other commercial microcarriers. Therefore, this
newly developed microcarrier could serve as a low-cost alternative to
commercial microcarriers available in the market today.


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