The idea of using small beads (0·2 mm),on which anchorage-dependent cells attach and grow, as a culture system wasfirst reported by van Wezel (1967). In this first experiment a positivelycharged ion-exchanger was utilized (DEAE-Sephadex) as microcarrier. Theproperties making this microcarrier effective were a charged surface, a largesurface area/volume ratio, a beaded form, transparency and a relatively lowdensity.
Using the microcarrier at a concentration of 1 g/L, van Wezel provedthat cells (HEL, human embryonic lung) were able to grow to high densities and,after inoculation with virus, the titres achieved were comparable with thosenoted with other growth systems. However, the use of this microcarriers at ahigher concentration could result in toxic effects which simultaneously effectsthe cell density. The first product tobe produced industrially using microcarriers (an inactivated polio vaccine) wasdeveloped by van Wezel himself several years later (Castilho et.al, 2008). The technology developed rapidly in the 1980s and achieved noticeablesuccess. The use of Sephadex as starting material and substituting the matrixwith DEAE groups to 1.5 meq/g dry product had brought about the generation ofmicrocarrier, Cytodex 1 which is appropriate for the growth of many kind ofcells (Hirtenstein et.al, 1980; Hirtenstein & Clark, 1980; Clark &Hirtenstein, 1980).
The use of Cytodex1 microcarriers at a concentration ofmore than 1 g/L does not produce toxic effects like DEAE Sephadex A-50 and atthe same time is able to produce high density of cells. This reduced-charge productwas the first to permit the full potential of microcarrier culture to be usedin culture volumes of up to several hundred litres (Meignier et.al, 1980; VanWezel & Van Der Velden-de Groot, 1980; Montagnon & Fanget, 1981).
Itwas specially designed for animal cell culture and fulfilled the generalrequirements for an ideal microcarrier (Van Wezel, 1976; Hirtenstein et.al,1980). The prospects formicrocarrier culture of animal cells have been widened by the development ofCytodex 3. Since charged groups are essential only for cell attachment, theyneed to be confined to the surface of the microcarriers. The development ofCytodex 3 had introduced a new concept in microcarrier culture. Instead of using synthetic charged groups topromote cell attachment, it has a surface layer of denatured collagen. Thesurface upon which cells attach is thus alike to that found in vivo.This type of surface provides maximum plating efficiency, growth and functionof certain cell types and affords itself to unique possibilities for harvestingcells from microcarrier cultures.
Nilssonand Mosbach (1980) have also analysed this approach. The followingmain step forward was macroporous gelatin microcarriers developed by Nilssonet.al (1986), which permitted growth inside thebeads, 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 suspensioncells in high cell density production systems. Cytopore was yet a furtherdevelopment that kept most of the properties similar to Cytodex but increasedthe surface area through a macroporous structure. Cytoline was developed forthe fluidized bed application, which is why the particles were weighted withsilica (Blüml et.
al, 1992). As a result, the commercialization of microcarriershad expanded and there are a variety of commercial microcarriers availabletoday such as Hillex, Glass Coated, Plastic Plus Coated, Rapid Cell P,Cytodex-3, Cytodex-2, and Cytodex-1. According to arecent study conducted by Arifin et.al (2016) a new microcarrier known as theUltraviolet/ozone (UVO3) treated polystyrene (PS) microcarrier had beendeveloped for animal cell culture using methods that are relatively easy,simple and very low-cost. The use ofthis UVO3 treated polystyrene microcarriers had resulted in a higher density ofcells compared to the use of other commercial microcarriers.
Therefore, thisnewly developed microcarrier could serve as a low-cost alternative tocommercial microcarriers available in the market today.