Heparin-carrying polystyrene to mediate cellular attachment and growth via interaction with growth factors

Abstract

Various sugar-carrying polystyrenes (PSs), which consist of synthetic styrene and sugar moieties, are glycoconjugates that are able to attach to polymeric surfaces. Heparin-carrying PS (HCPS) is especially able to retain the binding of heparin-binding growth factors (GFs) such as vascular endothelial GF 165 (VEGF(165)) or fibroblast GF 2 (FGF-2). Human skin fibroblast cells, human coronary smooth muscle cells, and human coronary endothelial cells have good adherence to the HCPS-coated plate. The growth rate of fibroblast cells on HCPS-coated plates is higher than or comparable to fibronectin-coated, gelatin-coated, or tissue culture treated plates, and the HCPS coating inhibits the growth of smooth muscle cells. On the other hand, the growth rate of endothelial cells on HCPS-coated plates in the presence of either VEGF(165) or FGF-2 is comparable to that on fibronectin-coated, gelatin-coated, and tissue culture treated plates. Endothelial cells grow at a higher rate on HCPS-coated plates retained with either VEGF(165) or FGF-2 than on the other coated plates. These results indicate that growth of various cells can be controlled by the HCPS coating, thereby retaining the bioactivity of molecules such as heparin-binding GFs. Thus, HCPS-coated surfaces control selective growth of various cells.

Periodate-treated, non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) affects angiogenesis and inhibits subcutaneous induced tumour growth and metastasis to the lung

“…In addition, immobilization of Hep onto Matrigel was important for the inhibitory effect of NAC-HCPS on tumour cell adhesion to Matrigel. As we reported previously, NAC-HCPS is effectively adsorbed to various polymeric surfaces (Ishihara et al, 2000a), collagen (type I)-substratum (Ishihara et al, 2001) and Matrigel (data not shown) through a hydrophobic interaction between the hydrophobic surface and polystyrene core of NAC-HCPS. And cell adhesion of tumour cells (B16 and 3LL) were similarly inhibited by immobilisation of NAC-HCPS on the Matrigel (data not shown).…”

“…Periodate-oxidised (IO 4 -) Hep and periodate-oxidised, alkaline-degraded low molecular weight (IO 4 -LMW-) Hep (Fransson and Carlstedt, 1974;Fransson, 1978) are known for not having a specific pentasaccharide structure to interact with antithrombin III (Conrad and Guo, 1991), and therefore its anti-coagulant activity (APTT and PT) is much lower than Hep (Figure 2). We previously reported the preparation of NAC-HCPS using the IO 4 -LMW-Hep (Ishihara et al, 2000a). In this study, we have demonstrated that NAC-HCPS inhibits subcutaneously induced tumour growth and metastasis to lung of B16 melanoma and 3LL (Lewis lung cancer) cell line.…”

“…Non-anticoagulant Hep-carrying polystyrene was prepared as has been reported previously (Ishihara et al, 2000a). An outline of the used chemical reaction route to synthesise modified heparins and NAC-HCPS is presented in Figure 1.…”

“…The reaction solution was then slowly poured into an excess amount of ethanol to yield a polymeric precipitate. Water-soluble impurities were separated from the precipitate using ultra-filtration and finally the NAC-HCPS was obtained as a white powder after lyophilisation (Ishihara et al, 2000a). The weight fraction of NAC-Hep (non-reduced IO 4 -LMW-Hep) component in the NAC-HCPS was estimated to be 92% using a carbazole assay (Ishihara et al, 2001).…”

“…Periodate-treated, non-anticoagulant Hep-carrying polystyrene (NAC-HCPS) has been described previously as a synthetic glycoconjugate that is soluble in water and has an amphiphilic structural unit consisting of hydrophilic polysaccharides and hydrophobic polystyrene moieties (Ishihara et al, 2000a). It has been estimated that the molecular size of NAC-HCPS is approximately 80 -120 kDa and comprises of over ten periodate-oxidised, alkalinedegraded low molecular weight (IO 4 -LMW-) Hep chains enriched in trisulphated disaccharide structures linked to its polystyrene core (Ishihara et al, 2000a,b).…”