Impact of adjustable cryogel properties on the performance of prostate cancer cells in 3D

Background: Biochemical and physical characteristics of extracellular environment
play a key role in assisting cell behavior over different molecular pathways. In this study,
we investigated how the presence of chemical binding sites, the pore network and the
stiffness of designed scaffolds affected prostate cancer cells.
Methods: A blend of poly hydroxyethyl methacrylate–alginate–gelatin scaffold was
synthesized by cryogelation process using polyethyleneglycol diacrylate (PEGda) and
glutaraldehyde as cross linkers. The chemical and mechanical scaffold properties were
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varied by concentration of gelatin and PEGda, respectively. The pore network was
modified by applying different ‘freezing time’. Growth, spheroid formation and localization
of androgen receptor (AR) were measured to evaluate cell response within various
cryogel types.
Results: Insufficient porosity in combination with a brittle nature affects cell growth
negatively. Spheroid size was reduced by porosity, elasticity as well as by the absence
of the cell adhesive motif composed of arginine, glycine und aspartic acid (RGD). Localization
of AR indicates its activity and should be under normal culture conditions in the
nucleus. But in this study, we could investigate for the first time that AR remains in the
cytoplasm when AR positive prostate cancer cells are cultured in scaffolds without RGD
as well as in case of an insufficient pore network (total porosity under 10 %) and a too
less stiffness of around 10 kPa.
Conclusions: The results indicate that for getting a reliable preclinical drug screening
a three-dimensional prostate model system with appropriate biochemical and physical
surrounding is needed.

Background

Biochemical and physical characteristics of extracellular environment play a key role in assisting cell behavior over different molecular pathways. In this study, we investigated how the presence of chemical binding sites, the pore network and the stiffness of designed scaffolds affected prostate cancer cells.
Methods

A blend of poly hydroxyethyl methacrylate–alginate–gelatin scaffold was synthesized by cryogelation process using polyethyleneglycol diacrylate (PEGda) and glutaraldehyde as cross linkers. The chemical and mechanical scaffold properties were varied by concentration of gelatin and PEGda, respectively. ... mehrThe pore network was modified by applying different ‘freezing time’. Growth, spheroid formation and localization of androgen receptor (AR) were measured to evaluate cell response within various cryogel types.
Results

Insufficient porosity in combination with a brittle nature affects cell growth negatively. Spheroid size was reduced by porosity, elasticity as well as by the absence of the cell adhesive motif composed of arginine, glycine und aspartic acid (RGD). Localization of AR indicates its activity and should be under normal culture conditions in the nucleus. But in this study, we could investigate for the first time that AR remains in the cytoplasm when AR positive prostate cancer cells are cultured in scaffolds without RGD as well as in case of an insufficient pore network (total porosity under 10 %) and a too less stiffness of around 10 kPa.
Conclusions

The results indicate that for getting a reliable preclinical drug screening a three-dimensional prostate model system with appropriate biochemical and physical surrounding is needed.
Keywords